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Gonadotropin releasing hormone (GnRH) and estradiol (E(2)) regulation of cell cycle in gonadotrophs. The number of pituitary cells, their size, hormonal content and release and response to external cues varies between day and night and during the estrus cycle. Previous studies have demonstrated that pituitary cells proliferate rhythmically and that estradiol (E(2)) is a mitogen of alpha T3 cells. We, therefore, studied the effect of gonadotropin releasing hormone (GnRH) and E(2), on the cell cycle in primary cultures of mouse pituitary cells and in the gonadotroph cell line L beta T2. We found that GnRH and E(2) modulate the cell cycle in a time dependent manner and induce proliferation in cultures of mouse pituitary and L beta T2 cells. GnRH induces proliferation in cells isolated in the morning of the estrus day and increases the number of cells in G2 stage when isolated in noon and evening. However, the transition into the G1 stage is enabled only by co-addition of E(2) and GnRH. GnRH stimulates LH release from L beta T2 cells after 2 days via exocytosis while after 4 days in culture, the increase in LH release may be accounted for by the increase in cell number. E(2) enhanced the GnRH response after 2 days, and abolished it after 4 days in culture. Furthermore, E(2) has no effect on LH release and cell number after 2 days in culture, however, after 4 days in culture, E(2) had no effect on the total amount of LH released but inhibited LH release per cell due to increase in cell number. Our results show that GnRH and E(2) function to shorten the cell cycle and regulate the cell number of each stage of the cell cycle. The effect of GnRH and E(2) on the cell cycle is dependent on the circadian time. This mechanism may serve to modulate the size and function of the pituitary cell population and consequently the function of pituitary gonadotrophs regulating the surge of LH release before ovulation.

Safe injection practice among health care workers, Gharbiya, Egypt. A cross-sectional study was conducted in 25 health care facilities in Gharbiya governorate to assess safe injection practices among health care workers (HCWs). Two questionnaires, one to collect information about administrative issues related to safe injection and the other to collect data about giving injections, exposure to needle stick injuries, hepatitis B vaccination status and safe injection training. Practices of injections were observed using a standardized checklist. The study revealed that there was lack of both national and local infection control policies and lack of most of the supplies needed for safe injection practices. Many safe practices were infrequent as proper needle manipulation before disposal (41%), safe needle disposal (47.5%), reuse of used syringe & needle (13.2%) and safe syringe disposal (0%). Exposure to needle stick injuries were common among the interviewed HCWs (66.2%) and hand washing was the common post exposure prophylaxis measure (63.4%). Only 11.3% of HCWs had full course hepatitis B vaccination. Infection control -including safe injections- training programs should be afforded to all HCWs.

Purification and characterization of novel trypsin-like serine proteases from mouse spleen. Novel trypsin-like serine proteases (mouse trypsin-type serine proteases 1 and 2 [MTSP-1 and -2]) were purified to homogeneity from mouse spleen. Each protease consisted of a single polypeptide with a molecular mass of about 29 kDa, as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis under reducing conditions. Both were totally inhibited by diisopropylfluorophosphate, soybean trypsin inhibitor, aprotinin, antipain, and leupeptin and partially inhibited by chymostatin and dithiothreitol, suggesting that they are trypsin-like serine proteases. They hydrolyzed synthetic substrates for trypsin-like proteases but not those for chymotrypsin-like proteases, elastase and kallikrein. MTSP-1 hydrolyzed tert-butyloxycarbonyl (Boc)-Asp(OBzl)Pro-Arg-amino-4-methyl-coumaryl-7-amide (MCA) and Boc-Ile-Glu-Gly-Arg-MCA faster than Boc-Phe-Ser-Arg-MCA. On the other hand, MTSP-2 hydrolyzed Boc-Phe-Ser-Arg-MCA most rapidly, with a specific activity 15 times higher than that of MTSP-1. The N-terminal amino acid sequence of MTSP-1 was Ile-Val-Gly-Gly-Tyr-Thr-His-Leu-Asp-Asn-Gln-Val-Pro-Tyr. This sequence was 71% homologous with the N-terminal of bovine trypsin. The Boc-Phe-Ser-Arg-MCA hydrolyzing activity of mouse spleen significantly (p < 0.01) increased to about 1.5-fold the basal activity 2 weeks after an injection of Freund's complete adjuvant, suggesting that these proteases are involved in the immune response.

The differential effect of methadone dose and of chronic pain on pain perception of former heroin addicts receiving methadone maintenance treatment. The reports on pain perception among former heroin addicts receiving methadone maintenance treatment (MMT) vary with regard to pain and intolerance threshold, and perception of suprathreshold stimuli has not been previously evaluated. Our aim was to systematically assess perception of threshold and suprathreshold noxious and innocuous stimuli with special attention to the effect of MMT dose and the presence of chronic pain. Noxious and innocuous, thermal and mechanical thresholds and ratings of suprathreshold heat-pain stimuli were measured among 31 MMT subjects receiving high and low MMT dose, with and without chronic pain, and in 17 healthy controls. The characteristics of chronic pain were also evaluated. MMT dose and chronic pain differentially affected pain perception. Whereas MMT dose did not affect thresholds, chronic pain MMT subjects exhibited increased pain threshold and pain-free MMT subjects exhibited decreased pain threshold compared with controls. MMT in general was associated with decreased perception of suprathreshold pain; however, MMT subjects with chronic pain exhibited increased suprathreshold pain ratings. It appears that subjects receiving MMT are hyperalgesic but that chronic pain in these subjects interferes with threshold measurements, inducing an apparent hypoalgesia. On the other hand, chronic pain reduces the analgesic effect of methadone seen in pain-free MMT subjects, amplifying suprathreshold pain perception. Factors such as chronic pain and MMT dose should be taken into account in future studies on pain perception in this population. We show that the presence of chronic pain and methadone dose significantly affects perception of pain in former heroin addicts receiving MMT. Studying the alteration in pain perception in these subjects may contribute to understanding the high rates of chronic pain among them and may promote better treatment.

Trauma deaths in a rural area. This study was undertaken in order to clarify the causes of death amongst rural trauma victims in Union County, Arkansas. Over a five-year time interval, seventy-two percent (n = 60) of the trauma deaths occurred at the geographical site of injury before the arrival of any emergency medical services. Thus, prolonged time to discovery of trauma victims accounts for the most significant factor leading to trauma deaths in Union County. Education regarding injury prevention must continue to be emphasized to the public.

Phase I dose-escalation study of tumor necrosis factor-alpha and concomitant radiation therapy. Tumor necrosis factor-alpha enhances x-ray killing of human tumor cells in vitro and enhances tumor control when combined with radiation in animal tumor models. To determine the toxicity and maximal tolerated dose of tumor necrosis factor-alpha given daily during radiotherapy, we conducted a phase I dose-escalation study combining tumor necrosis factor-alpha and radiation. Thirty-one patients, including 14 patients with locally advanced primary tumors and 17 patients with metastatic sites, were entered into this study. Recombinant human tumor necrosis factor-alpha was administered intravenously at doses ranging from 10 microg/m2 to 150 microg/m2 4 hours prior to each radiation therapy session, which was given on consecutive days for a minimum of 2 weeks. Radiation was prescribed to localized fields, with dose fractions ranging from 150 to 300 cGy/day for palliation or control of locally advanced tumors. Major toxicity requiring withdrawal from the study was independent of tumor necrosis factor-alpha dose and occurred in seven patients. Symptoms included angina in two patients, and hypotension, respiratory distress, atrial fibrillation, allergic reaction, and progressive leukopenia in one patient each. A tumor necrosis factor-alpha dose of 150 microg/m2 was the maximum dose administered. No single dose-limiting toxicity was observed and a maximal tolerated dose could not be defined. There was no obvious increase in in-field toxicity. Response to treatment was assessed in 20 patients. Complete regression within the irradiated field was achieved in four patients, partial regression in four, and a minimal response in four. A trend toward a greater response rate at higher doses of tumor necrosis factor-alpha was observed. The maximal tolerated dose of tumor necrosis factor-alpha when given with radiotherapy is at least 150 microg/m2 and a dose-limiting toxicity was not observed. Future studies will show whether responses to treatment are increased over those expected with radiation alone. Tumor localization of tumor necrosis factor-alpha by gene therapy combined with radiation therapy may eliminate the systemic toxicity we observed.

Parents with learning difficulties in the child protection system: experiences and perspectives. The article documents the views and feelings of parents with learning difficulties as they reflect on their first-hand experience of going through care proceedings. Drawing on interviews conducted as part of a wider study of how cases involving mothers and fathers with learning difficulties are handled by the child protection system and the family courts, the authors provide a parental perspective on assessments, support, case conferences and the court process as well as the after-effects on the families themselves.

An emerging role of dipeptidyl peptidase 4 (DPP4) beyond glucose control: potential implications in cardiovascular disease. The introduction of dipeptidyl peptidase 4 (DPP4) inhibitors for the treatment of Type 2 diabetes acknowledges the fundamental importance of incretin hormones in the regulation of glycemia. Small molecule inhibitors of DPP4 exert their effects via inhibition of enzymatic degradation of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). The widespread expression of DPP4 in tissues such as the vasculature and immune cells suggests that this protein may play a role in cardiovascular function. DPP4 is known to exert its effects via both enzymatic and non-enzymatic mechanisms. A soluble form of DPP4 lacking the cytoplasmic and transmembrane domain has also been recently recognized. Besides enzymatic inactivation of incretins, DPP4 also mediates degradation of many chemokines and neuropeptides. The non-enzymatic function of DPP4 plays a critical role in providing co-stimulatory signals to T cells via adenosine deaminase (ADA). DPP4 may also regulate inflammatory responses in innate immune cells such as monocytes and dendritic cells. The multiplicity of functions and targets suggests that DPP4 may play a distinct role aside from its effects on the incretin axis. Indeed recent studies in experimental models of atherosclerosis provide evidence for a robust effect for these drugs in attenuating inflammation and plaque development. Several prospective randomized controlled clinical trials in humans with established atherosclerosis are testing the effects of DPP4 inhibition on hard cardiovascular events.

Clinical utility of antioxidant gene expression levels in circulating cancer cell clusters for the detection of prostate cancer in patients with prostate-specific antigen levels of 4-10 ng/mL and disease prognostication after radical prostatectomy. To test antioxidant genes (AOX) expression in circulating cancer cell clusters (CCC). A novel method using molecular, polymerase chain reaction (PCR)-based detection of CCC was applied for predicting prostate cancer and to assess the effect of radical prostatectomy (RP) on reducing CCC and for prognostication of relapse-free survival (RFS), as serum total prostate-specific antigen (tPSA) has limited specificity at 4-10 ng/mL. In all, 240 patients were enrolled in the study, 129 for tumour diagnosis and 111 after RP for disease prognostication. Filtration assay in previously fractionated mononuclear cells (MNC) was used to enrich the CCC and large cells, which were retained in a mesh of 20 microm width. To establish the malignant nature of these cells they were analysed for genomic imbalances detected via PCR-assays of loss of heterozygosity in tumour suppressor loci and of DNA amplification in protooncogen loci. As a screening test in daily practice, real-time reverse transcription (RT)-PCR of AOX was introduced to overcome the laborious and expensive DNA tests. The AOX chosen were glutathione peroxidase (GPX1), Mn-dependent superoxide dismutase 2 (SOD2) and thioredoxine reductase (TXNRD1); selected from 67 marker candidate genes according to sensitivity and specificity data. AOX overexpression in CCC serves as a general marker for solid tumours needing, however, organ markers to relate to the organ of origin. Androgen receptor (AR), PSA and prostate-specific membrane antigen mRNAs served as organ markers for the prostate. Signals were detected in patients' MNC and to a minor level in CCC, rendering to CCC a substantial loss in epithelial features equivalent to a lower grade of epithelial differentiation. Organ markers in the MNC fraction were positive in <85% of AOX testing. The AOX test was tumour predicting (P < 0.001) with a sensitivity of 86%, specificity 82%, positive predictive value 69%, negative predictive value 92%, accuracy 83% and odds ratio (OR) of 28. SOD2 and TXNRD1 expression correlated to tumour size and Gleason score. Objective assessment for the evaluation of the molecular cell markers was achieved by receiver operating characteristic (ROC) curves. The areas under the ROC curve values of the AOXs were 0.7-0.9. RP was followed by a complete clearance of AOX-expressing cells. After RP, a subgroup of patients had residual CCC over-expressing only SOD2 and GPX1 indicating incomplete clearance by RP. Sustained overexpression of SOD2 and GPX1 accounted as risk factors for distant tumour recurrence (P = 0.003) mainly for bone metastases (97% M1b) as evaluated by Kaplan-Meier curves. In univariate analysis the tumour size had a limited effect on the probability of RFS (P = 0.05). In multivariate analysis tumour size, nodal status and Gleason score had no effect. This can partially be attributed to the higher risk level of pathological variables in the AOX over-expressing group but also to ineffective endocrine therapy resulting in marked overexpression of ARs and GPX1, the lead prognosticator gene. The AOX expression level allowed the identification of patients with high progression risk, who have more favourable pathological variables. The AOX testing of CCC is a novel method with excellent prognostic and predictive properties enabling the monitoring of therapies, e.g. effects of RP and endocrine therapy. We speculate that the continuing elevated expression of AOX with special emphasis on GPX1 acts as survival and defence mechanism in CCC required in an atypical environment prone to escape from immune surveillance.

Synthesis of enantiopure cyclopropyl esters from (-)-levoglucosenone. The biorenewable chiral synthon (-)-levoglucosenone has been converted to enantiopure cyclopropyl esters using the base-promoted carbocyclisation of 4,5-epoxyvalerates. This protocol was applied to the enantiospecific synthesis of the GABAc receptor agonist (1R,2R)-trans-2-aminomethylcyclopropanecarboxylic acid ((-)-TAMP) and its enantiomer. The process was also extended to generate 1,1,2- and 1,2,3-trisubstituted cyclopropanes resulting in a formal synthesis of the selective glutamate receptor antagonist PCCG-4.

