Underwater, low-frequency noise in a coastal sea turtle habitat.
Underwater sound was recorded in one of the major coastal foraging areas for juvenile sea turtles in the Peconic Bay Estuary system in Long Island, New York. The recording season of the underwater environment coincided with the sea turtle activity season in an inshore area where there is considerable boating and recreational activity, especially during the summer between Independence Day and Labor Day. Within the range of sea turtle hearing, average noise pressure reached 110 dB during periods of high human activity and diminished proportionally, down to 80 dB, with decreasing human presence. Therefore, during much of the season when sea turtles are actively foraging in New York waters, their coastal habitats are flooded with underwater noise. During the period of highest human activity, average noise pressures within the range of frequencies heard by sea turtles were greater by over two orders of magnitude (26 dB) than during the lowest period of human activity. Sea turtles undoubtedly are exposed to high levels of noise, most of which is anthropogenic. Results suggest that continued exposure to existing high levels of pervasive anthropogenic noise in vital sea turtle habitats and any increase in noise could affect sea turtle behavior and ecology.


Perceived ethicality of guided imagery in rape research.
In our first study, undergraduate students (30 men, 30 women) evaluated the ethical acceptability of two previously published studies that used guided imagery in rape situations. In one, women imagined themselves as rape victims; in the other, men imagined themselves as rapists. Most students rated the research acceptable, but there was a significant interaction (p less than .05): Women found the study of women as victim less ethical, and men found the study of men as rapist less ethical. In our second study, 30 noncollege women evaluated the research on women as rape victims. After reading the scenario, none of these women said they would have agreed to participate or thought the research was ethically acceptable. We discuss issues of informed consent, demands of the research situation, and potential benefits and risks.


The effect of generic switching on concerns about medicine and non-persistence among Danish adults in a general practice setting.
Generic substitution means that one medicinal product is replaced by another product containing the same active substance. Generic substitution has existed in Denmark since 1991, and pharmacies are obliged to substitute a generic version of a medication, unless the general practitioner (GP) has explicitly stated that it should not be done, or the patient insists on having the more expensive drug. Generic prescribing, that is prescribing the substance name, is not allowed in Denmark. Some specialists and patients cast doubt on the real interchange-ability of generics, although international studies have shown that most patients have positive attitudes towards generic substitution. The severity of disease is known to be associated with patients being more concerned about generic substitution. The generic substitution scheme implies changing from one drug to another that may vary in brand-name, form, size, colour and taste. Speculations have been raised as to whether these medication changes between generic brands or from brand-name drugs to generics or vice versa may cause patient concerns. Qualitative studies have shown problems in recognising the substituted medicine and lack of confidence in the identical effect of the substitutable medicines. Several studies have focused on one specific drug group such as antihypertensive drugs. However, the influence of generic switching may affect concerns about medicine differently, depending on drug categories. Research on generic substitution often focuses on incident drug users, whose prescription is substituted at their first redemption. Most of these studies did not identify significant associations between generic substitution and non-adherence, but one study assessing the association between generic substitution and persistence showed reduced persistence. So far, studies of the effect of generic drug substitution on drug continuation have not focused on patients' overall experience of generic switches within one specific drug. To analyse associations between generic substitution and patient characteristics as well as patients' views on generic medicines, confidence in the healthcare system, beliefs about medicine, and experience with earlier generic substitution. To investigate the possible association between a specific generic switch and patients' concerns about their medicine. To examine how generic switch influences persistence with long-term treatment with special focus on importance of patients' concerns and views on generic medicine. The design was a combined cross-sectional questionnaire and register study and additionally a cohort study. The study was conducted among 6,000 medicine users, who had redeemed generically substitutable drugs with general reimbursement in September 2008 (2,000 users of antidepressants, 2,000 users of antiepileptics and 2,000 users of other substitutable drugs), who were aged 20 years or older and living in the Region of Southern Denmark. The medicine users were identified through Odense PharmacoEpidemiologic Database (OPED). The purpose of the questionnaire survey was to elucidate patients' experience with medicine, combined with information from OPED on a single well-defined generic switch of the index drug. The questionnaire was adapted to the individual subject with reference to their specific drug (index drug) in every question and index date printed on the questionnaire. The questionnaire comprises scales from the validated Beliefs about Medicine Questionnaire (BMQ) and ad hoc constructed scales. By means of OPED data it was possible to conduct a cohort study comprising information on all purchased medicine during the 12 months following the index date. The cohort comprised users of antidepressants and users of antiepileptics. A total of 2,476 patients (44.1%) were included in the analyses. Experience with earlier generic switches within the index ATC code was associated with experience of a generic switch on the index day (OR 5.93; 95% CI 4.70-7.49). However, experience with earlier generic switches was drug-specific, e.g. having had more than five earlier switches within other ATC codes reduced the odds of experiencing a generic switch on the index day. Having negative views on generic medicines also reduced the odds of experiencing a generic switch on the index day. The second study showed no statistically significant associations between experiencing a generic switch on the index day and having more or less concerns about the index medicine (-0.02 95% CI: -0.10-0.05). Patients experiencing their first-time switch of a specific drug were at higher risk of non-persistence, hazard ratio 2.98, 95% CI 1.81-4.89, versus those who have never switched, and 35.7% became non-persistent during the first year of follow-up. Generic switching did not influence persistence considerably in those having previous experience with generic switching of the specific drug. The overall results from the thesis showed that experience with earlier generic switches of a specific drug was associated with making a future generic switch and did not cause additional concerns about the index medicine. The effect of previous experience with generic substitution has been shown to be drug-specific. The third study showed that patients, who are first-time switchers of a specific drug, were at higher risk of becoming non-persistent compared to never switchers and those having experienced previous generic switching.


Recent advances in sample pre-treatment for emerging methods in proteomic analysis.
The objective of proteomics is the study of proteins (including their structure elucidation, the characterization of their role in biochemical process, the detection and identification of anomalous modifications in their structures and behavior, etc.) from both a qualitative and quantitative point of view. These studies have to face several difficulties as (a) the intrinsic complexity of protein molecules, (b) the low concentrations of the studied proteins, (c) the complexity of the biological samples (which could lead to interferences from the components of these matrixes), etc. Thus, the sample preparation procedure has a critical importance in order to obtain good separations and sensitivity in the results. In this paper, recent sample treatment methodologies for proteomic studies are reviewed and discussed. These methods include recent innovations in nanoparticle enrichment pre-treatment (for both the selective pre-concentration of the studied protein and the microwave-assisted digestion of the sample), treatments for tissue imaging (based on surface analysis of the studied biological tissues) and protein microarrays analysis (which allows the simultaneous determination of a high number of different proteins or associated species on a glass slide support).


Outcome of Cardiac Rehabilitation Following Off-Pump Versus On-Pump Coronary Bypass Surgery.
A few studies have compared the cardiac rehabilitation (CR) outcome between those who undergo conventional on-pump bypass surgery and off-pump surgery. We compared this outcome among the patients differentiated by the On-pump and off-pump surgical procedures about cardiovascular variables and psychological status. This longitudinal study recruited 318 and 102 consecutive patients who had undergone CABG (on-pump surgery, n = 318 and off-pump surgery, n = 102) and been referred to the CR clinic. The off-pump surgery patients had more improvement in their metabolic equivalents (METs) value. The physical and mental components of health-related quality of life (QOL) (based on SF-36 questionnaire) as well as depression-anxiety (based on Costello-Comrey Depression and Anxiety Scale) were notably improved in the two study groups after the CR program, while changes in the QOL components scores and also depression-anxiety score were not different between the off-pump and on-pump techniques. Regarding QOL and psychological status, there were no differences in the CR outcome between those who underwent off-pump bypass surgery and those who underwent on-pump surgery; nevertheless, the off-pump technique was superior to the on-pump method on METs improvement following CR.


A simple technique of laparoscopic port closure.
Laparoscopic and robotic surgery is widely practiced in modern medicine. The operative procedure is not complete until the port sites are closed with a fascial suture. We report a simple new technique that is easy, cost-effective, and quick to apply using 2 S-retractors for suture placement under direct visualization to secure the abdominal wall fascia and peritoneum. As a prospective consecutive case series, this technique was used for fascial closure after laparoscopy ports > 8 mm using 2 S-retractors. One S-retractor is used as a barrier protecting the contents of the abdominal cavity, reducing the risk of visceral injuries. The second S-retractor allows us to directly visualize the different layers, exposing the needle tip during its course through the fascia. This method was used in 100 patients with no intraoperative incidents, additional operative time, or need to access costly instruments. Currently, this technique is also used by many surgeons in our institution without any difficulty. No bowel injuries or port-site hernias were reported during a mean follow-up of 6 wk postoperation and 12-mo annual follow-up. The procedure is simple, easy, cost-effective, and quick to apply.


The significance of nursing home managers' leadership-longitudinal changes, characteristics and qualifications for perceived leadership, person-centredness and climate.
The aim was to explore changes in nursing home managers' leadership, person-centred care and psychosocial climate comparing matched units in a five-year follow-up and to explore the significance of managers' educational qualifications and the ownership of nursing homes for perceived leadership, person-centred care and psychosocial climate in the follow-up data. Leadership has been described as crucial for person-centred care and psychosocial climate even though longitudinal data are lacking. The significance of managerial leadership, its characteristics, managerial qualifications and ownership of nursing homes for perceived leadership, person-centred care and psychosocial climate also needs further exploration. Repeated cross-sectional study. This study used valid and reliable measures of leadership, person-centred care, psychosocial climate and demographic variables collected from managers and staff n = 3605 in 2014 and n = 2985 in 2019. Descriptive and regression analyses were used. The STROBE checklist was used in reporting this study. Leadership was still positively significantly associated to person-centred care in a five-year follow-up, but no changes in strength were seen. Leadership was still positively significantly associated with psychosocial climate, with stronger associations at follow-up. Six leadership characteristics increased over time. It was also shown that a targeted education for nursing home managers was positively associated with person-centred care. Leadership is still pivotal for person-centred care and psychosocial climate. Knowledge of nursing home managers' leadership, characteristics and educational qualifications of significance for person-centred delivery provides important insights when striving to improve such services. The findings can be used for management and clinical practice development initiatives because it was shown that nursing home managers' leadership is vital to person-centred care practices and improves the climate for both staff and residents in these environments.


