Glucose dependence of imidazoline-induced insulin secretion: different characteristics of two ATP-Sensitive K+ channel-blocking compounds.
The glucose dependence of the insulinotropic action of KATP channel-blocking imidazoline compounds was investigated. Administration of 100 micromol/l phentolamine, but not 100 micromol/l efaroxan, markedly increased insulin secretion of freshly isolated mouse islets when the perifusion medium contained 5 mmol/l glucose. When the glucose concentration was raised to 10 mmol/l in the continued presence of either imidazoline, a clear potentiation of secretion occurred as compared with 10 mmol/l glucose alone. In the presence of efaroxan, a brisk first-phase-like increase was followed by a sustained phase, whereas a more gradual increase resulted in the presence of phentolamine. Administration of 100 micromol/l phentolamine was somewhat more effective than 100 micromol/l efaroxan to inhibit KATP channel activity in intact cultured beta-cells (reduction by 96 vs. 83%). Both compounds were similarly effective to depolarize the beta-cells. When measured by the perforated patch-technique, the depolarization by efaroxan was often oscillatory, whereas that by phentolamine was sustained. In perifused cultured islets, both compounds increased the cytosolic calcium concentration ([Ca2+]c) in the presence of 5 and 10 mmol/l glucose. Efaroxan induced large amplitude oscillations of [Ca2+]c, whereas phentolamine induced a sustained increase. It appears that a KATP channel block by imidazolines is not incompatible with a glucose-selective enhancement of insulin secretion. The glucose selectivity of efaroxan may involve an inhibitory effect distal to [Ca2+]c increase and/or the generation of [Ca2+]c oscillations.


Acupuncture in the treatment of alcohol withdrawal symptoms: a randomized, placebo-controlled inpatient study.
Thirty-four alcoholics were treated with acupuncture to the ear and the body in a randomized single-blind placebo-controlled design over 14 days. Orthodox points and placebo needles to orthodox points were used daily for a total of 10 treatments starting on the first day of admission as add-on therapy to standard medication with carbamazepine. The primary outcome was the Clinical Institute Withdrawal Assessment (CIWA-Ar-scale) assessed on days 1-6, 9 and 14. No initial differences were found regarding sociodemographic data, drinking history and alcohol-related data, indicating successful randomization. Longitudinal analysis of the Clinical Institute Withdrawal Assessment (CIWA-Ar-scale) data showed that patients assigned to acupuncture had a general tendency towards better outcome results and significantly fewer withdrawal symptoms on day 14 (Wilcoxon-W=177.500, Z=-2.009, p = 0.045). No significant differences were found in the Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI X1 and X2) and Eigenschaftswoerterliste (EWL S60). We conclude that acupuncture as an adjunctive treatment to carbamazepine medication shows promise for the treatment of alcohol withdrawal symptoms. Further investigation of this treatment modality appears to be warranted.


Pharmacokinetics of acarbose. Part I: Absorption, concentration in plasma, metabolism and excretion after single administration of [14C]acarbose to rats, dogs and man.
The absorption, disposition, metabolism, and excretion of acarbose (O-4,6-dideoxy-4-[[(1S, 4R, 5S, 6S)-4,5,6-trihydroxy-3- (hydroxymethyl)-2- cyclohexen-1-yl]amino]-a-D-glucopyranosyl- (1----4)-O-a-D-glucopyranosyl- (1----4) -D-glucopyranose, Bay g 5421) have been studied following a single administration of the 14C-labelled compound to rats and dogs via different routes (intravenous, oral, intraduodenal) in the dose range of 2-200 mg.kg-1 as well as to man in a single oral dose of 200 mg. After intravenous administration [14C]acarbose was eliminated rapidly and completely via the renal route. There was no indication for a systemic metabolization of [14C]acarbose. The (renal) clearance for [14C]acarbose was in the range of the glomerular filtration rate. After oral administration [14C]acarbose was very poorly absorbed (1-2% of dose in rats and man and 4% in dogs). Additionally, up to 35% of the radioactivity of [14C]acarbose were absorbed after degradation by digestive enzymes and/or intestinal microorganisms. The delayed and biphasic absorption of the radioactivity strongly influenced the plasma concentration vs time profiles of total radioactivity. Maximum concentrations dependent on the degree of microbial degradation (dog less than rat, man) and on the intestinal transit time were reached at 1.2 h (dogs), 8 h (rats) and 14-24 h (man). The excretion of the radioactivity absorbed occurred rapidly and completely mostly via the renal route.(ABSTRACT TRUNCATED AT 250 WORDS)


Inhibition of infectious bursal disease virus by vector delivered SiRNA in cell culture.
Infectious Bursal Disease (IBD) is major threat to poultry industry. It causes severe immunosuppression and mortality in chicken generally at 3 to 6 weeks of age. RNA intereference (RNAi) emerges as a potent gene regulatory tool in last few years. The present study was conducted to evaluate the efficiency of RNAi to inhibit the IBD virus (IDBV) replication in-vitro. VP2 gene of virus encodes protein involved in capsid formation, cell entry and induction of protective immune responses against it. Thus, VP2 gene of IBDV is the candidate target for the molecular techniques applied for IBDV detection and inhibition assay. In this study, IBDV was isolated from field cases and confirmed by RT-PCR. The virus was then adapted on chicken embryo fibroblast cells (CEF) in which it showed severe cytopathic effects (CPE). The short hairpin RNA (shRNAs) constructs homologous to the VP2 gene were designed and one, having maximum score and fulfilling maximum Reynolds criteria, was selected for evaluation of effective inhibition. Selected shRNA construct (i.e., VP2-shRNA) was observed to be the most effective for inhibiting VP2 gene expression. Real time PCR analysis was performed to measure the relative expression of VP2 gene in different experimental groups. The VP2 gene was less expressed in virus infected cells co-transfected with VP2-shRNA as compared to mock transfected cells and IBDV+ cells (control) at dose 1.6 µ g. The result showed ∼95% efficient down regulation of VP2 gene mRNA in VP2-shRNA treated cells. These findings suggested that designed shRNA construct achieved high level of inhibition of VP2 gene expression in-vitro.


Prevalence of diabetes and hypertension among geriatric population in a rural community of Tamilnadu.
Elderly population contributed to 7% of total population of India in 2001 and it will rise to 9% by 2016. In 2010,100 million people were aged above 60 years and by 2020 it will be 177 million. Ageing process is as such complex and multi-factorial. Chronic morbidities like diabetes and hypertension are becoming common health problems among the geriatric population. To assess the prevalence of diabetes and hypertension among geriatric population in a rural community of Tamilnadu. A cross-sectional study was conducted on 400 geriatric population at Attayampatti village, rural community in Salem district by using a pre-tested, semi-structured questionnaire. House to house visit was done on simple random basis. Their height and weight was measured and body mass index was calculated. The diabetic status was confirmed by using random blood sugar estimation and hypertension was assessed by using a standard sphygmomanometer apparatus. The overall prevalence of diabetes among study population was 36% and the prevalence of hypertension was 59%. Among diabetes, the prevalence in males was 22% and in females it was 15%. Among hypertensives, the prevalence in males was 33.3% and in females it was 26.2%. Their mean BP was 140/100 and the mean random blood sugar was 180 mgs/dl. Factors like age, BMI and smoking showed statistical significant association towards diabetes and hypertension. Early identification of chronic geriatric morbidities like diabetes and hypertension should be ensured through periodic screening and regular health checkups.


Phage Tail Fiber Protein as a Specific Probe for Recognition of Shiga Toxin-Producing Escherichia coli O91, O103, and O111.
The ability to quickly identify specific serotypes of Shiga toxin-producing Escherichia coli (STEC) could facilitate the monitoring and control of STEC pathogens. In this study, we identified the receptors and receptor-binding proteins (RBPs) of three novel phages (pO91, pO103, and pO111) isolated from hospital wastewater. Recombinant versions of these RBPs (pO91-ORF43, pO103-ORF42, and pO111-ORF8) fused to a fluorescent reporter protein were then constructed. Both fluorescence microscopy and transmission electron microscopy showed that all three recombinant RBPs were bound to the bacterial surface. Indirect enzyme-linked immunosorbent assay was used to verify that each recombinant RBP bound specifically to E. coli O91, O103, or O111, but not to any of the 83 strains of E. coli with different O-antigens, nor to 10 other bacterial species that were tested. The recombinant RBPs adsorbed to their respective host bacteria within 10 min of incubation. The minimum concentration of bacteria required for detection by the recombinant RBPs was 33 colony-forming units (CFU)/mL (range: 3.3 × 10 to 3.3 × 108 CFU/mL). Furthermore, each recombinant RBP was also able to detect bacteria in lettuce, chicken breast meat, and infected mice, indicating that their usage will facilitate the detection of STEC and may help to reduce the spread of STEC-related infections and diseases.


Productivity Losses Associated with Head and Neck Cancer Using the Human Capital and Friction Cost Approaches.
Previous studies suggest that productivity losses associated with head and neck cancer (HNC) are higher than in other cancers. These studies have only assessed a single aspect of productivity loss, such as temporary absenteeism or premature mortality, and have only used the Human Capital Approach (HCA). The Friction Cost Approach (FCA) is increasingly recommended, although has not previously been used to assess lost production from HNC. The aim of this study was to estimate the lost productivity associated with HNC due to different types of absenteeism and premature mortality, using both the HCA and FCA. Survey data on employment status were collected from 251 HNC survivors in Ireland and combined with population-level survival estimates and national wage data. The cost of temporary and permanent time off work, reduced working hours and premature mortality using both the HCA and FCA were calculated. Estimated total productivity losses per employed person of working age were EUR253,800 using HCA and EUR6800 using FCA. The main driver of HCA costs was premature mortality (38% of total) while for FCA it was temporary time off (73% of total). The productivity losses associated with head and neck cancer are substantial, and return to work assistance could form an important part of rehabilitation. Use of both the HCA and FCA approaches allowed different drivers of productivity losses to be identified, due to the different assumptions of the two methods. For future estimates of productivity losses, the use of both approaches may be pragmatic.