Vascular catheters with a nonleaching poly-sulfobetaine surface modification reduce thrombus formation and microbial attachment. Adherence of proteins, cells, and microorganisms to the surface of venous catheters contributes to catheter occlusion, venous thrombosis, thrombotic embolism, and infections. These complications lengthen hospital stays and increase patient morbidity and mortality. Current technologies for inhibiting these complications are limited in duration of efficacy and may induce adverse side effects. To prevent complications over the life span of a device without using active drugs, we modified a catheter with the nonleaching polymeric sulfobetaine (polySB), which coordinates water molecules to the catheter surface. The modified surface effectively reduced protein, mammalian cell, and microbial attachment in vitro and in vivo. Relative to commercial catheters, polySB-modified catheters exposed to human blood in vitro had a >98% reduction in the attachment and a significant reduction in activation of platelets, lymphocytes, monocytes, and neutrophils. Additionally, the accumulation of thrombotic material on the catheter surface was reduced by >99% even after catheters were exposed to serum in vitro for 60 days. In vivo, in a highly thrombogenic canine model, device- and vessel-associated thrombus was reduced by 99%. In vitro adherence of a broad spectrum of microorganisms was reduced on both the external and the internal surfaces of polySB-modified catheters compared to unmodified catheters. When unmodified and polySB-modified catheters were exposed to the same bacterial challenge and implanted into animals, 50% less inflammation and fewer bacteria were associated with polySB-modified catheters. This nonleaching, polySB-modified catheter could have a major impact on reducing thrombosis and infection, thus improving patient health.

Plasma ammonia levels in very low birth weight preterm infants. The mean plasma ammonia level at birth of 36 very low birth weight infants (< or = 32 weeks of gestation) was 71 +/- 26 mumol/L (121 +/- 45 micrograms/dl), which is similar to the mean level in preterm infants born at > or = 32 weeks of gestational age. Plasma ammonia levels declined to 42 +/- 14 mumol/L (72 +/- 24 micrograms/dl) at 7 days of age; mean ammonia levels at 14, 21, and 28 days of age were similar to that at 7 days of age and to the mean plasma ammonia level of 14 healthy term infants at birth (45 +/- 9 mumol/L (77 +/- 16 micrograms/dl)).

Low-dimensional chainlike assemblies of TiO2 nanorod-stabilized Au nanoparticles. A simple and versatile light-based strategy to grow low-dimensional gold superstructures is presented; prolonged UV-irradiation of TiO2 nanorod-stabilized Au nanoparticles in organic media promotes the progressive formation of distinctive chainlike metal assemblies, namely segments of a few gold particles, 2D or quasi-1D large structures composed of interlacing lines of hundreds of metal units over areas of about 500 nm2.

Learning and attention in multidimensional identification and categorization: separating low-level perceptual processes and high-level decisional processes. Four observers completed identification and categorization tasks. Learning and attention processes were examined by applying general recognition theory (F. G. Ashby & J. T. Townsend, 1986), which separates perceptual, decisional, and attentional processes. Learning led to decision regions that became more nearly optimal. Learning had little effect on perceptual processes in identification and decisional integration categorization tasks but affected perceptual processes in decisional selective attention categorization tasks, leading to perceptual selective attention. These findings suggest that (a) identification and categorization invoke decision strategies that are localized in the striatum (F. G. Ashby, E. M. Waldron, W. W. Lee, & A. Berkman, 2001) and (b) perceptual and decisional attention systems exist and are mediated by distinct brain structures (M. I. Posner & S. E. Petersen, 1990).

Thermoluminescent determination of prehistoric heat treatment of chert artifacts. In recent years archeologists have become interested in the extent to which prehistoric peoples heat-treated chert prior to shaping it into tools. Thermoluminescent determination of the radiation dose accumulated by an artifact since it was formed or last heated provides a simple, reliable test for such heat treatment. This test can be applied to single artifacts without the need for raw source material for comparison. Results on 25 artifacts from four sites indicate that, for many chert sources, color and luster are not useful indicators of heat treatment by prehistoric peoples.

Perilymphatic communication routes in the auditory and vestibular system. Horseradish peroxidase was injected into the foramen magnum and oval window of guinea pigs to determine perilymphatic communication routes and boundaries. The primary route to the auditory system appeared to be through the cochlear aqueduct. Perineural spaces of the eighth nerve contributed to this communication and provided the principal perilymphatic communication routes to the vestibular system. Light and electron microscopic examination were used to identify membrane permeability and define boundaries in the epithelial lining of the auditory and vestibular endorgans.

[Emotion-focused couples therapy--treatment approach--evaluating effectiveness and process research]. Emotionally-Focused Couple/Marital Therapy will be examined and discussed in terms of methods of treatment, its effectiveness and underlying therapy processes. Four different evaluation studies have demonstrated the effectiveness of Emotionally-Focused Couple/Marital Therapy when used to resolve difficulties between couples with slight to moderately severe problems relatively in regard to pertinent treatment alternatives and absolutely in comparision to nontreatment. In addition, its clinical relevance has been demonstrated. Moreover, five studies on the investigation of procedures have reached conclusions which concur with the theory of treatment postulated.

Sex, shame and the transcendent function: the function of fantasy in self development. This paper explores a developmental approach to the sense of self-agency and to its influence on conscious and unconscious fantasy. I suggest that the emerging sense of self-agency offers an over-arching framework for our understanding of the nature and function of fantasy. In this context, intrusive and compulsive sexual fantasies which a person experiences as perverted and shameful, can be seen to serve differing psychic purposes, depending on the level of self-agency which is predominant. The fantasies can serve both as warning signals of the dangers of relationship and as opportunities for the mind to reflect on its own processes. Differing psychodynamic theories of fantasy are examined in terms of the developmental sense of self-agency that they represent.

Intracellular localization of (99m)Tc-d,l-HMPAO in rat blood. The objective of this study was to investigate the intracellular localization of technetium 99m-hexamethylpropylene amine oxime ((99m)Tc-d,l-HMPAO) in rat red blood cells (RBCs) and plasma. Sprague-Dawley rats (n = 36) were injected with 129.5 MBq (99m)Tc-d,l-HMPAO. Using a heparinized syringe, 2-ml blood samples were withdrawn from the rats 10, 20, 30, 40, 50 and 60 min after (99m)Tc-d,l-HMPAO injection. Blood was centrifuged for 10 min at 2,240 rpm to separate RBCs from plasma. A chloroform/methanol/distilled water mixture was added to the RBCs and plasma in separate tubes to extract (99m)Tc-d,l- HMPAO into aqueous (Aq) and lipid (Lp) phases. The (99m)Tc-d,l-HMPAO activities in Aq and Lp phases were measured separately using a dose calibrator. The data were analyzed using Student's t test and a one-way ANOVA. More than 70% of the injected dose of (99m)Tc-d,l-HMPAO was retained in the RBCs for up to 60 min, compared to less than 20% in plasma. The uptakes in the Aq for plasma were 88.77 +/- 1.04, 94.23 +/- 2.42, 90.15 +/- 1.88, 98.59 +/- 0.89, 96.42 +/- 1.50 and 97.59 +/- 1.92% at 10, 20, 30, 40, 50 and 60 min after injection, respectively. The corresponding uptakes in the Lp phases were: 11.23 +/- 0.04, 5.77 +/- 0.07, 9.85 +/- 0.06, 1.41 +/- 0.08, 3.58 +/- 0.04 and 2.41 +/- 0.06, respectively. Similar values (% +/- SE) and trends were obtained in the Aq and Lp phases for RBCs. A highly significant difference between the Aq and Lp phases at each time point studied was observed (p < 0.0001). There was no statistically significant difference between the time points in the Aq phase, but there was a significant difference (p < 0.001) between time points in the Lp phase. This study demonstrated that most of the intracellular localization of (99m)Tc-d,l-HMPAO was in the Aq phase compared to Lp phase in both RBCs and plasma up to 60 min.

Seated saline suppression testing for the diagnosis of primary aldosteronism: a preliminary study. Failure of aldosterone suppression by sodium loading during fludrocortisone suppression testing (FST) or saline suppression testing (SST) confirms primary aldosteronism (PA). We previously found recumbent SST (RSST) to lack sensitivity. Aldosterone levels can be higher upright (e.g. seated) than recumbent in patients with PA and upright levels are used during FST. We therefore hypothesized that seated SST (SSST) is more sensitive than RSST, especially for posture-responsive PA. Of 66 patients who underwent FST (upright plasma aldosterone levels measured at 10am basally and after 4 days fludrocortisone 0.1 mg 6-hourly and oral salt loading), 31 underwent SST (aldosterone levels measured basally at 8am and after infusion of 2 L normal saline over 4h) both recumbent and seated in randomized order and at least 2 weeks apart. FST confirmed PA in 23 of 31 patients (day 4 upright aldosterone level >165 pmol/L), excluded PA in three and was originally "inconclusive" in five. However, one with "inconclusive" FST had PA confirmed by lateralizing AVS and was reclassified "unilateral PA". Of 24 with confirmed PA (eight unilateral, 11 bilateral, and five undetermined subtype), 23 (96%) tested positive by SSST (4-h aldosterone level >165 pmol/L) compared with 8 (33%) by RSST (4-h plasma aldosterone level >140 pmol/L) (P < .001). RSST missed one unilateral, all bilateral, and four with as-yet undetermined subtype. RSST was positive in 7 of 10 (70%) posture-unresponsive vs one of 14 (7.1%) posture-responsive patients (P < .005). These preliminary results suggest that seated SST may be superior to recumbent SST in terms of sensitivity for detecting PA, especially posture-responsive forms, and may represent a reliable alternative to FST.

Spinal anaesthesia and non-invasive positive pressure ventilation for hip surgery in an obese patient with advanced chronic obstructive pulmonary disease. We describe the use of non-invasive positive pressure ventilation combined with spinal anaesthesia to allow the insertion of a dynamic hip screw in an obese patient with advanced chronic obstructive pulmonary disease. The technique avoided the hazards of intubation and general anaesthesia in this high-risk patient.

Lycopene: chemistry, biology, and implications for human health and disease. A diet rich in carotenoid-containing foods is associated with a number of health benefits. Lycopene provides the familiar red color to tomato products and is one of the major carotenoids in the diet of North Americans and Europeans. Interest in lycopene is growing rapidly following the recent publication of epidemiologic studies implicating lycopene in the prevention of cardiovascular disease and cancers of the prostate or gastrointestinal tract. Lycopene has unique structural and chemical features that may contribute to specific biological properties. Data concerning lycopene bioavailability, tissue distribution, metabolism, excretion, and biological actions in experimental animals and humans are beginning to accumulate although much additional research is necessary. This review will summarize our knowledge in these areas as well as the associations between lycopene consumption and human health.

Constrictive bronchiolitis associated with paraneoplastic autoimmune multi-organ syndrome. Constrictive bronchiolitis is a rare and potentially fatal manifestation of paraneoplastic autoimmune multi-organ syndrome (PAMS), also called paraneoplastic pemphigus. The current review aimed to assess the frequency and clinical features of constrictive bronchiolitis occurring in patients with PAMS. A computer-assisted search of medical records identified 17 patients with PAMS seen during the period 1994-2007. Medical records, radiological studies and biopsy results were reviewed. There were 10 men and 7 women; the median age at diagnosis of PAMS was 60 years (range 33-72 years). Non-Hodgkin's lymphoma and chronic lymphocytic leukaemia were the underlying neoplasms in over two-thirds of these patients. Constrictive bronchiolitis was diagnosed in three patients who had respiratory symptoms, severe airflow obstruction on pulmonary function testing and evidence of air trapping on CT scanning with no other identifiable cause for these findings. In contrast to previous reports, two of the three patients with constrictive bronchiolitis presented with skin and respiratory manifestations in the absence of a known neoplasm. Seven patients with PAMS died (41%) after a median interval of 13 months (range 1-33 months) and the deaths included two of the constrictive bronchiolitis patients who continued to worsen despite immunosuppressive therapy. In a minority of patients with PAMS, constrictive bronchiolitis occurs and tends to cause progressive airflow obstruction that responds poorly to immunosuppressive therapy. Constrictive bronchiolitis in these patients may be manifest prior to the discovery of the underlying neoplasm and the diagnosis of PAMS.

Epithelial downgrowth following the removal of iris inclusion cysts. We present three patients in whom epithelial downgrowth occurred following the excision of iris inclusion cysts. The sheet-like downgrowth was aggressively treated and successfully eradicated in two of the three patients. Early identification and prompt therapy are essential.

Patient safety in emergency medical services: executive summary and recommendations from the Niagara Summit. Emergency medical services (EMS) personnel care for patients in challenging and dynamic environments that may contribute to an increased risk for adverse events. However, little is known about the risks to patient safety in the EMS setting. To address this knowledge gap, we conducted a systematic review of the literature, including nonrandomized, noncontrolled studies, conducted qualitative interviews of key informants, and, with the assistance of a pan-Canadian advisory board, hosted a 1-day summit of 52 experts in the field of EMS patient safety. The intent of the summit was to review available research, discuss the issues affecting prehospital patient safety, and discuss interventions that might improve the safety of the EMS industry. The primary objective was to define the strategic goals for improving patient safety in EMS. Participants represented all geographic regions of Canada and included administrators, educators, physicians, researchers, and patient safety experts. Data were collected through electronic voting and qualitative analysis of the discussions. The group reached consensus on nine recommendations to increase awareness, reduce adverse events, and suggest research and educational directions in EMS patient safety: increasing awareness of patient safety principles, improving adverse event reporting through creating nonpunitive reporting systems, supporting paramedic clinical decision making through improved research and education, policy changes, using flexible algorithms, adopting patient safety strategies from other disciplines, increasing funding for research in patient safety, salary support for paramedic researchers, and access to graduate training in prehospital research.

Natural history of an acute glomerulonephritis epidemic in children. An 11- to 12-year follow-up. During an epidemic of poststreptococcal acute glomerulonephritis (PSAGN) in Israel during the second half of 1968, 155 children were hospitalized. All of them were initially followed up for 6 mo to 2 yr, during which period no evidence of continuing kidney damage was found. Fifty-five of the group were hospitalized over the next 2 to 10 yr for reasons unrelated to their original illness, at which time they also were found to be free of renal damage. Eighty children were examined 11 to 12 yr after the epidemic, and in them, too, urine examination, blood chemistry and blood pressure were within normal limits. It seems reasonable to conclude that the PSAGN of the 1968 epidemic was a benign disease with no lasting ill effects. Since most of the cases were associated with an M-55 skin Streptococcus and pyoderma, we suggest that glomerulonephritis due to pyoderma associated with this strain does not give rise to chronic renal disease.