Effects of bias voltage on diamond like carbon coatings deposited using titanium isopropoxide (TIPOT) and acetylene/argon mixtures onto various substrate materials.
RF-PECVD was used to prepare amorphous of carbon (DLC) onto stainless steel 316 and glass substrates. The substrates were negatively biased at between 100 V to 400 V. Thin films of DLC have been deposited using C2H2 and titanium isopropoxide (TIPOT). Argon was used to generate the plasma in the PECVD system chamber. DEKTAK 8 surface stylus profilometer was used to measure the film thickness and the deposition rate was calculated. Micro Raman spectroscopy was employed to determine the chemical structure and bonding present in the films. Composition analysis of the samples was carried out using VGTOF SIMS (IX23LS) instrument. In addition, X-ray photoelectron spectroscopy (XPS) was used to analyze the composition and chemical state of the films. The wettability of the films was examined using the optical contact angle meter (CAM200) system. Two types of liquids with different polarities were used to study changes in the surface energy. The as-grown films were in the thickness range of 200-400 nm. Raman spectroscopy results showed that the I(D)/I(G) ratio decreased when the bias voltage on the stainless steel substrates was increased. This indicates an increase in the graphitic nature of the film deposited. In contrast, on the glass substrates the I(D)/I(G) ratio increased when the bias voltage was increased indicates a greater degree of diamond like character. Chemical composition determined using XPS showed the presence of carbon and oxygen in both samples on glass and stainless steel substrates. Both coatings the contact angle of the films decreased except for 400 V which showed a slight increase. The oxygen is thought to play an important role on the polar component of a-C.


Cyto-IL-15 synergizes with the STING agonist ADU-S100 to eliminate prostate tumors and confer durable immunity in mouse models.
Prostate cancer is one of the most commonly diagnosed malignancies in men with high mortality rates. Despite the recent therapeutic advances, such as immunotherapies, survival of patients with advance disease remains significantly low. Blockade of immune checkpoints has led to low response rates in these patients probably due to the immunosuppressive microenvironment and low mutation burden of prostate tumors. Combination of multiple immunotherapeutic regimes has also been unsatisfactory due to augmented adverse effects. To activate multiple immune-stimulatory pathways in the hostile prostate cancer microenvironment, we used a combination of cytotopically modified interleukin-15 (cyto-IL-15) with the stimulator of interferon genes (STING) agonist, ADU-S100. To determine whether this combination regime could lead to both local and systemic anti-tumor effects, intratumoral administration of these agents was used in murine models of prostate cancer. Tumor growth and mouse survival were monitored, and ex vivo analyses, and RNA sequencing were performed on the tumors. Intratumorally injected ADU-S100 and cyto-IL-15 synergized to eliminate tumors in 58-67% of mice with unilateral tumors and promoted abscopal immunity in 50% of mice with bilateral tumors treated only at one side. Moreover, this combination regime offered immunoprotection against tumor rechallenge in 83% of cured mice. The efficacy of the combination treatment was associated with a strong innate and adaptive immune activation and induction of apoptotic and necrotic cell death. Cytokines, including type I and II interferons, and cytokine signalling pathways were activated, NK and T cell mediated cytotoxicity was increased, and B cells were activated both locally and systemically. While ADU-S100 led to an ulcerative pathology at the injection site, no other adverse effects were observed. Localised administration of a STING agonist together with cyto-IL-15 can confer significant systemic benefits and long-lasting immunity against prostate tumors while reducing immune related toxicities.


Spectrofluorometric determination of alogliptin an antidiabetic drug in pure and tablet form using fluorescamine, a fluorogenic agent: application to content uniformity test.
Alogliptin is an antidiabetic drug that belongs to a group called dipeptidyl peptidase-4 enzyme inhibitors. As the drug contains a primary amino group in its structure, it readily reacts with fluorescamine in slightly alkaline medium (borate buffer, pH 8.8) to form a highly fluorescent product. Emission of this product was measured at 477 nm (λex = 387 nm). The linear range between the fluorescence intensity and the drug concentration was 0.1-0.5 μg ml-1 with a good correlation coefficient (0.9986). Limits of detection and quantitation were 22 and 72 ng ml-1 , respectively. Guidelines of the International Conference for Harmonisation were followed to validate the developed method with acceptable results. Alogliptin content was determined successfully in its commercial dosage form using the fluorescamine method with good recovery (98.60-101.26%). The method has excellent levels of accuracy and precision compared with the reported method as assessed using Student's t-test and Fisher's exact test. The method was applied successfully for the content uniformity test with high recovery and low relative standard deviation.


Endothelial Gab1 deficiency aggravates splenomegaly in portal hypertension independent of angiogenesis.
Certain pathological changes, including angiogenesis, actively contribute to the pathogenesis of splenomegaly in portal hypertension (PH), although the detailed molecular and cellular mechanisms remain elusive. In this study, we demonstrated that endothelial Grb-2-associated binder 1 (Gab1) plays a negative role in PH-associated splenomegaly independent of angiogenesis. PH, which was induced by partial portal vein ligation, significantly enhanced Gab1 expression in endothelial cells in a time-dependent manner. Compared with controls, endothelium-specific Gab1 knockout (EGKO) mice exhibited a significant increase in spleen size while their PH levels remained similar. Pathological analysis indicated that EGKO mice developed more severe hyperactive white pulp and fibrosis in the enlarged spleen but less angiogenesis in both the spleen and mesenteric tissues. Mechanistic studies showed that the phosphorylation of endothelial nitric oxide synthase (eNOS) in EGKO mice was significantly lower than in controls. In addition, the dysregulation of fibrosis and inflammation-related transcription factors [e.g., Krüppel-like factor (KLF) 2 and KLF5] and the upregulation of cytokine genes (e.g., TNF-α and IL-6) were observed in EGKO mice. We thus propose that endothelial Gab1 mediates multiple pathways in inhibition of the pathogenesis of splenomegaly in PH via prevention of endothelial dysfunction and overproduction of proinflammatory/profibrotic cytokines.


Carbon monoxide stimulates insulin release and propagates Ca2+ signals between pancreatic beta-cells.
A key question for understanding the mechanisms of pulsatile insulin release is how the underlying beta-cell oscillations of the cytoplasmic Ca2+ concentration ([Ca2+]i) are synchronized within and among the islets in the pancreas. Nitric oxide has been proposed to coordinate the activity of the beta-cells by precipitating transients of [Ca2+]i. Comparing ob/ob mice and lean controls, we have now studied the action of carbon monoxide (CO), another neurotransmitter with stimulatory effects on cGMP production. A strong immunoreactivity for the CO-producing constitutive heme oxygenase (HO-2) was found in ganglionic cells located in the periphery of the islets and in almost all islet endocrine cells. Islets from ob/ob mice had sixfold higher generation of CO (1 nmol.min-1.mg protein-1) than the lean controls. This is 100-fold the rate for their constitutive production of NO. Moreover, islets from ob/ob mice showed a threefold increase in HO-2 expression and expressed inducible HO (HO-1). The presence of an excessive islet production of CO in the ob/ob mouse had its counterpart in a pronounced suppression of the glucose-stimulated insulin release from islets exposed to the HO inhibitor Zn-protoporhyrin (10 microM) and in a 16 times higher frequency of [Ca2+]i transients in their beta-cells. Hemin (0.1 and 1.0 microM), the natural substrate for HO, promoted the appearance of [Ca2+]i transients, and 10 microM of the HO inhibitors Zn-protoporphyrin and Cr-mesoporphyrin had a suppressive action both on the firing of transients and their synchronization. It is concluded that the increased islet production of CO contributes to the hyperinsulinemia in ob/ob mice. In addition to serving as a positive modulator of glucose-stimulated insulin release, CO acts as a messenger propagating Ca2+ signals with coordinating effects on the beta-cell rhythmicity.


Antibiotic resistance patterns of ocular bacterial flora: a prospective study of patients undergoing anterior segment surgery.
To determine the antibiotic susceptibility patterns of conjunctival bacterial flora isolated preoperatively from patients undergoing anterior segment surgery. Prospective observational study. One hundred fifty-six eyes from 139 patients scheduled for anterior segment surgery were enrolled over a 6-month period from August 2001 to February 2002. Conjunctival cultures were obtained on the day of surgery before povidone-iodine or antibiotic application. Bacterial isolates were identified and tested for antibiotic susceptibility using the Kirby-Bauer disc-diffusion technique. Among the 156 eyes studied, 36 were from patients who had undergone either bilateral surgery or more than one surgery in the same eye. Only the first eyes of the 120 patients that underwent initial ocular surgery were included in our analysis. Of these 120 eyes, 21 (18%) showed no bacterial growth. Of the 143 bacterial strains isolated from the remaining 99 eyes, 112 (78%) were coagulase-negative staphylococci (CNS). Among the CNS, greater than 90% were susceptible to cefotaxime, levofloxacin, imipenem, meropenem, vancomycin, and each of the aminoglycosides except neomycin. Between 70% and 90% of the CNS were susceptible to cefazolin, neomycin, ciprofloxacin, ofloxacin, norfloxacin, and chloramphenicol. Less than 70% of the isolated CNS were sensitive to the penicillin analogues, ceftazidime, erythromycin, and tetracycline. Preoperative conjunctival isolates of CNS seem to be most sensitive to vancomycin, the aminoglycosides (except neomycin), and levofloxacin.


Effect of UVC radiation on mouse fibroblasts deficient for FAS-associated protein with death domain.
Ultraviolet (UV) radiation-induced apoptosis enabled us to study the mechanism of DNA damage and to investigate how cells avoid consequences of damaged DNA. Cells with extensive DNA damage activate extrinsic and intrinsic pathways of apoptosis. The extrinsic pathway is coupled to a FAS-associated protein with death domain (FADD), an adaptor protein molecule necessary for mediating apoptotic signals through the cell. Viability and apoptosis of wild-type and FADD-deficient mouse embryonic fibroblasts were investigated 1, 3, 24 and 48 h after exposure to three doses (50, 75 and 300 J/m(2)) of UVC radiation. Morphological changes were observed using DNA binding dyes (Hoechst and propidium iodide) while biochemical changes were monitored using immunodetection of the poly (ADP-ribose) polymerase (PARP) protein cleavage and caspase-3 activity assay. Results showed that the difference in cell death response between wild-type and FADD-deficient cells depended on dose and incubation time after exposure to UVC radiation. FADD-deficient cells are more sensitive to UVC radiation. Even though FADD-deficient cells lack an adapter protein of apoptotic extrinsic pathway, higher doses of UVC triggered their apoptotic response, while wild-type cells die mainly due to necrosis. A different pattern of caspase 3 activity and PARP cleavage was observed 24 h after radiation between two cell lines confirming higher apoptotic response in FADD-deficient cells. Wild-type cells can execute apoptosis via both, the mitochondrial and the receptor-mediated pathway whereas FADD-deficient cells can only activate the intrinsic pathway. There is a difference in UVC radiation response between two cell lines indicating the role of FADD in the selection of cell death modality.