Morphology and sensory modality of mushroom body extrinsic neurons in the brain of the cockroach, Periplaneta americana.
Mushroom bodies are paired centers in insect brains that are thought to be crucial in olfactory learning and memory. Early neuroanatomical descriptions suggested that the mushroom bodies comprise rather simple arrangements of nerve cells. Intrinsic neurons within each mushroom body were believed to receive olfactory afferents and to supply long, branched axons to extrinsic neurons that lead from the mushroom body into the protocerebrum. More recent suggestions that the mushroom bodies integrate several sensory modalities find support from intracellular and extracellular recordings of extrinsic neurons in the brains of crickets, honey bees, and cockroaches. Here, we describe two major classes of extrinsic neurons, simple and complex cells, in the mushroom bodies of the cockroach Periplaneta americana. Each class is defined by its pattern of branching in the brain. Simple neurons correspond to extrinsic neurons described from other species that have one set of dendrites only within the mushroom bodies. Complex extrinsic neurons possess dendrite-like branches within and outside the mushroom bodies. This arrangement may account in part for their observed multimodality, as might newly identified afferent neurons that terminate in the mushroom body lobes among the dendrites of extrinsic neurons and that respond to multimodal stimuli. Organizational complexity within the mushroom bodies is suggested by the grouping of intrinsic cell axons into discrete laminae. These are intersected by the block-like arrangements of dendritic fields of extrinsic neurons in a manner reminiscent of Purkinje cell dendrites intersecting parallel fibers in the cerebellum. The present results demonstrate that the cockroach mushroom body processes multimodal sensory information and that its neural arrangements contribute to a precise architecture consisting of discrete longitudinal and transverse subdivisions.


High p95HER2/HER2 Ratio Associated With Poor Outcome in Trastuzumab-Treated HER2-Positive Metastatic Breast Cancer NCCTG N0337 and NCCTG 98-32-52 (Alliance).
Purpose: p95HER2 is a truncated form of HER2 that confers resistance to trastuzumab in vitro, but clinical results have been conflicting to date. Given that p95HER2 levels correlate with total HER2 expression levels, which confer better outcomes, we sought to evaluate the p95HER2/HER2 ratio in the North Central Cancer Treatment Group N0337 and N98-32-52 trials.Experimental Design: The HERmark assay and VeraTag technology (Monogram Biosciences) were used to measure total HER2 and p95HER2 expression levels in 91 patient samples.Results: In the multivariate model, increasing total HER2 level was significantly associated with longer (OS; HR, 0.33; P = 0.002) and decreasing p95HER2 level was significantly associated with longer OS (HR, 4.2; P = 0.01). Total HER2 expression level was significantly associated with longer progression-free survival (PFS) (HR, 0.57; P = 0.04), whereas p95HER2 level was not (HR, 1.7; P = 0.25). However, there was a positive association between p95HER2 and total HER2 expression levels (R2 = 0.48; P < 0.001). Consistent with our hypothesis, the ratio of p95HER2/HER2 was significantly associated with worsening PFS (HR, 1.7; P = 0.04) and OS (HR, 2.8; P = 0.002). Patients with the highest tertile of p95HER2/HER2 values had significantly less favorable PFS (HR, 1.8; P = 0.06) and OS (HR, 2.3; P = 0.02).Conclusions: A high p95HER2/HER2 ratio identified patients with metastatic breast cancer with poor outcomes on trastuzumab-based therapies. Further investigation of the p95HER2/HER2 ratio as a potential prognostic or predictive biomarker for HER2-targeted therapy is warranted. Clin Cancer Res; 24(13); 3053-8. ©2018 AACR.


Ultraviolet charge-transfer-to-solvent spectroscopy of halide and hydroxide ions in subcritical and supercritical water.
The temperature dependence of the vacuum ultraviolet charge-transfer-to-solvent (CTTS) absorption spectra of aqueous halide and hydroxide ions was measured for the first time up to 380 °C in subcritical and supercritical water. With increasing temperature, absorption spectra are observed to broaden and redshift, much in agreement with previous measurements below 100 °C. These changes are discussed alongside classic cavity models of the solvated species, which tie in the configuration of the adjoining polarized medium and its critical role in light absorption for electronic transitions. The data seemingly confirm the validity of the "diffuse" model pioneered by Platzman and Franck and later revised by Stein and Treinin, which has largely gone untested for nearly 60 years due to lack of experimental data in this extended temperature range. A gradual increase in anion cavity size is inferred as a function of increasing temperature while the enthalpy and entropy of hydration are largely unaffected. The changes in solvation properties are considered in the context of recent studies of the ultraviolet spectroscopy of subcritical and supercritical water and historic studies of the CTTS absorption. The "diffuse" polarizable continuum model succeeds in describing the absorption due to lack of well-defined ion hydration shells for these ions. CTTS spectra for iodide in supercritical water show no energy shift as a function of pressure/density, suggesting dielectric saturation of the I- anion by the adjacent H2O molecules at all experimental pressures/densities.


Tumour suppressor p53 down-regulates the expression of the human hepatocyte nuclear factor 4alpha (HNF4alpha) gene.
The liver is exposed to a wide variety of toxic agents, many of which damage DNA and result in increased levels of the tumour suppressor protein p53. We have previously shown that p53 inhibits the transactivation function of HNF (hepatocyte nuclear factor) 4alpha1, a nuclear receptor known to be critical for early development and liver differentiation. In the present study we demonstrate that p53 also down-regulates expression of the human HNF4alpha gene via the proximal P1 promoter. Overexpression of wild-type p53 down-regulated endogenous levels of both HNF4alpha protein and mRNA in Hep3B cells. This decrease was also observed when HepG2 cells were exposed to UV irradiation or doxorubicin, both of which increased endogenous p53 protein levels. Ectopically expressed p53, but not a mutant p53 defective in DNA binding (R249S), down-regulated HNF4alpha P1 promoter activity. Chromatin immunoprecipitation also showed that endogenous p53 bound the HNF4alpha P1 promoter in vivo after doxorubicin treatment. The mechanism by which p53 down-regulates the P1 promoter appears to be multifaceted. The down-regulation was partially recovered by inhibition of HDAC activity and appears to involve the positive regulator HNF6alpha. p53 bound HNF6alpha in vivo and in vitro and prevented HNF6alpha from binding DNA in vitro. p53 also repressed stimulation of the P1 promoter by HNF6alpha in vivo. However, since the R249S p53 mutant also bound HNF6alpha, binding HNF6alpha is apparently not sufficient for the repression. Implications of the p53-mediated repression of HNF4alpha expression in response to cellular stress are discussed.


Effects of growth hormone, prolactin, and placental lactogen on insulin content and release, and deoxyribonucleic acid synthesis in cultured pancreatic islets.
The direct effects of human GH (hGH), ovine pituitary PRL (oPRL), and human chorionic somatomammotropin [placental lactogen (hPL)] on the endocrine pancreas were studied in isolated pancreatic islets maintained in tissue culture. Islets of Langerhans were isolated by collagenase treatment of pancreatic tissue obtained from adult NMRI mice and adult or newborn Wistar rats. The islets were maintained for up to 3 weeks in petri dishes containing tissue culture medium RPMI 1640 supplemented with newborn calf serum or normal human serum. The release of insulin during culture and the islet content of insulin, glucagon, and DNA after culture were determined. The DNA synthesis in the newborn rat islets was evaluated by the incorporation of [methyl-3H]thymidine into islet cell DNA. In mouse islets, 1 micrograms/ml hGH, oPRL, or hPL markedly stimulated insulin release during a 2-week culture period and caused a significant increase in the insulin content in the islets after culture. While hGH did not affect the DNA content in adult mouse islets, an increase was observed in adult rat islets after 2-3 weeks of culture. In islets isolated from 3- to 5-day-old rats cultured for 2 weeks with hGH, there was a 30-40% higher DNA content than that found without hGH. Correspondingly, a significant stimulation of the incorporation of [methyl-3H]thymidine could be demonstrated 24 h after the addition of hGH, oPRL, or hPL. hCG and porcine ACTH had no effect. In conclusion, these results indicate that GH and related hormones have a direct stimulatory effect on both the insulin production and DNA synthesis in isolated islets of Langerhans. Whether the effect is directly on the beta-cell or mediated via locally produced growth factors remains to be determined.


A synbiotic composed of Lactobacillus fermentum CECT5716 and FOS prevents the development of fatty acid liver and glycemic alterations in rats fed a high fructose diet associated with changes in the microbiota.
We investigated the effect of a high fructose diet (HFD) on Sprague Dawley rats and the impact of a synbiotic composed of Lactobacillus fermentum CECT5716 and fructooligosaccharides. Feeding the HFD for 5 weeks resulted in liver steatosis and insulin resistance but not obesity. These changes were associated with increased production of short-chain fatty acids and increased Bacteroidetes in feces, with an augmented Bacteroidetes/Firmicutes ratio, among other changes in the microbiota. In addition, barrier function was weakened, with increased LPS plasma levels. These data are consistent with increased fructose availability in the distal gut due to saturation of absorptive mechanisms, leading to dysbiosis, endotoxemia, hepatic steatosis, and insulin resistance. Treatment with the synbiotic prevented some of the pathological effects, so that treated rats did not develop steatosis or systemic inflammation, while dysbiosis and barrier function were greatly ameliorated. In addition, the synbiotic had hypolipidemic effects. The synbiotic composed by L. fermentum CECT5716 and fructooligosaccharides has beneficial effects in a model of metabolic syndrome induced by a HFD, suggesting it might be clinically useful in this type of condition, particularly considering that high fructose intake has been related to metabolic syndrome in humans.


Maspin. A tumor suppressing serpin.
Maspin, a serpin found in mammary epithelial cells, has been shown to have tumor suppressor activity. The gene is expressed in normal human mammary epithelial cells but down-regulated in invasive breast carcinomas. Similar patterns of expression at the RNA and protein levels are seen by Northern analysis with cells grown in culture and by immunostaining of tissues. Biological assays of invasion by tumor cells through Matrigel membranes and of motility have shown that recombinant maspin inhibits both processes, and that its inhibitory action is totally lost by a single cleavage at the reaction center. Tumor transfectants expressing maspin are inhibited in growth and metastasis in nude mice. Maspin is located in the cell membrane and extracellular matrix, and does not behave as a classical inhibitory serpin against any known target protease. Its mode of action is presently unknown.