Considering the needs of indigenous and local populations in conservation programs. Local rural and indigenous communities have assumed increasing responsibility for conservation within and between areas buffering the impacts of agricultural or resource-extraction zones and protected areas. Empowering local communities as central partners in conservation and climate-change mitigation has allowed many people to gain access to land and citizenship rights but has provided limited improvements in access to social services and economic opportunities even as expectation about their role as environmental stewards grows. These expectations, however, are inconsistent with reality. We conducted multiple field studies in Brazil since the mid-1980s to illustrate the discrepancies between conservation programs and local conditions and expectations. We suggest that public policies and conservation programs should not delegate responsibility for managing protected areas to local and indigenous communities without considering local needs and expectations and locals' attitudes toward conservation. In other words, behavior that maintains or improves the environment should not be treated as traditional based on the expectations of outsiders. Framing local populations as traditional environmentalists creates contradictions and frustrations for local populations and for conservation professionals and policy makers.

Repair but not potentiation observed in mouse lung irradiated with neon ions. The lungs of mice were irradiated with 1, 4, or 7 fractions of X rays or neon ions in a 4-cm spread Bragg peak. Lung function as a function of total radiation dose was tested at 7 and 12 months after irradiation by measuring the resting breathing rate in a whole-body plethysmograph. The isoeffect doses increased sequentially with X rays for 1 through 4 to 7 fractions, demonstrating repair of sublethal radiation injury as previously reported. There was also a significant increase of isoeffect dose with neon ions between 1 and 4 fractions but no further increase at 7 fractions. Thus repair instead of potentiation of radiation injury in lung clearly occurred after neon ion irradiation. The effectiveness of neon ions appeared to be closer to that of neutrons with a mean energy of 8 meV than those with a mean energy of 2.3 meV.

Marcelian charm in nursing practice: the unity of agape and eros as the foundation of an ethic of care. In the nursing literature, a number of qualities are associated with loving care. Reference is made to, among other things, humility, attentiveness, responsibility and duty, compassion, and tenderness. The author attempts to show that charm, in the Marcelian sense, also plays a central role. It is argued that the moral foundation of charm is a unity of agape and eros. An impartial giving of the self for others is clearly of fundamental importance in an ethic of care. Including charm in the discussion points to the fact that eros also plays a crucial role. Eros produces a passion for people and for life. It is a physical and spiritual energy that animates a person in all facets of her life, including her caring work.

Group differences in anterior hippocampal volume and in the retrieval of spatial and temporal context memory in healthy young versus older adults. The ability to retrieve temporal and spatial context information from memory declines with healthy aging. The hippocampus (HC) has been shown to be associated with successful encoding and retrieval of spatio-temporal context, versus item recognition information (Davachi, Mitchell, & Wagner, 2003; Nadel, Samsonovich, Ryan, & Moscovitch, 2000; Ross & Slotnick, 2008). Aging has been linked to volume reduction in the HC (Bouchard, Malykhin, Martin, Hanstock, Emery, Fisher, & Camicioli, 2008; Malykhin, Bouchard, Camicioli, & Coupland, 2008; Raz et al., 2005). As such, age-associated reductions in anterior HC volume may contribute to the context memory deficits observed in older adults. In the current MRI study we investigated whether item recognition, spatial context and temporal context memory performance would be predicted by regional volumes in HC head (HH), body (HB) and tail (HT) volumes, using within group multiple regression analyses in a sample of 19 healthy young (mean age 24.3) and 20 older adults (mean age 67.7). We further examined between age-group differences in the volumes of the same HC sub-regions. Multiple regression analyses revealed that in younger adults both spatial and temporal context retrieval performance was predicted by anterior HC volume. Older age was associated with significant volume reductions in HH and HB, but not HT; and with reduced ability to retrieve spatial and temporal contextual details from episodic memory. However, HC volumes did not predict context retrieval performance in older adults. We conclude that individual differences in anterior, not posterior, HC volumes predict context memory performance in young adults. With age there may be a posterior-to-anterior shift from using HC-related processes, due to HC volume loss, to employing the prefrontal cortex to aid in the performance of cognitively demanding context memory tasks. However, due to concomitant changes in the prefrontal system with age, there are limits to compensation in the aging brain.

A monoclonal antibody which recognizes a glycosaminoglycan epitope in both dermatan sulfate and chondroitin sulfate proteoglycans of human skin. Studies have been initiated to identify various cell surface and matrix components of normal human skin through the production and characterization of murine monoclonal antibodies. One such antibody, termed PG-4, identifies both cell surface and matrix antigens in extracts of human foetal and adult skin as the dermatan sulfate proteoglycans, decorin and biglycan, and the chondroitin sulfate proteoglycan versican. Treatment of proteoglycans with chondroitinases completely abolishes immunoreactivity for all of these antigens which suggests that the epitope resides within their glycosaminoglycan chains. Further evidence for the carbohydrate nature of the epitope derives from competition studies where protein-free chondroitin sulfate chains from shark cartilage react strongly; however, chondroitin sulfate chains from bovine tracheal cartilage fail to exhibit a significant reactivity, an indication that the epitope, although present in some chondroitin sulfate chains, does not consist of random chondroitin 4- or 6-sulfate disaccharides. The presence of the epitope on dermatan sulfate chains and on decorin was also demonstrated using competition assays. Thus, PG-4 belongs to a class of antibodies that recognize native epitopes located within glycosaminoglycan chains. It differs from previously described antibodies in this class in that it identifies both chondroitin sulfate and dermatan sulfate proteoglycans. These characteristics make PG-4 a useful monoclonal antibody probe to identify the total population of proteoglycans in human skin.

Microbial transformation of rubijervine. Preparative-scale fermentation of rubijervine (1), the known 22,26-epiminocholestane Veratrum alkaloid, with Cunninghamella echinulata ATCC 9244 has resulted in the isolation of the new metabolites 7alpha-hydroxyrubijervine (2) and solanid-5-ene-3beta,12alpha-diol-1-one (3). Structure elucidation of these metabolites was based primarily on 1D- and 2D-NMR analyses. The microbe C. echinulata ATCC 9244 was able to metabolize rings A and B of rubijervine but failed to metabolize rings C, D or its N-containing side chain, a finding which is analogous to the results of previous fermentation studies of steroidal alkaloids.

[Serum B-protein in patients with nasopharyngeal carcinoma]. B-protein is an acidic glycoprotein that appears in the serum of cancer patients, although it is not produced by cancer cells. It is not a cell surface antigen but can serve as a biological marker for detecting malignancies and monitoring cancer therapy. From January to August 1987, serum samples were collected from 133 patients with nasopharyngeal carcinoma (NPC) and 19 patients without cancer as the control group. The positive rates of B-protein in NPC patients without distant metastasis (107) and with distant metastasis (26) were 78.5% and 84.6% respectively. The overall positive rate of B-protein in NPC patients was 79.7%, which did not correlate with tumor stage and sex. The positive rate of B-protein in the control group was 5.3%. The difference in positive rates between NPC and the control group was significant (p less than 0.001). The quantitative changes of B-protein did not correlate with the tumor burden of NPC patients. Therefore, B-protein assay is not recommended in monitoring the treatment of NPC.

Ketamine interferes with the proliferation and differentiation of neural stem cells in the subventricular zone of neonatal rats. Previous studies have shown ketamine can alter the proliferation and differentiation of neural stem cells (NSCs) in vitro. However, these effects have not been entirely clarified in vivo in the subventricular zone (SVZ) of neonatal rats. The present study was designed to investigate the effects of ketamine on the proliferation and differentiation of NSCs in the SVZ of neonatal rats in vivo. Postnatal day 7 (PND-7) male Sprague-Dawley rats were administered four injections of 40 mg/kg ketamine at 1-h intervals, and then 5-bromodeoxyuridine (BrdU) was injected intraperitoneally at PND-7, 9 and 13. NSC proliferation was assessed with Nestin/BrdU double-labeling immunostaining. Neuronal and astrocytic differentiation was evaluated with β-tubulin III/BrdU and GFAP/BrdU double-labeling immunostaining, respectively. The expressions of nestin, β-tubulin III and GFAP were measured using Western blot analysis. The apoptosis of NSCs and astrocytes in the SVZ of neonatal rats was evaluated using nestin/caspase-3 and GFAP/caspase-3 double-labeling immunostaining. Neonatal ketamine exposure significantly reduced the number of nestin/BrdU and GFAP/BrdU double-positive cells in the SVZ. Meanwhile, the expressions of nestin and GFAP in the SVZ from the ketamine group were significantly decreased compared those in the control group. Still, no double-positive cells for nestin/caspase-3 and GFAP/caspase-3 were found after ketamine exposure. In addition, the neuronal differentiation of NSCs in the SVZ was markedly promoted by ketamine with an increased number of β-tubulin III/BrdU double-positive cells and enhanced expression of β-tubulin III. These effects of ketamine on the NSCs in the SVZ often lasted at least 1 week after ketamine anesthesia. In the present study, it was demonstrated that ketamine could alter neurogenesis by inhibiting the proliferation of NSCs, suppressing their differentiation into astrocytes and promoting the neuronal differentiation of the NSCs in the SVZ of neonatal rats during a critical period of their neurodevelopment.

Absence of mutations in the granulocyte colony-stimulating factor (G-CSF) receptor gene in patients with myelodysplastic syndrome/acute myeloblastic leukaemia occurring after treatment of aplastic anaemia with G-CSF. The development of myelodysplastic syndrome/acute myeloblastic leukaemia (MDS/AML) has been reported in patients with aplastic anaemia (AA) after administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF). Similarly, patients with severe congenital neutropenia (SCN) have an increased risk of developing MDS/AML after treatment with rhG-CSF. Point mutations in the G-CSF receptor gene are found in about 20% of SCN patients who are predisposed to MDS/AML. We investigated the occurrence of mutations in the G-CSF receptor in eight patients with AA who developed MDS/AML. No mutations were detected around the cytoplasmic domain of the gene in our patients, indicating that the mechanisms of clonal evolution to MDS/AML in patients with AA might be different from those with SCN.

Human papillomavirus type 16 E5 inhibits interferon signaling and supports episomal viral maintenance. Human papillomaviruses (HPVs) infect keratinocytes of stratified epithelia. Long-term persistence of infection is a critical risk factor for the development of HPV-induced malignancies. Through the action of its oncogenes, HPV evades host immune responses to facilitate its productive life cycle. In this work, we have discovered a previously unknown function of the HPV16 E5 oncoprotein in the suppression of interferon responses. This suppression is focused on keratinocyte-specific IFNκ and is mediated through E5-induced changes in growth factor signaling pathways as identified through phosphoproteomics analysis. The loss of E5 in keratinocytes maintaining the complete HPV16 genome results in the de-repression of IFNK transcription and subsequent JAK/STAT-dependent upregulation of several ISGs at both mRNA and protein levels. We also establish a link between the loss of E5 and the subsequent loss of genome maintenance and stability, resulting in increased genome integration.Importance Persistent human papillomavirus infections can cause a variety of significant cancers. The ability of HPV to persist depends on evasion of the host immune system. In this study, we show that the HPV16 E5 protein can suppress an important aspect of the host immune response. In addition, we find that the E5 protein is important for helping the virus avoid integration into the host genome, which is a frequent step along the pathway to cancer development.

The role of the membrane-bound iron-sulphur centres A and B in the photosystem I reaction centre of spinach chloroplasts. Photosystem I particles prepared from spinach chloroplast using Triton X-100 were frozen in the dark with the bound iron-sulphur Centre A reduced. Illumination at cryogenic temperatures of such samples demonstrated the photoreduction of the second bound iron-sulphur Centre B. Due to electron spin-electron spin interaction between these two bound iron-sulphur centres, it was not possible to quantify amounts of Centre B relative to the other components of the Photosystem I reaction centre by simulating the line-shape of its EPR spectrum. However, by deleting the free radical signal I from the EPR spectra of reduced Centre A alone or both Centres A plus B reduced, it was possible to double integrate these spectra to demonstrate that Centre B is present in the Photosystem I reaction centre in amounts comparable to those of Centre A and thus also signal I (P-700) and X. Oxidation-reduction potential titrations confirmed that Centre A had Em congruent to -550 mV, Centre B had Em congruent to -585 mV. These results, and those presented for the photoreduction of Centre B, place Centre B before Centre A in the sequence of electron transport in Photosystem I particles at cryogenic temperatures. When both A and B are reduced, P-700 photooxidation is reversible at low temperature and coupled to the reduction of the component X. The change from irreversible to reversible P-700 photooxidation and the photoreduction of X showed the same potential dependence as the reduction of Centre B with Em congruent to -585 mV, substantiating the identification of X as the primary electron acceptor of Photosystem I.

Is Helicobacter pylori really present in the adenoids of children? Adenoid hyperplasia is a common cause of nasal obstruction in the pediatric age group. Recently, the adenoids were shown to harbor Helicobacter pylori (HP) based only on the rapid urease test (RUT). We conducted this pilot study to identify the presence of HP in the adenoids histologically and assess the reliability of both the RUT and histology in detecting HP in an extragastric location, using nested (two-steps) polymerase chain reaction (nPCR). Consecutive patients undergoing adenoidectomy for obstructive adenoid hyperplasia were enrolled. Adenoid specimens were subjected to the RUT. Histological sections stained with hematoxylin and eosin, Giemsa and Warthin-Starry were examined. We then used nPCR to detect the presence of HP in the studied specimens. Twenty-five patients (3-10 years; mean of 5.5 years) were enrolled. Twenty-one (84%) adenoids were positive by the RUT. Seventeen (68%) had bacteria on histological sections; four (16%) contained HP-like organisms. However, all specimens were negative by nPCR. No patient had a history of symptoms suggestive of laryngopharyngeal reflux within 6 months of the study. In conclusion, the children enrolled in this study did not have HP in their adenoids. High false positive results can occur with the RUT when used on adenoid tissues. It is not possible to rely solely on morphology to detect HP in an extragastric location. The nPCR remains the best way to identify HP accurately, but does not imply its presence in an active role.

