Exome sequencing establishes diagnosis of Alström syndrome in an infant presenting with non-syndromic dilated cardiomyopathy.
Idiopathic dilated cardiomyopathy is a heritable, genetically heterogeneous disorder characterized by progressive heart failure. Dilated cardiomyopathy typically exhibits autosomal dominant inheritance, yet frequently remains clinically silent until adulthood. We sought to discover the molecular basis of idiopathic, non-syndromic dilated cardiomyopathy in a one-month-old male presenting with severe heart failure. Previous comprehensive testing of blood, urine, and skin biopsy specimen was negative for metabolic, mitochondrial, storage, and infectious etiologies. Ophthalmologic examination was normal. Chromosomal microarray and commercial dilated cardiomyopathy gene panel testing failed to identify a causative mutation. Parental screening echocardiograms revealed no evidence of clinically silent dilated cardiomyopathy. Whole exome sequencing was carried out on the family trio on a research basis, filtering for rare, deleterious, recessive and de novo genetic variants. Pathogenic compound heterozygous truncating mutations were identified in ALMS1, diagnostic of Alström syndrome and prompting disclosure of genetic findings. Alström syndrome is a known cause for dilated cardiomyopathy in children yet delayed and mis-diagnosis are common owing to its rarity and age-dependent emergence of multisystem clinical manifestations. At six months of age the patient ultimately developed bilateral nystagmus and hyperopia, features characteristic of the syndrome. Early diagnosis is guiding clinical monitoring of other organ systems and allowing for presymptomatic intervention. Furthermore, recognition of recessive inheritance as the mechanism for sporadic disease has informed family planning. This case highlights a limitation of standard gene testing panels for pediatric dilated cardiomyopathy and exemplifies the potential for whole exome sequencing to solve a diagnostic dilemma and enable personalized care.


Gender specific effect of psychological stress and cortisol reactivity on adolescent risk taking.
The purpose of this study was to evaluate how psychological stress, gender and cortisol response to stress relate to risk behavior among 132 14-18 year old adolescents. Participants completed a laboratory based risk task prior to and immediately after a computerized psychological stress task, and salivary cortisol was collected from pre-stress to 60 min following initial stress exposure. Results indicate that adolescent boys (n = 59) and girls (n = 73) demonstrate different patterns of risk taking (RT) in response to stress, such that boys evidenced an increase in RT following stress exposure, whereas girls evidenced a decrease in RT. In addition, a gender by cortisol interaction demonstrated that for boys, both a smaller total cortisol output (AUCg) and peak cortisol response to stress (PC) was associated with greater stress-induced RT. Both cortisol measures were unrelated to stress-induced RT among girls. Taken together, data suggest that among boys, a blunted cortisol response to stress underlies an increase in risk taking in the context of psychological stress. Further research with an additional behavioral stress task is needed prior to drawing conclusions regarding the relation between female gender, cortisol response to stress, and risk taking in the context of psychological stress.


Vitamin K2-induced cell growth inhibition via autophagy formation in cholangiocellular carcinoma cell lines.
Vitamin K2 (MK4) has antitumor effects on various types of cancer cell lines in vitro, and its efficacy has also been reported in clinical applications for patients with leukemia, myelodysplastic syndrome, and hepatocellular carcinoma (HCC). However, details of the mechanism of the antitumor effects of MK4 remain unclear. In the present study, we examined the antitumor effects of MK4 on cholangiocellular carcinoma (CCC) cell lines and its mechanism of action using the HL-60 leukemia cell line that exerts MK4-induced cell growth inhibition via apoptosis induction and cell cycle arrest as a control. MK4 exerted dose-dependent antitumor effects on all three types of CCC cell lines. However, apoptosis occurred in a smaller percentage of cells and there was less cell cycle arrest compared with other cancer cell lines studied previously, which suggested slight MK4-induced cell growth inhibition via apoptosis induction and cell cycle arrest. On the contrary, histopathological fidings showed a large number of cells containing vacuoles in their cytoplasm, and electron microscopic findings showed a large number of cytoplasmic autophagosomes and autolysosomes. These findings suggested evidence of autophagy-related cell death. Fluorescence microscopy following acridine orange staining revealed an increase in the number of cytoplasmic acidic vesicular organelles characteristic of autophagy. Moreover, there were few cells forming autophagic vesicles in the control group, while the percentage of cells containing vacuoles in the MK4-treated group increased with the duration of culture. These results suggested that, unlike in leukemia, gastric cancer, HCC, and other cancer cells, the antitumor effects of MK4 on CCC cells are induced via autophagy formation.


Referral to autopsy: effect of antemortem cardiovascular disease: a population-based study in Olmsted County, Minnesota.
Autopsy studies can provide insight into disease trends and their determinants, including data on the prevalence of atherosclerosis. However, such studies are subject to autopsy bias, which limits their generalizability to the source population. The impact of this bias on autopsy based estimates of time trends in heart disease prevalence is unknown. To report on the trends over time in autopsy rates in Olmsted County, MN, to examine the association between clinical diagnoses of cardiovascular diseases (CVDs) and referral to autopsy and how this association may have changed over time. We examined the trends in autopsy rates between 1979 and 1994 in Olmsted County, and the association between antemortem characteristics including cardiovascular diagnoses and autopsy referral. From 1979 to 1994, a total of 9110 residents died in Olmsted County. The average annual autopsy rate was 30%. Autopsy rates declined from 36% in 1979 to 23% in 1994, corresponding to an average decline of 0.6%/year (p < 0.01). Referral to autopsy was positively associated with younger age, male sex, in-hospital place of death, antemortem diagnoses of myocardial infarction (MI) or peripheral vascular disease (PVD), and earlier calendar period. There was no evidence of an interaction between calendar period and any of these predictor variables. Antemortem diagnosis of heart failure was associated with a decrease in the odds of referral to autopsy over time as compared to persons without such diagnosis. In Olmsted County, autopsy rates, although declining over time, have remained on average approximately 30%. Antemortem diagnoses of MI or PVD are associated with autopsy referral but this association did not change over time. While the greater decline overtime in the use of autopsy observed among decedents with an antemortem diagnosis of congestive heart failure (CHF) deserves further studies, the present findings reduce the concern for bias of time trends in the prevalence of atherosclerosis by changes in the clinical characteristics of decedents referred to autopsy.


Arcobacter Isolation from Minced Beef Samples in Costa Rica.
The presence of Arcobacter spp. in minced meat (including beef) samples has been well documented in different countries, with varying frequencies. Nevertheless, the only Latin American country reporting this bacterium in minced beef samples is Mexico, with a 28.8% frequency in 2003. Previous studies in Costa Rica have demonstrated the presence of Arcobacter species in samples taken from the poultry production chain, but still there are no studies performed in bovine meat. The aim of this study was to determine the frequency of this bacterium in 120 samples of minced beef acquired from the Central Valley region of Costa Rica and to describe the antibiotic sensitivity pattern of the isolates obtained. A total of 75 different Arcobacter strains were isolated from minced beef samples, for a final frequency of 48.3%. After species PCR identification, the strains were classified as A. butzleri (37.3%), A. cibarius (14.7%), A. thereius (12%), and Arcobacter spp. (36%). All samples were sensitive to gentamicin but were resistant to ampicillin, levofloxacin, nalidixic acid, and ciprofloxacin. The results obtained in this study show that the frequency of isolation of Arcobacter in minced beef samples is high and that there is a high resistance rate for antibiotics in common use. This suggests that Arcobacter represents a health risk for Costa Rica and that control measures should be developed to decrease its potential impact.