Stakeholder Participation for Legitimate Priority Setting: A Checklist.
Accountable decision-makers are required to legitimize their priority setting decisions in health to members of society. In this perspective we stress the point that fair, legitimate processes should reflect efforts of authorities to treat all stakeholders as moral equals in terms of providing all people with well-justified, reasonable reasons to endorse the decisions. We argue there is a special moral concern for being accountable to those who are potentially adversely affected by decisions. Health authorities need to operationalize this requirement into real world action. In this perspective, we operationalize five key steps in doing so, in terms of (i) proactively identifying potentially adversely affected stakeholders; (ii) comprehensively including them in the decision-making process; (iii) ensuring meaningful participation; (iv) communication of recommendations or decisions; and (v) the organization of evaluation and appeal mechanisms. Health authorities are advised to use a checklist in the form of 29 reflective questions, aligned with these five key steps, to assist them in the practical organization of legitimate priority setting in healthcare.


Reflections on "Replicating Milgram" (Burger, 2009).
In "Replicating Milgram: Would People Still Obey Today?" Jerry M. Burger reported a high base rate of obedience, comparable to that observed by Stanley Milgram (1974). Another condition, involving a defiant confederate, failed to significantly reduce obedience. This commentary discusses the primary contributions of Burger's study in terms of (a) its novel methodological variation on Milgram's original paradigm (the "150-volt solution") and (b) its attention to ethical concerns so as to minimize participant discomfort and ensure institutional review board approval. Burger's technique could unlock research on behavioral aspects of obedience, which has been essentially muted for several decades. However, Burger's intensive efforts to improve the ethics of the study may be exaggerated, are uncertain in their effectiveness, and pose impractical demands. Different procedures used by Milgram and Burger in the modeled refusal condition preclude a clear explanation for the results and challenge Burger's emphasis on the comparability of his and Milgram's experiments. This study documents the complexities of extending research on destructive obedience in the context of contemporary ethical guidelines.


[Chikungunya, emerging disease in Latin America. Description of the first cases in Chile].
Chikungunya (CHIK) was introduced in The Americas in 2013, spreading rapidly. In 2014, the first imported case was diagnosed in Chile. To identify patients with clinical suspicion of CHIK and describe their clinical and laboratory characteristics. Patients with suspected CHIK were enrolled. All were confirmed by PCR, IgM or IgG CHIK. A structured survey was applied, which included demographic questions, travel characteristics, clinical manifestations, and laboratory results. 21 patients were enrolled and CHIK was confirmed in 16, who were further analyzed; 12 were female (75%), average age 39 years (27-52). The Caribbean and South Americawere the most frequent sites of exposure. In 63%, the initial symptom was arthralgia. Most frequent symptoms were myalgias, malaise (both 100%), fever, and polyarthralgia (both 94%). The median duration of arthralgias was 90 days (3-262); in 53% arthralgias lasted ≥ 3 months. Main joints involved were ankles, hands, and wrists; 87% reported invalidating pain. Arthritis lasted longer in men than in women (p < 0.001). 38% of patients presented lymphopenia and one patient mild thrombocytopenia. Two patients required hospitalization, one with severe headaches, the other with acute pyelonephritis. Chikungunya should be suspected in returning travelers presenting with fever and severe polyarthralgia. Travelers to endemic areas should apply prevention measures to avoid mosquito bites.


Cell-mediated lympholytic responses against autologous cells modified with haptenic sulfhydryl reagents. I. Effector cells can recognize two distinct classes of hapten-reactive self sites on cell surface proteins.
Mouse spleen cells were modified with a sulfhydryl-reactive reagent, N-iodoacetyl-N'-(5-sulfonic-1-naphthyl) ethylene diamine (I-AED) and used as stimulator cells in primary in vitro cultures with unmodified spleen cells of the same strain. CTL could be readily demonstrated when tested on hapten-modified syngeneic target cells. These CML responses were hapten specific and H-2 restricted. In the H-2b strain, effector cell populations were identified that recognized AED in association with K-end and D-end coded self MHC products. Functional modification of the target cells by I-AED can be effectively blocked by prereacting the cells with other SH-reagents, which is consistent with CTL recognition of the hapten on cysteine residues. Since these premodifications of the cell surface do not block the functional modification by trinitrobenzene sulfonate (TNBS), the sulfhydryl-reactive compounds and TNBS modify distinct classes of cell surface groups as determined by CTL function. The results of antibody inhibition experiments are also consistent with this interpretation. Using fluorescent labeled anti-hapten antibodies, FACS II analysis showed that there are approximately 20-fold fewer AED than TNP groups on the approximately 20-fold fewer AED than TNP groups on the cell surface when equivalent concentrations of I-AED and TNBS are compared. The possibility is discussed that these sulfhydryl-reactive compounds can be used together with the H-2Kb mutants for the localization of H-2 coded self determinants recognized in association with foreign antigens.


Reversal of medication abortion with progesterone: a systematic review.
We sought to determine whether there is evidence to recommend progesterone for individuals not wishing to complete a medication abortion after taking mifepristone. We undertook an updated systematic review including a primary search for studies in which individuals received progesterone to reverse the effects of mifepristone, and a secondary search for studies in which individuals received mifepristone alone. We searched PubMed, Embase, Cochrane, CINAHL and grey literature up to December 2022. We used the Joanna Briggs Institute critical appraisal tools for risk of bias assessment. We compared ongoing pregnancy rates among individuals treated with progesterone to those managed expectantly. We did not find new studies in our secondary search. For the main search, we included three case series and one randomised controlled trial. Data were available for 561 individuals who received progesterone after mifepristone, of whom 271 (48%) had ongoing pregnancies. The quality of the evidence in the case series was low due to methodological and ethical issues. Enrollment in the randomised trial stopped early due to bleeding events in both arms. The ongoing pregnancy rate for individuals ≤7 weeks who received progesterone was 42% (95% CI 37-48) compared with 22% (95% CI 11-39) for mifepristone alone. At 7-8 weeks, the ongoing pregnancy rate was 62% (95% CI 52-71) in the progesterone group and 50% (95% CI 15- 85) in the mifepristone alone group. Based mostly on poor-quality data, it appears the ongoing pregnancy rate in individuals treated with progesterone after mifepristone is not significantly higher compared to that of individuals receiving mifepristone alone.


Identifying trajectories of alcohol use in a sample of secondary school students in Ontario and Alberta: longitudinal evidence from the COMPASS study.
Despite evidence indicating a rapid progression in use of alcohol during adolescence, little is known about the ways patterns of drinking develop over time. This study investigated patterns of alcohol use within a cohort of youth in Ontario and Alberta and the probability of changes between patterns. The sample consists of two-year linked longitudinal data (school year 2013/14 to 2014/15) from 19 492 students in Grades 9 to 12 in 89 secondary schools across Ontario and Alberta, Canada, who participated in the COMPASS study. The latent class analysis used two self-reported items about the frequency of drinking (measured as none, monthly, weekly, or daily use) and the frequency of binge drinking (measured as none, less than or once a month, 2-4 times a month, or more than once week) to characterize patterns of alcohol use. The effects of gender, ethnicity and cannabis and cigarette use on alcohol use patterns were examined. The study identified four drinking patterns: non-drinker, periodic drinker (reported monthly drinking and no binge drinking), low-risk drinker (reported monthly drinking and limited binge drinking) and high-risk regular drinker (reported drinking 1-3 times a week and binge drinking 2-4 times a month). Non-drinker was the most prevalent pattern at baseline (55.1%) and follow-up (39.1%). Periodic drinkers had the highest likelihood of an increase in alcohol consumption, with 40% moving to the low-risk pattern. A notable proportion of participants returned to a lower severity pattern or transitioning out of drinking. There are four distinct youth alcohol-use patterns. The high probability of transitioning to drinking during the secondary school years suggests the need for preventive interventions in earlier stages of use, before drinking becomes habitual.


How to do better health reform: a snapshot of change and improvement initiatives in the health systems of 30 countries.
Health systems are continually being reformed. Why, and how? To answer these questions, we draw on a book we recently contributed, Healthcare Reform, Quality and Safety: Perspectives, Participants, Partnerships and Prospects in 30 Countries. We analyse the impact that these health-reform initiatives have had on the quality and safety of care in an international context-that is, in low-, middle- and high-income countries-Argentina, Australia, Brazil, Chile, China, Denmark, England, Ghana, Germany, the Gulf states, Hong Kong, India, Indonesia, Israel, Italy, Japan, Mexico, Myanmar, New Zealand, Norway, Oman, Papua New Guinea (PNG), South Africa, the USA, Scotland and Sweden. Popular reforms in less well-off countries include boosting equity, providing infrastructure, and reducing mortality and morbidity in maternal and child health. In countries with higher GDP per capita, the focus is on new IT systems or trialling innovative funding models. Wealthy or less wealthy, countries are embracing ways to enhance quality of care and keep patients safe, via mechanisms such as accreditation, clinical guidelines and hand hygiene campaigns. Two timely reminders are that, first, a population's health is not determined solely by the acute system, but is a product of inter-sectoral effort-that is, measures to alleviate poverty and provide good housing, education, nutrition, running water and sanitation across the population. Second, all reformers and advocates of better-quality of care should include well-designed evaluation in their initiatives. Too often, improvement is assumed, not measured. That is perhaps the key message.


Technical Meets Traditional: Language, Culture, and the Challenges Faced by Hmong Medical Interpreters.
Ineffective intercultural communication can occur due to inaccurate medical interpreting for limited English proficiency (LEP) patients. Research shows that Hmong patients experience poorer quality interpreter services than other LEP populations. This study's purpose is to understand Hmong medical interpreters' perceptions of the factors that affect their ability to make accurate medical interpretations during clinical encounters. A qualitative study was conducted with Hmong-speaking medical interpreters. The interviews were semistructured, audio recorded, and analyzed using conventional content analysis. 13 interpreters aged 29 to 49 years participated in the study. Three factors affected the interpreters' ability to make accurate medical interpretations for Hmong-speaking patients: (a) matched gender between the interpreter and patient, (b) culturally taboo topics in communicating about reproductive body parts and sexual health/activity, and (c) culture and generational language differences between interpreters and Hmong patients. Clinical encounters that match patient-interpreter ages, gender, and/or local culture may reduce communication barriers.