[On a case of aphasia with thalamic lesion (author's transl)]. The possibility of aphasic disorder caused by thalamic lesions has been supported by anatomo-clinical findings, stereotaxic surgery and more recently by radiological investigations with new techniques, i.e. ct and brain scan. A case of thalamic aphasia investigated with these techniques and the Luria's neuropsychological test is reported in this paper. The case concerns a 50 years old woman who developed a sudden right hemiplegia with marked motor aphasia. C.T. and radioisotope brain scan revealed a left capsular haemorrhage with involvement of thalamic structures. Later, when this patient's aphasia decreased, Luria's test showed reduction of spontaneous speech, anomia, paraphasic and disarthric disorder, distractibility without impairment of comprehension and repitition. These findings are similar to those reported by some AA. in left thalamic lesions and similar to aphasic syndromes caused by cortical lesions. Another important observation was the presence of widespread cortical functional disorder involving the left fronto-temporo-parietal region without evidence of cortical anatomical alteration. The above data and those reported in the literature suggest a very close relationship between thalamic structures, other central nuclei and cortical areas particularly in the control of speech.

Depressive symptom experiences among older women: a comparison of alternative measurement approaches. Age differences in depressive symptom experiences were investigated in a community sample of women (N = 287, ages 55-95 years). The purpose of the analysis was to compare the age-depression relation using 3 different measurement approaches: (a) a standard screening scale, (b) a clinical diagnostic, and (c) a latent variable measurement approach. The analysis, which uses structural equation modeling procedures, extends earlier confirmatory factor analyses of the Symptom Checklist-90--Revised Depression and Additional Symptoms scales conducted by Newmann, Engel, & Jensen (1990, 1991a, 1991b). Findings show that each measurement approach leads to different conclusions about the age-depression relation, with only the latent variable measurement showing a significant increase in depressive symptoms with advancing age. Implications of these findings for future research on aging depression are discussed.

Atypical heel pain. Hyperparathyroidism-induced stress fracture of the calcaneus. The authors present a case of atypical heel pain masquerading as plantar fasciitis. The patient was subsequently diagnosed with hyperparathyroidism-induced stress fracture of the calcaneus. The clinical entity of hyperparathyroidism and its manifestations in the skeletal system are presented, as well as a review of stress fractures and pertinent imaging studies.

Emergency surgery for extrinsic coronary compression after percutaneous pulmonary valve implantation. Coronary artery compression is a rare and potentially fatal complication after percutaneous pulmonary valve implantation. We report on a case of an acute antero-septal non-ST myocardial infarction secondary to the partial laceration of the conduit and the creation of a thrombus giving an extrinsic compression of left anterior descendent coronary artery after Melody valve implantation.

Biochemical changes of the human semen produced by chlorambucil, testosterone propionate and human chorionic gonadotropin administration. Biochemical analysis and morphological studies were carried out in six patients with lymphomas during and after withdrawal treatment with chlorambucil, testosterone propionate (TP) and human chorionic gonadotropins (HCG). In the course of the treatment with chlorambucil patients developed severe oligozoospermia or azoospermia. The spermatogenesis recovered after a variable period of time following suspension of treatment. During the drug administration seminal fructose and citric acid concentrations increase but the recovery after withdrawal takes a longer period of time. Simultaneous treatment with HCG or TP normalized the biochemical parameters without restoring spermatogenesis.

[Pulmonary tuberculosis as detected by different methods]. As a result of the study of clinico-roentgenologic pictures of 379 patients with newly-diagnosed pulmonary tuberculosis, asymptomatic and undetectable development of the disease was found in 64.2% of the cases with non-destructive and in 35.0% with destructive processes. Besides, clinical symptoms of 36.1% of the patients were neglected. The above situation proves it necessary to conduct preventive fluorographic examinations of the chest at least once every 2 years. Their quality should be significantly improved, as many patients had fluorographic changes on the prior examination, which were missed or misinterpreted. The organization of early tuberculosis detection cannot be judged from the proportion of destructive processes in the pattern of tuberculosis morbidity.

Sepsis programme successes are responsible for the increased detection of bacteraemia. Escherichia coli bacteraemia reduction targets are challenging but, in West Wales, this was the key infection surrogate measure set by the local health board in 2013, prior to the introduction of a Welsh Government target. The initial plateau of cases was not maintained and prompted this review. To review all blood cultures submitted between 2002 and 2016, both positive and negative. With access to a microbiology data warehouse in Wales, all blood culture results were collected, extracted to Excel tables and analysed using change point analysis. Just under 200,000 blood culture results were examined. This study found an increase in blood culture submissions, but the positivity rate remained constant throughout the period and the increased number of E. coli reflected the increased number of blood cultures taken. This demonstrated the success of sepsis awareness and the use of sepsis bundles for rapid diagnosis and management. Success in one area (sepsis management) conflicts with 'failure' in reducing E. coli bacteraemia. It is argued that targets need to be considered carefully in the light of all available information, which have currently set the National Health Service up to fail.

Bioelectrochemical recovery of waste-derived volatile fatty acids and production of hydrogen and alkali. Volatile fatty acids (VFA) are organic compounds of great importance for various industries and environmental processes. Fermentation and anaerobic digestion of organic wastes are promising alternative technologies for VFA production. However, one of the major challenges is development of sustainable downstream technologies for VFA recovery. In this study, an innovative microbial bipolar electrodialysis cell (MBEDC) was developed to meet the challenge of waste-derived VFA recovery, produce hydrogen and alkali, and potentially treat wastewater. The MBEDC was operated in fed-batch mode. At an applied voltage of 1.2 V, a VFA recovery efficiency of 98.3%, H2 of 18.4 mL and alkali production presented as pH of 12.64 were obtained using synthetic fermentation broth. The applied voltage, initial VFA concentrations and composition were affecting the VFA recovery. The energy balance revealed that net energy (5.20-6.86 kWh/kg-VFA recovered) was produced at all the applied voltages (0.8-1.4 V). The coexistence of other anionic species had no negative effect on VFA transportation. The VFA concentration was increased 2.96 times after three consecutive batches. Furthermore, the applicability of MBEDC was successfully verified with digestate. These results demonstrate for the first time the possibility of a new method for waste-derived VFA recovery and valuable products production that uses wastewater as fuel and bacteria as catalyst.

Note on the genus Morimospasma Ganglbauer with description of two new species from China (Coleoptera: Cerambycidae: Lamiinae). The genus Morimospasma Ganglbauer, 1890 is reviewed. Two new species, M. jiangi sp. nov. and M. dalaolingensis sp. nov., are described and illustrated. M. paradoxum Ganglbauer is newly recorded from Anhui, China. Taxonomic status of M. nitidituberculatus Hua is discussed. The Chinese names of M. jiangi sp. nov. and M. dalaolingensis sp.nov. are designated, respectively, as Jiǎngshì Jùliútiānniú and Dàlǎolǐng Jùliútiānniú in Chinese phonetic alphabet. A key to all six species of Morimospasma is provided.

Sun oils: effect of the applied dose on SPF determined by using in vitro method. The relationship between skin cancer and exposure to the sun is now clearly established. It is therefore necessary to ensure that consumers have effective sun protection. The effectiveness of the anti-solar products is quantified using a universal indicator, the SPF (sun protection factor). This value can be given in two different ways: by in vivo (standard ISO 24444:2010) and in vitro methods. The in vitro method was adopted for this study, for ethical reasons. The protective effect regarding non-melanoma cancers given by sun products has been proven. It is nevertheless a fact that consumers need to be made aware. Indeed, the quantity of sun protection product applied in reality by the consumer is clearly lower than the recommended amount. Under these conditions, the following question can be asked: What is the level of protection attained if half or even a quarter of the recommended dose of product is applied? In order to answer this question, 20 oils available on the market were tested in vitro at five different doses (5, 7.5, 10, 12.5, 15.0 mg over a surface of 25 cm(2)). We showed that a ratio of two polynomial functions exists between the SPF and the final mass of the product. The factors reducing the efficacy when the dose is divided by 2 are very variable, ranging from 2 to 4 according to which product is studied.

Comparative analysis of detecting monocytic cells and their aberrancy. Detection of monocytic cells (MCs) and their aberrancy is important in the diagnoses of monocytic leukemias [chronic myelomonocytic leukemia (CMML), acute MML (AMML), and acute monocytic/monoblastic leukemia (AMoL)]. MCs may be identified by cytomorphology (CM), enzyme cytochemical staining with nonspecific esterases, flow cytometric analysis (FCA), and immunohistochemical analysis (IHCA); their aberrancy, by FCA or IHCA. As aberrant antigen expression on MCs is not detected by CM or enzyme cytochemical staining and as there may be instances of "dry tap" or a fresh bone marrow aspirate is not available for further analysis, the primary and specific purpose of this study is to globally compare the detection of MCs and their aberrancy by the 2 methods of FCA and IHCA. Forty bone marrow (aspirate, clot, and biopsy) samples (7 CMMLs; 33 AMMLs and AMoLs) are evaluated by CM, FCA (complete immunophenotypic panel), and retrospective IHCA (CD2, CD3, CD14, CD33, CD56, CD68, CD123, and CD163). Forty-five percent showed a higher percentage of MCs by FCA than by CM. In addition, CD14, CD2, and CD56 detections on MCs showed greater sensitivity by FCA than by IHCA. By IHCA, CD14 showed the highest specificity for MCs (CD163, less specificity; CD68 and CD33, low specificity). CD123 did not correlate with CD14 or CD163, stained a subset of AMMLs/AMoLs, and stained no CMMLs. By comparing IHCA in clot versus biopsy sections, CD56 showed highest correlation (93%), followed by CD14 (85%) and CD33 (70%). CD68, CD163, and CD123 showed greater reactivities in clots (48%, 44%, and 35%, respectively), likely because of decalcification. FCA is most sensitive in detecting MCs and their aberrancy. By IHCA, CD14 is most specific. CD123 inconsistently marks AMMLs/AMoLs. Further evaluation of CD123 may determine the usefulness of CD123 in AML subtyping and possible prognostic implications and targeted therapy.

Somatostatin sst2 receptor knock-out mice: localisation of sst1-5 receptor mRNA and binding in mouse brain by semi-quantitative RT-PCR, in situ hybridisation histochemistry and receptor autoradiography. The peptide hormone/neurotransmitter somatostatin (somatotropin release inhibiting factor; SRIF) and its receptors (sst(1)-sst(5)) appear to regulate many physiological functions in the CNS. Semi-quantitative analysis of the densities of mRNA expression for sst(1-5) receptors and SRIF receptor binding sites were established in sst(2) receptor knock-out (KO) mice. Patterns of sst(1-5) receptor mRNA expression were largely conserved for sst(1,3,4) and sst(5) selective oligonucleotide probes; whereas sst(2) signals were completely absent in KO mouse brain. Autoradiographic analysis demonstrated [(125)I]LTT SRIF(28), [(125)I]CGP 23996 (two radioligands known to label all five recombinant SRIF receptors) and [(125)I]Tyr(3)-octreotide (sst(2) and sst(5) receptor selective) binding in wild type (WT) mouse brain sections; yet no specific binding of [(125)I]Tyr(3)-octreotide in KO mice. In contrast, [(125)I]LTT SRIF(28) and [(125)I]CGP 23996 binding was still present in a number of brain areas in KO mice, although to a lesser degree than in those regions where [(125)I]Tyr(3)-octreotide binding was found, in WT animals. The present data suggest first, that both sst(2) receptor protein and mRNA were completely absent in the brain of these KO animals. Second, there was little evidence of compensatory regulation, at the mRNA level, of the other SRIF receptors as a consequence of the sst(2) KO. Third, the absence of any [(125)I]Tyr(3)-octreotide binding, in KO mice, suggests that this particular ligand is selective for the sst(2) receptor subtype (under the conditions utilised); or that sst(5) receptors are only marginally expressed in brain. Fourth, there were regions where the binding of [(125)I]LTT SRIF(28) and [(125)I]CGP 23996 were moderately affected by the sst(2) KO, suggesting that additional SRIF receptors may well contribute to the binding of the aforementioned radioligands. Finally, since the relative distribution of these two ligands were not entirely superimposable, it suggests that their respective selectivity profiles towards the different SRIF receptor subtypes in situ are not identical.

Morin hydrate mitigates rapid eye movement sleep deprivation-induced neurobehavioural impairments and loss of viable neurons in the hippocampus of mice. Rapid eye movement sleep deprivation distorts the body's homeostasis and results in oxidative breakdown which may be responsible for a variety of neurological disorders. Some naturally occurring compounds of plant origin with antioxidant and neuroprotective properties are known to attenuate the detrimental effects of REM sleep deprivation. Morin hydrate, a flavonoid from Mulberry has demonstrated antioxidant and neuroprotective activities but its effect in sleep disturbed mice is unknown. The study was designed to explore the neuroprotective effect of Morin hydrate on 48 h. REM sleep deprivation-induced behavioural impairments and neuronal damage in mice. Mice were allotted into six treatment groups (n = 6): groups 1 and 2 received vehicle (10 ml/kg normal saline), groups 3-5 received Morin hydrate (5, 10, 20 mg/kg i.p) while group 6 received ginseng (25 mg/kg) which served as the reference drug. Treatment was performed daily for 5 days and animals were sleep-deprived on the last 48 h. Various behavioural tests (Elevated plus maze, Y-maze, locomotor activity) followed by oxidative parameters (malondialdehyde, nitric oxide, reduced glutathione) and histolopathological changes in the Cornu ammonis 1 (CA1) region of the hippocampus were assessed. Data were analysed using ANOVA at α0.05. Morin hydrate (5, 10, 20 mg/kg) significantly enhanced memory performance, improves anxiolytic-like behaviour, reverses hyperlocomotion, restored depleted reduced glutathione, attenuated raised malondialdehyde and nitric oxide levels as compared to control animals and protects against loss of hippocampal neurons. Results of this present study suggest that Morin hydrate possess neuroprotective effects against sleep deprivation-induced behavioural impairments, oxidative stress and neuronal damage.

Decreased alternative splicing of estrogen receptor-α mRNA in the Alzheimer's disease brain. In this study we identified 62 estrogen receptor alpha (ERα) mRNA splice variants in different human brain areas of Alzheimer's disease (AD) and control cases and classified them into 12 groups. Forty-eight of these splice forms were identified for the first time. The distribution of alternatively spliced ERα mRNAs was brain area- and case-specific. The dominant negative deletion (del.) 7 isoform appeared to be the major splice variant. The average number of ERα splice forms per brain area was lower in AD cases compared with controls, although the incidence of large deletions with alternative usage of 5' and 3' splice sites inside exons was more frequent in AD female cases. Relative transcription levels of del. 7 and del. 2 (missing exon 2) variants were decreased in the temporal cortex of AD patients, whereas the expression of the wild type ERα mRNA did not change. Our data show that alternative splicing of ERα mRNA is diminished in the AD brain and more prominently in AD female cases.