Role of membrane-associated thiol groups in the functional regulation of gastric microsomal (H+ + K+)-transporting ATPase system.
The distribution of free thiol groups associated with the membrane proteins of the purified pig gastric microsomal vesicles was quantified, and the relation of thiol groups to the function of the gastric (H+ + K+)-transporting ATPase system was investigated. Two different thiol-specific agents, carboxypyridine disulphide (CPDS) and N-(1-naphthyl)maleimide (NNM) were used for the study. The structure-function relationship of the membrane thiol groups was studied after modification by the probes under various conditions, relating the inhibition of the (H+ + K+)-transporting ATPase to the ATP-dependent H+ accumulation by the gastric microsomal vesicles. On the basis of the extent of stimulation of the microsomal (H+ + K+)-transporting ATPase in the presence and absence of valinomycin (val) about 85% of the vesicles were found to be intact. CPDS at 1 mM completely inhibits the valinomycin-stimulated ATPase and the associated p-nitrophenyl phosphatase with a concomitant inhibition of vesicular H+ uptake. Both the enzyme and dye-uptake activities were fully protected against CPDS inhibition when the treatment with CPDS was carried out in the presence of ATP. ATP also offered protection (about 65%) against NNM inhibition of the (H+ + K+)-transporting ATPase system and vesicular H+ uptake. Under similar conditions ATP also protected about 10 and 6 nmol of thiol groups/mg of protein respectively from CPDS and NNM reaction. Our data suggest that the thiol groups on the outer surface of the vesicles are primarily involved in gastric (H+ + K+)-transporting ATPase function. Furthermore, at least about 15% of the total microsomal thiol groups appear to be associated with the ATPase system. The data have been discussed in terms of the structure-function relationship of gastric microsomes.


[Factors affecting the health-related quality of life according to age in vulnerable aged men].
The purpose of this study was to investigate the factors that influenced the health-related quality of life of young-old (65-74 yr) men, old-old (75-84 yr) men, and oldest-old (85 yr or above) men in vulnerable aged received home care from public health center. The participants for this study were 318 aged Korean men living in D city. The data was collected from August to October, 2009 using structured questionnaires. Chi-square, One way ANOVA, Duncan test, Pearson's Correlation Coefficient and multiple regression with the SPSS WIN 14.0 program were used to analyze the data. There were statistically significant differences among young-old, old-old, and oldest-old men regarding the health-related quality of life, health promoting behavior, IADL (Instrumental Activities of Daily Living), rehabilitation, depression, and social support. The model including variables related to physical, psychological, and social aspects of life, explained variance of the health-related quality of life of aged men differently, such as 39.6% of young-old, 35.4% of old-old, and 47.0% of oldest-old. Finally, IADL and social support were predictors in explaining the level of health-related quality of life among vulnerable old men regardless of age. Based on the findings of the study, nursing interventions should be developed to improve health-related quality of life of vulnerable aged men according to age differences.


Endoscopic tissue sampling - Part 1: Upper gastrointestinal and hepatopancreatobiliary tracts. European Society of Gastrointestinal Endoscopy (ESGE) Guideline.
1: ESGE recommends that, where there is a suspicion of eosinophilic esophagitis, at least six biopsies should be taken, two to four biopsies from the distal esophagus and two to four biopsies from the proximal esophagus, targeting areas with endoscopic mucosal abnormalities. Distal and proximal biopsies should be placed in separate containers.Strong recommendation, low quality of evidence. 2: ESGE recommends obtaining six biopsies, including from the base and edge of the esophageal ulcers, for histologic analysis in patients with suspected viral esophagitis.Strong recommendation, low quality of evidence. 3: ESGE recommends at least six biopsies are taken in cases of suspected advanced esophageal cancer and suspected advanced gastric cancer.Strong recommendation, moderate quality of evidence. 4: ESGE recommends taking only one to two targeted biopsies for lesions in the esophagus or stomach that are potentially amenable to endoscopic resection (Paris classification 0-I, 0-II) in order to confirm the diagnosis and not compromise subsequent endoscopic resection.Strong recommendation, low quality of evidence. 5: ESGE recommends obtaining two biopsies from the antrum and two from the corpus in patients with suspected Helicobacter pylori infection and for gastritis staging.Strong recommendation, low quality of evidence. 6: ESGE recommends biopsies from or, if endoscopically resectable, resection of gastric adenomas.Strong recommendation, moderate quality of evidence. 7: ESGE recommends fine-needle aspiration (FNA) and fine-needle biopsy (FNB) needles equally for sampling of solid pancreatic masses.Strong recommendation, high quality evidence. 8: ESGE suggests performing peroral cholangioscopy (POC) and/or endoscopic ultrasound (EUS)-guided tissue acquisition in indeterminate biliary strictures. For proximal and intrinsic strictures, POC is preferred. For distal and extrinsic strictures, EUS-guided sampling is preferred, with POC where this is not diagnostic.Weak recommendation, low quality evidence. 9: ESGE suggests obtaining possible non-neoplastic biopsies before sampling suspected malignant lesions to prevent intraluminal spread of malignant disease.Weak recommendation, low quality of evidence. 10: ESGE suggests dividing EUS-FNA material into smears (two per pass) and liquid-based cytology (LBC), or the whole of the EUS-FNA material can be processed as LBC, depending on local experience.Weak recommendation, low quality evidence.


A coupled fluid-structure finite element model of the aortic valve and root.
The study aim was to develop a three-dimensional coupled fluid-structure finite element model of the aortic valve and root. This model extends previous purely structural finite element models, and represents a significant step toward realistic simulation of the complex interactions among tissue material properties and valvular function. The aortic root and valve geometry were extracted from magnetic resonance images and imported into the LS-Dyna explicit finite element package. Leaflet and root tissue were modeled with elastic material properties, and blood was modeled as a Newtonian liquid. A dynamic, fully unsteady analysis was performed in which blood flow through the valve was computed along with the motion of the leaflets and root in response to standard physiologic pressure wave profiles. The opening and closing of the aortic valve under physiological loading conditions was successfully simulated, and feasibility of the model illustrated. The motion of the simulated leaflets was consistent with that seen in intact hearts. Analysis of fluid flow patterns revealed eddy structures in the sinus regions and flow into the coronary circulation. The addition of blood flow to structural models of the aortic valve and root is a significant advance in modeling, and allows a closer simulation of valvular function. The model will be used to further assess normal and abnormal physiology as well as the effects of surgical intervention.


Id1 overexpression is independent of repression and epigenetic silencing of tumor suppressor genes in melanoma.
The full molecular consequences of oncogene activation during tumorigenesis are not well understood, but several studies have recently linked oncogene activation to epigenetic silencing of specific genes 1, 2. Transcriptional repressor Id1 is overexpressed in many malignancies including melanoma, and Id1 targets include tumor suppressor genes TSP1, CDKN2A (p16) and CDKN1A (p21), which are frequently epigenetically silenced in cancer. We confirmed that both TSP1 and CDKN2A have abnormal promoter region DNA methylation in primary melanoma, but the mechanism by which this silencing occurs remains unknown. Here we explore the effects of stable lentiviral Id1 overexpression on the expression of these Id1 target genes in human melanoma cell lines. Overexpressed Id1 was functional and bound transcriptional activator E2A, but did not sequester E2A from gene promoters and repress gene expression. Therefore, these Id1 target genes were resistant to Id1-mediated gene silencing. Our results suggest that Id1 activation may need to occur at discrete stages in cooperation with additional gene dysregulation to repress and induce epigenetic silencing of tumor suppressor genes during melanoma progression.