Genomic damage in endstage renal disease-contribution of uremic toxins.
Patients with end-stage renal disease (ESRD), whether on conservative, peritoneal or hemodialysis therapy, have elevated genomic damage in peripheral blood lymphocytes and an increased cancer incidence, especially of the kidney. The damage is possibly due to accumulation of uremic toxins like advanced glycation endproducts or homocysteine. However, other endogenous substances with genotoxic properties, which are increased in ESRD, could be involved, such as the blood pressure regulating hormones angiotensin II and aldosterone or the inflammatory cytokine TNF-α. This review provides an overview of genomic damage observed in ESRD patients, focuses on possible underlying causes and shows modulations of the damage by modern dialysis strategies and vitamin supplementation.


Sympatric divergence and clinal variation in multiple coloration traits of Ficedula flycatchers.
Geographic variation in phenotypes plays a key role in fundamental evolutionary processes such as local adaptation, population differentiation and speciation, but the selective forces behind it are rarely known. We found support for the hypothesis that geographic variation in plumage traits of the pied flycatcher Ficedula hypoleuca is explained by character displacement with the collared flycatcher Ficedula albicollis in the contact zone. The plumage traits of the pied flycatcher differed strongly from the more conspicuous collared flycatcher in a sympatric area but increased in conspicuousness with increasing distance to there. Phenotypic differentiation (PST ) was higher than that in neutral genetic markers (FST ), and the effect of geographic distance remained when statistically controlling for neutral genetic differentiation. This suggests that a cline created by character displacement and gene flow explains phenotypic variation across the distribution of this species. The different plumage traits of the pied flycatcher are strongly to moderately correlated, indicating that they evolve non-independently from each other. The flycatchers provide an example of plumage patterns diverging in two species that differ in several aspects of appearance. The divergence in sympatry and convergence in allopatry in these birds provide a possibility to study the evolutionary mechanisms behind the highly divergent avian plumage patterns.


Nano- and microsized zeolites as a perspective material for potentiometric biosensors creation.
A number of potentiometric biosensors based on coimmobilization of enzymes with different types of zeolite on pH-ion-sensitive field-effect transistor (ISFET) have been developed. Their working characteristics have been determined and compared. It was shown that clinoptilolite and zeolite Beta polymorph A (BEA) are more promising for creating biosensors than zeolite A. Changing the concentration of zeolite BEA in membranes, it is possible to extend the biosensor linear measurement range. The two-layer method of deposition of the enzyme with clinoptilolite was found to provide a significant increase in the biosensor sensitivity to substrates, whereas thermal modification of the zeolite BEA crystals can improve analytical characteristics of potentiometric biosensors for detection of toxic substances. These results show that it is possible to regulate the ISFET characteristics for different enzyme-based biosensors by tailoring the electrode surfaces via different zeolites. This makes zeolites strong candidates for integration into biosensors as ISFET modifiers.


Assisted human reproduction--legal rights of the unborn in respect of avoidable damage.
The author describes various risks to the foetus arising from assisted reproduction technology (ART). These risks are examined from the legal viewpoint, especially considering the rights of the foetus as interpreted in a number of jurisdictions. He distinguishes between the avoidable and inherent risks to the foetus resulting from ART and the potential hazards of ART relevant to criminal law. The basic internationally accepted conventions on foetal rights are compared relative to decisions in a number of cases heard and decided.


5-Year control and treatment of edema and increased capillary filtration in venous hypertension and diabetic microangiopathy using O-(beta-hydroxyethyl)-rutosides: a prospective comparative clinical registry.
This independent prospective controlled trial evaluates the efficacy of O-(beta-hydroxyethyl)-rutosides (HR) during 5 years of administration against signs and symptoms and further degeneration of microcirculatory disturbances. The protective effect of HR in preventing end-point complications such as venous ulceration is evaluated. This study is based on evaluation of edema and the capillary filtration rate (CFR) in association with a clinical score scale. Patients having a severe degree of chronic venous insufficiency (CVI) and venous microangiopathy and completing at least 5 years of treatment are included. The following 4 groups are considered: group A (patients with CVI but without diabetes mellitus, receiving 1500 mg/d of HR), group B (patients with CVI and diabetes mellitus, receiving 2 g/d of HR), group C (control subjects receiving no pharmacologic or compression treatment), and group D (patients using elastic compression stockings only). All patients received the "best" available treatment. No adverse effects or intolerance is noted, with good compliance (>85%). In group A, there is a statistically significant decrease in the CFR during 5 years of follow-up. In group B, the decrease in the CFR is greater than that in group A. Reductions in edema, swelling, and the CFR during 5 years are notable, and values approach normal levels. During 5 years, HR is effective in treating venous edema and hypertension and in preventing deterioration of the distal venous system. The prevention of ulcerations with HR is another important observation. The effects of HR seem to be partially dose related, and tolerability and compliance are good.


Bone histogenesis mediated by nonosteogenic cells.
Intramuscular implantation of several established, nonfibroblastic epithelial cell lines of various origin causes endochondral ossification at the site of cell graft. Heterotopically-induced bone is also a site of myelopoiesis. Myelohistograms of ectopic bone marrow do not differ substantially from that of marrow present in orthotopic (skeletal) bones. Heterotopically-induced bones are not covered by a periosteal membrane with a functioning cambium layer. The nature of the bone-inducing principle of epithelial cells is not known as yet, although it was established that cells able to induce heterotopic bone formation are characterized by a high alkaline-phosphatase activity and have an epithelial status. Cells responding to the osteoinducing principle are distributed among skeletal muscles and are absent in the peritoneal cavity or in the kidney parenchyma. Periosteal membranes of skeletal bones are activated by a variety of agents (Moloney sarcoma virus-induced tumors, numerous nonvirus-induced neoplasms, T-lymphocyte mitogens, and activated lymphocytes) to proliferate and lay down new bone. The same agents can also activate in vivo perichondral membranes. It is theorized that cells involved in antitumor reaction produce a chondroblast/osteoblast activating factor(s), in addition to the osteoclast-activating one.


Derivation of the Critical Point Scaling Hypothesis Using Thermodynamics Only.
Based on the foundations of thermodynamics and the equilibrium conditions for the coexistence of two phases in a magnetic Ising-like system, we show, first, that there is a critical point where the isothermal susceptibility diverges and the specific heat may remain finite, and second, that near the critical point the entropy of the system, and therefore all free energies, do obey scaling. Although we limit ourselves to such a system, we elaborate about the possibilities of finding universality, as well as the precise values of the critical exponents using thermodynamics only.


Rapid induction of multiple resistance mechanisms in Aspergillus fumigatus during azole therapy: a case study and review of the literature.
Nine consecutive isogenic Aspergillus fumigatus isolates cultured from a patient with aspergilloma were investigated for azole resistance. The first cultured isolate showed a wild-type phenotype, but four azole-resistant phenotypes were observed in the subsequent eight isolates. Four mutations were found in the cyp51A gene of these isolates, leading to the substitutions A9T, G54E, P216L, and F219I. Only G54 substitutions were previously proved to be associated with azole resistance. Using a Cyp51A homology model and recombination experiments in which the mutations were introduced into a susceptible isolate, we show that the substitutions at codons P216 and F219 were both associated with resistance to itraconazole and posaconazole. A9T was also present in the wild-type isolate and thus considered a Cyp51A polymorphism. Isolates harboring F219I evolved further into a pan-azole-resistant phenotype, indicating an additional acquisition of a non-Cyp51A-mediated resistance mechanism. Review of the literature showed that in patients who develop azole resistance during therapy, multiple resistance mechanisms commonly emerge. Furthermore, the median time between the last cultured wild-type isolate and the first azole-resistant isolate was 4 months (range, 3 weeks to 23 months), indicating a rapid induction of resistance.


Impact of the COVID-19 pandemic on the health care of >1,000 People living with multiple sclerosis: A cross-sectional study.
People with multiple sclerosis (PwMS) experienced changes in health behaviors and access to MS care due to the COVID-19 pandemic. The USA has the highest recognized number of Covid19 infections globally. The extent of the impact of COVID-19 has not been well characterized in large samples of PwMS to date. The MS patient perspective on COVID-19 would complement the physician-reported cases of MS and COVID-19 in the literature. A cross-sectional survey of adult PwMS was performed online, using the U.S.-based patient-powered iConquerMS™ platform, in April 2020. There were 1,145 respondents (response rate: 20%). 1,019 had a diagnosis of MS and responded completely (average age: 54.2 years, range: 20-81; 79% female; 64% relapsing remitting, 22% secondary progressive, 12% primary progressive; 88% in the USA). 748 (73%) used a DMT in the last year, primarily higher-efficacy therapies: ocrelizumab (n=238), dimethyl fumarate (n=85), fingolimod (n=80). The most frequent comorbidities were depression (41%), hypertension (26%), and asthma (12%). Women were more worried than men about COVID-19 (p=0.001); non-white-identifying PwMS believed it was a greater danger to their health than white-identifying PwMS (p=0.002). Through the continuum of symptoms to care, 61% of PwMS (n=617) reported symptoms associated with COVID-19, 39% (n=395) knew someone exposed to COVID-19, 4% (n=38) were aware of a personal COVID-19 exposure, 13% (n=128) wanted testing for COVID-19 but could not access it, and 4% (n=43) were tested. Specific to their MS care, 64% (n=650) canceled a medical visit, 22% (n=222) canceled a neurologist visit, 11% (n=112) canceled an MRI, 21% (n=212) canceled a laboratory test, and 10% (n=98) changed their DMT in some way due to COVID19 including 65 delaying at least one dose. 37% (n=382) had a telehealth visit due to COVID-19. 37% of PwMS (n=374) experienced employment changes, most commonly working from home (n=194) and having work hours reduced (n=65) while 32 lost their jobs. Of the 7 cases who tested positive for COVID-19 (<1% of participants) (5 female; age range: 29-64 years), DMTs included dimethyl fumarate (n=2), ocrelizumab (n=1), rituximab (n=1), and a clinical trial drug (n=1). A majority of people with MS reported interruptions to their MS care along the MS care pathway alongside limited access to COVID-19 testing. Postponements and delays in care were common with 10% of participants reporting a change in their DMT administration. Less than 1% of this self-referred convenience online cohort had a positive test for COVID-19 although more than half reported symptoms that are associated with COVID-19.