Aggregatibacter actinomycetemcomitans Growth in Biofilm versus Planktonic State: Differential Expression of Proteins.
Aggregatibacter actinomycetemcomitans (Aa) is a pathogenic bacterium residing in the subgingival plaque biofilm strongly associated with the pathogenesis of periodontitis. The aim of this investigation was to study the protein differential expression of Aa when growing on biofilm compared with planktonic state using proteomic analysis by the 2D-DIGE system. Eighty-seven proteins were differentially expressed during biofilm growth (1.5-fold, p < 0.05), with 13 overexpressed and 37 down-expressed. Those repressed were mainly proteins involved in metabolism, biosynthesis, and transport. The overexpressed proteins were outer membrane proteins (OMPs) and highly immunogenic proteins such as YaeT (OMP), FtsZ, OMP39, OMP18/16, the chaperone GroEL, OMPA, adenylate kinase (Adk), and dihydrolipoamide acetyltransferase. The enrichment fractions of the OMPs from biofilm and planktonic states were obtained, and these proteins were analyzed by Western blotting with human serum from a periodontitis patient and one healthy control. These immunogenic proteins overexpressed in the biofilm may represent candidate virulence factors.


Jejunal cavernous lymphangioma.
Cavernous lymphangiomas are usually identified in infants and children with the majority of lesions found around the head and neck, trunk or extremities. Tumours affecting the intra-abdominal organs are rare. The authors report a case of small bowel cavernous lymphangioma arising within the jejunum of a 34-year-old woman presenting with dyspnoea and anaemia, and review the existing literature relating to this uncommon tumour.


DCB combined with provisional DES implantation in the treatment of De Novo Medina 0,1,0 or 0,0,1 left main coronary bifurcation lesions: A proof-of-concept study.
To investigate the safety and efficacy of a percutaneous revascularization strategy that is based on the use of drug-coated balloon for the treatment of patients with acute coronary syndrome and de novo Medina type 0,1,0 or 0,0,1 left main stem bifurcation lesions. In this multicenter, prospective, proof-of-concept study, patients fulfilling the above criteria were enrolled and received treatment with drug-coated balloon combined with provisional drug-eluting stent implantation in the proximal major branches of the left main stem. Patients who declined this revascularization approach were treated with drug-eluting stent implantation 1-2 mm distally to the left anterior descending or left circumflex artery ostium followed by drug-coated balloon therapy for the ostial disease. The primary endpoint of the study was the calculation of percent diameter stenosis on quantitative coronary angiography post-procedure as well as event rate at 8 months follow-up. A total of 30 patients were enrolled in the study; their mean age was 60.3 ± 7.8 years, while 22 (73.3%) were male. Twenty-two patients were treated only with drugcoated balloon and provisional drug-eluting stent implantation and 8 had drug-eluting stent implantation followed by drug-coated balloon therapy of the ostium of the left main stem major branch. All the procedures were successful with no immediate complications. The percent diameter stenosis of lesion decreased significantly post-procedure from 87.5% (80.0-90.0) to 20% (17.5-30.0), P <.001. During the follow-up period, no major adverse cardiac events were reported. This proof-of-concept study indicates that ostial drug-coated balloon therapy of the left main stem major branches is safe and effective. Larger clinical data and longer follow-up are needed before advocating its regular use in clinical practice.


Independence of glycogen accumulation and glucose-6-phosphate dehydrogenase induction in rat liver.
The responses of liver glycogen and glucose-6-phosphate dehydrogenase (G6PD) (EC 22.214.171.124) to a high glucose, adequate protein diet were compared between rats previously starved 2 days, then refed a high protein, carbohydrate-free diet for 2 days, and rats previously fed the high protein diet for 4 days. Glycogen levels increased dramatically during the first day the high carbohydrate diet was fed, then decreased gradually on the second day. The response was the same regardless of whether the rats had been starved more before the high protein diet was fed. Liver G6PD activity also increased when the high carbohydrate diet was fed, and continued to increase on the second day. The increase in G6PD, however, was significantly greater in the rats which had been starved before the high protein diet was fed. It is suggested that some process occurs during starvation that predisposes the induction of G6PD upon refeeding a high carbohydrate diet, over and above any effect of glycogen accumulation and breakdown. Glucose or glucose-6-phosphate derived from glycogen does not appear to be the primary inducer of G6PD in rat liver.


Diversity-Oriented Synthesis of Glycosylphosphatidylinositol Probes Based on an Orthogonally Protected Pentasaccharide.
Two glycosylphosphatidylinositol (GPI) derivatives having an alkynyl group at different positions were derived from the same orthogonally protected pentasaccharide that in turn was assembled by a convergent [3+2] glycosylation strategy. The resultant alkynylated GPIs are useful biological probes and are suitable for further modification by click reaction to obtain other GPI probes. The pentasaccharide is a versatile platform for the synthesis of various uniquely functionalized GPI probes.


Changes in gene expression during male meiosis in Petunia hybrida.
We analyzed changes in gene expression during male meiosis in Petunia by combining the meiotic staging of pollen mother cells from a single anther with cDNA-AFLP transcript profiling of mRNA from the synchronously developing sister anthers. The transcript profiling experiments focused on the identification of genes with a modulated expression profile during meiosis, while premeiotic archesporial cells and postmeiotic microspores served as a reference. About 8000 transcript tags, estimated at 30% of the total transcriptome, were generated, of which around 6% exhibited a modulated gene expression pattern at meiosis. Cluster analysis revealed a transcriptional cascade that coincides with the initiation and progression through all stages of the two meiotic divisions. Fragments that exhibited high expression specifically during meiosis I were characterized further by sequencing; 90 out of the 293 sequenced fragments showed homology with known genes, belonging to a wide range of gene classes, including previously characterized meiotic genes. In-situ hybridization experiments were performed to determine the spatial expression pattern for five selected transcript tags. Its concurrence with cDNA-AFLP transcript profiles indicates that this is an excellent approach to study genes involved in specialized processes such as meiosis. Our data set provides the potential to unravel unique meiotic genes that are as yet elusive to reverse genetics approaches.


New insights into proton surface mobility processes in PEMFC catalysts using isotopic exchange methods.
The surface chemistry and the adsorption/desorption/exchange behavior of a proton-exchange membrane fuel cell catalyst are analyzed as a case study for the development of tailor-made support materials of enhanced performance and stability. By using H2, D2, and CO as probe molecules, the relevance of some surface functional groups of the catalyst support on several diffusion processes taking place during the adsorption is shown. Sulfonic groups associated with the vulcanized carbon black surface have been detected by means of spectroscopic techniques (X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy) and by analysis of the desorbed products during temperature-programmed desorption tests by mass spectrometry. Such hydrophilic species have been observed to favor proton surface mobility and exchange with Pt-adsorbed deuterium even in the presence of adsorbed CO. This behavior is relevant both for the proper characterization of these kinds of catalysts using adsorption probes and for the design of new surface-modified carbon supports, enabling alternative proton-transfer pathways throughout the catalytic layers toward the membrane.


Knowledge, attitude and seropositivity of hepatitis B virus among blood donors in the Bamenda Regional Hospital Blood Bank, Cameroon.
despite the existence of a preventive vaccine against hepatitis B viral (HBV) infection, approximately 250 million people are infected with the virus worldwide. This study aimed at evaluating the level of knowledge, attitude and seropositivity of the disease among apparently healthy, potential blood donors at the blood service of the Bamenda Regional Hospital Blood Bank. a cross-sectional study was carried out from March to May 2019 among 250 blood donors. Following screening for hepatitis B surface antigen (HBsAg) using the one-step HBsAg test strip, information on the level of knowledge and attitude towards the infection was obtained using a self-administered questionnaire. The correlation analysis was done to assess relationships between selected factors and knowledge of hepatitis B, p-value of 0.05 was considered as statistical significance. the seropositivity of HBV was 6.4% (n = 16). Overall, 46.8% (n = 19) of the study participants had adequate knowledge while 76.3% (n = 31) had a positive attitude toward the disease. The highest seropositivity was observed in singles (7.1%; n = 13), primary school leavers (14.3%; n = 5), unskilled laborers (14.5%; n = 8) and replacement donors (9.33%; n = 7). The probability of being hepatitis B seropositive was higher in males, students (aOR: 8.8, 95% CI 0.7-96.1; p = 0.046) and those who had attained higher education (aOR: 3.2, 95% CI 0.8-12.7; p = 0.016). Independent factors responsible for higher odds of inadequate knowledge were being a male and attaining secondary education. On the contrary, students (aOR: 0.3, 95% CI 0.1-0.8; p = 0.012) and those with a history of blood donation (aOR: 0.5, 95% CI 0.2-0.9; p = 0.042) recorded lower odds of inadequate knowledge. the prevalence of hepatitis B among blood donors in this blood service is in the high intermediate category. Overall, the level of knowledge on this infection among these blood donors is average. These findings suggest that health education on HBV infection should be provided to the public as a major strategy to curb the infection.


Topographical distribution of 5-methylcytosine in animal and plant DNA.
The topographical distribution of 5-methylcytosine on animal and plant cell DNA has been examined with methyl-sensitive restriction enzymes and gel electrophoresis analysis. These DNAs digested with the enzyme HpaII have a partially bimodal size distribution, indicating the existence of clusters of methylated and unmethylated CCGG sites in the DNA. By analyzing the methylation state of all CG moieties in restricted DNA fractions, it was possible to show that these genomes are, in general, arranged as clusters of relatively highly methylated and undermethylated regions. Plant DNA also contains 5-methylcytosine in the prototype sequence C-X-G. Restriction of this DNA with EcoRII revealed that these methyl groups are also distributed in clusters, suggesting that this is a general phenomenon. The undermethylated areas may correspond to the active fraction of the genome.