Incidence of Heart Failure and Cardiomyopathy Following Initiation of Medications for Attention-Deficit/Hyperactivity Disorder: A Descriptive Study.
Stimulant abuse is associated with cardiomyopathy, but cardiomyopathy rates with therapeutic use of stimulants for attention-deficit/hyperactivity disorder (ADHD) are poorly characterized. Labels for methylphenidate, amphetamine, and atomoxetine caution against use in patients with cardiovascular disease. We sought to assess the incidence of new-onset heart failure or cardiomyopathy among initiators of these medications. Using the Sentinel distributed database, we analyzed new-onset heart failure or cardiomyopathy among initiators of selected ADHD medications (amphetamine products including lisdexamfetamine, methylphenidate, and atomoxetine), by duration of use (0-90, 91-180, 181-270, 271-365, 366-730, and 731-1095 days) and age group (<22, 22-44, 45-64, and ≥65 years). In our sample of 2,012,948 initiators of ADHD medications, 44.6% were female, and 54.1% were younger than 22 years. Heart failure/cardiomyopathy rates in the age groups younger than 22 and 22 to 44 years old were less than 50 per 10,000 person-years, without clear trends by duration of use. The highest rates occurred soon after treatment initiation in the age group 65 years or older, with 1 case per 10.5 person-years of follow-up, or 950 cases per 10,000 person-years, for days 0-90. Heart failure/cardiomyopathy rates were not higher over 3 years of ADHD medication use compared with shorter-term treatment. In older age groups, lower rates later in treatment could reflect depletion of patients predisposed to the outcome if they develop it soon after starting treatment.


Nuts: a new protective food against coronary heart disease.
Recent epidemiological findings indicate that frequent nut consumption offers protection from fatal and non-fatal coronary heart disease events. Although human nutrition studies seem to indicate that nut consumption lowers total and LDL cholesterol, the unique nutrient composition of nuts invites speculation on other mechanisms of protection.


Production of α-galactosidase from Aspergillus foetidus MTCC 6322 by solid state fermentation and its application in soymilk hydrolysis.
The production of α-galactosidase from the wild fungal strain Aspergillus foetidus MTCC 6322 using solid state fermentation (SSF), its characterization, and its efficacy in the hydrolysis of soymilk using response surface methodology were studied. The optimum conditions for production of α-galactosidase by SSF were: wheat bran (10 g), moisture content (64%), inoculum volume (1.0 mL; 6 x 10(7) spores/mL) with a yield of 4.1 x 10(3) units per gram dry substrate (U/gds) at 96 h. The enzyme showed optimum activity at 6.0, temperature 40 degrees C, pH stability between 5.0-8.0, and temperature stability between 30-40 degrees C. The enzyme was stable in the presence of trypsin, lipase, and collagenase and it showed susceptibility of the substrates such as raffinose, melibiose, guar gum and soymilk to hydrolysis in varying degrees. The optimized conditions for soymilk hydrolysis were: soymilk (10 mL) from defatted soybean meal (1.5%), α-galactosidase (0.15 UmL(-1) at 30 degrees C, pH 6.0 and duration of 1 h.


Assessment of Poisson, probit and linear models for genetic analysis of presence and number of black spots in Corriedale sheep.
Black skin spots are associated with pigmented fibres in wool, an important quality fault. Our objective was to assess alternative models for genetic analysis of presence (BINBS) and number (NUMBS) of black spots in Corriedale sheep. During 2002-08, 5624 records from 2839 animals in two flocks, aged 1 through 6 years, were taken at shearing. Four models were considered: linear and probit for BINBS and linear and Poisson for NUMBS. All models included flock-year and age as fixed effects and animal and permanent environmental as random effects. Models were fitted to the whole data set and were also compared based on their predictive ability in cross-validation. Estimates of heritability ranged from 0.154 to 0.230 for BINBS and 0.269 to 0.474 for NUMBS. For BINBS, the probit model fitted slightly better to the data than the linear model. Predictions of random effects from these models were highly correlated, and both models exhibited similar predictive ability. For NUMBS, the Poisson model, with a residual term to account for overdispersion, performed better than the linear model in goodness of fit and predictive ability. Predictions of random effects from the Poisson model were more strongly correlated with those from BINBS models than those from the linear model. Overall, the use of probit or linear models for BINBS and of a Poisson model with a residual for NUMBS seems a reasonable choice for genetic selection purposes in Corriedale sheep.


Comparison of video assisted thoracoscopic surgery and thoracotomy for treatment of pleural infection stage II and III: a literature review.
Pleural infection is associated with significant mortality and morbidity worldwide, with a steadily increasing incidence. We sought to investigate whether video-assisted thoracic surgery (VATS) or thoracotomy provides the best outcomes in the treatment of stage II and III pleural infection as indications remain controversial. Systematic review of relevant articles from the PubMed database. Nine non-randomized retrospective studies published between 1996 and 2020 with a total of 2,121 patients were included. Results varied between studies, but overall shorter operative and recovery times and greater patient satisfaction were demonstrated using VATS compared with thoracotomy. Although VATS and thoracotomy are viable treatment options for stage II and III pleural infection, VATS has potential advantages in terms of decreased operation time, fewer days with tube drainage, shorter postoperative hospital stay, reduced postoperative pain, increased patient satisfaction with the procedure, and wound appearance. VATS has limitations in the treatment of patients with stage III pleural infection, where delayed surgical referral has been shown to increase the risk of intraoperative conversion to thoracotomy. The data to date implies that debridement by VATS should be proposed as soon as possible in stage II pleural infection and considered in cases of stage III pleural infection.


The pathway of the asialoglycoprotein-ligand during receptor-mediated endocytosis: a morphological study with colloidal gold/ligand in the human hepatoma cell line, Hep G2.
The human hepatoma cell line, Hep G2, was used as a model system to delineate the morphological aspects of receptor-mediated endocytosis of asialoglycoproteins (ASGP). These hepatoma cells, which have several structural features in common with liver parenchymal cells, contain a well-differentiated endocytotic apparatus which includes coated vesicles and CURL (compartment of uncoupling receptor and ligand) similar to that found in rat liver cells in vivo (Geuze et al., 1983). In order to precisely identify the route of ligand from the cell surface to the CURL sorting vesicles, Hep G2 cells were allowed to endocytose in synchrony ASGP bound to 12 nm colloidal gold for 5 to 60 min. Thereafter the subcellular distribution of the gold particles was examined in ultrathin cryosections. This study demonstrates that, once internalized, ASGP ligand enters a system of CURL tubules prior to delivery to the lumenal contents of attached endocytotic vesicles. These vesicles then in turn transform into multivesicular bodies and secondary lysosomes. Thus, the tubular portions of CURL provide the entry for ASGP ligand into the sorting compartment.


Does the 'gateway' matter? Associations between the order of drug use initiation and the development of drug dependence in the National Comorbidity Study Replication.
The 'gateway' pattern of drug initiation describes a normative sequence, beginning with alcohol and tobacco use, followed by cannabis, then other illicit drugs. Previous work has suggested that 'violations' of this sequence may be predictors of later problems but other determinants were not considered. We have examined the role of pre-existing mental disorders and sociodemographics in explaining the predictive effects of violations using data from the US National Comorbidity Survey Replication (NCS-R). The NCS-R is a nationally representative face-to-face household survey of 9282 English-speaking respondents aged 18 years and older that used the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI) to assess DSM-IV mental and substance disorders. Drug initiation was estimated using retrospective age-of-onset reports and 'violations' defined as inconsistent with the normative initiation order. Predictors of violations were examined using multivariable logistic regressions. Discrete-time survival analysis was used to see whether violations predicted progression to dependence. Gateway violations were largely unrelated to later dependence risk, with the exception of small increases in risk of alcohol and other illicit drug dependence for those who initiated use of other illicit drugs before cannabis. Early-onset internalizing disorders were predictors of gateway violations, and both internalizing and externalizing disorders increased the risks of dependence among users of all drugs. Drug use initiation follows a strong normative pattern, deviations from which are not strongly predictive of later problems. By contrast, adolescents who have already developed mental health problems are at risk for deviations from the normative sequence of drug initiation and for the development of dependence.