[The sibling relationship in the event of death]. The sibling relationship in the event of death. For adults and children, the death of a loved one is an unbearable loss. Although individual support is available for families, very little attention is paid to brothers and sisters. Yet, a grieving child is exposed not only on a personal level, but also, when brothers and sisters are involved, in terms of sibling dynamics.

Neuropeptide Y counteracts the anorectic and weight reducing effects of ciliary neurotropic factor. Ciliary neurotrophic factor (CNTF), a cytokine of the interleukin-6 superfamily, has been shown to induce hypophagia and weight loss. Neuropeptide Y (NPY) and orexin are potent orexigenic signals in the hypothalamus. Anorexia, normally seen in response to infection, injury and inflammation, may result from diminished hypothalamic orexigenic signalling caused by persistently elevated cytokines, including CNTF. To test this hypothesis, we first examined the effects of chronic intracerebroventricular (i.c.v.) infusion of CNTF for 6-7 days on food intake and body weight as well as hypothalamic NPY and orexin gene expression in male rats. Subsequently, the effectiveness of NPY replacement to counteract the effects of CNTF by coinfusion of NPY and CNTF was evaluated. Chronic i.c.v. infusion of CNTF (2.5 microg/day) reduced body weight (14.3% vs control) at the end of 7 days. Food intake remained suppressed for 5 days postinfusion and subsequently gradually returned to the control range by day 7. Serum leptin concentrations in these rats were in the same range seen in control rats. Chronic i.c.v. infusion of higher doses of CNTF (5.0 microg/day) produced sustained anorexia and body weight loss (29% vs controls) through the entire duration of the experiment. This severe anorexia was accompanied by markedly suppressed serum leptin concentrations. Furthermore, CNTF infusion alone significantly reduced hypothalamic NPY gene expression (P < 0. 05) without affecting orexin gene expression. As expected, in fusion of NPY alone (18 microg/day) augmented food intake (191.6% over the initial control, P < 0.05) and produced a 25.1% weight gain in conjunction with a 10-fold increase in serum leptin concentrations at the end of the 7-day period. Interestingly, coinfusion of this regimen of NPY with the highly effective anorectic and body reducing effects of CNTF (5.0 microg/day) not only prevented the CNTF-induced anorexia and weight loss, but also normalized serum leptin concentrations and hypothalamic NPY gene expression. These results demonstrate that chronic central infusion to produce a persistent elevation of the cytokine at pathophysiological levels (a situation that may normally manifest during infection, injury and inflammation) produced severe anorexia and weight loss in conjunction with reduction in both serum leptin concentrations and hypothalamic NPY gene expression. Reinstatement of hypothalamic NPY signalling by coinfusion of NPY counteracted these CNTF-induced responses.

Distribution of leukotriene B4 receptors in human hematopoietic cells. Leukotriene B4 (LTB4), a product of arachidonic acid metabolism, plays an important role in inflammatory responses. We have cloned from human erythroleukemia cells, a G protein-coupled receptor, designated P2Y(7), which was later identified as the receptor for LTB4 (B-LTR). We have investigated the distribution of LTB4 receptors in various hematopoietic cells. Northern blotting and reverse transcription-coupled polymerase chain reaction (RT-PCR) analyses using radiolabeled LTB4 receptor cDNA as a probe indicated the presence of LTB4 receptor mRNA in peripheral blood leukocytes but not in platelets. Flow cytometry analysis of peripheral blood cells using specific LTB4 receptor antibodies revealed that monocytes, granulocytes, and lymphocytes, but not platelets, express LTB4 receptors. RT-PCR-Southern hybridization analysis revealed that peripheral blood leukocytes and human umbilical vein endothelial cells express the LTB4 receptor. Of the hematopoietic cell lines tested, promonocytic U937 cells, promyelocytic HL-60 cells, K562 cells, and human erythroleukemia cells express the LTB4 receptor. These results suggest a physiological role for the LTB4 receptor in the stimulation of monocytes, neutrophils, and endothelial cells.

Cadmium phytotoxicity: Quantitative sensitivity relationships between classical endpoints and antioxidative enzyme biomarkers. In this work, cadmium phytotoxicity and quantitative sensitivity relationships between different hierarchical endpoints in plants cultivated in a contaminated soil were studied. Thus, germination rate, biomass growth and antioxidative enzyme activity (i.e. superoxide dismutase, peroxidase, catalase and glutathione reductase) in three terrestrial plants (Avena sativa L., Brassica campestris L. cv. Chinensis, Lactuca sativa L. cv. hanson) were analyzed. Plant growth tests were carried out according to an International Standard Organization method and the results were analyzed by ANOVA followed by Williams' test. The concentration of Cd2+ that had the smallest observed significant negative effect (LOEC) on plant biomass was 6.25, 12.5 and 50 mg Cd/kg dry soil for lettuce, oat and Chinese cabbage, respectively. Activity of all enzymes studied increased significantly compared to enzyme activity in plant controls. For lettuce, LOEC values (mg Cd/kg dry soil) for enzymic activity ranged from 0.05 (glutathione reductase) to 0.39 (catalase). For oat, LOEC values (mg Cd/kg dry soil) ranged from 0.19 (for superoxide dismutase and glutathione reductase) to 0.39 (for catalase and peroxidase). For Chinese cabbage, LOEC values (mg Cd/kg dry soil) ranged from 0.19 (peroxidase, catalase and glutathione reductase) to 0.39 (superoxide dismutase). Classical (i.e. germination and biomass) and biochemical (i.e. enzyme activity) endpoints were compared to establish a sensitivity ranking, which was: enzyme activity>biomass>germination rate. For cadmium-soil contamination, the determination of quantitative sensitivity relationships (QSR) between classical and antioxidative enzyme biomarkers showed that the most sensitive plant species have, generally, the lowest QSR values.

Associations between general parenting, restrictive snacking rules, and adolescent's snack intake. The roles of fathers and mothers and interparental congruence. Little research has been done on the role of fathers and parenting congruence between mothers and fathers. This study aimed to clarify the roles of general parenting and restrictive snacking rules set by fathers and mothers, and to explore parenting congruence in explaining adolescents' snack intake. Adolescents aged 11 to 15 completed a questionnaire assessing their perception of general parenting constructs (i.e. nurturance, structure, behavioral control, coercive control, and overprotection), restrictive snacking rules set by their fathers and mothers, and their own energy-dense snack intakes between meals. Scores for mothers were significantly higher on all constructs than for fathers, except for coercive control. Generally, higher scores on general parenting constructs were associated with higher scores on restrictive snacking rules (most of the associations being significant). Most general parenting constructs were unrelated to the respondents' number of snacks consumed. The use of restrictive snacking rules by both fathers and mothers was significantly and negatively related to respondents' snack intake. Moderation analyses indicated that high levels of incongruence between parents attenuated the favorable impact of fathers' rules and nurturance on their children's snacking, but interactions of congruence with three other paternal scales and all maternal scales were absent. Our findings indicate that both paternal and maternal general parenting and restrictive snacking rules play important roles in adolescents' snacking, and that high parental incongruence regarding restrictive snacking rules and nurturance could be undesirable.

The immediate early genes of human cytomegalovirus upregulate expression of the interleukin-2 and interleukin-2 receptor genes. Human cytomegalovirus (HCMV) immediate early (IE) genes act as trans-acting factors to upregulate various viral promoters. We used various IE plasmid constructs in transient transfection assays and demonstrated that the HCMV IE2 gene product upregulated expression from the interleukin (IL)-2 and IL-2 receptor (IL-2R) promoters and increased amounts of endogenous, steady-state IL-2 and IL-2R RNA. In marked contrast, the IE1 gene product, which can upregulate the major IE promoter and the IL-1 beta promoter, had no effect on the IL-2 and IL-2R promoters. These studies suggest a role for the HCMV IE2 gene product as a modulator of the inflammatory response associated with HCMV infection.

Two-plate fixation for humeral shaft non-unions. PURPOSE. To review 22 patients who underwent 2-plate fixation for non-union of the humeral shaft. METHODS. 13 women and 9 men aged 32 to 76 (mean, 48) years underwent fixation for non-union of the humeral shaft, using a 2-plate construct, together with decortication, debridement, and bone grafting. The two 3.5-mm reconstruction plates were parallel and lying at 90 degrees to each other and fixed with screws purchasing into at least 6 cortices of each fragment for both plates. Fractures were located in the upper third (n=8) or middle third (n=14) of the humerus. Initial treatments included casting (n=9), coaptation splinting (n=8), multiple retrograde pinning (n=4), and Marchetti-Vicenzi nailing (n=1). 18 non-unions were atrophic and 4 were hypertrophic. Shoulder and elbow range of motion as well as functional results were evaluated. RESULTS. The time for union was 4.6 (range, 4-6) months. No implants were loose or broken. No nonunion or infection was noted. Functional results were excellent in 17 and good in 5 patients. One patient had iatrogenic radial nerve palsy that recovered within 3 months. CONCLUSION. Two-plate fixation achieves good results for humeral shaft non-unions.

Concentrated RD114-pseudotyped MFGS-gp91phox vector achieves high levels of functional correction of the chronic granulomatous disease oxidase defect in NOD/SCID/beta -microglobulin-/- repopulating mobilized human peripheral blood CD34+ cells. In previous studies amphotropic MFGS-gp91phox (murine onco-retrovirus vector) was used in a clinical trial of X-linked chronic granulomatous disease (X-CGD) gene therapy to achieve transient correction of oxidase activity in 0.1% of neutrophils. We later showed that transduced CD34+ peripheral blood stem cells (CD34+ PBSCs) from this trial transplanted into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice resulted in correction of only 2.5% of human neutrophils. However, higher rates of transduction into stem cells are required. In the current study we demonstrate that the same vector (MFGS-gp91phox) pseudo-typed with RD114 envelope in a 4-day culture/transduction regimen results in a 7-fold increase in correction of NOD/SCID mouse repopulating X-CGD CD34+ PBSCs (14%-22% corrected human neutrophils; human cell engraftment 13%-67%). This increase may result from high expression of receptor for RD114 that we demonstrate on CD34+CD38- stem cells. Using RD114-MFGS encoding cyan fluorescent protein to allow similar studies of normal CD34+ PBSCs, we show that progressively higher levels of gene marking of human neutrophils (67%-77%) can be achieved by prolongation of culture/transduction to 6 days, but with lower rates of human cell engraftment. Our data demonstrate the highest reported level of functional correction of any inherited metabolic disorder in human cells in vivo with the NOD/SCID mouse system using onco-retrovirus vector.

A novel method of self-pulling and latter transected reconstruction in totally laparoscopic total gastrectomy: feasibility and short-term safety. This study depicts a novel reconstruction method of self-pulling and latter transection (SPLT) in totally laparoscopic total gastrectomy (TLTG) and evaluates its feasibility and short-term safety by comparing its surgical and postoperative outcomes with the conventional TLTG. Forty patients with gastric cancer from June 2014 to December 2015 received SPLT-TLTG. Data of clinicopathologic characteristics, surgical and postoperative outcomes, and follow-up findings in SPLT cases were collected and retrospectively compared with those of conventional TLTG to clarify the clinical benefits. The mean duration of the operation was 179.5 ± 37.7 min in SPLT-TLTG, including 23.2 ± 8.8 min of reconstruction; both were significantly shorter than the conventional TLTG (P = 0.030; P < 0.001). There were no significant differences in blood loss, time of the first flatus and postoperative hospital stays between two groups. SPLT-TLTG developed no complication beyond the conventional TLTG. SPLT-TLTG is safe, feasible and minimally invasive. It may serve as a promising procedure for gastric cancer that helps to expand the indication of TLTG to cases with even high level of tumor invasion and requires less in both surgical skills and clinical costs.

Melorheostosis of the upper limb: a report of two cases. The etiology, diagnosis, and treatment of two cases of melorheostosis are reported. The hyperostotic lesion corresponded well with both C7 and C8 segments of a sclerotome. The accompanying subcutaneous tumors in case 1 originated from the medical cutaneous nerve of the forearm, whose axons were coming mainly from the C8 dorsal root ganglion. These findings strongly suggest that the primary disorder exists in sensory nerves. Pain originating from the hyperostosis could be suppressed by the disodium salt of (1-hydroxyethylidene) diphosphonic acid.

The sensitivity of versican from rabbit lung to gelatinase A (MMP-2) and B (MMP-9) and its involvement in the development of hydraulic lung edema. Large chondroitinsulphate-containing proteoglycan (versican) isolated from rabbit lung was cleaved by purified gelatinase A (MMP-2) and gelatinase B (MMP-9), as well as by crude enzyme extract from rabbit lung with hydraulic edema. Gelatine zymography, performed after purification of gelatinases by affinity chromatography, demonstrated that the enzyme extract contained two main gelatinolytic bands at about 92 kDa and 72 kDa, identified by specific antisera as the latent proMMP-9 and proMMP-2, respectively. Moreover, enzyme extract from edematous lung showed an increased amount of the proteolytically activated forms of both gelatinases with respect to normal controls. These results suggest that MMP-2 and MMP-9 are involved in the breakdown of versican occurring in rabbit lung during the development of hydraulic edema.

Empirically supported psychological treatments and the Research Domain Criteria (RDoC). The Research Domain Criteria (RDoC) has been developed as an alternative approach to studying psychiatric disorders. The RDoC constructs and units of analysis, from genes up through paradigms, are intended to describe a hierarchy of priority measurements. Several of these have been investigated in the context of empirically-supported treatments, as either moderators or mediators of outcome. This review considers the available research on the moderating and mediating role of genes, molecules, circuits and physiology in cognitive-behavior therapy (CBT) outcome studies for negative valence system conditions. Based on the review, research has aspired to identify candidate genes, molecules, circuits and physiological moderators or mediators of treatment, but no definitive tests have been conducted. Instead, several candidate variables have been found that deserve further investigation. The available research is based on diagnoses from the DSM, whereas the RDoC initiative endeavors to determine empirically valid taxonomic signs. The results of this review are discussed in the joint context of developments in empirically-supported psychological therapy and the specific aims of the RDoC initiative, and conclude with recommendations for future research.