Oral Administration of Liposome-Apatinib and Locally Delivery of Docetaxel/MPEG-PCL by Fibrin Glue Synergistically Improve Therapeutic Effect in Colorectal Cancer.
Colorectal cancer is one of the most common and malignant cancer in the world wide. Recently, combination of target therapy and chemotherapy has generated new promise for colorectal cancer. Apatinib mesylate is a novel and highly selective VEGFR-2 inhibitor, presented with an outstanding activity of anti-angiogensis, which has the potential for treating various tumors. As a traditional chemotherapeutic drug, docetaxel (Taxotere) is a widely used semisynthetic taxoid in solid tumors. In this study, Liposome and Methoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) were constructed as drug delivery system for the delivery of apatinib (Lipo-Apa) and docetaxel (DOC/M), respectively. Co-administration of Lipo-Apa and DOC/M showed synergistically effects on inhibiting cell proliferation and inducing cell apoptosis of CT26 cells in vitro. Moreover, fibrin glue, as a biocompatible adherent hemostat, was used as a kind of vehicle for locally delivery of DOC/M in animal models, for achieving locally high concentration and prolonging releasing time. Combination of Lipo-Apa by gavage and locally delivery of DOC/M showed significantly improved anti-tumor activity in a subcutaneous xenograft model as well as in the abdominal metastasis model of colorectal cancer. In addition, promoted tumor apoptosis, inhibited proliferation and decreased tumor angiogenesis were presented by the co-administration. Finally, our study suggested that combination of oral administration of Lipo-Apa and locally delivery of DOC/M by fibrin glue, has the potential to be applied clinically in colorectal cancer therapy.


Somatostatin protects human retinal pericytes from inflammation mediated by microglia.
Diabetic retinopathy (DR) is usually considered a microvascular disease. However, involvement of the neuroretina in the early stages of DR has recently gained major credit. Inflammatory processes, leading to glial activation and neuronal apoptosis, develop early in the retina of diabetic subjects. Pericytes constitute a link between the vascular and the neural retina, play a central role in blood-retinal barrier maintenance, and may influence neuroinflammation. Somatostatin (SST) is a potent neuroprotective factor, which is down-regulated during early DR. In this paper, we have investigated the effects of the inflammatory signals triggered by the activation of microglia on inflammation and apoptosis/survival pathways in pericytes. Microglia cells (Bv-2) were stimulated with lipopolysaccharide (LPS) and/or SST. Human retinal pericytes (HRP) were exposed to conditioned media (CM) collected from Bv-2 cells in physiological conditions and in the settings described above. A panel of inflammation, apoptosis and survival mediators was analyzed. HRP treated with LPS-CM showed a significant increase of pro-inflammatory (iNos and TNFα) and pro-apoptotic mediators (FasL, active caspase-8, tBid and Bax), and a concomitant decrease in pro-survival factors (BclxL and pAkt). SST added to LPS was able to counteract these effects in all conditions. In conclusion, SST is able to modulate apoptosis/survival pathways in HRP during microglia-mediated inflammation. These results demonstrate a crosstalk between microglia and retinal pericytes, evidencing a possible defensive role of microglia in the early phases of DR.


The effect of sevoflurane on the transmural dispersion of repolarisation in patients with type 2 diabetes mellitus: a prospective observational study.
The 'torsadogenic' property of a drug is linked to its ability to increase the transmural dispersion of repolarisation, represented by the interval between the peak of, and the end of, the T-wave (Tp-e interval) in an electrocardiogram. Reports have consistently shown that sevoflurane does not increase the Tp-e interval. Type 2 diabetes is a risk factor for increased QTc (rate-corrected QT interval), QTcd (rate-corrected QTc dispersion: difference between the maximum and the minimum QTc interval), and Tp-e, as well as the rate-corrected Tp-e (Tp-e/QTc ratio). The study aimed to ascertain whether sevoflurane increased the Tp-e interval and Tp-e/QTc ratio in patients with diabetes, thereby increasing their risk of torsades. We enrolled 35 female patients; 17 with type 2 diabetes and 18 controls undergoing non-laparoscopic surgery under sevoflurane anaesthesia. The Tp-e interval, Tp-e/QTc ratio, QTc and QTcd were recorded after intubation, 5, 10, 30 and 60 minutes into the anaesthetic, and were compared between the groups. No significant increase in the Tp-e interval or Tp-e/QTc was observed between or within the groups (a 13 ms increase was considered significant). In the control group, the QTc was significantly increased from baseline immediately after intubation (449 versus 414 ms, P <0.001); at 5 minutes (434 versus 414 ms, P=0.01); at 10 minutes (444 versus 414 ms, P=0.002); at 30 minutes (439 versus 414 ms, P=0.001) and at 60 minutes (442 versus 414 ms; P <0.001) (a 20 ms increase was considered significant). No significant increase in QTc was observed in the diabetic group. There were no between or within group differences observed for QTcd. Our findings suggest that sevoflurane does not have a significant predictable pro-arrhythmic effect in type 2 diabetic patients in the absence of other factors affecting ventricular repolarisation.


The clinical diagnosis of acute graft-versus-host disease: a diversity of views amongst marrow transplant centers.
The diagnosis and grading of acute graft-versus-host disease (AGVHD) is based on a spectrum of clinical and laboratory features. To evaluate the reliability of current diagnostic and scoring criteria, six clinical vignettes were evaluated by 49 transplant physicians from 42 bone marrow transplant center worldwide. Responses were analysed to determine: (1) the degree of concordance among transplanters in diagnosing, scoring and treating AGVHD, and (2) the degree of concordance in assigning primary and contributing causes of death in patients with multiple complications of bone marrow transplantation. Concordance for the diagnosis of AGVHD ranged from 24 to 76%; concordance for grading AGVHD was 55%. Concordance for the decision to treat for AGVHD ranged from 43 to 55%; concordance for assigning the primary cause of death ranged from 71 to 100%. The findings demonstrate the need for (1) improved uniformity of reporting complications of bone marrow transplantation; (2) periodic revision and validation of diagnostic and grading criteria, and (3) methods of analysis that allow for multiple causes of death.


Sexual Dynamics of Married Women with Interpersonal Dependency: A Qualitative Study on Iranian Women.
Considering the lack of documented research on the sexuality of dependent persons, this qualitative study examined sexual dynamics among Iranian married women with excessive interpersonal dependency. Interviews with 18 married women with high interpersonal dependency were coded using thematic analysis. Three major areas emerged from the data under which the themes clustered. These were (1) intrapersonal level which included confused sexual cognitions, intrusive thoughts during sex, preoccupation by sexual thoughts, low tolerance for reduction or interruption of sexual activity, and emotional distress during sex, (2) interactional dynamics including imposing pressure on the husband to have sex and assuming a submissive and receptive role during sex, and (3) contextual processes including social stigma and the effects of social phenomena. These findings presented a relatively clear understanding of the impacts of interpersonal dependency on the sexuality of Iranian women. The majority of the women reported maladaptive sexual strategies, attitudes, and emotions. Moreover, there were several similarities between the sexual dynamics of the women and those of individuals with anxious attachment style. These findings suffer from some limitations in terms of generalization due to the small size of the sample and clinical and cultural considerations. The implications of these findings for practitioners are also considered.


An evaluation of the efficacy of aspirin and benzydamine hydrochloride gargle for attenuating postoperative sore throat: a prospective, randomized, single-blind study.
Postoperative sore throat (POST), although a minor complication, remains a source of postoperative morbidity. We compared the efficacy of dispersible aspirin gargle to benzydamine hydrochloride (a topical nonsteroidal anti inflammatory drug) gargles for prevention of POST. We enrolled 60 consecutive female patients, 16-60 yr of age, ASA physical status I or II, undergoing elective modified radical mastectomy under general anesthesia in this prospective, randomized, placebo-controlled, single-blind study. Patients were randomly divided into 3 groups of 20 subjects each: Group 1 (C) mineral water; Group 2 (AS) tab aspirin 350 mg; and Group 3 (BH) 15 mL of benzydamine hydrochloride (0.15%). All the medications were made into 30 mL of solution. Patients were asked to gargle this mixture for 30 s, 5 min before induction of anesthesia. Grading of POST was done at 0, 2, 4, and 24 h postoperatively on a 4-point scale (0-3). Aspirin gargles reduced the incidence of POST for 4 h whereas benzydamine hydrochloride gargles reduced POST for 24 h. POST was more severe in the control group at 0 and 2 h (P < 0.05). Aspirin and benzydamine hydrochloride gargles significantly reduced the incidence and severity of POST (P < 0.05).


New biomarkers for diagnosis and prognosis of localized prostate cancer.
The diagnostics and management of localized prostate cancer is complicated because of cancer heterogeneity and differentiated progression in various subgroups of patients. As a prostate cancer biomarker, FDA-approved detection assay for serum prostate specific antigen (PSA) and its derivatives are not potent enough to diagnose prostate cancer, especially high-grade disease (Gleason ≥7). To date, a collection of new biomarkers was developed. Some of these markers are superior for primary screening while others are particularly helpful for cancer risk stratification, detection of high-grade cancer, and prediction of adverse events. Two of those markers such as proPSA (a part of the Prostate Health Index (PHI)) and prostate specific antigen 3 (PCA3) (a part of the PCA3 Progensa test) were recently approved by FDA for clinical use. Other markers are not PDA-approved yet but are available from Clinical Laboratory Improvement Amendment (CLIA)-certified clinical laboratories. In this review, we characterize diagnostic performance of these markers and their diagnostic and prognostic utility for prostate cancer.


Evolution of human alpha 2-macroglobulin.
A papain-binding protein (PBP) resembling human alpha 2-macroglobulin (alpha 2M) but of Mr half that of alpha 2M was purified from plaice (Pleuronectes platessa L.) plasma. The plaice protein displayed most of the distinctive inhibitory properties of the human macroglobulin, and was therefore considered, despite its smaller molecular size, to be homologous with alpha 2M. Plaice PBP was shown to consist of four dissimilar subunits; two I chains (Mr 105 000) and two II chains (Mr 90 000). Each of the larger I chains contained a "bait region" sensitive to proteolytic attack by a variety of proteinases, and an autolytic site analogous to the autolytic site of alpha 2M. Subunit I, almost certainly at the autolytic site, formed SDS-stable, covalent links with methylamine or a proportion of the trapped proteinase molecules. A scheme is proposed for the evolution of human alpha 2M from the smaller fish protein, and the possibility of a shared evolutionary origin for alpha 2M and the complement components C3 and C4 is discussed.