Detection of hepatitis B virus x transcripts in human hepatocellular carcinoma tissues.
The hepatitis B virus (HBV) or hepatitis C virus (HCV) sequences were frequently detected in hepatocellular carcinoma (HCC) tissues by the method of polymerase chain reaction (PCR). However, the expression levels of HBV and HCV in HCC tissues remain to be documented. This study evaluates the mRNA expression levels of those virus sequences in the human HCC tissues through Northern blot hybridization. We performed Northern blot hybridization to identify the HBV x mRNA and HCV RNA in HCC tissues of 14 cases excised at Chiba University Hospital. The HBV x transcripts could be identified in the tumor tissues from all three serum HBsAg-positive cases and two cases among 11 HBsAg-negative patients. One HBsAg-negative case showed the most intensive signal in those five cases. However, HCV RNA could not be identified by this method. The HBV x gene transcript is predicted to have a size of about 0.7 kb; however, the molecular weight of HBV x specific mRNA is not consistent and is distributed between approximately 2.0 and 9.0 kb. The hybridization signal intensity is also variable according to the cases. These observations suggest that HBV x gene may be transcribed with flanking cellular sequences and the carcinogenic activity may be different according to the expressed levels. The identification of HBV x transcripts in HCC tissues on the Northern blot level also suggests that HBV x mRNA expression might be significant and concerned with the development of human HCC even in HBsAg-negative cases.


Red cell distribution width values and red cell distribution width-to-platelet ratio in Thoroughbred foals in the first 24 hours of life.
To report red cell distribution width (RDW) values, to calculate RDW-to-platelet ratio (RPR), and to investigate a possible correlation of RDW and RPR index values in neonatal foals classified as healthy or at risk based on clinical information from a population of foals up to 24 hours of life. Retrospective study conducted from records and CBCs of foals born between June and November from 2018 to 2020 foaling seasons. Breeding farm. Three hundred and nine neonatal full-term Thoroughbred foals. None. Foals were evaluated by a veterinarian within 15 minutes after birth, and a blood sample was collected within 24 hours of life. Based on clinical information, 88 of 309 foals (28.4%) were considered at risk of perinatal disease, and 201 were healthy. Mean gestational age for the foals was 346.3 ± 9.7 days. RDW values did not differ between groups. Gestational length demonstrated to have a negative correlation with RDW (r = -0.156, P = 0.005) and mean corpuscular volume (r = -0.135, P = 0.01), indicating a link of these variables to foal maturity. RPR index was higher for at-risk (0.073 ± 0.018) than for healthy foals (0.068 ± 0.014, P = 0.01). RPR might be a promising early indicator of disease for the field triage of neonatal foals.


Dry powder inhaler performance of spray dried mannitol with tailored surface morphologies as carrier and salbutamol sulphate.
Nowadays, dry powder inhalation as applied in the therapy of pulmonary diseases is known as a very effective route of drug delivery to the lungs. Here, the system of coarse carrier and fine drug particles attached to the carrier surface has successfully been applied to overcome the cohesiveness of small drug particles. Particle properties of both carrier and drug are known to affect drug dispersion as has widely been discussed for lactose monohydrate and various drugs. This study utilises particle-engineered mannitol as an alternative carrier to discover the effect of mannitol carrier particle properties like particle shape, surface roughness, flowability or particle size on aerodynamic performance during inhalation. Spray drying as a technique to accurately control those properties was chosen for the generation of carrier sizes between 50 and 80 μm and different morphologies and therefore various carrier flowabilities. A set of these carriers has then been blended with different spray dried and jet-milled qualities of salbutamol sulphate as model drug to examine the influence of carrier particle properties on aerodynamic behaviour and at the same time to cover the effect of drug particle properties on particle-particle interactions. This experimental setup allowed a general view on how drug and carrier properties affect the Fine Particle Fraction (FPF) as indicator for inhalation performance and gave the first study to distinguish between mannitol carrier particle shape and surface roughness. Further it was possible to relate carrier particle size and shape to drug accumulation and detachment mechanisms during inhalation as size and shape had the main influence on drug detachment. The addition of jet-milled mannitol fines provided an initial insight into the improving effect of ternary powder blends as has been intensively studied for lactose monohydrate but not for mannitol yet.


With or without you: predictive coding and Bayesian inference in the brain.
Two theoretical ideas have emerged recently with the ambition to provide a unifying functional explanation of neural population coding and dynamics: predictive coding and Bayesian inference. Here, we describe the two theories and their combination into a single framework: Bayesian predictive coding. We clarify how the two theories can be distinguished, despite sharing core computational concepts and addressing an overlapping set of empirical phenomena. We argue that predictive coding is an algorithmic/representational motif that can serve several different computational goals of which Bayesian inference is but one. Conversely, while Bayesian inference can utilize predictive coding, it can also be realized by a variety of other representations. We critically evaluate the experimental evidence supporting Bayesian predictive coding and discuss how to test it more directly.


Temperature modulates the impacts of wastewater exposure on the physiology and behaviour of fathead minnow.
Municipal wastewater treatment plant (WWTP) effluent is a substantial source of pollution in aquatic habitats that can impact organisms across multiple levels of biological organization. Even though wastewater effluent is discharged continuously all year long, its impacts across seasons, specifically during winter, have largely been neglected in ecotoxicological research. Seasonal differences are of particular interest, as temperature-driven metabolic changes in aquatic organisms can significantly alter their ability to respond to chemical stressors. In this study, we examined the effects of multiple levels of wastewater effluent exposure (0, 25, or 50% treated effluent) on the physiological and behavioural responses of adult fathead minnow (Pimephales promelas) at temperatures simulating either summer (20 °C) or winter (4 °C) conditions. At 20 °C, wastewater exposure posed a metabolic cost to fish, demonstrated by higher standard metabolic rate and was associated with increased haematocrit and a reduction in boldness. In contrast, fish exposed to wastewater at 4 °C experienced no change in metabolic rate but performed fewer social interactions with their conspecifics. Taken together, our results demonstrate that wastewater exposure can lead to metabolic and behavioural disruptions, and such disruptions vary in magnitude and direction depending on temperature. Our findings highlight the importance of studying the interactions between stressors, while also underscoring the importance of research during colder periods of the year to broaden and deepen our understanding of the impacts of wastewater contamination in aquatic ecosystems.


Independent evolution toward larger body size in the distinctive Faroe Island mice.
Most phenotypic traits in nature involve the collective action of many genes. Traits that evolve repeatedly are particularly useful for understanding how selection may act on changing trait values. In mice, large body size has evolved repeatedly on islands and under artificial selection in the laboratory. Identifying the loci and genes involved in this process may shed light on the evolution of complex, polygenic traits. Here, we have mapped the genetic basis of body size variation by making a genetic cross between mice from the Faroe Islands, which are among the largest and most distinctive natural populations of mice in the world, and a laboratory mouse strain selected for small body size, SM/J. Using this F2 intercross of 841 animals, we have identified 111 loci controlling various aspects of body size, weight and growth hormone levels. By comparing against other studies, including the use of a joint meta-analysis, we found that the loci involved in the evolution of large size in the Faroese mice were largely independent from those of a different island population or other laboratory strains. We hypothesize that colonization bottleneck, historical hybridization, or the redundancy between multiple loci have resulted in the Faroese mice achieving an outwardly similar phenotype through a distinct evolutionary path.