[Anterior tarsectomy for cavus foot. Retrospective study of 52 cases]. The authors reviewed 34 patients treated by tarsectomy for idiopathic pes cavus deformity between 1977 and 1996. Fifty two feet were treated surgically. All patients had undergone previous conservative treatment. The average age was 40 years. Podoscopic examination revealed 24 cavus feet stage 2, 28 cavus feet stage 3, adduction of the forefoot in 15 cases and an equinus deformity in 8 cases. On radiographic examination, Djian-Annonier's angle was 108 degrees on average. All patients were evaluated with a minimum ot two years follow-up, according to the evaluation system of the Massachusetts General Hospital. With an average follow-up of six years and six months, overall results were; 65.5% very good and good, 21% fair, 13.5% poor. The morphological correction was poor in 9 cases. Djian-Annonier's angle was 125 degrees on average. A number of cavus feet do not justify surgical treatment, because they are well tolerated, sometimes with orthopedic orthoses. Tarsectomy must be avoided in neurological conditions. We do not advise release of soft tissue or Dwyer's calcaneal osteotomy. In our opinion, the choice indication for anterior tarsectomy is the nonrigid cavus foot. It must be combined with lengthening of the Achilles tendon when a deficit of dorsiflexion of the foot persists following tarsectomy. According to their importance, associated deformations will be treated in the same operative session or not.

Design, synthesis and in vitro evaluation of novel ursolic acid derivatives as potential anticancer agents. A series of novel ursolic acid (UA) derivatives modified at the C-3 and the C-28 positions were designed and synthesized in an attempt to develop potential antitumor agents. The in vitro cytotoxicity were evaluated against five cancer cell lines (MGC-803, HCT-116, T24, HepG2 and A549 cell lines) and a normal cell (HL-7702) by MTT assay. The screening results indicated that some of these target compounds displayed moderate to high levels of antiproliferative activities compared with ursolic acid and 5-fluorouracil (5-FU), and exhibited much lower cytotoxicity than 5-FU, indicating that the targeted compounds had selective and significant effect on the cell lines. The induction of apoptosis and affects on the cell cycle distribution of compound 6r were investigated by acridine orange/ethidium bromide staining, Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining and flow cytometry, which revealed that the antitumor activity of 6r was possibly achieved through the induction of cell apoptosis by G1 cell-cycle arrest. Western blot and qRT-PCR (quantitative real-time PCR) experiments demonstrated that compound 6r may induce apoptosis through both of intrinsic and extrinsic apoptosis pathway.

What to expect from rational drug design. For more than 20 years, rational methods of drug design have belonged to the methodological core of drug development. Rational drug design based on structural knowledge of protein targets and on computational modelling of drug-target interaction holds out the promise of a predictable development process for highly innovative drugs. Still, it remains a challenge to make the available structural information fruitful for lead design. As a consequence, rational design is becoming increasingly interwoven with high-throughput screening. In addition, the relationship to the emerging systems-oriented approaches has yet to be specified.

Role of microRNA-26a in cartilage injury and chondrocyte proliferation and apoptosis in rheumatoid arthritis rats by regulating expression of CTGF. This study is carried out to investigate the role of microRNA-26a (miR-26a) in cartilage injury and chondrocyte proliferation and apoptosis in rats with rheumatoid arthritis (RA) by regulating expression of CTGF. A rat model of RA induced by type II collagen was established. The rats were assigned into normal, RA, RA + mimics negative control (NC), and RA + miR-26a mimics groups, and the cells were classified into blank, mimics NC, and miR-26a mimics groups. The degree of secondary joint swelling and arthritis index, expression of miR-26a, pathological changes, proliferation and apoptosis of chondrocytes, and expression of CTGF, interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α, Bax, and Bcl-2 were also determined through a series of experiments. The targeting relationship between miR-26a and CTGF was verified. Initially, downregulated miR-26a was found in cartilage tissues and inflammatory articular chondrocytes of RA rats. In addition, CTGF was determined as a direct target gene of miR-26a, and upregulation of miR-26a inhibited CTGF expression in cartilage tissues of RA rats. Furthermore, upregulation of miR-26a reduced swelling and inflammation of joints, inhibited cartilage damage, apoptosis of chondrocytes, inflammatory injury, promotes proliferation, and inhibited apoptosis of inflammatory articular chondrocytes, which may be correlated with the targeting inhibition of CTGF expression. Collectively, the results demonstrate that upregulating the expression of miR-26a could attenuate cartilage injury, stimulate the proliferation, and inhibit apoptosis of chondrocytes in RA rats.

"Mechanisms of change in a brief, online relationship intervention": Correction to Roddy et al. (2019). Reports an error in "Mechanisms of change in a brief, online relationship intervention" by McKenzie K. Roddy, Caitlin A. Stamatis, Karen Rothman and Brian D. Doss (Journal of Family Psychology, Advanced Online Publication, Aug 05, 2019, np). In the article, the effect sizes listed in the "Mech. slope→CSI slope" and "Indirect effect of treatment" columns of Table 2 were calculated incorrectly and mistakenly reported as Cohen's d values. These errors do not change any of the conclusions of the study. However, the correct values, column heads, and associated footnote are presented in the erratum. (The following abstract of the original article appeared in record 2019-44071-001.) Internet delivery of couple interventions is becoming increasingly popular; however, little is known about mechanisms of change during these interventions. One online, self-help relationship intervention-the OurRelationship program-has been shown to improve relationship satisfaction (Doss et al., 2016) during the intervention and to maintain gains through 12-months follow-up (Doss, Roddy, Nowlan, Rothman, & Christensen, 2019). This study seeks to understand mechanisms during and following this program using the same sample of 300 couples (600 individuals) randomly assigned to the program or a waitlist control group. Results from the bivariate growth curves revealed that greater increases in relationship satisfaction during the intervention were explained by improvements in negative communication, emotional intimacy, as well as target problem confidence and severity. However, changes in acceptance of targeted relationship problems, positive communication, and self-protective orientation were not related to changes in satisfaction during the intervention. Additionally, in a multivariate model, relationship target problem severity alone remained significant in the presence of other mechanisms. Improvements in positive and negative communication during the intervention and level of negative communication at the end of the intervention predicted maintenance of gains in satisfaction over 12-month follow-up. Results replicate previous findings that communication (Doss, Thum, Sevier, Atkins, & Christensen, 2005) and emotional intimacy (Doss et al., 2005; Hawrilenko, Gray, & Córdova, 2016) are key components in initial decreases in relationship distress. Furthermore, results suggest that improvements in communication may help couples more effectively navigate problems following the intervention-above and beyond its associations with prepost improvements in satisfaction. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Concept of fat balance in human obesity revisited with particular reference to de novo lipogenesis. The measurement of fat balance (fat input minus fat output) involves the accurate estimation of both metabolizable fat intake and total fat oxidation. This is possible mostly under laboratory conditions and not yet in free-living conditions. In the latter situation, net fat retention/mobilization can be estimated based on precise and accurate sequential body composition measurements. In case of positive balance, lipids stored in adipose tissue can originate from dietary (exogenous) lipids or from nonlipid precursors, mainly from carbohydrates (CHOs) but also from ethanol, through a process known as de novo lipogenesis (DNL). Basic equations are provided in this review to facilitate the interpretation of the different subcomponents of fat balance (endogenous vs exogenous) under different nutritional circumstances. One difficulty is methodological: total DNL is difficult to measure quantitatively in man; for example, indirect calorimetry only tracks net DNL, not total DNL. Although the numerous factors (mostly exogenous) influencing DNL have been studied, in particular the effect of CHO overfeeding, there is little information on the rate of DNL in habitual conditions of life, that is, large day-to-day fluctuations of CHO intakes, different types of CHO ingested with different glycemic indexes, alcohol combined with excess CHO intakes, etc. Three issues, which are still controversial today, will be addressed: (1) Is the increase of fat mass induced by CHO overfeeding explained by DNL only, or by decreased endogenous fat oxidation, or both? (2) Is DNL different in overweight and obese individuals as compared to their lean counterparts? (3) Does DNL occur both in the liver and in adipose tissue? Recent studies have demonstrated that acute CHO overfeeding influences adipose tissue lipogenic gene expression and that CHO may stimulate DNL in skeletal muscles, at least in vitro. The role of DNL and its importance in health and disease remain to be further clarified, in particular the putative effect of DNL on the control of energy intake and energy expenditure, as well as the occurrence of DNL in other tissues (such as in myocytes) in addition to hepatocytes and adipocytes.

Significance of D-dimer concentrations during and after cardiopulmonary bypass. To determine whether D-dimer fragments predictably increase during cardiopulmonary bypass (CPB), and if so, whether increases correlate with postoperative blood loss or predict postoperative coagulopathy. Prospective observational study of 65 consecutive patients undergoing first-time coronary artery bypass graft (CABG) or first-time valve replacement. Single center University teaching hospital. Male and female patients between the ages of 30 and 90 years undergoing first-time CABG or valve replacement surgery using CPB. Patients were excluded from study for prolonged preoperative bleeding time, preoperative warfarin therapy, perioperative intra-aortic balloon pump support, thrombolytic therapy in the week preceding operation, reoperation, and emergency operation. None. Blood sampling for platelet count, prothrombin time, partial thromboplastin time, thrombin time, fibrinogen, activated coagulation time (ACT) and D-dimer concentrations was obtained at four times during each case; (1) preoperatively, after insertion of the internal jugular introducer, before insertion of pulmonary artery catheter; (2) during CPB at 28 degrees C, immediately before rewarming; (3) after heparin neutralization (20 minutes after initial protamine dose); (4) 12 to 24 hours postoperatively. Blood loss in the intensive care unit was calculated by measuring total mediastinal drainage output at 1 and 4 hours after arrival from the operating room. An initial decrease in fibrinogen was noted during bypass, but no increase in D-dimer was identified. A few patients developed a modest increase in D-dimer after heparin neutralization, but none greater than 2.0 ug/mL. Postoperatively, fibrinogen concentration increased toward baseline levels. However, this is when six patients developed significant (> 2.0 ug/mL) D-dimer formation. Results suggest appropriate physiologic response-normalization of fibrinogen with new synthesis and remodeling of clot in the operative site causing D-dimer formation. Patients with highest D-dimer levels at 12 to 24 hours postoperatively had the highest blood loss at 4 hours postoperatively, suggesting that early postoperative excess bleeding predisposed to increased clot formation and subsequent clot remodeling causing elevated D-dimer concentrations. D-dimer concentration is not usually elevated in patients undergoing CPB when adequately anticoagulated as monitored using the ACT. When mild elevation of D-dimer occurs, it is most often after heparin neutralization and/or in the postoperative period and is not predictive of increased postoperative blood loss. Elevations of D-dimer concentrations in the postoperative period without corresponding decreases in fibrinogen concentrations may occur and do not signify coagulopathy.

Post-poliomyelitis sequelae: A pathophysiologic basis for management. Management of the late sequelae of poliomyelitis is based on their underlying pathophysiology and on a limited number of research reports. The key elements of management including the history, assessment and possible interventions are described in this article. The indications for intervention and its parameters are determined on an individual basis to maximise the benefit-to-risk ratio. Heavy resistive or exhaustive exercise, for example, cannot be supported physiologically as a means of preserving function in most patients. However rest, pacing of activities, lifestyle modification, orthotic fitting, weight control, use of aids and devices should be of value. Despite the importance of rest, inactivity is associated with detrimental side effects which can be accentuated in the patient with the sequelae of poliomyelitis. Research is needed to establish criteria for prescribing therapeutic interventions including rest and low-intensity exercise for the post-poliomyelitis population.

Predicting protein crystallization from a dilute solution property. A dilute solution parameter obtained from static light-scattering measurements is proposed as a predictor for protein crystallization experiments. The osmotic second virial coefficients, B(22), have been measured for a variety of proteins in solvents that are known to promote crystallization and the values for B(22) were found to lie within a fairly narrow range which we refer to as a crystallization slot. Solution conditions which were known not to favor crystallization of the proteins resulted in B(22) values well outside the crystallization slot.

Perceptions of ideal and typical middle and old age. An investigation of attitudes toward typical and ideal old age was carried out with seventy-eight undergraduate students. Half of the participants responded to semantic differential scales for typical and ideal old age and half to middle age stimulus objects. The scales were analyzed in terms of three dimensions produced in previous research. No difference was found between the middle and old age conditions for the personal acceptability dimension but differences were found for both the autonomous-dependent and instrumental-ineffective dimensions. The old and middle age objects were rated alike at ideal but the old age objects was rated less autonomous and less instrumental at typical.

Dairy management practices associated with incidence rate of clinical mastitis in low somatic cell score herds in France. An epidemiological prospective study was carried out in French dairy herds with Holstein, Montbéliarde, or Normande cows and with low herd somatic cell scores. The objective was to identify dairy management practices associated with herd incidence rate of clinical mastitis. The studied herds were selected on a national basis, clinical cases were recorded through a standardized system, and a stable dairy management system existed. In the surveyed herds, mean milk yield was 7420 kg/cow per yr and mean milk somatic cell score was 2.04 (132,000 cells/mL). Overdispersion Poisson models were performed to investigate risk factors for mastitis incidence rate. From the final model, the herds with the following characteristics had lower incidence rates of clinical mastitis: 1) culling of cows with more than 3 cases of clinical mastitis within a lactation; 2) more than 2 person-years assigned to dairy herd management; 3) balanced concentrate in the cow basal diet. Moreover, herds with the following characteristics had higher incidence rates of clinical mastitis: 1) milking cows loose-housed in a straw yard; 2) no mastitis therapy performed when a single clot was observed in the milk; 3) clusters rinsed using water or soapy water after milking a cow with high somatic cell count; 4) 305-d milk yield >7435 kg; 5) herd located in the South region; 6) herd located in the North region; 7) cows with at least 1 nonfunctional quarter; and 8) premilking holding area with a slippery surface. The underlying mechanisms of some highlighted risk factors, such as milk production level and dietary management practices, should be investigated more thoroughly through international collaboration.