Diagnosis and Management of Polycystic Ovary Syndrome in Adolescent Girls.
Polycystic ovary syndrome (PCOS) is a common endocrine disorder in adolescent girls that has both reproductive and metabolic implications. Patients with PCOS typically present to their pediatrician for evaluation of menstrual irregularity and/or signs of hyperandrogenism, such as hirsutism and acne. The diagnosis of PCOS is made by clinical symptoms and laboratory evaluation. Because of the long-term health consequences that can accompany the disorder, pediatricians should consider PCOS in their initial evaluation of menstrual irregularity. Lifestyle modification is the cornerstone of treatment for girls with PCOS; however, hormonal medication such as oral contraceptive pills and insulin-sensitizing agents are useful and effective adjuncts to therapy. The goals of treatment for girls with PCOS are to improve clinical manifestations of the disorder, health-related quality of life, and long-term health outcomes.


Investigation of Plant Species with Identified Seed Oil Fatty Acids in Chinese Literature and Analysis of Five Unsurveyed Chinese Endemic Species.
Diverse fatty acid structures from different plant species are important renewable resources for industrial raw materials and as liquid fuels with high energy density. Because of its immense geographical and topographical variations, China is a country with enormous diversity of plant species, including large numbers of plants endemic to China. The richness of this resource of species provides a wide range of fatty acids in seeds or other tissues, many of which have been identified by Chinese scientists. However, in the past, most publications describing analysis of these plants were written in Chinese, making access for researchers from other countries difficult. In this study, we investigated reports on seed and fruit oil fatty acids as described in Chinese literature. Six books and more than one thousand papers were collected and the identified fatty acids and relevant plant species were summarized. In total, about 240 fatty acids from almost 1,500 plant species were identified from available Chinese literature. Only about one third of these species were retrieved in the PhyloFAdb and SOFA online databases of plant fatty acids. By referring to a summary of plant species endemic to China, 277 Chinese endemic species from 68 families have been surveyed for seed fatty acids. These account for <2% of total Angiosperm species endemic to China indicating the scope of species yet to be surveyed. To discover additional new fatty acid structures that might benefit society, it is important in the future to study oilseed fatty acids of the many other Chinese endemic plants. As an example, seeds of five unsurveyed species were collected and their fatty acids were analyzed. Ricinoleic acid was detected for the first time in the Salicaceae family.


Cutaneous leishmaniasis: co-ordinate expression of granzyme A and lymphokines by CD4+ T cells from susceptible mice.
We have recently demonstrated that the frequency of T cells expressing granzyme A is significantly higher in skin lesions and spleens of susceptible BALB/c mice compared with resistant C57BL/6 mice infected with Leishmania major, a cause of human cutaneous leishmaniasis. In the present study, we have performed in vitro studies to characterize the subpopulation, the antigen responsiveness and the lymphokine production pattern of granzyme A-expressing T cells in L. major-infected mice. Using a limiting dilution system for functional analysis of selected T cells at the clonal level, we could show that granzyme A activity in infected BALB/c mice can be assigned to L. major-reactive CD4+ T cells secreting interleukin-2 (IL-2) and IL-4. Granzyme A production was most pronounced in the early phase of infection. On the other hand, granzyme A expression could not be detected in C57BL/6-derived T cells responding to L. major. The data support the suggestion that granzyme A is produced by L. major-responsive CD4+ T cells facilitating lesion formation and the dissemination of infection.


(3R,6R)-4-methyl-6-(1-methylethyl)-3-phenylmethyl-perhydro-1,4-oxazine-2,5-dione: an apoptosis-inducer from the fruiting bodies of Isaria japonica.
(3R,6R)-4-methyl-6-(1-methylethyl)-3-phenylmethylperhydro-1,4-oxazine-2,5-dione (1) was isolated from the fruiting bodies of Isaria japonica as an apoptosis-inducing agent. The complete structural assignment of the compound was accomplished on the basis of spectroscopic methods and chemical transformations. Compound 1 induced apoptotic cell death of the human leukemia cells (HL-60) in a dose-dependent manner, ranging from 5.0 microg/ml to 100.0 microg/ml.


A complex ensemble of cis-regulatory elements controls the expression of a Vicia faba non-storage seed protein gene.
We have identified cis-regulatory elements within the 5'-upstream region of a Vicia faba non-storage seed protein gene, called usp, by studying the expression of usp-promoter deletion fragments fused to reporter genes in transgenic tobacco seeds. 0.4 kb of usp upstream sequence contain at least six, but probably more, distinct cis-regulatory elements which are responsible for seemingly all quantitative, spatial and temporal aspects of expression. Expression-increasing and -decreasing elements are interspersed and include an AT-rich sequence, a G-box element and a CATGCATG motif. The latter acts as a negative element in contrast to what has been found for the same motif in legumin- and vicilin-type seed storage protein gene promoters. Seed specificity of expression is mainly determined by the -68/+51 region which confers, however, only very low levels of expression. The data support the combinatorial model of promoter function.


Bony cochlear nerve canal and internal auditory canal measures predict cochlear nerve status.
The bony cochlear nerve canal is the space between the fundus of the internal auditory canal and the base of the cochlear modiolus that carries cochlear nerve fibres. This study aimed to determine the distribution of bony labyrinth anomalies and cochlear nerve anomalies in patients with bony cochlear nerve canal and internal auditory canal atresia and stenosis, and then to compare the diameter of the bony cochlear nerve canal and internal auditory canal with cochlear nerve status. The study included 38 sensorineural hearing loss patients (59 ears) in whom the bony cochlear nerve canal diameter at the mid-modiolus was 1.5 mm or less. Atretic and stenotic bony cochlear nerve canals were examined separately, and internal auditory canals with a mid-point diameter of less than 2 mm were considered stenotic. Temporal bone computed tomography and magnetic resonance imaging scans were reviewed to determine cochlear nerve status. Cochlear hypoplasia was noted in 44 out of 59 ears (75 per cent) with a bony cochlear nerve canal diameter at the mid-modiolus of 1.5 mm or less. Approximately 33 per cent of ears with bony cochlear nerve canal stenosis also had a stenotic internal auditory canal and 84 per cent had a hypoplastic or aplastic cochlear nerve. All patients with bony cochlear nerve canal atresia had cochlear nerve deficiency. The cochlear nerve was hypoplastic or aplastic when the diameter of the bony cochlear nerve canal was less than 1.5 mm and the diameter of the internal auditory canal was less than 2 mm. The cochlear nerve may be aplastic or hypoplastic even if temporal bone computed tomography findings indicate a normal cochlea. If possible, patients scheduled to receive a cochlear implant should undergo both computed tomography and magnetic resonance imaging of the temporal bone. The bony cochlear nerve canal and internal auditory canal are complementary structures, and both should be assessed to determine cochlear nerve status.


X-ray characterization of alpha-Fe(2)O(3) single crystals containing 2.2% and 95% (57)Fe.
alpha-Fe(2)O(3) single crystals containing 2.2% and 95% (57)Fe isotopes were characterized by means of X-ray topography, the diffraction rocking curve and the integrated intensity. These crystals were revealed to be nearly perfect and suitable for a further nuclear-resonant Bragg-scattering study.


[Late consequences of untreated lyme borreliosis].
The study aimed to evaluate late clinical symptoms and serological changes in persons with erythema migrans (EM) diagnosed 4-11 years ago who were not treated with antibiotics. Among initially included into the study 28 untreated EM cases, twelve persons responded for invitation to the Department. The symptoms and signs which could be related to previous Borrelia burgdorferi infection were present in 9 (75%) untreated patients. They included ischialgia (42%), arthritis (33%) and positive serological tests results (33% of patients, including 2 with clinical signs). These results demonstrate that lack of antibiotic treatment in the early LB stage can result in the development of late disease manifestations.


Biologics in the treatment of calcium pyrophosphate deposition disease: a systematic literature review.
The main aim of this systematic literature review (SLR) was to summarise the evidence in the use of biological therapies in calcium pyrophosphate deposition disease (CPPD). We performed a SLR using PubMed, Embase and Cochrane databases. Only studies reporting the efficacy of biologics in CPPD were selected. The search resulted in 83 articles; 11 were further evaluated in the SLR. Seventy-six patients were included: 2 received infliximab, whereas 74 anakinra. Anakinra was used in refractory disease (85.1%) or in patients with contraindications to standard treatments (23.0%). Clinical response to anakinra was observed in 80.6% of patients with acute and 42.9% of those with chronic CPPD. Short-term treatment was well tolerated and adverse events were reported in 4.1% of the cases. This review provides evidence in favour of the use of anakinra as a therapeutic option in patients with CPPD, especially in acute refractory CPPD or when standard treatments are contraindicated.


Thyroid dysfunction and cardiological management in patients receiving amiodarone.
To determine the prevalence of thyroid dysfunction in patients receiving amiodarone, and the possible associated factors. The study also aimed at assessing the effect of amiodarone on thyroid function through the application of a questionnaire to cardiologists. Fifty-six patients chronically (> 3 months) receiving amiodarone were assessed by measurement of their serum levels of TSH, free T4, total T3, and anti-TPO antibodies. Patients with changes in TSH levels were defined as having thyroid dysfunction (TD). The prevalence of thyroid dysfunction was 33.9%. No difference was observed between this group and that of patients with no dysfunction, except for the greater prevalence of anti-TPO positivity in patients with TD (P=0.02). Subclinical hypothyroidism was diagnosed in 10 (17.9%) patients and clinical hypothyroidism in 6 (10.7%). The prevalence of subclinical hyperthyroidism was 3.6% and that of clinical hyperthyroidism was 1.8%. Anti-TPO antibodies were positive in 5 (8%) patients (of whom, 4 had thyroid dysfunction). When compared with patients negative for anti-TPO antibodies, that group had a greater prevalence of dysfunction (80% vs 29.4%; P=0.04). Only 49.2% of the cardiologists routinely treated their patients' thyroid function, and the prevalence of the referred dysfunction for most of them ranged from 1 to 10%. The prevalence of thyroid dysfunction in our population was high, showing the need for implementing a laboratory routine. The cardiologists disagreed greatly in regard to the type of follow-up required for patients using amiodarone.


[Who doesn't benefit from psychosomatic rehabilitation?].
The aim of this study was to examine how far treatment success in psychosomatic rehabilitation can be predicted by patients' characteristics, therapy motivation and disorder. Data of 307 patients with psychosomatic disease were included. External and self-evaluations were operationalized as criterion for success. Data were collected using the Brief Symptom Inventory (BSI), Patients' Questionnaire of Therapy Motivation (PAREMO-20) and Disorder Severity Score (BSS). Hierarchical linear regression analysis was used for data analysis. A sceptical attitude, low education and long time of incapacity for work prior to rehabilitation can predict a lower treatment success. High levels of readiness for change and 6-8 working hours daily seem to favourably impact coping with disease in the framework of inpatient psychosomatic rehabilitation.