Use of a platelet filter test in patients with thrombocytosis.
In the differential diagnosis of primary and secondary thrombocytosis platelet function tests may play an important role. We examined the applicability of a platelet filter test (shear-dependent platelet aggregation) as a tool, to differentiate primary thrombocytosis (cases with myeloproliferative disorders) from secondary (reactive) thrombocytosis. The test was carried out in 53 patients suffering from myeloproliferative disorders associated with primary thrombocytosis and in 21 patients with other diseases complicated by secondary thrombocytosis. Using citrate as anticoagulant, the sensitivity of the O'Brien's test proved to be 77.1%, and its specificity 94.4%. Using heparin as anticoagulant the sensitivity and specificity of the test were found to be also reliably high. Based on these studies we suggest the use of the O'Brien's filterometer as a screening test in the differential diagnosis in patients with elevated platelet count. In the case of normal results, the causes of reactive thrombocytosis should be clarified first, while with abnormal results, haematological examination of the patients should be performed.


The Neurobiological Basis of Cognition: Identification by Multi-Input, Multioutput Nonlinear Dynamic Modeling: A method is proposed for measuring and modeling human long-term memory formation by mathematical analysis and computer simulation of nerve-cell dynamics.
The successful development of neural prostheses requires an understanding of the neurobiological bases of cognitive processes, i.e., how the collective activity of populations of neurons results in a higher level process not predictable based on knowledge of the individual neurons and/or synapses alone. We have been studying and applying novel methods for representing nonlinear transformations of multiple spike train inputs (multiple time series of pulse train inputs) produced by synaptic and field interactions among multiple subclasses of neurons arrayed in multiple layers of incompletely connected units. We have been applying our methods to study of the hippocampus, a cortical brain structure that has been demonstrated, in humans and in animals, to perform the cognitive function of encoding new long-term (declarative) memories. Without their hippocampi, animals and humans retain a short-term memory (memory lasting approximately 1 min), and long-term memory for information learned prior to loss of hippocampal function. Results of more than 20 years of studies have demonstrated that both individual hippocampal neurons, and populations of hippocampal cells, e.g., the neurons comprising one of the three principal subsystems of the hippocampus, induce strong, higher order, nonlinear transformations of hippocampal inputs into hippocampal outputs. For one synaptic input or for a population of synchronously active synaptic inputs, such a transformation is represented by a sequence of action potential inputs being changed into a different sequence of action potential outputs. In other words, an incoming temporal pattern is transformed into a different, outgoing temporal pattern. For multiple, asynchronous synaptic inputs, such a transformation is represented by a spatiotemporal pattern of action potential inputs being changed into a different spatiotemporal pattern of action potential outputs. Our primary thesis is that the encoding of short-term memories into new, long-term memories represents the collective set of nonlinearities induced by the three or four principal subsystems of the hippocampus, i.e., entorhinal cortex-to-dentate gyrus, dentate gyrus-to-CA3 pyramidal cell region, CA3-to-CA1 pyramidal cell region, and CA1-to-subicular cortex. This hypothesis will be supported by studies using in vivo hippocampal multineuron recordings from animals performing memory tasks that require hippocampal function. The implications for this hypothesis will be discussed in the context of "cognitive prostheses"-neural prostheses for cortical brain regions believed to support cognitive functions, and that often are subject to damage due to stroke, epilepsy, dementia, and closed head trauma.


[Molecular-genetic mechanisms of regulation of synthesis of individual types of rat hemoglobin].
The effects of actinomycin D and erythropoietically active serum (EAS) on the synthesis of beta-like chains of haemoglobin in the erythroid cells of rat bone marrow in vivo and in vitro were studied. It was shown that in the whole population of erythroid elements of bone marrow actinomycin D sharply decreases the synthesis of beta c-chains, whereas in early erythroblasts it predominantly inhibits the synthesis of beta b-chains. In the whole population of rat bone marrow cells EAS activates the predominant formation of beta b-chains. Under a combined administration of actinomycin D and EAS the stimulating effect of the latter manifests itself not earlier than 24 hrs after the antibiotic injection. The effect of actinomycin D is removed after injection of EAS to the animals, especially during the first 12 hrs. In the culture of anaemic animals bone marrow in the presence of EAS the highest amount of the label is detected in the beta c-chains, whereas in the erythroid elements treated with the erythropoietic factors in vivo--in the beta b-chains. Actinomycin D has no pronounced effect on the rate of beta-like chain formation in a short-time culture of bone marrow. The molecular mechanisms which control the switch-off of the predominant synthesis in different polypeptide types are discussed.


Beliefs about weight gain and attitudes toward relapse in a sample of women and men with obesity.
The purpose of this study was to examine beliefs regarding reasons for weight gain, likely responses to weight loss relapse, notions of reasonable weight loss, and correlations between beliefs and attitudes in a large nonclinical sample of men and women with obesity. Participants were 3,394 white women (n=1,674) and men (n=1,720) with obesity who had responded to a survey about body image and eating behaviors conducted by Consumer Reports magazine. Women and men indicated that the most important reasons for their weight gain were lack of exercise and enjoying eating; the least important reason was a need to avoid social or sexual situations. Both groups reported that their most likely response to relapse is to start watching food intake, whereas their least likely response is to ask a friend, spouse, or family member for help. Women rated depression, stress, low self-esteem, and need to avoid situations as more important reasons for their weight gain than did men, and women were more likely to feel terrible and regain as a response to relapse. There was no relationship between an individual's beliefs about weight gain, responses to relapse, or notions of reasonable weight loss. Implications of these findings for the treatment of obesity are discussed.


Mortality and use of the auxiliary score in extensive toxic epidermal necrolysis patients admitted to an adult burns referral centre.
Toxic epidermal necrolysis (TEN) is a rare but fatal condition characterised by cutaneous exfoliation of the dermoepidermal layer and mucosal surfaces. Extensive TEN with epidermal detachment >30% of the total body surface area has been associated with a high mortality. This study aims to evaluate factors associated with mortality in extensive TEN. In the absence of data to qualify scoring systems such as SCORTEN, this study also aims to evaluate the use of the auxiliary score as a tool for calculating expected mortality. A retrospective chart review of all patients presenting to our burns service with extensive TEN was undertaken. Application and evaluation of the auxiliary score was also undertaken for this patient population. In extensive TEN, age and delay in admission to a burns centre were factors associated with mortality. Applying the auxiliary score to our patient population, there were no significant differences between expected mortality and observed mortality. Mortality was associated with age and delay in definitive treatment in extensive TEN. Whilst SCORTEN is the gold standard prognostic tool for patients with TEN, in the absence of SCORTEN values, the auxiliary score provides an alternative scoring system to evaluate expected mortality.


Lesser tuberosity avulsions in adolescents.
Subscapularis tendon avulsions of the lesser tuberosity are relatively rare and often missed acutely and their characteristic appearance is frequently not recognized or is misinterpreted for an osteochondroma or a neoplastic process. This report reviews our experience with six adolescents who had subscapularis tendon avulsions of the lesser tuberosity. Six male adolescents (12-15 years) presented with shoulder pain following history of trauma during amateur sport. Clinical notes including range of motion, strength tests, and pain assessment were reviewed along with imaging studies pre- and post treatment. Treatment consisted of either surgical or conservative measures. Two of the six patients had a large avulsion that simulated an exostosis of the proximal humerus that was misdiagnosed as an osteochondroma at two different outside institutions. All six cases were diagnosed with subscapularis tendon avulsion of the lesser tuberosity following clinical and imaging evaluation at our institution. Five of the patients underwent surgical repair and fixation of the tendon and the lesser tuberosity with suture anchors. One patient was treated conservatively. All patients had a good outcome with recovery of full shoulder strength and motion upon follow-up. Clinicians should have a high index of suspicion of lesser tuberosity avulsions in adolescents who present with loss of internal rotation and anterior shoulder pain following traumatic injuries. In addition, an osseous fragment or exostosis along the inferomedial humeral head should suggest a subscapularis tendon avulsion and also should not be confused with an osteochondroma or a neoplastic process.