Effect of light curing and dark reaction phases on the thermomechanical properties of a Bis-GMA based dental restorative material.
The effects of light curing units (LCU) and energy doses on the chemical and physical properties of a dental composite were investigated. The effects on the chemical and physical properties of a bisphenol A diglycidylether methacrylate (Bis-GMA) based dental restorative material were evaluated through photospectrometry, differential scanning calorimetry, and mechanical measurements. The light curing conditions associated with direct and indirect restorations were replicated in vitro using optical investigation techniques. A slight attenuation resulted independently of the LCU and a strong attenuation was measured for the cement luting a thick inlay, as well as for the deepest layer of a composite filling increment. Calorimetric measurements indicated that the curing degree is very sensitive to the light energy dose rather than to the LCU. Mechanical testing showed a transient phase during which properties increased. The delay of the composite in reaching adequate properties is strongly dependent on the energy dose. It is recommended that composites subject to unfavorable light curing conditions undergo a prolonged light curing process.


On being forgotten: Memory and forgetting serve as signals of interpersonal importance.
Our memories contain a wealth of social information-including details of past interactions, facts about others, and others' identities. Yet, human memory is imperfect, and we often find ourselves unable to recall such information in social interactions. Conversely, people routinely find themselves on the receiving end of others' memory failures; that is, people sometimes find themselves forgotten. Despite the apparent pervasiveness of such experiences, modern science possesses no explanatory framework for understanding the psychological impact of being forgotten in part or in whole. Here, we propose that evidence of memory in social interactions is a powerful signal of the subjective importance attached to an object of memory and that interpretation of such signals has important consequences for interpersonal relationships. We further proposed that attributional explanations for forgetting and that the closeness of the relationship between the people involved in forgetting might moderate the impact of being forgotten. We tested this framework in four studies examining the experience of being forgotten in daily life (Study 1), in experimentally controlled firsthand encounters (Study 2), and in third party perceptions of forgetting (Studies 3 and 4). Results converged to support our proposed framework as well as the moderating role of attribution. Surprisingly, we found no evidence supporting the moderating role of initial relationships closeness. These results advance a systematic model of an understudied but important phenomenon and suggest rich and varied avenues of additional exploration. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


miR-124 regulates fetal pulmonary epithelial cell maturation.
MicroRNAs are a family of small noncoding RNAs that regulate the expression of their target proteins at the posttranscriptional level. Their functions cover almost every aspect of cell physiology. However, the roles of microRNAs in fetal lung development are not completely understood. The objective of this study is to investigate the regulation and molecular mechanisms of alveolar epithelial cell maturation during fetal lung development by miR-124. We discovered that miR-124 was downregulated during rat fetal lung development and predominantly expressed in the epithelial cells at late stage of the lung development. Overexpression of miR-124 with an adenovirus vector led to the inhibition of epithelial maturation in rat fetal lung organ cultures and fetal alveolar epithelial type II cells, as demonstrated by a decrease in the type II cell marker expression and an increase in glycogen content. We further demonstrated by luciferase reporter assays that miR-124 inhibited the NF-κB, cAMP/PKA, and MAPK/ERK pathways. In addition, nuclear factor I/B (NFIB), a critical protein in fetal lung maturation, was validated as a direct target of miR-124. Furthermore, miR-124 expression was induced by the Wnt/β-catenin signaling pathway through a direct interaction of LEF1 and the miR-124 promoter region. We concluded that miR-124 downregulation is critical to fetal lung epithelial maturation and miR-124 inhibits this maturation process at least partially through the inhibition of NFIB.


The long-term caregiver burden in World Health Organization grade I and II meningioma: It is not just the patient.
Little is known about long-term caregiver burden in meningioma patients. We assessed meningioma caregiver burden, its association with informal caregiver's well-being and possible determinants. In this multicenter cross-sectional study, informal caregivers completed the Caregiver Burden Scale (five domains and total score). Patients completed a disease-specific health-related quality of life (HRQoL) questionnaire focusing on symptoms (EORTC QLQ-BN20) and underwent neurocognitive assessment. Both groups completed a generic HRQoL questionnaire (SF-36) and the Hospital Anxiety, and Depression Scale. We assessed the association between caregiver burden and their HRQoL, anxiety and depression. Furthermore, we assessed determinants for the caregiver burden. Multivariable regression analysis was used to correct for confounders. One hundred and twenty-nine informal caregivers were included (median 10 years after patients' treatment). Caregivers reported burden in ≥1 domain (34%) or total burden score (15%). A one-point increase in total caregiver burden score was associated with a clinically relevant decrease in caregiver's HRQoL (SF-36) in 5/8 domains (score range: -10.4 to -14.7) and 2/2 component scores (-3.5 to -5.9), and with more anxiety (3.8) and depression (3.0). Patients' lower HRQoL, increased symptom burden, and increased anxiety and depression were determinants for higher caregiver burden, but not patients' or caregivers' sociodemographic characteristics, patients' neurocognitive functioning, or tumor- and treatment-related characteristics. Ten years after initial treatment, up to 35% of informal caregivers reported a clinically relevant burden, which was linked with worse HRQoL, and more anxiety and depression in both patients and caregivers, emphasizing the strong interdependent relationship. Support for meningioma caregivers is therefore warranted.


'You're basically calling doctors torturers': stakeholder framing issues around naming intersex rights claims as human rights abuses.
In this article we address activist, patient advocate and medic perspectives on framing intersex, variations of sex characteristics and disorders/differences in sex development medical treatment as human rights abuses. Problematic aspects of intersex medical treatment have increasingly been highlighted in national debates and international human rights bodies. Some intersex activists have framed aspects of intersex medical treatment as human rights abuses since the 1990s. Other stakeholders in shaping medical treatment, such as patient advocates and medical professionals, are not always content with human rights framing, or even the term intersex. In order to address the different perspectives in this arena we provide background on the primary rights claims that have arisen followed by key human rights framing of these claims. We provide a short discussion of activism styles, looking at pan-intersex social movements and variation-specific patient associations as different styles of health social movements. The analysis of stakeholder perspectives on the use of human rights strategy in health areas provides a useful case study for medical sociology and policy in general.


Integrating case-control and TDT studies.
Genetic-association studies are widely expected to unravel the genetic basis of complex diseases. The population-based case-control study, a commonly used approach for association studies, is subject to the problem of population admixture. Consequently, evidence of disease-marker associations obtained from such studies is ideally confirmed by alternative methods. The Transmission/Disequilibrium Test (TDT) is suitable to assess evidence of association obtained from case-control studies. Since data are increasingly available from both case-control and TDT studies of the same disease-marker association, it is useful to obtain a combined estimate of disease-marker association. The odds ratio is a commonly used measure of the magnitude of a disease-marker association that can be easily obtained in case-control studies. Here we show how an odds ratio estimate and its' associated standard error can be obtained from TDT results. Furthermore, we suggest a method for integrating results from case-control studies and the TDT to provide a combined estimate of disease-marker association. Such combined estimates can be used to contrast the results of the two studies and provides an overall picture of the effect size attributable to such polymorphism. An illustrative application is made to a published data set on type 2 diabetes.


Effect of calcium supplementation on hip fractures.
There have been numerous studies of the effects of calcium supplementation, with or without vitamin D, on fractures. Individually, they have not provided clarity regarding calcium's anti-fracture efficacy, though they have established that calcium does have beneficial effects on bone density throughout the skeleton in women. Meta-analysis of these data suggests that total fracture numbers are diminished. However, the data from the 5,500 women involved in trials of calcium monotherapy show consistent adverse trends in numbers of hip fractures (relative risk 1.50, 95% CI 1.06-2.12). Observational data from the Study of Osteoporotic Fractures show a similar increase in risk of hip fracture associated with calcium use. We hypothesize that reduced periosteal expansion in women using calcium supplementation might account for the differences in anti-fracture efficacy of calcium at the hip, in comparison with other sites. Until there are further trial results to clarify this area, the present findings suggest that reliance on high calcium intakes to reduce the risk of hip fracture in older women is not appropriate. In addition, those at risk should be looking to other agents with a proven capacity to prevent hip fractures, such as bisphosphonates.


Knowledge of cervical tuberculosis lymphadenitis and its treatment in pastoral communities of the Afar region, Ethiopia.
Infection with Mycobacterium bovis (Mb) predominantly causes cervical TB lymphadenitis (TBL). Raw milk is considered the main source of Mb infection and raw milk is a major food source for Afar pastoralists. The aim of this study was to assess Afar pastoralists' knowledge concerning cervical TBL and its treatment. A community-based cross-sectional survey involving 818 interviewees was conducted in two districts of the Afar Region, Ethiopia. In addition, two focus group discussions (FGDs) were conducted in each of the study areas, one with men and the other with women. Of the 818 interviewees [357 (43.6%) females and 461 (56.4%) males], 742 (90.7%) reported that they had knowledge of cervical TBL, mentioning that swelling(s) on the neck resulting in a lesion and scar are common symptoms. However, only 11 (1.5%) individuals mentioned that bacteria or germs are the causative agents of TBL. Three interviewees and a male discussant mentioned drinking raw milk as the cause of TBL. A considerable proportion (34.2%) of the interviewees and almost all the discussants suggested herbal medicine as an effective treatment. Male study participants were 1.82 times more likely to have overall knowledge of TBL than female study participants (adjusted OR, 1.82; 95% CI, 1.32 to 2.51, p < 0.001). The pastoral community members in the study areas had little biomedical knowledge of the cause, the source of infection and the transmission route of cervical TBL. Furthermore, most community members believed that herbal medicines are the most effective treatment for TBL. Therefore, TB control programs in the Afar Region require the incorporation of public health education introducing current biomedical knowledge of the disease. In addition, further studies are important to elucidate which medicinal plants are used by Afar pastoralists to treat TBL.