The acute toxic effects of imidazolium-based ionic liquids with different alkyl-chain lengths and anions on zebrafish (Danio rerio).
With the increasing applications of ionic liquids (ILs), the toxicity of ILs has drawn increasing attention in recent years, especially the influences of different anions and alkyl-chain lengths on the acute toxicity to aquatic organisms. We performed a study on the acute toxicity of 1-alkyl-3-methylimidazolium nitrate ([Cnmim]NO3 (n=2, 4, 6, 8, 10, 12)), 1-hexyl-3-methylimidazolium ILs ([C6mim]R (R=Cl-, Br-, BF4-, PF6-)) to zebrafish (Danio rerio). We also evaluated the sensibility of the investigated animals and the stability of ILs in water via high performance liquid chromatography (HPLC, Agilent 1260, Agilent Technologies Inc., USA) to prove the reliability of the present study. The results illustrated that the test zebrafish (Danio rerio) were sensitive to the reference toxicant and that the investigated ILs in water were stable. The 50% lethal concentration (LC50) was used to represent the acute toxicity to zebrafish (Danio rerio). The present study showed that the highest toxic IL is [C12mim]NO3 and the lowest toxic IL is [C2mim]NO3 on Danio rerio. The LC50s for ILs with different anions had similar values. Accordingly, we believe that ILs with different alkyl-chain lengths cause greater effects than other anions on acute toxicity to aquatic organisms. Furthermore, the present study can also provide scientific methods for future studies to select and assess ILs.


Estrogen receptor-beta regulates psoriasin (S100A7) in human breast cancer.
We have previously observed a paradoxical relationship of the psoriasin/S100A7 gene with estrogen response in-vitro in ERalpha positive cells but its association with ERalpha negative status in-vivo raising the possibility that S100A7 might be regulated by ERbeta in breast cancer. Using doxycycline-inducible ERbeta and ERalpha expressing MCF-7 cells the hypothesis that psoriasin/S100A7 is ERbeta regulated was investigated To explore the relationship between psoriasin/S100A7 and ERbeta expression in-vivo, we also assessed a cohort of 233 ERalpha negative breast tumors using tissue microarrays and immunohistochemistry. Psoriasin/S100A7 was increased by 17beta-estradiol (E2) following ERbeta induction, in several clones of ERbeta over-expressing but not in the original MCF-7 cells, nor clones over-expressing ERalpha. The effect of E2 on psoriasin/S100A7 was inhibited by 4-hydroxytamoxifen and ICI 182780 but not with a selective ERalpha antagonist. An ERbeta selective-agonist but not an ERalpha selective-agonist, induced psoriasin/S100A7. This induction still occurred after stable down-regulation of ERalpha using siRNA in ERbeta inducible cells. E2 increased psoriasin/S100A7 mRNA but cycloheximide treatment inhibited this effect. A relationship between ERbeta and psoriasin/S100A7 was observed in the p53 immunohistochemically negative subset of invasive breast tumors in-vivo (r = 0.225, p = 0.046, n = 79). In conclusion we demonstrate that E2 induction of psoriasin/S100A7 can be specifically regulated through ERbeta in-vitro and associated with ERbeta in-vivo. These data support the hypothesis that psoriasin/S100A7 is specifically regulated by ERbeta activity and could be useful to guide future therapies targeting ERbeta in certain phenotypic subsets of breast cancers in-vivo.


Genome-scale profiling of histone H3.3 replacement patterns.
Histones of multicellular organisms are assembled into chromatin primarily during DNA replication. When chromatin assembly occurs at other times, the histone H3.3 variant replaces canonical H3. Here we introduce a new strategy for profiling epigenetic patterns on the basis of H3.3 replacement, using microarrays covering roughly one-third of the Drosophila melanogaster genome at 100-bp resolution. We identified patterns of H3.3 replacement over active genes and transposons. H3.3 replacement occurred prominently at sites of abundant RNA polymerase II and methylated H3 Lys4 throughout the genome and was enhanced on the dosage-compensated male X chromosome. Active genes were depleted of histones at promoters and were enriched in H3.3 from upstream to downstream of transcription units. We propose that deposition and inheritance of actively modified H3.3 in regulatory regions maintains transcriptionally active chromatin.


Racial Distribution of Neighborhood-Level Social Deprivation in a Retrospective Cohort of Prostate Cancer Survivors.
Background: A better understanding of neighborhood-level factors' contribution is needed in order to increase the precision of cancer control interventions that target geographic determinants of cancer health disparities. This study characterized the distribution of neighborhood deprivation in a racially diverse cohort of prostate cancer survivors. Methods: A retrospective cohort of 253 prostate cancer patients who were treated with radical prostatectomy from 2011 to 2019 was established at the Medical University of South Carolina. Individual-level data on clinical variables (e.g., stage, grade) and race were abstracted. Social Deprivation Index (SDI) and Healthcare Professional Shortage (HPS) status was obtained from the Robert Graham Center and assigned to participants based on their residential census tract. Data were analyzed with descriptive statistics and multivariable logistic regression. Results: The cohort of 253 men consisted of 168 white, 81 African American, 1 Hispanic and 3 multiracial men. Approximately 49% of 249 men lived in areas with high SDI (e.g., SDI score of 48 to 98). The mean for SDI was 44.5 (+27.4), and the range was 97 (1−98) for all study participants. African American men had a significantly greater likelihood of living in a socially deprived neighborhood compared to white men (OR = 3.7, 95% C.I. 2.1−6.7, p < 0.01), while men who lived in areas with higher HPS shortage status were significantly more likely to live in a neighborhood that had high SDI compared to men who lived in areas with lower HPS shortages (OR = 4.7, 95% C.I. = 2.1−10.7, p < 0.01). African Americans had a higher likelihood of developing biochemical reoccurrence (OR = 3.7, 95% C.I. = 1.7−8.0) compared with white men. There were no significant association between SDI and clinical characteristics of prostate cancer. Conclusions: This study demonstrates that SDI varies considerably by race among men with prostate cancer treated with radical prostatectomy. Using SDI to understand the social environment could be -particularly useful as part of precision medicine and precision public health approaches and could be used by cancer centers, public health providers, and other health care specialists to inform operational decisions about how to target health promotion and disease prevention efforts in catchment areas and patient populations.


Integrating structural and mutagenesis data to elucidate GPCR ligand binding.
G protein-coupled receptors (GPCRs) represent the largest family of human membrane proteins, as well as drug targets. A recent boom in GPCR structural biology has provided detailed images of receptor ligand binding sites and interactions on the molecular level. An ever-increasing number of ligands is reported that exhibit activity through multiple receptors, binding in allosteric sites, and bias towards different intracellular signalling pathways. Furthermore, a wealth of single point mutants has accumulated in literature and public databases. Integrating these structural and mutagenesis data will help elucidate new GPCR ligand binding sites, and ultimately design drugs with tailored pharmacological activity.


Anti-osteoclastogenesis of Mineral Trioxide Aggregate through Inhibition of the Autophagic Pathway.
Mineral trioxide aggregate (MTA) regulates bone remodeling, particularly osteoclast differentiation. However, intracellular mechanisms underlying the anti-osteoclastogenesis of MTA remain unclear. This study aimed to evaluate the potential alterations of autophagic pathway during anti-osteoclastogenic effects by MTA in vitro and investigate their underlying mechanisms. Osteoclast precursors were treated with MTA extracts containing the receptor activator of nuclear factor-kappa B ligand (RANKL). Rapamycin was used to activate autophagy. RANKL-induced osteoclast differentiation was stained with tartrate-resistant acid phosphatase. Several specific autophagy features in osteoclast precursors were measured by using immunofluorescence, monodansylcadaverine, and transmission electron microscope. Autophagy-related proteins were investigated via Western blot analysis. The mRNA expression involved in autophagic and osteoclastic activities was detected with quantitative real-time polymerase chain reaction. MTA extracts inhibited osteoclast differentiation via preventing the fusion of osteoclast precursors without cytotoxicity. MTA extracts interrupted RANKL-induced acidic vesicular organelle formation and autophagic vacuole appearance in osteoclast precursors. Moreover, autophagic genes and proteins stimulated with RANKL diminished with MTA extracts. Notably, autophagy activation through rapamycin promoted multinucleated osteoclasts formation and increased osteoclastic genes expression, which almost reversed MTA-mediated anti-osteoclastogenic effects. MTA inhibited osteoclastogenesis for bone repair through attenuating the autophagic pathway.


[99Tcm]MAG3 gamma camera nephrography in epidemic nephritis.
There is a lack of systematic nephrographic studies on epidemic nephritis (EN). We studied 10 patients with EN using [99Tcm]MAG3 gamma camera nephrography and followed up 9 of them 22-68 days later when they had clinically recovered. Variables for renal clearance of [99Tcm]MAG3 and the retention of radioactivity in the kidneys and blood were calculated. In all patients renal function was impaired acutely. There was marked reconstitution of renal function in the control studies. [99Tcm]MAG3 clearance was inversely related to serum creatinine. On visual inspection the nephrograms showed no focal changes. Nephrography was more sensitive than sonography at identifying renal impairment. [99Tcm]MAG3 nephrography is a sensitive method for identifying renal involvement and reconstitution of renal function in EN. It may be a valuable adjunct to the diagnostic arsenal, especially in nonendemic areas where EN occurs only sporadically and where there may be diagnostic uncertainty in patients presenting acutely with EN.


DNA sequence-dependent epigenetic inheritance of gene silencing and histone H3K9 methylation.
Epigenetic inheritance mechanisms play fundamental roles in maintaining cellular memory of gene expression states. In fission yeast, histone H3 lysine 9 (H3K9) is methylated (H3K9me) at heterochromatic domains. These domains can be epigenetically inherited when epe1+ , encoding an enzyme that promotes H3K9 demethylation, is deleted. How native epigenetic states are stably maintained in epe1+ cells remains unknown. Here, we developed a system to examine the role of DNA sequence and genomic context in propagation of a cis-heritable H3K9me-dependent silenced state. We show that in epe1+ cells, in addition to sequence-independent mechanisms that propagate H3K9me, epigenetic inheritance of silencing requires binding sites for sequence-dependent activating transcription factor (ATF)-adenosine 3',5'-monophosphate (cAMP) response element-binding protein (CREB) family transcription factors within their native chromosomal context. Thus, specific DNA sequences contribute to cis inheritance of H3K9me and silent epigenetic states.