Effects of PCB congeners on the immune function of Mytilus hemocytes: alterations of tyrosine kinase-mediated cell signaling. Polychlorinated biphenyls (PCBs) are industrial chemicals which have been released into the environment resulting in widespread and persistent contamination. PCBs exist as 209 different congeners depending on the chlorine substitution on the biphenyl rings; the physical properties and the toxic effects of a PCB congener are structure-dependent. In this work, individual ortho-substituted non coplanar PCB congeners were tested for their effects on the function of mussel (Mytilus galloprovincialis Lam.) hemocytes. Moreover, the possibility that in mussel hemocytes different PCBs may affect the signal transduction pathways involved in the immune response was investigated, with particular regards to relevant components of tyrosine-kinase mediated cell signaling. The results were compared with those obtained with a model of non-ortho-substituted coplanar congener. The results demonstrate that the di-ortho-substituted, non coplanar PCB congeners P47 (2,2',4,4'-tetrachlorobiphenyl) and P153 (2,2',4,4',5,5'-hexachlorobiphenyl) can alter immune parameters of mussel hemocytes, such as microbicidal activity and lysosomal enzyme release, respectively. Both congeners, as well as the non-ortho, coplanar congener P77 (3,3',4,4'-tetrachlorobiphenyl) significantly reduced hemocyte lysosomal membrane stability; however, P77 had no effect on either bacterial killing or lysozyme release. P47, P153 and P77 affected different components of tyrosine kinase-mediated cell signalling; in particular, they lead to a time-dependent increase in the phosphorylation level of the stress activated p38 and JNK Mitogen Activated Protein Kinases (MAPKs), as evaluated by Western blotting of hemocyte protein extracts with specific anti-phospho-MAPK antibodies. P153 also increased the level of phosphorylated ERK (extracellularly regulated) MAPKs. Moreover, non coplanar P47 and P153 caused increased tyrosine phosphorylation of the transcription factor STAT5, thus possibly affecting gene expression, whereas coplanar P77 was ineffective. The results demonstrate that MAPKs, and in particular the stress-activated p38 and JNK MAPKs, that represents a key step in the response of mussel hemocytes to bacterial infection, are a target for different non coplanar and coplanar PCB congeners. The results also show functional differences between different PCB congeners with respect to the hemocyte functions. However, chlorine substitution at the ortho positions is not necessarily related to immunotoxicity: the hexachlorinated P128 (2,2',3,3',4,4'-hexachlorobiphenyl) had no significant effect on mussel hemocytes, whereas its isomer P153, that represents a major component of environmental PCBs, and that is accumulated in mussel tissues, significantly affected both aspects of the immune response and relevant signal transduction pathways. These are the first data on the effects and possible mechanisms of immunotoxicity of non coplanar PCBs in mussel hemocytes. The results support the hypothesis that the innate immune system is a sensitive target for these contaminants in both vertebrates and invertebrates. Moreover, when considering that non coplanar congeners are present both in commercial mixtures and, in higher proportions, in environmental samples, the results suggest that bivalve hemocytes represent a useful model for evaluating the potential immunotoxicity of PCB contamination.

Antibiotic exposure in early infancy and risk for childhood atopy. The increase in pediatric allergy and asthma parallels the increase in use of antibiotics. Antibiotics disturb the flora of the gastrointestinal tract, possibly perturbing the developing immune system. We evaluated whether antibiotic use during early infancy increased the risk for atopy. Antibiotic prescriptions documented in medical records were collected from a birth cohort born from 1987 through 1989 (n = 725). At 6 to 7 years of age, 448 were followed by means of examination, including skin prick tests and serum IgE measurements to common allergens. Adjusted odds ratios (aORs) and 95% CIs were calculated comparing children with any versus those with no antibiotic use in the first 6 months and the outcomes of atopy (any positive skin test response), seroatopy (any positive specific IgE test result), either atopy or seroatopy, and both atopy and seroatopy. Atopy increased with antibiotic use approaching statistical significance (aOR, 1.48; 95% CI, 0.94-2.34; P = .09); however, the risk was concentrated among children with less than 2 pets in the home (aOR, 1.73; 95% CI, 1.07-2.80; P = .024) and children breast-fed for 4 or more months (aOR, 3.02; 95% CI, 1.27-7.17; P = .013). The aORs were generally in the same direction for seroatopy and the combined categories. Antibiotic use in early life appears to contribute to increased risk for atopy in certain subgroups of children.

Aromatherapy massage: its use in a ward setting. This article describes the properties of essential oils and the use of aromatherapy in a ward setting to treat patients with a variety of conditions. It outlines some of the benefits and risks to patients.

Impact of lyophilized Lactobacillus salivarius DSPV 001P administration on growth performance, microbial translocation, and gastrointestinal microbiota of broilers reared under low ambient temperature. This study was undertaken with the aim of investigating the effects of dietary supplementation of probiotic strain Lactobacillus salivarius DSPV 001P on growth performance, microbial translocation, and gastrointestinal microbiota of broilers reared under low ambient temperature. Two hundred and forty, one-day-old male Cobb broilers were randomly distributed into two treatment groups, a probiotic group and a control group, with four replicates per treatment and 30 broilers per replicate. The temperature of the broiler house was maintained at 18-22°C during the first three weeks, after which the temperature was at range of 8°C to 12°C. The results showed that probiotic treatment significantly improved body weight of broilers when compared with the control group. After 42days, the weight means were 2905±365.4g and 2724±427.0g, respectively. Although there were no significant differences, dietary inclusion of L. salivarius tended to increase feed intake and to reduce feed conversion ratio during the six-week experimental period. Similarly, supplementation tended to reduce the rate of mortality, with 12 deaths occurring in the probiotic group, and 20 in the control group. However, no differences were observed in intestinal bacterial concentrations of Enterobacteriaceae, E.coli, and lactic acid bacteria in both crop and caecum among treatments. Through our study, it appears that L. salivarius DSPV 001P was non-pathogenic, safe and beneficial to broilers, which implies that it could be a promising feed additive, thus enhancing the growth performance of broilers and improving their health.

Influence of a paclitaxel coated balloon in combination with a bare metal stent on restenosis and endothelial function: comparison with a drug eluting stent and a bare metal stent. Different approaches of local intravascular drug delivery may influence endothelial and microvascular function. The aim of this trial was to study the influence of a paclitaxel coated balloon in combination with a bare metal stent (DCB + BMS) versus a bare metal stent (BMS) or a sirolimus-eluting stent (DES) on coronary restenosis and endothelial function. This prospective trial included 77 patients with coronary de novo lesions. The patients were assigned to either one of the treatment groups. After 9 months, patients underwent angiographic follow-up including invasive measurement of coronary endothelial function. After 9 months, late lumen loss in-stent was highest in the BMS group (0.85 ± 0.73 mm), lower in DCB + BMS (0.36 ± 0.46 mm); and lowest in the DES group (0.25 ± 0.34 mm; P = 0.001 [ANOVA]). When compared to the BMS group, in-segment late lumen loss was significantly reduced in the DCB + BMS group (0.27 ± 0.43 mm vs. 0.60 ± 0.55 mm, P = 0.029) and the DES group (0.28 ± 0.40 mm, P = 0.045). Coronary flow reserve was significantly higher with the DCB + BMS treatment (3.16 ± 0.97 vs. 2.42 ± 0.99 [BMS], P = 0.036) whereas the increase in the DES group did not reach the significance level (3.06 ± 1.39, P = 0.144 vs. BMS). Parameters of endothelial function like intracoronary flow velocity and vessel diameter distal to the stented area showed similar patterns of response to adenosine, acetylcholine, and nitro in all groups. DES and the combination of DCB + BMS showed a significant reduction of late lumen loss as compared to a BMS alone. Furthermore, both types of local drug delivery were not associated with a deterioration of microvascular function at 9 months [ClinicalTrials.gov Identifier: NCT00473499].

Early versus late immune mediated inflammatory diseases. Immune mediated inflammatory diseases (IMIDs) are life long conditions that cause substantial morbidity and disability. Though increasingly common and intensely studied, the cellular and molecular mechanisms underlying their pathogenesis are still unclear. Despite this incomplete knowledge, it is becoming increasingly evident that IMIDs evolve over time, not only from a clinical perspective but also a pathophysiological one. Evidence is accumulating that the events responsible for inflammation and damage in the target organs are not necessarily the same during the evolution of the IMID, and that the immune response evolves in parallel with the clinical manifestations. This has crucial implications for therapy because immunomodulatory interventions aimed at early pathogenic events may no longer be effective when these events have changed due to a different composition of the immune response. Therefore, it is crucial to better understand why and how the IMID associated immune abnormalities evolve over time, so that time-dependent therapies may be rationally implemented for an improved clinical outcome.

Nodulation competitiveness in the Rhizobium-legume symbiosis. Successful nodulation of legumes by rhizobia is a complex process that, in the open field, depends on many different environmental factors. Generally, legume productivity in an agricultural field may be improved by inoculation with selected highly effective N2-fixing root nodule bacteria. However, field legume inoculation with Rhizobium and Bradyrhizobium spp. has often been unsuccessful because of the presence in the soil of native strains that compete with the introduced strain in nodule formation on the host plants. This ability to dominate nodulation is termed 'competitiveness' and is critical for the successful use of inoculants.

Chill-coma recovery time, age and sex determine lipid profiles in Ceratitis capitata tissues. The remodeling of membrane composition by changes in phospholipid head groups and fatty acids (FA) degree of unsaturation has been associated with the maintenance of membrane homeostasis under stress conditions. Overall lipid levels and the composition of cuticle lipids also influence insect stress resistance and tissue protection. In a previous study, we demonstrated differences in survival, behavior and Cu/Zn superoxide dismutase gene expression between subgroups of Ceratitis capitata flies that had a reversible recovery from chill-coma and those that developed chilling-injury. Here, we analyzed lipid profiles from comparable subgroups of 15 and 30-day-old flies separated according to their recovery time after a chill-coma treatment. Neutral and polar lipid classes of chill-coma subgroups were separated by thin layer chromatography and quantified by densitometry. FA composition of polar lipids of chill-coma subgroups and non-stressed flies was evaluated using gas chromatography coupled to mass spectrometry. Higher amounts of neutral lipids such as triglycerides, diacylglycerol, wax esters, sterol esters and free esters were found in male flies that recovered faster from chill-coma compared to slower flies. A multivariate analysis revealed changes in patterns of storage and cuticle lipids among subgroups both in males and females. FA unsaturation increased after cold exposure, and was higher in thorax of slower subgroups compared to faster subgroups. The changes in neutral lipid patterns and FA composition depended on recovery time, sex, age and body-part, and were not specifically associated with the development of chilling-injury. An analysis of phospholipid classes showed that the phosphatidylcholine to lysophosphatidylcholine ratio (PC/LPC) was significantly higher, or showed a tendency, in subgroups that may have developed chilling-injury compared to those with a reversible recovery from coma.

Biophysical considerations concerning gravity receptors and effectors including experimental studies on Phycomyces blakesleeanus. Part I. Migration and Diffusion of Graviceptors: The physical action of gravitational and inertial forces on graviceptors is considered. The motion of graviceptors as influenced by physical dimensions, density, electric charge, composition of the suspending medium and flow variables is demonstrated. Part II. Observations on Geotropism in Phycomyces blakesleeanus: Mutants of Phycomyces blakesleeanus exhibit strikingly different rates of geotropic response. It is shown that Phycomyces grown in the dark lack normal geotropic responses: pre-exposure to light is necessary for the synthesis of structures responsible for geotropism. A physical model is presented that may account for some of the geotropic phenomena observed in Phycomyces.

Cefoxitin: an overview of clinical studies in the United States. Cefoxitin, a new cephamycin antibiotic that is active against aerobic and anaerobic bacteria, was studied by 35 investigators in the United States. Of 657 patients eligible for evaluation of efficacy of the compound, 69% were cured and 92% were cured or improved on clinical grounds. Bacteriologic response to therapy with cefoxitin was equally good for infections due to gram-positive cocci (94% cured), gram-negative bacilli (87% cured), and anaerobes (95% cured). Cefoxitin was effective clinically and bacteriologically in the eradication of infections due to organisms resistant to ampicillin, cephalothin, chloramphenicol, tetracycline, and aminoglycosides. Overall rates of favorable response to cefoxitin therapy by disease were: lower respiratory tract infections, 90%; urinary tract infections, 87%; intraabdominal infections, 90%; gynecologic infections, 94%; and septicemia, 84%. Cefoxitin was tolerated well, and major abnormalities of hematologic, hepatic, renal, or central nervous system function were encountered rarely. Resistance to cefoxitin did not develop among gram-negative cocci, anaerobes, or gram-negative bacilli in the medical centers in which the antibiotic was used.

Increased production of tumor necrosis factor activity by hemodialysis but not peritoneal dialysis patients. The production of tumor necrosis factor alpha (TNF alpha) activity by peripheral blood mononuclear cells (PBMC) was determined in uremic patients on chronic hemodialysis (HD; n = 27), continuous ambulatory peritoneal dialysis (CAPD; n = 19), and in patients with chronic renal failure who were not yet on dialysis (CRF-ND; n = 18). In the HD group blood was taken immediately prior to and immediately following an HD session utilizing a cellulose acetate dialyzer. Post-HD PBMC spontaneously (i.e. in serum free media) produced significantly more TNF alpha activity than the PBMC of all other patient groups as well as those of the normal controls (n = 41) (p < 0.003). Post-HD PBMC produced significantly more TNF alpha activity than pre-HD PBMC both spontaneously and in the presence of nonuremic sera (p < 0.003). PBMC prior to HD also produced significantly more. TNF alpha activity than CAPD PBMC and normal PBMC in the presence of autologous heat inactivated sera (p < 0.03). Under some culture conditions (i.e. in the presence of nonuremic sera) normal PBMC produced significantly (p < 0.003) more TNF alpha activity than CAPD PBMC. Finally, a positive correlation was found between PBMC TNF alpha activity and age for HD patients (r = 0.7, p < 0.004) but not for CAPD or CRF-ND patients. These findings suggest that PBMC of HD but not CAPD or CRF-ND patients are chronically stimulated to produce TNF alpha activity.(ABSTRACT TRUNCATED AT 250 WORDS)

RH locus contraction in a novel Dc-/D-- genotype resulting from separate genetic recombination events. The rare phenotypes Dc- and D-- lack the expression of E/e and CcEe antigens, respectively; their cotransmission in a single family has not been reported. Six members of a Chinese family with two exhibiting the Dc- phenotype were studied using standard serologic methods. Rh genotypes were analyzed by Southern blot, and RH loci, by exon PCR. Rh transcripts were characterized by gene-specific RT-PCR and sequencing. Although Rh typing detected two members as Dc- homozygotes, RFLP analysis and exon PCR showed them to be Dc- heterozygotes with a partial deletion of RHCE. cDNA sequencing showed the expression in the family of normal RHD and RHCe as well as hybrid transcripts, RHD(1-9)/RHCE(10) and RHCE(1-3)/RHD(4-10). Thus, the Dc- members had the genotype of Dc-/ D-- and expressed both hybrid genes that were inherited from their parents, respectively. This is the first demonstration in a family that the Dc- and D-- complexes neither are linked with a normal RHD or RHCE gene. The segregation of these two different hybrid genes with single break points suggests their independent genetic origin and provides molecular insights into the dynamic nature of genomic rearrangements leading to RH locus contraction.