Somatization in Latin America: a review of the classification of somatoform disorders, functional syndromes and medically unexplained symptoms.
medically unexplained symptoms are common and associated with mental illness in various contexts. Previous studies show that Latin American populations are prone to somatization. Given the reformulation of the International Classification of Diseases towards its 11th edition the peculiarities of the population from this region of the world shall be taken into consideration. The objective of this study is to provide information on somatization in Latin American populations to help the decision making about medically unexplained symptoms diagnostic categories in the 11th edition of the International Classification of Diseases. Extensive review of the academic production from 1995 to 2011 on somatization in populations of Latin American origin. The analysis of 106 studies included in this review was divided into 15 categories: systematic reviews, conceptual reviews, prevalence, primary care, depression and anxiety, risk factors, violence, organic conditions, relationship with health care, ethnicity, culture-bound syndromes, chronic fatigue syndrome, fibromyalgia, body dysmorphic disorder, and conversion and dissociation. The Latin American studies confirm the difficulty in defining medically unexplained symptoms categories. The supposed "somatizing trace" of Latin cultures may be linked more to cultural and linguistic expression than to an ethnic nature, and these peculiarities must be on the agenda for the new classification of these phenomena in the Classification of Diseases-11th edition.


The G protein-coupled receptor repertoires of human and mouse.
Diverse members of the G protein-coupled receptor (GPCR) superfamily participate in a variety of physiological functions and are major targets of pharmaceutical drugs. Here we report that the repertoire of GPCRs for endogenous ligands consists of 367 receptors in humans and 392 in mice. Included here are 26 human and 83 mouse GPCRs not previously identified. A direct comparison of GPCRs in the two species reveals an unexpected level of orthology. The evolutionary preservation of these molecules argues against functional redundancy among highly related receptors. Phylogenetic analyses cluster 60% of GPCRs according to ligand preference, allowing prediction of ligand types for dozens of orphan receptors. Expression profiling of 100 GPCRs demonstrates that most are expressed in multiple tissues and that individual tissues express multiple GPCRs. Over 90% of GPCRs are expressed in the brain. Strikingly, however, the profiles of most GPCRs are unique, yielding thousands of tissue- and cell-specific receptor combinations for the modulation of physiological processes.


Endoscopic management of orbital floor fractures.
The management of orbital floor fractures involves several issues. Different surgeons have diverse opinions about who needs surgery and how best to do it. This is especially so with regard to use of transantral diagnostic and therapeutic endoscopic surgery over traditional lower eyelid approaches. Transantral endoscopy provides precise and complete information about the orbital floor fracture and makes possible the repair of these fractures under unobstructed vision at all times, minimizing the risk of implant misplacement and, hence, enophthalmos. Contrary to popular belief, this technique is versatile and is applicable for most cases of primary repair of orbital floor fractures of variable sizes of defect, regardless of whether they are blowout or trap-door fractures or whether they are associated with other fractures. The great strength of this procedure is that improved visualization is accomplished while obviating the need for lower eyelid incisions and their associated risk of complications. This technique is safe in trained hands, giving predictably good results in suitable patients.


HeartMate 3: new challenges in ventricular tachycardia ablation.
To describe clinical characteristics, procedural details, specific challenges, and outcomes in patients with HeartMate3™ (HM3), a left ventricular assist device system with a magnetically levitated pump, undergoing ventricular tachycardia ablation (VTA). Data were collected from patients with an HM3 system who underwent VTA in seven tertiary centres. Data included baseline patient characteristics, procedural data, mortality, and arrhythmia-free survival. The study cohort included 19 patients with cardiomyopathy presenting with ventricular tachycardia (VT) (53% with VT storm). Ventricular tachycardias were induced in 89% of patients and a total of 41 VTs were observed. Severe electromagnetic interference was present on the surface electrocardiogram. Hence, VT localization required analysis of intra-cardiac signals or the use of filter in the 40-20 Hz range. The large house pump HM3 design obscured the cannula inflow and therefore multi imaging modalities were necessary to avoid catheter entrapment in the cannula. A total of 32 VTs were mapped and were successfully ablated (31% to the anterior wall, 38% to the septum and only 9% to the inflow cannula region). Non-inducibility of any VT was reached in 11 patients (58%). Over a follow-up of 429 (interquartile range 101-692) days, 5 (26%) patients underwent a redo VT ablation due to recurrent VTA and 2 (11%) patients died. Ventricular tachycardia ablation in patients with HM3 is feasible and safe when done in the appropriate setup. Long-term arrhythmia-free survival is acceptable but not well predicted by non-inducibility at the end of the procedure.


Recurrent neonatal seizures result in long-term increases in neuronal network excitability in the rat neocortex.
Neonatal seizures are associated with a high likelihood of adverse neurological outcomes, including mental retardation, behavioral disorders, and epilepsy. Early seizures typically involve the neocortex, and post-neonatal epilepsy is often of neocortical origin. However, our understanding of the consequences of neonatal seizures for neocortical function is limited. In the present study, we show that neonatal seizures induced by flurothyl result in markedly enhanced susceptibility of the neocortex to seizure-like activity. This change occurs in young rats studied weeks after the last induced seizure and in adult rats studied months after the initial seizures. Neonatal seizures resulted in reductions in the amplitude of spontaneous inhibitory postsynaptic currents and the frequency of miniature inhibitory postsynaptic currents, and significant increases in the amplitude and frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and in the frequency of miniature excitatory postsynaptic currents (mEPSCs) in pyramidal cells of layer 2/3 of the somatosensory cortex. The selective N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonovalerate eliminated the differences in amplitude and frequency of sEPSCs and mEPSCs in the control and flurothyl groups, suggesting that NMDA receptors contribute significantly to the enhanced excitability seen in slices from rats that experienced recurrent neonatal seizures. Taken together, our results suggest that recurrent seizures in infancy result in a persistent enhancement of neocortical excitability.


Baby boomers in retirement: what are their prospects?
This Issue Brief examines the baby boomers' retirement income prospects by analyzing trends in the elderly's income and pension participation among workers; examining saving behavior and critically evaluating studies of the adequacy of the boomers' saving; and looking at tenure trends, lump-sum distribution preservation, and changes in Social Security benefits. Since the mid 1970s, the real median income of individuals aged 65 and over has increased 18 percent. Sources of income have shifted, with employment-based pensions increasing and earnings and asset income decreasing as a proportion of income. The boomers' prospects are partly dependent on participation in employment-based retirement plans. After decreases in the sponsorship rates, participation rates, and vesting rates of workers during the 1980s, all three percentages increased during the early 1990s. Data do not support the perception that the U.S. work force is becoming increasingly mobile. Tenure levels for prime age workers in the 1980s and beginning of the 1990s were higher than those of previous decades. Still, in response to competitive pressures, employers may not offer the security of paternalistic benefit packages as in the past. Various studies have reached different conclusions regarding the adequacy of the boomers' financial preparation for retirement. Evidence indicates that boomers, in general, will enjoy a retirement standard of living exceeding that of their parents. It is less clear whether they will maintain a standard of living in retirement comparable to that of their working years. To the extent they are willing to tap housing wealth, they would appear at this early stage to be in good shape. Federal fiscal policy decisions will impact boomers by affecting their disposable income today, and thus their ability to save, as well as the benefits they will receive in retirement through Social Security and Medicare. The boomers are 17 to 35 years away from age 65. Given heterogeneity of the boomers, research is needed to identify what specific groups within the generation are at risk and the magnitude of that risk. Groups that would now appear to be at risk to some degree include non-homeowners, the less educated, the single, and the youngest boomers.


RNA interference can target pre-mRNA: consequences for gene expression in a Caenorhabditis elegans operon.
In nematodes, flies, trypanosomes, and planarians, introduction of double-stranded RNA results in sequence-specific inactivation of gene function, a process termed RNA interference (RNAi). We demonstrate that RNAi against the Caenorhabditis elegans gene lir-1, which is part of the lir-1/lin-26 operon, induced phenotypes very different from a newly isolated lir-1 null mutation. Specifically, lir-1(RNAi) induced embryonic lethality reminiscent of moderately strong lin-26 alleles, whereas the lir-1 null mutant was viable. We show that the lir-1(RNAi) phenotypes resulted from a severe loss of lin-26 gene expression. In addition, we found that RNAi directed against lir-1 or lin-26 introns induced similar phenotypes, so we conclude that lir-1(RNAi) targets the lir-1/lin-26 pre-mRNA. This provides direct evidence that RNA interference can prevent gene expression by targeting nuclear transcripts. Our results highlight that caution may be necessary when interpreting RNA interference without the benefit of mutant alleles.


Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA.
The K65R substitution in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) is the major resistance mutation selected in patients treated with first-line antiretroviral tenofovir disoproxil fumarate (TDF). 4'-ethynyl-2-fluoro-2'-deoxyadenosine (EFdA), is the most potent nucleoside analog RT inhibitor (NRTI) that unlike all approved NRTIs retains a 3'-hydroxyl group and has remarkable potency against wild-type (WT) and drug-resistant HIVs. EFdA acts primarily as a chain terminator by blocking translocation following its incorporation into the nascent DNA chain. EFdA is in preclinical development and its effect on clinically relevant drug resistant HIV strains is critically important for the design of optimal regimens prior to initiation of clinical trials. Here we report that the K65R RT mutation causes hypersusceptibility to EFdA. Specifically, in single replication cycle experiments we found that EFdA blocks WT HIV ten times more efficiently than TDF. Under the same conditions K65R HIV was inhibited over 70 times more efficiently by EFdA than TDF. We determined the molecular mechanism of this hypersensitivity using enzymatic studies with WT and K65R RT. This substitution causes minor changes in the efficiency of EFdA incorporation with respect to the natural dATP substrate and also in the efficiency of RT translocation following incorporation of the inhibitor into the nascent DNA. However, a significant decrease in the excision efficiency of EFdA-MP from the 3' primer terminus appears to be the primary cause of increased susceptibility to the inhibitor. Notably, the effects of the mutation are DNA-sequence dependent. We have elucidated the mechanism of K65R HIV hypersusceptibility to EFdA. Our findings highlight the potential of EFdA to improve combination strategies against TDF-resistant HIV-1 strains.


Induced current densities from low-frequency magnetic fields in a 2 mm resolution, anatomically realistic model of the body.
This paper presents calculations of current density in a fine-resolution (2 mm) anatomically realistic voxel model of the human body for uniform magnetic fields incident from the front, side and top of the body for frequencies from 50 Hz to 10 MHz. The voxel phantom, NORMAN, has a height of 1.76 m and a mass of 73 kg. There are 8.3 million voxels in the body differentiated into 37 tissue types. Both the impedance method and the scalar potential finite difference method were used to provide mutual corroboration. Results are presented for the current density averaged over 1 cm2 in muscle, heart, brain and retina.