Hydrogen bonding in 2-(2-oxothiazolidin-3-yl)-4,5-dihydrothiazolium hydrogen sulfate monohydrate.
The asymmetric unit of the title compound, C(6)H(9)N(2)OS(2)(+).HSO(4)(-).H(2)O, contains a heterocyclic cation, a hydrogen sulfate anion and a water molecule. There are strong hydrogen bonds between the hydrogen sulfate anions and water molecules, forming an infinite chain along the [010] direction, from which the cations are pendent. The steric, electronic and geometric features are compared with those of similar compounds. In this way, structural relationships are stated in terms of the influence of the sulfate group on the protonation of the heterocycle and on the tautomeric equilibrium in the solid state.


Ecological Assets and Academic Procrastination among Adolescents: The Mediating Role of Commitment to Learning.
Academic procrastination is defined as a purposive delay of academic tasks that must be completed. Within the framework of the ecological model of resiliency, this study examined how ecological assets were related to academic procrastination among adolescents. Participants in the study were 577 adolescents (53.5% boys) from Shanghai, China. They completed measures of ecological assets, commitment to learning, and academic procrastination. Structural equation modeling revealed that, as predicted, ecological assets were negatively associated with academic procrastination. In addition, commitment to learning fully mediated the association between ecological assets and academic procrastination. Implications of the present findings are discussed.


Transition boundaries for protistan species turnover in hypersaline waters of different biogeographic regions.
The identification of environmental barriers which govern species distribution is a fundamental concern in ecology. Even though salt was previously identified as a major transition boundary for micro- and macroorganisms alike, the salinities causing species turnover in protistan communities are unknown. We investigated 4.5 million high-quality protistan metabarcodes (V4 region of the SSU rDNA) obtained from 24 shallow salt ponds (salinities 4%-44%) from South America and Europe. Statistical analyses of protistan community profiles identified four salinity classes, which strongly selected for different protistan communities: 4-9%, 14-24%, 27-36% and 38-44%. The proportion of organisms unknown to science is highest in the 14-24% salinity class, showing that environments within this salinity range are an unappreciated reservoir of as yet undiscovered organisms. Distinct higher-rank taxon groups dominated in the four salinity classes in terms of diversity. As increasing salinities require different cellular responses to cope with salt, our results suggest that different evolutionary lineages of protists have evolved distinct haloadaptation strategies. Salinity appears to be a stronger selection factor for the structuring of protistan communities than geography. Yet, we find a higher degree of endemism in shallow salt ponds compared with less isolated ecosystems such as the open ocean. Thus, rules for biogeographic structuring of protistan communities are not universal, but depend on the ecosystem under consideration.


Outcomes of Laparoscopic Cholecystectomy for Biliary Dyskinesia in Children.
To determine the outcomes of laparoscopic cholecystectomy as a treatment for biliary dyskinesia in children. With ethics approval, a retrospective chart review was performed on children (<21 years) at a single center diagnosed with biliary dyskinesia (defined as gallbladder ejection fraction [EF] <35% and/or pain with cholecystokinin [CCK] on cholescintigraphy, in the absence of gallstones or cholecystitis on ultrasound) and treated with laparoscopic cholecystectomy between March 2010 and February 2016. Demographic, medical history, diagnostic imaging, pathology, and outcome data were collected and analyzed based on degree of symptom resolution. Laparoscopic cholecystectomy was performed in 215 children with biliary dyskinesia (156/215 [72.6%] female, age 13.8 ± 3.4 years, body mass index [BMI] 22.3 ± 6.3 kg/m2). 181/206 (87.9%) had EF <35%. CCK reproduced symptoms in 149/177 (84.2%). 34/215 (15.8%) were lost to follow-up. Median follow-up time was 2.7 weeks. Pain improved in 162/181 (89.5%). Chronic cholecystitis was found in 183/213 (85.9%) and unexpected cholelithiasis in 4/213 (1.9%) on pathology. Postoperatively, 6/181 (3.3%) had wound infections and 8/181 (4.4%) required common bile duct stents for the following indications: 6 sphincter of Oddi dysfunction, 1 choledocholithiasis, and 1 stricture. Virgin abdomen (odds ratio [OR] 4.03, confidence interval [95% CI] 1.12-14.53, P = .0460) and follow-up <6 months (OR 7.35, 95% CI 2.68-20.21, P = .0002) were associated with better outcomes. Laparoscopic cholecystectomy is safe and effective in symptom resolution for biliary dyskinesia in children. Virgin abdomen and follow-up <6 months were associated with better outcomes. Prospective long-term studies comparing surgical and nonoperative management of biliary dyskinesia are required to determine the utility of cholecystectomy.


Association between MMP1 -1607 1G>2G polymorphism and head and neck cancer risk: a meta-analysis.
MMP1 is an important member of the MMP endopeptidase family that plays a critical role in the development of head and neck cancer (HNC). Several studies have investigated the association between the MMP1 -1607 1G>2G polymorphism and risk of HNC, but their results have been inconsistent. Here, we conducted a meta-analysis to further explore the role of the MMP1 -1607 1G>2G polymorphism in HNC development. We identified all eligible studies in the electronic databases of PubMed, ISI Web of Knowledge, MEDLINE, Embase, and Google Scholar (from January 2000 to June 2012). A meta-analysis was performed to evaluate the association between the MMP1 -1607 1G>2G polymorphism and risk of HNC by calculating odds ratios (OR) and 95% confidence interval (CIs). Twelve studies were included in this meta-analysis. In overall comparison, significant associations were found using the recessive and allelic contrast models (OR, 1.38; 95% CI, 1.07-1.79 and OR, 1.27; 95% CI, 1.05-1.53, respectively), but no association was detected using the dominant model. In the stratified analyses by several variables, significant associations were observed using the recessive, dominant, and allelic contrast models in the Asian population (OR, 1.64; 95% CI, 1.29-2.08; OR, 1.39; 95% CI, 1.06-1.82; and OR, 1.41; 95% CI, 1.21-1.65, respectively), European population (OR, 0.58; 95% CI, 0.40-0.84; OR, 0.64; 95% CI, 0.44-0.92; and OR, 0.68; 95% CI, 0.54-0.85, respectively), and population-based subgroup (OR, 1.24; 95% CI,1.05-1.47; OR,1.48; 95% CI,1.04-2.12; and OR, 1.22; 95% CI, 1.07-1.38, respectively). Furthermore, significant associations were detected in oral cavity cancer and nasopharyngeal cancer under the recessive model. Our results suggest that the MMP1 -1607 1G>2G polymorphism is associated with risk of HNC and that it plays different roles in Asian and European populations. Further studies with large sample size are needed to validate our findings.


Correlation between Severity of Atopic Dermatitis and Sleep Quality in Children and Adults.
The atopic dermatitis (AD) can limit a patient's physical and psychosocial development as well as lower their overall quality of life (QOL), including sleep quality. The purpose of this study was to evaluate the relationships between clinical disease severity, QOL and sleep quality in children and adults with AD. The SCORing atopic dermatitis (SCORAD) was examined to evaluate the severity of AD in fifty adult AD patients and 50 children AD patients. A questionnaire based on the children's sleep habits questionnaire (CSHQ) and the children's dermatology life quality index (CDLQI) were used to evaluate QOL and sleep disturbance in children AD patients. The Pittsburgh sleep quality index (PSQI) and dermatology life quality index (DLQI) were used in adult AD patients. The SCORAD and CSHQ score, the SCORAD and CDLQI score and the CSHQ and CDLQI score demonstrated significant correlations. The SCORAD and PSQI score showed no significant correlation. However, there were significant correlations between the SCORAD and DLQI score and the PSQI and DLQI score. Increasing severity of AD affects sleep quality in child AD patients. In adults, even though the total score of the sleep questionnaire is not associated with the severity of AD, two components of sleep questionnaire are associated with the severity of AD. There is a significant correlation between sleep quality and QOL in both children and adults. Therefore, we suggest that evaluating the sleep quality as well as clinical severity of the disease is necessary in the management of AD patients.


Onset of convection in strongly shaken granular matter.
Strongly vertically shaken granular matter can display a density inversion: A high-density cluster of beads is elevated by a dilute gaslike layer of fast beads underneath ("granular Leidenfrost effect"). For even stronger shaking the granular Leidenfrost state becomes unstable and granular convection rolls emerge. This transition resembles the classical onset of convection in fluid heated from below at some critical Rayleigh number. The same transition is seen in molecular dynamics (MD) simulations of the shaken granular material. The critical shaking strength for the onset of granular convection can be calculated from a linear stability analysis of a hydrodynamiclike model of the granular flow. Experiment, MD simulations, and theory quantitatively agree.


Pharmacokinetics and biological effects of captopril and hydrochlorothiazide after acute and chronic administration either alone or in combination in hypertensive patients.
The pharmacokinetics of free unchanged captopril, total captopril and hydrochlorothiazide (HCTZ) were investigated in three groups of patients with moderate essential hypertension and normal renal function on the first and on the 45th days of an oral treatment with either captopril (50 mg once daily, n = 7) or HCTZ (25 mg once daily, n = 10) or their combination captopril 50 mg + HCTZ 25 mg once daily, n = 8. Simultaneously, the effects of the three treatments on plasma converting enzyme activity (PCEA) and plasma renin activity (PRA) were measured. Elimination half-lives of total captopril after acute (7.8 +/- 2.3 h) or chronic (7.0 +/- 0.5 h) captopril dosing were similar to those of HCTZ after acute (6.5 +/- 1.0 h) or chronic (8.0 +/- 2.5 h) HCTZ dosing. Elimination half-life of free unchanged captopril was 0.81 +/- 0.09 h after acute and 0.96 +/- 0.03 h after chronic captopril dosing. Addition of HCTZ to captopril induced no major change in free and total captopril pharmacokinetic parameters, in PCEA inhibition and in PRA increase (as they were determined after captopril alone) on acute as well as on chronic treatment. Addition of captopril to HCTZ induced no major change in HCTZ pharmacokinetic parameters and in PRA increase compared with those determined after HCTZ alone. Chronic treatment with captopril + HCTZ resulted, like chronic captopril treatment, in no accumulation of captopril, in no significant modification of free and total captopril pharmacokinetic parameters and of PCEA inhibition (as determined after acute administration) but led to a significant enhancement of the acutely induced increase in PRA. Chronic treatment with captopril + HCTZ resulted, like chronic HCTZ treatment, in no accumulation of HCTZ, in no significant modification of HCTZ pharmacokinetic parameters (as determined after acute administration) but also led to a significant enhancement of the acutely induced increase in PRA. Thus, the longer duration of the antihypertensive action of captopril + HCTZ as compared to that of captopril cannot be ascribed to a pharmacokinetic or biological interaction between captopril and HCTZ.