The Council of Emergency Medicine Residency Directors Academy for Scholarship Coaching Program: Addressing the Needs of Academic Emergency Medicine Educators.
Didactic lectures remain fundamental in academic medicine; however, many faculty physicians do not receive formal training in instructional delivery. In order to design a program to instill and enhance lecture skills in academic emergency medicine (EM) physicians we must first understand the gap between the current and ideal states. In 2012 the Council of Emergency Medicine Residency Directors (CORD) Academy for Scholarship designed a novel coaching program to improve teaching skills and foster career development for medical educators based on literature review and known teaching observation programs. In order to inform the refinement of the program, we performed a needs assessment of participants. Participants' needs and prior teaching experiences were gathered from self-reflection forms completed prior to engaging in the coaching program. Two independent reviewers qualitatively analyzed data using a thematic approach. We analyzed data from 12 self-reflection forms. Thematic saturation was reached after nine forms. Overall inter-rater agreement was 91.5%. We categorized emerging themes into three domains: participant strengths and weaknesses; prior feedback with attempts to improve; and areas of desired mentorship. Several overlapping themes and subthemes emerged including factors pertaining to the lecturer, the audience/learner, and the content/delivery. This study identified several areas of need from EM educators regarding lecture skills. These results may inform faculty development efforts in this area. The authors employed a three-phase, novel, national coaching program to meet these needs.


Sequential adaptive mutations enhance efficient vector switching by Chikungunya virus and its epidemic emergence.
The adaptation of Chikungunya virus (CHIKV) to a new vector, the Aedes albopictus mosquito, is a major factor contributing to its ongoing re-emergence in a series of large-scale epidemics of arthritic disease in many parts of the world since 2004. Although the initial step of CHIKV adaptation to A. albopictus was determined to involve an A226V amino acid substitution in the E1 envelope glycoprotein that first arose in 2005, little attention has been paid to subsequent CHIKV evolution after this adaptive mutation was convergently selected in several geographic locations. To determine whether selection of second-step adaptive mutations in CHIKV or other arthropod-borne viruses occurs in nature, we tested the effect of an additional envelope glycoprotein amino acid change identified in Kerala, India in 2009. This substitution, E2-L210Q, caused a significant increase in the ability of CHIKV to develop a disseminated infection in A. albopictus, but had no effect on CHIKV fitness in the alternative mosquito vector, A. aegypti, or in vertebrate cell lines. Using infectious viruses or virus-like replicon particles expressing the E2-210Q and E2-210L residues, we determined that E2-L210Q acts primarily at the level of infection of A. albopictus midgut epithelial cells. In addition, we observed that the initial adaptive substitution, E1-A226V, had a significantly stronger effect on CHIKV fitness in A. albopictus than E2-L210Q, thus explaining the observed time differences required for selective sweeps of these mutations in nature. These results indicate that the continuous CHIKV circulation in an A. albopictus-human cycle since 2005 has resulted in the selection of an additional, second-step mutation that may facilitate even more efficient virus circulation and persistence in endemic areas, further increasing the risk of more severe and expanded CHIK epidemics.


Occurrence of purple sulfur bacteria in a sewage treatment lagoon.
The ecology of purple sulfur bacteria in a sewage oxidation lagoon was investigated. Chemical changes in the lagoon were investigated by monitoring biochemical oxygen demand (BOD(5)), sulfide, sulfate, phosphate, total carbohydrates, volatile acids, alkalinity, and pH. Lagoon water temperatures were observed daily. Microbial ecological relationships were deduced by enumerating coliforms, total bacteria other than anaerobes [Tryptone Glucose Extract (TGE) agar], methane formers such as Methanobacterium formicicum, sulfate reducers, purple sulfur bacteria, and algae. Finally, two strains of purple sulfur bacteria were characterized. Two populations, purple sulfur bacteria and total bacteria (TGE agar), reached maximal concentrations in the warmest part of the 1967 summer. Purple sulfur bacteria reached maximal numbers as concentrations of sulfide and volatile acids were depleted, whereas carbohydrates and alkalinity remained unchanged. Low sulfate levels, which were not limiting for sulfate reducers, may be attributable to storage of sulfur within purple sulfur bacteria. No biological, chemical, or physical agent was linked to the removal of coliforms. The increase of algae in the late summer of 1967 may have been related to the low organic content of the lagoon during this period. Although lagoon pH (7.7 to 8.2) was favorable for purple sulfur bacterial growth, temperatures and sulfides were not optimal in the lagoon for these organisms. Chromatium vinosum and Thiocapsa floridana (the predominant lagoon purple sulfur organism in 1967 and 1968) utilized certain carbohydrates, amino acids, volatile acids, and Krebs cycle intermediates. Also purple sulfur bacteria lowered BOD levels as demonstrated by the growth of T. floridana in sterilized sewage.


Delay discounting and family history of psychopathology in children ages 9-11.
Delay discounting is a tendency to devalue delayed rewards compared to immediate rewards. Evidence suggests that steeper delay discounting is associated with psychiatric disorders across diagnostic categories, but it is unclear whether steeper delay discounting is a risk factor for these disorders. We examined whether children at higher risk for psychiatric disorders, based on family history, would demonstrate steeper delay discounting behavior using data from the Adolescent Brain Cognitive Development (ABCD) study, a nationally representative sample of 11,878 children. We looked at associations between delay discounting behavior and family history of alcohol problems, drug problems, depression, mania, schizophrenia, and suicidal behavior. Correlations between family history of psychopathology and delay discounting behavior were small, ranging from ρ = - 0.02 to 0.04. In mixed effects models controlled for sociodemographic factors, family history of psychopathology was not associated with steeper delay discounting behavior. Sociodemographic factors played a larger role in predicting delay discounting behavior than family history of psychopathology. These results do not support the hypothesis that children with greater risk for psychopathology display steeper delay discounting behavior.


Surgical waste audit of 5 total knee arthroplasties.
Operating rooms (ORs) are estimated to generate up to one-third of hospital waste. At the London Health Sciences Centre, prosthetics and implants represent 17% of the institution's ecological footprint. To investigate waste production associated with total knee arthroplasties (TKAs), we performed a surgical waste audit to gauge the environmental impact of this procedure and generate strategies to improve waste management. We conducted a waste audit of 5 primary TKAs performed by a single surgeon in February 2010. Waste was categorized into 6 streams: regular solid waste, recyclable plastics, biohazard waste, laundered linens, sharps and blue sterile wrap. Volume and weight of each stream was quantified. We used Canadian Joint Replacement Registry data (2008-2009) to estimate annual weight and volume totals of waste from all TKAs performed in Canada. The average surgical waste (excluding laundered linens) per TKA was 13.3 kg, of which 8.6 kg (64.5%) was normal solid waste, 2.5 kg (19.2%) was biohazard waste, 1.6 kg (12.1%) was blue sterile wrap, 0.3 kg (2.2%) was recyclables and 0.3 kg (2.2%) was sharps. Plastic wrappers, disposable surgical linens and personal protective equipment contributed considerably to total waste. We estimated that landfill waste from all 47 429 TKAs performed in Canada in 2008-2009 was 407 889 kg by weight and 15 272 m3 by volume. Total knee arthroplasties produce substantial amounts of surgical waste. Environmentally friendly surgical products and waste management strategies may allow ORs to reduce the negative impacts of waste production without compromising patient care. Level IV, case series.