Cervical disc prosthesis in humans: first failure.
Prospective preliminary trial of a cervical disc prosthesis. To study the feasibility, efficacy in maintaining intervertebral mobility, and complications of a low-profile disc prosthesis implanted after single-level cervical discectomy. Since studies reported by Baba et al, there is fear that degeneration of the intervertebral disc levels adjacent to cervical arthrodesis may be exacerbated by this arthrodesis. For this reason, several cervical prostheses have been designed as an alternative to arthrodesis. None of these prostheses, some of which are bulky, has been shown to be efficacious. Five women and five men (average age, 36 years) underwent implantation of the present disc prosthesis after single-level discectomy. The discectomy was performed for cervical disc herniation that resulted in cervicobrachial pain for more than 3 months. None of the patients exhibited intervertebral instability on bending films. Preoperative magnetic resonance studies showed a noncontained disc herniation in all 10 patients and osteophytes in 2 of the patients. The cervicobrachial pain resolved in all 10 patients. Intense neck pain developed in 1 patient who underwent revision surgery to remove the prosthesis and perform an arthrodesis. Another patient developed neck pain but refused the proposed revision operation. Bending films showed mobility of the intervertebral space containing the prosthesis in both of these patients. In the 8 patients who remained pain free after the operation, lateral bending films at follow-up found no mobility of the implanted disc level. Five of these eight patients had circumferential fusion, 2 had posterior fusion, and 1 had anterior fusion. This prosthesis failed to achieve the desired effect because the intended mobility failed to persist in 8 of the 10 patients and pain developed in the other 2 patients, in whom the mobility persisted.


Assistance of family carers for patients with COPD using nebulisers at home: a qualitative study.
For many patients with chronic conditions, such as chronic obstructive pulmonary disease (COPD), the assistance of family carers with medicines is vital for optimal treatment outcomes. The aim of this study was to identify the assistance carers provide to patients with COPD using nebuliser-delivered therapy at home, and the problems experienced that may impact on the safety and effectiveness of therapy and contribute to carer burden. A cross-sectional, qualitative descriptive study was conducted with participants recruited from primary and intermediate care. Home interviews were conducted with 14 carers who assisted a family member with COPD using a nebuliser. Qualitative procedures enabled analysis of nebuliser-related activities and problems experienced by carers. The carer sample included 10 female and 4 male carers, with a mean age of 61 years: 11 spouses and 3 daughters. They had assisted patients with use of their nebuliser and associated medications for, on average, 4.5 years. Assistance ranged from taking full responsibility for nebuliser use to providing help with particular aspects only when required. Nebuliser-related activities included assembling and setting up equipment, mixing medicines, operating the device, dismantling and cleaning equipment. Difficulties were described with all aspects of care. Carers reported concerns about medication side effects and the lack of information provided. The study revealed the vital role of carers in enabling effective therapy. The wide-ranging responsibilities assumed by carers and problems experienced relate to all aspects of COPD management with nebulisers, and have a potential impact on treatment outcomes and carer burden. A systematic approach to addressing carers' needs and prioritising support would be anticipated to have positive consequences for patients, carers and health services.


Accumulation of factors influencing respiratory illness in members of a national birth cohort and their offspring.
The aim was to investigate predictors of childhood lower respiratory tract illness in two generations, and predictors of adult lower respiratory disorders in the first generation. Data on respiratory health and environmental factors from a national birth cohort study were examined from birth to 36 years. Data were also collected on the parents of the subjects and on the subjects' first born offspring from birth to eight years. Main outcome measures were: reports of lower respiratory tract illness before 2 years; lower respiratory tract illness of a week or more between age 20 and 36 years; regular phlegm production at 25 and 36 years; reports of wheeze or asthma at age 36 years; peak expiratory flow rate (PEFR) at age 36 years measured by nurses during home visits; and mothers' reports of lower respiratory illness in first born offspring before 2 years. Subjects were a sample of 5362 single, legitimate births taken from all those occurring in England, Wales, and Scotland in one week in 1946, and studied regularly from birth to age 43 years. Data on the subjects' parents and on their 1676 first offspring born while they were aged 19-25 years were also collected. Lower respiratory tract illness before 2 years fell from 25% in the population born in 1946 to 13% in their first born offspring. In those born in 1946, poor home environment, parental bronchitis, and atmospheric pollution were the best predictors of lower respiratory illness before 2 years, and these three factors and childhood lower respiratory illness and later smoking were the best predictors of adult lower respiratory tract problems. Risk factors for lower respiratory illness in the offspring were manual social class, parental and grandparental lower respiratory disease, and parental smoking. Risks for adult lower respiratory problems accumulated in childhood through illness, poor social circumstances, and atmospheric pollution. Smoking exacerbated early life risks and was an independent risk factor. In the offspring generation, parental smoking was a risk factor for early life chest illness, together with parental illness and low social class. Reduction of prevalence in the offspring generation was probably accounted for by improvement in home circumstances, reduced atmospheric pollution, and lower rates of parental lower respiratory illness, but current rates of smoking seem likely to prevent much further reduction in early life lower respiratory illness, and thus in this aspect of risk for subsequent adult lower respiratory problems. The accumulation of risk in childhood and adolescence for later adult problems implies a long time scale for the reduction of adult lower respiratory disorders.


[Dynamics of motor components of optokinetic nystagmus during exposure of the vestibular apparatus to angular accelerations].
The effect of angular accelerations on the optokinetic nystagmus was studied on 25 test subjects using a special vestibulo-optokinetic trainer rotated according to five programs and electrooculography. Angular accelerations were found to induce indirectly changes in the amplitude and time of the optokinetic nystagmus via the vestibular apparatus. Optimization of parameters of the optokinetic nystagmus was reflected in the criterion of positive difference + delta between angular velocities of the slow component of the nystagmus and optokinetic stimuli. It is postulated that the criterion + delta is a necessary factor in the organization of optimal time relations between optokinetic stimuli and central processes that are responsible for the final result--sensory image of movement.


Diversity of type II restriction endonucleases that require two DNA recognition sites.
Orthodox Type IIP restriction endonucleases, which are commonly used in molecular biological work, recognize a single palindromic DNA recognition sequence and cleave within or near this sequence. Several new studies have reported on structural and biochemical peculiarities of restriction endonucleases that differ from the orthodox in that they require two copies of a particular DNA recognition sequence to cleave the DNA. These two sites requiring restriction endonucleases belong to different subtypes of Type II restriction endonucleases, namely Types IIE, IIF and IIS. We compare enzymes of these three types with regard to their DNA recognition and cleavage properties. The simultaneous recognition of two identical DNA sites by these restriction endonucleases ensures that single unmethylated recognition sites do not lead to chromosomal DNA cleavage, and might reflect evolutionary connections to other DNA processing proteins that specifically function with two sites.


Context Matters: Multiple Novelty Tests Reveal Different Aspects of Shyness-Boldness in Farmed American Mink (Neovison vison).
Animal personality research is receiving increasing interest from related fields, such as evolutionary personality psychology. By merging the conceptual understanding of personality, the contributions to both fields of research may be enhanced. In this study, we investigate animal personality based on the definition of personality traits as underlying dispositional factors, which are not directly measurable, but which predispose individuals to react through different behavioural patterns. We investigated the shyness-boldness continuum reflected in the consistency of inter-individual variation in behavioural responses towards novelty in 47 farmed American mink (Neovison vison), which were raised in identical housing conditions. Different stages of approach behaviour towards novelty, and how these related within and across contexts, were explored. Our experimental design contained four tests: two novel object tests (non-social contexts) and two novel animated stimuli tests (social contexts). Our results showed consistency in shyness measures across multiple tests, indicating the existence of personality in farmed American mink. It was found that consistency in shyness measures differs across non-social and social contexts, as well as across the various stages in the approach towards novel objects, revealing that different aspects of shyness exist in the farmed American mink. To our knowledge this is the first study to reveal aspects of the shyness-boldness continuum in the American mink. Since the mink were raised in identical housing conditions, inherited factors may have been important in shaping the consistent inter-individual variation. Body weight and sex had no effect on the personality of the mink. Altogether, our results suggest that the shyness-boldness continuum cannot be explained by a simple underlying dispositional factor, but instead encompasses a broader term of hesitating behaviour that might comprise several different personality traits.


Ecological surveillance of bat coronaviruses in Sarawak, Malaysian Borneo.
Coronaviruses (CoVs) are natural commensals of bats. Two subgenera, namely Sarbecoviruses and Merbecoviruses have a high zoonotic potential and have been associated with three separate spillover events in the past 2 decades, making surveillance of bat-CoVs crucial for the prevention of the next epidemic. The study was aimed to elucidate the presence of coronavirus in fresh bat guano sampled from Wind Cave Nature Reserve (WCNR) in Sarawak, Malaysian Borneo. Samples collected were placed into viral transport medium, transported on ice within the collection day, and preserved at - 80 °C. Nucleic acid was extracted using the column method and screened using consensus PCR primers targeting the RNA-dependent RNA polymerase (RdRp) gene. Amplicons were sequenced bidirectionally using the Sanger method. Phylogenetic tree with maximum-likelihood bootstrap and Bayesian posterior probability were constructed. CoV-RNA was detected in ten specimens (47.6%, n = 21). Six alphacoronavirus and four betacoronaviruses were identified. The bat-CoVs can be phylogenetically grouped into four novel clades which are closely related to Decacovirus-1 and Decacovirus-2, Sarbecovirus, and an unclassified CoV. CoVs lineages unique to the Island of Borneo were discovered in Sarawak, Malaysia, with one of them closely related to Sarbecovirus. All of them are distant from currently known human coronaviruses.