Surgical technique of temporary arterial occlusion in the operative management of spinal hemangioblastomas. Spinal hemangioblastomas (SH) are definitively treated by en bloc microsurgical resection. Although benign, their highly vascular nature makes resection challenging. A major difficulty involves intraoperative differentiation of vessels supplying the tumor from those supplying the spinal cord. Twenty patients with SH treated surgically at a single institution were reviewed. Median age was 49 years (range 24 to 70 years). Eleven patients had von Hippel-Lindau syndrome. Six underwent preoperative angiography, of which five underwent embolization. All tumors were posterior and resected through a laminectomy approach. Temporary arterial occlusion (TAO) by aneurysm clip placement with concurrent neuromonitoring was used at the tumor edge to differentiate arteries supplying the tumor from those supplying the healthy spinal cord. Arteries were assumed to not supply important regions of the cord and divided at the tumor surface if there was no change in evoked potentials after 4 minutes of occlusion. Of the 20 patients, 5 improved, 13 remained stable, and 2 worsened. Of the five treated with TAO, two improved, three remained stable, and none worsened. Median McCormick's functional grade of patients treated with TAO was II and improved to I after the operation, whereas that of those not treated with TAO remained unchanged at II (Wilcoxon rank-sum, P = .35). Temporary arterial occlusion with neuromonitoring is a safe, effective, and simple method of differentiating arteries supplying the tumor only from those that supply the functionally normal spinal cord in the operative management of difficult SH.

MR enterography in Crohn's disease: current consensus on optimal imaging technique and future advances from the SAR Crohn's disease-focused panel. MR enterography is a powerful tool for the non-invasive evaluation of patients with Crohn's disease (CD) without ionizing radiation. The following paper describes the current consensus on optimal imaging technique, interpretation, and future advances from the Society of Abdominal Radiology CD-focused panel.

The role of metformin and statins in the incidence of epithelial ovarian cancer in type 2 diabetes: a cohort and nested case-control study. To obtain evidence of the effects of metformin and statins on the incidence of ovarian cancer in women with type 2 diabetes (T2D). A retrospective cohort study and nested case-control study. The data were obtained from a diabetes database (FinDM) combining information from several nationwide registers. A cohort of 137 643 women over 40 years old and diagnosed with T2D during 1996-2011 in Finland. In full cohort analysis Poisson regression was used to estimate the hazard ratios (HR) in relation to ever use of metformin, insulin other oral anti-diabetic medication or statins. In the nested case-control analysis 20 controls were matched to each case of ovarian cancer. Conditional logistic regression was used to estimate HRs in relation to medication use and cumulative use of different medications. The estimates were adjusted for age and duration of T2D. Incidence of ovarian cancer. In all, 303 women were diagnosed with ovarian cancer during the follow up. Compared with other forms of oral anti-diabetic medication, metformin (HR 1.02, 95% CI: 0.72-1.45) was not found to be associated with the incidence of ovarian cancer. Neither was there evidence for statins to affect the incidence (HR 0.99, 95% CI: 0.78-1.25). In nested case-control analysis the results were essentially similar. No evidence of an association between the use of metformin or statins and the incidence of ovarian cancer in women with T2D was found. No evidence found for metformin or statins reducing the incidence of ovarian cancer.

Statins attenuate polymethylmethacrylate-mediated monocyte activation. Periprosthetic osteolysis precipitates aseptic loosening of components, increases the risk of periprosthetic fracture and, through massive bone loss, complicates revision surgery and ultimately is the primary cause for failure of joint arthroplasty. The anti-inflammatory properties of HMG-CoA reductase inhibitors belonging to the statin family are well recognized. We investigated a possible role for status in initiating the first stage of the osteolytic cycle, namely monocytic activation. We used an in vitro model of the human monocyte/macrophage inflammatory response to poly-methylmethacrylate (PMMA) particles after pretreat-ing cells with cerivastatin, a potent member of the statin family. Cell activation based upon production of TNF-alpha and MCP-1 cytokines was analyzed and the intracellular Raf-MEK-ERK signal transduction pathway was evaluated using western blot analysis, to identify its role in cell activation and in any cerivastatin effects observed. We found that pretreatment with cerivastatin significantly abrogates the production of inflammatory cytokines TNF-alpha and MCP-1 by human monocytes in response to polymethylmethacrylate particle activation. This inflammatory activation and attenuation appear to be mediated through the intracellular Raf-MEK-ERK pathway. We propose that by intervening at the upstream activation stage, subsequent osteoclast activation and osteolysis can be suppressed. We believe that the anti-inflammatory properties of statins may potentially play a prophylactic role in the setting of aseptic loosening, and in so doing increase implant longevity.

FT, a mobile developmental signal in plants. Plants synchronise their flowering with the seasons to maximise reproductive fitness. While plants sense environmental conditions largely through the leaves, the developmental decision to flower occurs in the shoot apex, requiring the transmission of flowering information, sometimes over quite long distances. Interestingly, despite the enormous diversity of reproductive strategies and lifestyles of higher plants, a key component of this mobile flowering signal, or florigen, is contributed by a highly conserved gene: FLOWERING LOCUS T (FT). The FT gene encodes a small globular protein that is able to translocate from the leaves to the shoot apex through the phloem. Plants have evolved a variety of regulatory networks that control FT expression in response to diverse environmental signals, enabling flowering and other developmental responses to be seasonally timed. As well as playing a key role in flowering, recent discoveries indicate FT is also involved in other developmental processes in the plant, including dormancy and bud burst.

Simultaneous Quantification of Syringic Acid and Kaempferol in Extracts of Bergenia Species Using Validated High-Performance Thin-Layer Chromatographic-Densitometric Method. A rapid, sensitive, selective and robust quantitative densitometric high-performance thin-layer chromatographic method was developed and validated for separation and quantification of syringic acid (SYA) and kaempferol (KML) in the hydrolyzed extracts of Bergenia ciliata and Bergenia stracheyi. The separation was performed on silica gel 60F254 high-performance thin-layer chromatography plates using toluene : ethyl acetate : formic acid (5 : 4: 1, v/v/v) as the mobile phase. The quantification of SYA and KML was carried out using a densitometric reflection/absorption mode at 290 nm. A dense spot of SYA and KML appeared on the developed plate at a retention factor value of 0.61 ± 0.02 and 0.70 ± 0.01. A precise and accurate quantification was performed using linear regression analysis by plotting the peak area vs concentration 100-600 ng/band (correlation coefficient: r = 0.997, regression coefficient: R(2) = 0.996) for SYA and 100-600 ng/band (correlation coefficient: r = 0.995, regression coefficient: R(2) = 0.991) for KML. The developed method was validated in terms of accuracy, recovery and inter- and intraday study as per International Conference on Harmonisation guidelines. The limit of detection and limit of quantification of SYA and KML were determined, respectively, as 91.63, 142.26 and 277.67, 431.09 ng. The statistical data analysis showed that the method is reproducible and selective for the estimation of SYA and KML in extracts of B. ciliata and B. stracheyi.

Occurrences and changes of disinfection by-products in small water supply systems. The small water supply systems (WSSs) often report high concentrations of disinfection by-products (DBPs) in drinking water. In this study, occurrences of trihalomethanes (THMs) and haloacetic acids (HAAs) in Newfoundland and Labrador (NL), Canada, were investigated from 441 WSSs for a period of 18 years (1999-2016). The WSSs were divided into groundwater (GWP) and surface water (SWP) systems, which were further classified into eight sub-groups (P1-P8) based on the population served (≤ 100; 101-250; 251-500; 501-1000; 1001-3000; 3001-5000; 5001-10,000; and 10,000+, respectively). The DBPs with probable and possible carcinogenic forms were estimated. Overall, 31.1% of WSSs were GWP, in which averages of THMs and HAAs were 32.2 and 27.7 μg/L, respectively, while the SWP had averages of THMs and HAAs of 97.6 and 129.2 μg/L, respectively. The very small WSSs (P1-P3) of GWP had averages of THMs and HAAs in the ranges of 29.1-43.5 and 15.8-64.3 μg/L, respectively. The P1-P3 of SWP had averages of THMs and HAAs in the ranges of 92.6-112.8 and 108.0-154.0 μg/L, respectively, which often exceeded the Canadian guideline limits. If the samples represented the populations homogenously, the total populations exposed to THMs or HAA5 above the guideline values would be in the range of 132.08-181.38 in thousands (30.3-41.6% of total populations). The probable and possible carcinogenic forms of THMs in GWP and SWP were in the ranges of 4.8-48.8 and 4.4-7.0% of THMs, respectively. In HAAs, carcinogenic forms were in the ranges of 82.6-98.4 and 97.6-98.7%, respectively. The findings indicated that the SWP might need further attention to better protect human health.

Chromatin structure of the human dihydrofolate reductase gene promoter. Multiple protein-binding sites. The chromatin structure of the promoter region of the human dihydrofolate reductase gene was determined using a variety of nucleases including DNase I, micrococcal nuclease, several restriction endonucleases, exonuclease III, and Bal31. Two separate regions from -670 to -340 (the distal hypersensitive region) and from -170 to +150 (the proximal hypersensitive region) were shown to be essentially free of proteins as indicated by their accessibility to both endo- and exonucleases. Within the proximal hypersensitive region, one protein appears to be bound at the start site for transcription. A 170-base pair fragment between the two hypersensitive regions was highly resistant to all nucleases tested. Multiple barriers against exonuclease digestion and resistance to dissociation by high salt concentrations suggest that more than one protein is tightly bound to this region. The upstream sequence from -670 and the downstream sequence from +150 were shown to be packaged into nucleosomes. The selective accessibility of certain sites to micrococcal nuclease cutting indicates that the initial nucleosomes are phased upstream from the distal hypersensitive region. There appears to be a protein bound between the phased nucleosomes and the upstream boundary of the distal hypersensitive region. These results suggest that the normal nucleosome array is interrupted by about 900 base pairs of nucleosome-free DNA to which several nuclear proteins bind in a DNA sequence-specific manner.

[Laparoscopic and retroperitoneoscopic resection of the kidney]. The surgeons of the clinic at the chair of endoscopic urology operated 32 patients (18 males, 14 females, age 40-78, mean age 55 +/- 0.8 years) with renal carcinoma (RC) from 2007 to 2010: 31 patients had RC stageT1N0M0, 1 patient--T2N0M0, 12 patients had RC of the right kidney, 19--of the left kidney, bilateral RC was in 1 patient. A laparoscopic transperitoneal approach was used in 14 cases. Indications for such approach were the following: size of the tumor 2.2-4 cm, location of the tumor in the upper anterior segment (n = 13), in the middle segment (n = 1). Ischemia was made in 5 patients. Resection of the kidney via a laparoscopic retroperitoneal approach was made in 11 patients. Indications were the following: size of the tumor 1.1-4 cm, posterior tumor location. Ischemia (17 and 24 min) was used in 2 cases, mean blood loss 118 ml (from 50 to 250 ml). Nine patients were operated with application of YAG:Nd laser (Lazurit) which resected an extraorganic tumor of a small size (1.1-2.2 cm) without ischemia and significant blood loss. Laparoscopic assisted resection of the kidney was performed in 9 cases. Hand assistance was indicated in large tumors (4.3 to 8.9 cm), posterior tumor location (n = 4), upper location (n = 2). One-stage bilateral resection of the kidneys in the middle segment was made in one patient. Hand assistance was also required in one patient for one-stage resection of two tumors of the right kidney. Laparoscopic resection of the kidney is indicated in bilateral tumor, in a single functioning kidney, in affection of the contralateral kidney, or disease with potential contralateral kidney affection. Indications for endovideosurgical methods of treatment need detailed specification and perfection. Choice of one of the above approaches should be based on tumor size and its location.

Patterns of health resource utilization, costs, and intensity of need for primary care clients receiving public health nursing case management. Case management has been promoted as a managed care strategy that improves quality of care and contains costs. Health resource utilization patterns and associated costs were examined for a generalized primary care population receiving a public health nursing model of case management intervention during a 30-week period. Subjects were referred by providers practicing in an academic health science center and included two client subsamples: chronically ill adults and younger families requiring health maintenance. Health resource utilization patterns and associated costs were examined in relation to intensity of need for care levels as determined by the Community Health Intensity Rating Scale. Results of this pilot study suggest that during public health nursing case management intervention, health resource utilization patterns changed from the preintervention period. Total health resource utilization costs were correlated with care needs related to health management behavior of the chronically ill.

Unilateral facial pain and lung cancer. The symptom of unilateral facial pain as a non-metastatic presentation of lung cancer is rare. This report describes a patient in whom unilateral face pain preceded the diagnosis of lung cancer by 9 months. The neural mechanism of this syndrome is discussed and the literature reviewed.

The Phonological Mean Length of Utterance: methodological challenges from a crosslinguistic perspective. The present study assesses the phonological development of 17 children acquiring Finnish at the developmental point of 25 words (ages 1; 2-2;0). The analysis is made using the PHONOLOGICAL MEAN LENGTH OF UTTERANCE (PMLU) method (Ingram & Ingram, 2001; Ingram, 2002), which focuses on the children's whole-word productions. Two separate analyses are carried out: the first analysis concentrates on consonants and follows the procedure devised by Ingram and Ingram (2001), and the second analysis also scores the correctness of vowels. The PMLU results of both analyses are found to be much higher than those reported for children acquiring English. The results show the apparent need for more language-specific research in order to develop the PMLU method suitable for various language environments.

Clinical and epidemiological study in an AIDS patient with Microsporum gypseum infection. A 37 years old homosexual male with AIDS was diagnosed as having Tinea cruris and Tinea corporis. The patient was a garden designer and therefore he used to handle soil very often. Microsporum gypseum was identified on cultures from skin-scrapings and biopsy material taken from different cutaneous lesion. The same species was isolated from samples of soil the patient used to work with. The clinical history of the patient and its epidemiological aspects were deeply studied by the authors. We stress the value of identifying possible sources of dermatophytic infections in order to give advice to patients.