Exploring DNA groove water dynamics through hydrogen bond lifetime and orientational relaxation.
Dynamics of water molecules in the grooves of DNA are of great interest both for practical (functionality of DNA) and fundamental (as examples of confined systems) interest. Here the authors employ atomistic molecular dynamics simulations to understand varying water dynamics at the minor and the major grooves of a 38 base-pair long DNA duplex in water. In order to understand and quantify the diversity in the nature of hydrogen bond due to many hydrogen bond donors and acceptors present in the four bases, they have undertaken study of hydrogen bond lifetime (HBLT) correlation functions of all the specific hydrogen bonds between the base atoms and water molecules. They find that the HBLT correlation functions are in general multiexponential, with the average lifetime depending significantly on the specificity and may thus be biologically relevant. The average hydrogen bond lifetime is longer in the minor groove than that in the major groove by almost a factor of 2. Analysis further shows that water hydrogen bonds with phosphate oxygen have substantially shorter lifetimes than those with the groove atoms. They also compute two different orientational time correlation functions (OTCFs) of the water molecules present at the major and the minor grooves and attempt to correlate OTCF with HBLT correlation function. The OTCFs in the minor groove exhibit three time scales, with the time constant of the slowest component one to two orders of magnitude longer than what is observed for bulk water. A slow component is also present for the major groove water but with shorter time constant. Interestingly, correlation between reformations allowed HBLT correlation function [C(HB)(t)] and the OTCF markedly deviates from each other in the grooves, indicating enhanced rigidity of water molecules in the grooves.


The relationship between achievement goal profile groups and perceptions of motivational climates in sport.
The purpose of the present study was to expand on previous research that has found compatibility between individuals' views on achievement and the type of achievement that was promoted in the sport environment they belonged to. However, this line of research has ignored the fact that the two main goal orientations are largely independent and that their impact in combination is often different from their effects examined separately. The present study, therefore, examined which combinations of goal orientations are compatible with perceptions of mastery and performance climates in a sample of 146 British university students. With regard to mastery climate, the analysis showed that the critical factor was the degree of task orientation since those with high scores in this factor (irrespective of the degree of their ego orientation) perceived the climate as more mastery-oriented than those with low scores in task orientation. This was substantiated by the large differences in effect sizes between the high- and low-task groups. As far as performance climate was concerned, the most negative perceptions of climate were held by those who were rated both low in task orientation and high in ego orientation. A general inference from these results is that high task orientation is motivationally adaptive, whereas high ego orientation is not motivationally detrimental as long as it is accompanied by a high task orientation. These findings are in contrast with previous suggestions that have called for the enhancement of task orientation with the concurrent suppression of ego orientation. Our results are, however, consonant with studies which have employed a goal profiles analysis in sport and in physical education, and with empirical evidence from real sport settings.


Particular characteristics of atopic eczema in tropical environments. The Tropical Environment Control for Chronic Eczema and Molecular Assessment (TECCEMA) cohort study.
Atopic dermatitis is a prevalent health problem in the world. Allergic sensitization is an important risk factor, but the roles of other factors, inherent in tropic region, are unknown. A cohort study was designed in a tropical city to investigate molecular and environmental risk factors for eczema, considering as particular features perennial exposure to mites, poor living conditions and others tropical characteristics. 433 patients were included at baseline and biological samples were collected during 24 months of follow-up. Clinical information was collected using questionnaires (SCORAD, DLQI and a subjective scale) during each clinical assessment. The prevalence of atopic eczema was 93%, with similar frequency between children and adults; parents history of eczema and polysensitization to mites, dogs, cats, cockroaches and birds, were risk factors for severe and persistent eczema and allergic comorbidities. Food sensitization was present in 16% of patients but food-induced allergies were scarce. Psychiatric, dental and ocular disorders were the most frequent non-allergic comorbidities. selection bias. We presented a tropical cohort of patients with eczema and we identified some risk factors for severe and persistent dermatitis. Some patterns of sensitization were associated with severe eczema and respiratory symptoms, and the natural history of "atopic march" is different to that described in some industrialized countries. The collection of biological samples will contribute to the understanding of the gene/environment interactions leading to allergy inception and evolution.


Identifying homing interactions in T-cell traffic in human disease.
Description of the molecular mechanisms which regulate the traffic of lymphocyte populations over recent years [for useful reviews see (1, 2)] has significantly enhanced our understanding of the processes underlying acquired immunity and also permitted the development of therapies targeted at specific leukocyte subpopulations. Such therapies are dependent upon a detailed knowledge of the molecular regulation of lymphocyte adhesion to and migration through endothelium in specific tissues. Whereas animal models have been central to understanding the underlying mechanisms, it is crucial to confirm and extend observations in man by using analysis of tissues and in vitro cell-based models. In this chapter, we discuss expertise developed in our laboratory for the isolation of specific lymphocyte and endothelial populations from explanted human liver tissue specimens. We then move on to provide specific examples of assays such as the Stamper-Woodruff assay, the transmigration assay and the tissue-specific endothelial static and flow-based adhesion assays, which can be used to interrogate the tissue-specific adhesion and migration of lymphocyte subsets. Although our own experience is with human liver tissue, the general principles apply to analysing any organ of interest.


A five-year study of prematurity.
To get a comprehensive picture of prematurity and neonatal death or survival, all factors on the maternal and fetal records that might be pertinent were recorded. This information, having to do with factors such as age, gravida of the mother, blood group incompatibility, period of gestation, weight at birth, type of delivery, medication and anesthesia administered to the mother, is presented in tabular form. In the study of perinatal mortality it was noted that failure to establish normal pulmonary ventilation is the most common cause of death in the neonatal period. Maternal history of relative infertility, that is, previous abortions, stillbirths and premature deliveries, was the most impressive finding in the stillborn series. In the follow-up study of premature infants who survived the neonatal period, 8.5 per cent were found to be severely handicapped. In four cases the handicap was due to congenital anomalies, in two others probably to infection, leaving 12 with complications possibly ascribable to prematurity. Six of these had retrolental fibroplasia as a major handicap. In seven, mental retardation was the presenting problem. Most of the handicapped children had multiple handicaps, which included spasticity, delayed motor development, strabismus, etc. The incidence of the necessity for corrective measures for feet and legs appeared relatively high. In general, survivors compared favorably with the rest of the childhood population. Complications and twinning were associated inordinately often.


Determination of topiramate in human plasma by capillary electrophoresis with indirect UV detection.
A rapid capillary zone electrophoresis method with indirect UV detection for the determination of topiramate in human plasma was developed and validated. The analyses were carried out with a background electrolyte composed of 10mM sulfamethoxazole as chromophore in phosphate buffer (25 mM, pH 12.0); gabapentin was selected as the internal standard. Application of a voltage of +15 kV led to an analysis time shorter than 5 min; indirect UV detection was operated at 256 nm. Isolation of topiramate from plasma was accomplished by a carefully implemented solid-phase extraction procedure on C18 cartridges. The method provided a linear response over the concentration range of 2-60 microg of topiramate per mL of plasma. The limit of detection (LOD) was 0.8 microg mL(-1) and the limit of quantitation (LOQ) was 2.0 microg mL(-1). Precision, expressed as relative standard deviation, was always lower than 7.3%, extraction yields were always greater than 92%. The results obtained analysing plasma samples from epileptic patients undergoing therapy with topiramate were satisfactory in terms of precision and selectivity.


An autopsy of the coloniality of suicide: Modernity's completed genocide.
From the Latin American modernity/coloniality project, we address the inhospitality of the modern/colonial and globally designed world-system in relation to suicidality. In our vernacular Spanglish, guided by epistemological disobedience, and responding to epistemicide, we interpellate ourselves to unmask the hidden colonial structures of power of modernity's global design on suicide knowledge. Our intent is to argue, specifically from the perspective of coloniality and our racialized, gendered, and monetized bodies, that suicide is rather an extension of modernity's colonial genocide. From the decolonial geo and body-politics of knowledge, our discussion on modernity's Eurocentric rhetoric on suicide departs from the materialization of suicidality in our flesh. We story experiences of our bodies with life and pleas of death, within the context of our immigrant backgrounds, and as family therapists in the United States (U.S.). We adopt autopsy as an analogy from where to advance such analysis to contest Eurocentric configurations of suicide from within, but against modernity. We emphasize the hidden racism and capitalism of suicide embedded within the persuasive Eurocentric promises of the Anglo scientific method and the U.S. American Dream. We address the concepts of epistemicide, coloniality of knowledge and of being. It is our hope to contribute to further advance decolonizing possibilities to reinscribe options that would border with the current Western knowledge on suicide. This may require other configurations of the body, knowledge, hence ways of being, doing, thinking, sensing, feeling, imagining, and dreaming to coexist among pluriversal hospitable worlds of life and death.


Spatiotemporally restricted arenavirus replication induces immune surveillance and type I interferon-dependent tumour regression.
Immune-mediated effector molecules can limit cancer growth, but lack of sustained immune activation in the tumour microenvironment restricts antitumour immunity. New therapeutic approaches that induce a strong and prolonged immune activation would represent a major immunotherapeutic advance. Here we show that the arenaviruses lymphocytic choriomeningitis virus (LCMV) and the clinically used Junin virus vaccine (Candid#1) preferentially replicate in tumour cells in a variety of murine and human cancer models. Viral replication leads to prolonged local immune activation, rapid regression of localized and metastatic cancers, and long-term disease control. Mechanistically, LCMV induces antitumour immunity, which depends on the recruitment of interferon-producing Ly6C+ monocytes and additionally enhances tumour-specific CD8+ T cells. In comparison with other clinically evaluated oncolytic viruses and to PD-1 blockade, LCMV treatment shows promising antitumoural benefits. In conclusion, therapeutically administered arenavirus replicates in cancer cells and induces tumour regression by enhancing local immune responses.