HLA-G2, -G3, and -G4 isoforms expressed as nonmature cell surface glycoproteins inhibit NK and antigen-specific CTL cytolysis.
HLA-G is a nonclassical MHC class I molecule that plays a major role in maternal-fetal tolerance. Four membrane-bound (HLA-G1 to -G4) and two soluble (HLA-G5, and -G6) proteins are generated by alternative splicing. Only HLA-G1 has been extensively studied in terms of both expression and function. We provide evidence here that HLA-G2, -G3, and -G4 truncated isoforms reach the cell surface of transfected cells, as endoglycosidase H-sensitive glycoproteins, after a 2-h chase period. Moreover, cytotoxicity experiments show that these transfected cells are protected from the lytic activity of both innate (NK cells) and acquired (CTL) effectors. These findings highlight the immunomodulatory role that HLA-G2, -G3, and -G4 proteins will assume during physiologic or pathologic processes in which HLA-G1 expression is altered.


Undulatory physical resistance training program increases maximal strength in elderly type 2 diabetics.
To investigate the effects of a specific protocol of undulatory physical resistance training on maximal strength gains in elderly type 2 diabetics. The study included 48 subjects, aged between 60 and 85 years, of both genders. They were divided into two groups: Untrained Diabetic Elderly (n=19) with those who were not subjected to physical training and Trained Diabetic Elderly (n=29), with those who were subjected to undulatory physical resistance training. The participants were evaluated with several types of resistance training's equipment before and after training protocol, by test of one maximal repetition. The subjects were trained on undulatory resistance three times per week for a period of 16 weeks. The overload used in undulatory resistance training was equivalent to 50% of one maximal repetition and 70% of one maximal repetition, alternating weekly. Statistical analysis revealed significant differences (p<0.05) between pre-test and post-test over a period of 16 weeks. The average gains in strength were 43.20% (knee extension), 65.00% (knee flexion), 27.80% (supine sitting machine), 31.00% (rowing sitting), 43.90% (biceps pulley), and 21.10% (triceps pulley). Undulatory resistance training used with weekly different overloads was effective to provide significant gains in maximum strength in elderly type 2 diabetic individuals.


Hybrid Doctors: The Need Risen From Informed Patients.
In the last decade, we have seen a significant surge in the number of patients whom we can term as "Informed patients". Informed patients are well read on the medical condition that they are looking to resolve. They may have often over researched and may be paranoid about what they may be going through; they may also know all potential medications that may be used for treatment and also potential side effects of these. However, they may not be in a position to judge what is actually right and what is actually applicable for what they are going through. This causes patients to go through, what we define as hyper information, where they have a lot of information but are unaware what applies to them. In this paper, we classify patients driven by this hyper-information, and discuss how this may lead to different patient states. We also discuss the need for doctors to adapt themselves to become what we call Hybrid Doctors. We briefly discuss how Hybrid Doctors can handle informed patients of various types and states.


Elevation of IgG antibodies against tissue transglutaminase as a diagnostic tool for coeliac disease in selective IgA deficiency.
IgA serum autoantibodies against tissue transglutaminase (tTG) have an established diagnostic value in coeliac disease, and high efficacy tests are widely available for their detection. However, serological evaluation of IgA deficient subjects is still difficult. To evaluate the diagnostic potential of IgG class anti-tTG autoantibodies measured quantitatively using an enzyme linked immunosorbent assay (ELISA) compared with immunofluorescent detection of coeliac autoantibodies. We tested serum samples from 325 IgA deficient subjects, including 78 patients with coeliac disease, 73 disease controls, and 174 blood donors. IgG antibodies against human recombinant tTG were measured with an ELISA. IgG antiendomysium antibodies (EMA) were assayed by indirect immunofluorescence on human jejunum and appendix sections. The IgG anti-tTG ELISA had a sensitivity of 98.7% and a specificity of 98.6%, and the correlation with IgG EMA titres was high (r(s)=0.91). One coeliac patient, initially negative in all autoantibody tests, displayed both IgG anti-tTG antibodies and IgG EMA during later gluten exposure. IgG anti-tTG antibodies and EMA titres showed significant decreases (p<0.001) in treated patients. The frequency of IgG anti-tTG autoantibody positivity was 9.8% among IgA deficient blood donors and 11 of the 12 positive subjects with known HLA-DQ haplotypes carried DQ2 or DQ8 alleles. IgG anti-tTG and IgG EMA autoantibody tests are highly efficient in detecting coeliac disease in IgA deficient patients. The high prevalence of coeliac antibodies among symptom free IgA deficient blood donors who also carry coeliac-type HLA-DQ genes indicates that all IgA deficient persons should be evaluated for coeliac disease.


Determination of antifungal susceptibility patterns among the environmental isolates of Aspergillus fumigatus in Iran.
In recent years, triazole-resistant environmental isolates of Aspergillus fumigatus have emerged in Europe and Asia. Azole resistance has been reported in patients who are treated with long-term azole therapy or exposure of the fungus spores to the azole fungicides used in agriculture. To date, a wide range of mutations in A. fumigatus have been described conferring azole-resistance, which commonly involves modifications in the cyp51A gene. We investigated antifungal susceptibility pattern of environmental isolates of A. fumigatus. In this study, 170 environmental samples collected from indoors surfaces of three hospitals in Iran. It was used β-tubulin gene to confirm the all of A. fumigatus isolates, which was identified by conventional methods. Furthermore, the antifungal susceptibility of itraconazole, voriconazole, and posaconazole was investigated using broth microdilution test, according to European Committee on Antimicrobial Susceptibility testing reference method. From a total of 158 environmental molds fungi obtained from the hospitals, 58 isolates were identified as A. fumigatus by amplification of expected size of β-tubulin gene (~500 bp). In this study, in vitro antifungal susceptibility testing has shown that there were not high minimum inhibitory concentration values of triazole antifungals in all of the 58 environmental isolates of A. fumigatus. Our findings demonstrated that there was not azole-resistant among environmental isolates of A. fumigatus. Medical triazoles compounds have structural similarity with triazole fungicide compounds in agriculture, therefore, resistance development through exposure to triazole fungicide compounds in the environment is important but it sounds there is not a serious health problem in drug resistance in environmental isolates in Iran.


Outcomes of patients with left ventricular assist device infected with SARS-CoV-2.
The aim of this study was to describe clinical characteristics, course, and outcomes of the novel coronavirus disease 2019 (COVID-19) in heart failure patients with left ventricular assist device. Between November 2020 and August 2021, a total of 20 patients (18 males, 2 females; mean age: 57.0+10.0 years; range, 30 to 71 years) with left ventricular assist device and who were diagnosed by the COVID-19 polymerase chain reaction testing were included. For each patient, disease-related factors were evaluated including presence of hospitalization, home quarantine, presence of lung damage, antiviral medication strategy, symptomatology and complications following COVID-19. Seven patients 35% patients died in our cohort following the COVID-19. All these patients experienced variety of complications following COVID-19 including subarachnoid hemorrhage and right heart failure. Three patients were already hospitalized due to COVID-19 and decompensated progressively, resulting in death on Days 14, 4, and 7 after the initial diagnosis. COVID-19 seems to be an important cause of mortality in patients with LVAD who have borderline cardiopulmonary function. Great care should be taken to avoid interruption in routine follow-ups with these patients, since they present a more sensitive population.


Divergent heparin-induced fibrillation pathways of a prion amyloidogenic determinant.
Polysaccharides and glycosaminoglycans (GAGs), particularly heparin, have been shown to directly affect fibrillation phenomena and the biological activities of amyloid proteins. We present a systematic analysis of the impact of heparin upon fibrillation of the amyloidogenic determinant of the prion protein PrP(106-126). Experimental data, including thioflavin T fluorescence, transmission electron microscopy, and circular dichroism, demonstrate that heparin induced dramatically diverging aggregation pathways of PrP(106-126). Specifically, enhanced β-sheet formation of the prion fragment leading to fibril assemblies occurred in solutions containing low heparin/prion mole ratios, while mixtures containing a greater abundance of heparin showed almost complete inhibition of PrP(106-126) fibril formation. Based upon the experimental data we have proposed a unified model accounting for the interplay between the roles of heparin as a scaffold for nucleation and fibril growth on the one hand and as a disruptor of fibrillation through electrostatic affinity with the monomeric peptide units on the other. This study clarifies previous conflicting studies, and concludes that GAGs inhibit fibrillation and amyloid toxicity in some cases, and promote amyloidogenesis in others.


Does workplace health promotion in Denmark reach relevant target groups?
The aim of the current study was to investigate whether Workplace Health Promotion (WHP) is available for workers with poor health status (overweight, musculoskeletal disorders, sickness absence and poor self-rated health) or health behaviour (smoking, poor diet and sedentarism) and whether they participate in WHP. In total, 9835 workers responded to questions regarding availability to 6 different types of WHP through The Danish Work Environment Cohort Study in 2010. Logistic regression analyses adjusted for age, gender and industry were performed to calculate odds ratios for availability and participation of WHP among groups with different health behaviours and health status. In general, poor health behaviours were associated with reduced availability of and participation in WHP. In contrast, poor health status was generally associated with higher availability of WHP and increased participation. However, poor self-rated health was associated with lower availability of several types of WHP and reduced participation. In general, workers with health challenges that are visible to others had WHP available, whereas workers with less visible health challenges had WHP less frequently available. Health challenges visible to others were associated with higher participation in WHP, whereas poor health behaviour and reduced self-rated health were associated with reduced participation in WHP programmes.


Biopsychosocial model of irritable bowel syndrome.
Irritable bowel syndrome (IBS) is a common chronic disorder seen in gastroenterology and primary care practice. It is characterized by recurrent abdominal pain or discomfort associated with disturbed bowel function. It is a heterogeneous disorder with varying treatments, and in this regard physicians sometimes struggle with finding the optimal approach to management of patients with IBS. This disorder induces high health care costs and variably reduces health-related quality of life. IBS is in the class of functional gastrointestinal disorders, and results from dysregulation of central and enteric nervous system interactions. Psychosocial factors are closely related to their gut physiology, associated cognitions, symptom manifestations and illness behavior. Therefore, it is important for the physician to recognize the psychosocial issues of patients with IBS and in addition to build a good patient-physician relationship in order to optimize treatment. This review focuses on the interaction between psychological and physiological factors associated with IBS by using a biopsychosocial model. In this article, we describe (1) the predisposing psychological features seen in early life; (2) the psychological factors associated with life stress, the symptom presentation, and their associated coping patterns; (3) gut pathophysiology with emphasis on disturbances in motility, visceral hypersensitivity and brain-gut interactions; and finally (4) the clinical outcomes and effective treatments including psychotherapeutic methods.