Choroidal thickness changes after a single administration of coffee in healthy subjects.
To investigate the changes in the subfoveal choroidal thickness measured by enhanced depth imaging optical coherence tomography after a single administration of a cup of coffee in healthy subjects. In this prospective study, 62 healthy subjects (study group) who received a cup of 100 mL Turkish coffee (57 mg caffeine/100 mL) and 54 healthy subjects (control group) who received the same amount of water were enrolled. In the study group, the participants underwent enhanced depth imaging optical coherence tomography scanning at baseline, and at 5 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, and 6 hours after coffee drinking. The participants of the control group simultaneously underwent enhanced depth imaging optical coherence tomography scanning. Subfoveal choroidal thickness measurements were performed on both groups at another time. Baseline choroidal thickness was 328 ± 79 μm in the study group and 311 ± 79 μm in the control group (P = 0.381). In the study group, choroidal thickness was significantly lower at 5 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, and 4 hours after coffee drinking when compared with the baseline measurement (P < 0.001, for all); however, there were no significant differences between the measurements at 6 hours and 24 hours after coffee drinking and the baseline measurement (P = 0.113 and P = 0.342, respectively). In the control group, no significant difference was found between each choroidal thickness measurement (P > 0.05, for all). The findings of this study revealed that drinking of a cup of coffee causes a significant decrease in choroidal thickness for at least 4 hours after coffee drinking.


ISL-1 promotes pancreatic islet cell proliferation by forming an ISL-1/Set7/9/PDX-1 complex.
Islet-1 (ISL-1), a LIM-homeodomain transcription factor, has been recently found to be essential for promoting postnatal pancreatic islet proliferation. However, the detailed mechanism has not yet been elucidated. In the present study, we investigated the mechanism by which ISL-1 promotes β-cell proliferation through regulation of CyclinD1 in HIT-T15 and NIT-1 cells, as well in rat islet mass. Our results provide the evidence that ISL-1 promotes adult pancreatic islet β-cell proliferation by activating CyclinD1 transcription through cooperation with Set7/9 and PDX-1 to form an ISL-1/Set7/9/PDX-1 complex. This complex functions in an ISL-1-dependent manner, with Set7/9 functioning not only as a histone methyltransferase, which increases the histone H3K4 tri-methylation of the CyclinD1 promoter region, but also an adaptor to bridge ISL-1 and PDX-1, while PDX-1 functions as a RNA pol II binding modulator. Furthermore, the formation of the ISL-1/Set7/9/PDX-1 complex is positively associated with insulin-like growth factor-1 treatment in NIT and HIT-T15 cells in vitro, while may be negatively correlated with age in vivo.


[Effect of self-hypnosis in patients with pollinosis].
The aim of this study in hypnosis was the exemplary verification of a regulatory intervention in patients with pollinosis. Hypnosis and self-hypnosis are established methods in medicine. 52 patients with pollinosis participated in this clinical study. It lasted over two pollen seasons. Self-hypnosis was learned quite easily. It resulted in a clear yet statistically weak beneficial effect on the subjective assessment of the pollinosis symptoms, on the consumption of drugs and on other objective findings. From a methodological point of view this study might suggest that the classical comparison of experimental groups in clinical research could hide some larger therapeutic effects in individual patients. Therefore, it would be desirable to consider also individual data analysis in all future studies dealing with psychological or psychosomatic mechanisms and in all studies which capture parameters interactive at different levels. The beneficial effect of hypnosis on the swelling of the nasal mucous membrane in a provocation test initiated a subsequent small project on the possible mode of action of hypnosis in this pollinosis study. However, the results were inconclusive.


[Preparation of a standard for antinuclear antibodies].
The authors prepared a laboratory standard of antinuclear antibodies from the serum pool of patients suffering from systemic lupus erythematosis. This standard was tested in respect to normal human serum and an international standard of antinuclear antibodies BRS ANA 66/233. A possibility of quantitative determination of the usefulness of the sera of patients suffering from systemic lupus erythematosis for the preparation of the standard was demonstrated.


Odontogenic cysts. A clinicopathological study.
To determine the relative frequency of OC, and compare it with previous studies. A retrospective review of histopathology archives in the College of Dentistry, King Saud University, Riyadh, Kingdom of Saudi Arabia of the period 1984-2010 was carried out from September 2010 to February 2011. Diagnosis was confirmed according to the World Health Organization histological classification for odontogenic tumors published in 2005. The relevant clinicopathological data were analyzed. A total of 470 cases satisfied the diagnostic criteria as OC. They represented approximately 11% of all pathologic specimens accessioned. Apical radicular cyst (64.3%) was the most frequent OC, followed by dentigerous cyst (25.1%). The overall male to female ratio was 1.40:1. The mean age of patients at diagnosis was 30 years. It peaked at the second to third decade. The mandible was involved in 48.5%, and the maxilla in 43.6% of the cases. The prevalence of OC is similar to those reported in other studies, in which most OC were inflammatory in origin. They peaked at the second to third decade with the posterior mandible and anterior maxilla being the most frequent sites affected. Studies from different regions of KSA are needed to further understand these lesions.


High abundance of virulence gene homologues in marine bacteria.
Marine bacteria can cause harm to single-celled and multicellular eukaryotes. However, relatively little is known about the underlying genetic basis for marine bacterial interactions with higher organisms. We examined whole-genome sequences from a large number of marine bacteria for the prevalence of homologues to virulence genes and pathogenicity islands known from bacteria that are pathogenic to terrestrial animals and plants. As many as 60 out of 119 genomes of marine bacteria, with no known association to infectious disease, harboured genes of virulence-associated types III, IV, V and VI protein secretion systems. Type III secretion was relatively uncommon, while type IV was widespread among alphaproteobacteria (particularly among roseobacters) and type VI was primarily found among gammaproteobacteria. Other examples included homologues of the Yersinia murine toxin and a phage-related 'antifeeding' island. Analysis of the Global Ocean Sampling metagenomic data indicated that virulence genes were present in up to 8% of the planktonic bacteria, with highest values in productive waters. From a marine ecology perspective, expression of these widely distributed genes would indicate that some bacteria infect or even consume live cells, that is, generate a previously unrecognized flow of organic matter and nutrients directly from eukaryotes to bacteria.


Magneto-optical circulator designed for operation in a uniform external magnetic field.
We propose an approach for the design of resonant cavities employed in magnetophotonic crystal (MPC) circulators and isolators. Starting from the analysis of a model circularly symmetric cavity, we show how to obtain a significant splitting of the eigenfrequencies of the two counterrotating cavity modes without introducing subdomains magnetized in opposite directions. Using the multiple-scattering method extended to handle uniaxial gyrotropic materials, we demonstrate numerically an MPC circulator working in a uniform external magnetic field.


Prevalence and determinants of defensive medicine among physicians: a systematic review and meta-analysis.
Defensive medicine, characterized by physicians' inclination toward excessive diagnostic tests and procedures, has emerged as a significant concern in modern healthcare due to its high prevalence and detrimental effects. Despite the growing concerns among healthcare providers, policymakers, and physicians, comprehensive synthesis of the literature on the prevalence and determinants of defensive medicine among physicians has yet been reported. A comprehensive literature search was conducted to identify eligible studies published between 1 January 2000 and 31 December 2022, utilizing six databases (i.e. Web of Science, PubMed, Embase, Scopus, PsycINFO, and Cochrane Library). A meta-analysis was conducted to determine the prevalence and determinants of defensive medicine. Of the 8892 identified articles, 64 eligible studies involving 35.9 thousand physicians across 23 countries were included. The overall pooled prevalence of defense medications was 75.8%. Physicians engaged in both assurance and avoidance behaviors, with the most prevalent subitems being increasing follow-up and avoidance of high-complication treatment protocols. The prevalence of defensive medicine was higher in the African region [88.1%; 95% confidence interval (CI): 80.4%-95.8%] and lower-middle-income countries (89.0%; 95% CI: 78.2%-99.8%). Among the medical specialties, anesthesiologists (92.2%; 95% CI: 89.2%-95.3%) exhibited the highest prevalence. Further, the pooled odds ratios (ORs) of the nine factors at the individual, relational, and organizational levels were calculated, and the influence of previous experience in medical-legal litigation (OR: 1.65; 95% CI: 1.13-2.18) should be considered. The results of this study indicate a high global prevalence of defensive medicine among physicians, underscoring the necessity of implementing targeted interventions to reduce its use, especially in certain regions and specialties. Policymakers should implement measures to improve physicians' medical skills, enhance physician-patient communication, address physicians' medical-legal litigation fears, and reform the medical liability system. Future research should focus on devising and assessing interventions to reduce the use of defensive medicine and to improve the quality of patient care.


How perceived threat increases synchronization in collectively moving animal groups.
Nature is rich with many different examples of the cohesive motion of animals. Previous attempts to model collective motion have primarily focused on group behaviours of identical individuals. In contrast, we put our emphasis on modelling the contributions of different individual-level characteristics within such groups by using stochastic asynchronous updating of individual positions and orientations. Our model predicts that higher updating frequency, which we relate to perceived threat, leads to more synchronized group movement, with speed and nearest-neighbour distributions becoming more uniform. Experiments with three-spined sticklebacks (Gasterosteus aculeatus) that were exposed to different threat levels provide strong empirical support for our predictions. Our results suggest that the behaviour of fish (at different states of agitation) can be explained by a single parameter in our model: the updating frequency. We postulate a mechanism for collective behavioural changes in different environment-induced contexts, and explain our findings with reference to confusion and oddity effects.


Changes in phosphodiesterase activity of human subcutaneous adipose tissue during starvation.
The phosphodiesterase (PDE) activity, the basal rate of lipolysis and the basal cyclic AMP level in adipose tissue were determined in hypogastric and gluteal specimens obtained from 14 obese healthy subjects before and after one week of starvation. During starvation there was a significant increase in both the tissue level of cyclic AMP and the rate of lipolysis, whereas the apparent values of Vmax of the low and high Km forms of PDE decreased significantly-i.e. by about 50 and 30 percent. respectively. The substrate concentration of cyclic AMP at Vmax of the low Km PDE corresponded to the tissue level of the nucleotide. During, but not before, starvation there was a positive correlation between Vmax of the low Km PDE and the cyclic AMP level (r = 0.7-0.8). The metabolism in the tissues from the two fat depots exhibited similar variations during starvation. The findings suggest that the low Km form of PDE is inhibited during starvation. This may be one factor responsible for the starvation-mediated increase in the cyclic AMP levels and the rate of lipolysis in adipose tissue.


Clinical application of neuromuscular electrophysiology in the dog: a review.
A review of the literature concerning the application of electromyography and electroneurography in canine neurology is presented. Measurements of amplitude and duration of motor unit potentials in normal dogs varied largely in the various reports. It was therefore concluded that these measurements are of limited clinical value. The results of motor and sensory nerve conduction studies in normal dogs are summarised. The differences between the methods used are discussed. It is concluded that variations in reported normal values are due mainly to differences in method. The application of electromyography and electroneurography in neuromuscular disorders in the dog is systematically presented, based upon the reported diagnoses. The considerable number of first descriptions of newly-recognised and described neuromuscular diseases appears to be related to the introduction of neuromuscular electrophysiology into veterinary medicine.


Catheter-associated bacteriuria. Failure to reduce attack rates using periodic instillations of a disinfectant into urinary drainage systems.
We assessed the efficacy of periodic instillations of hydrogen peroxide into urinary drainage systems in the prevention of catheter-associated bacteriuria in a prospective and randomized clinical study of 668 patients with indwelling urethral catheters. Bacteriuria was documented in 68 (10%) of the 668 patients after a mean duration of four days of catheterization. There was no difference between the hydrogen peroxide group and the control group in the mean duration of catheterization before the onset of bacteriuria, in the attack rate for bacteriuria, or in the spectrum of etiologic agents recovered. Bag contamination with the same organism responsible for bacteriuria preceded infection in only five (7%) of the 68 patients, three patients using hydrogen peroxide and two in the control group. We conclude that infections arising intraluminally from contamination of the drainage bag are uncommon among catheterized patients and that the periodic instillation of disinfectants into closed sterile drainage systems is not effective in reducing the incidence of catheter-associated bacteriuria.


Increased abundance of frost mRNA during recovery from cold stress is not essential for cold tolerance in adult Drosophila melanogaster.
Frost (Fst) is a candidate gene associated with the response to cold in Drosophila melanogaster because Fst mRNA accumulation increases during recovery from low temperature exposure. We investigated the contribution of Fst expression to chill-coma recovery time, acute cold tolerance and rapid cold hardening (RCH) in adult D. melanogaster by knocking down Fst mRNA expression using GAL4/UAS-mediated RNA interference. In this experiment, four UAS-Fst and one tubulin-GAL4 lines were used. We predicted that if Fst is essential for cold tolerance phenotypes, flies with low Fst mRNA levels should be less cold tolerant than flies with normal levels of cold-induced Fst mRNA. Cold-induced Fst abundance and recovery time from chill-coma were not negatively correlated in male or female flies. Survival of 2 h exposures to sub-zero temperatures in Fst knockdown lines was not lower than that in a control line. Moreover, a low temperature pretreatment increased survival of severe cold exposure in flies regardless of Fst abundance level during recovery from cold stress, suggesting that Fst expression is not essential for RCH. Thus, cold-induced Fst accumulation is not essential for cold tolerance measured as chill-coma recovery time, survival to acute cold stress and RCH response in adult D. melanogaster.


The long-term effects of conventional and atypical antipsychotics in patients with probable Alzheimer's disease.
The authors sought to determine the effects of conventional and atypical antipsychotic use on time to nursing home admission and time to death in a group of outpatients with mild to moderate probable Alzheimer's disease. The authors examined time to nursing home admission and time to death in 957 patients with the diagnosis of probable Alzheimer's disease who had at least one follow-up evaluation (mean follow-up time, 4.3 years [SD=2.7]; range, 0.78-18.0 years) using Cox proportional hazard models adjusted for age, gender, education level, dementia severity, hypertension, diabetes mellitus, heart disease, extrapyramidal signs, depression, psychosis, aggression, agitation, and dementia medication use. A total of 241 patients (25%) were exposed to antipsychotics at some time during follow-up (conventional, N=138; atypical, N=95; both, N=8). Nursing home admission (63% compared with 23%) and death (69% compared with 34%) were more frequent in individuals taking conventional than atypical antipsychotics. In a model that included demographic and cognitive variables, hypertension, diabetes mellitus, heart disease, incident strokes, and extrapyramidal signs, only conventional antipsychotic use was associated with time to nursing home admission. However, the association was no longer significant after adjustment for psychiatric symptoms. Psychosis was strongly associated with nursing home admission and time to death, but neither conventional nor atypical antipsychotics were associated with time to death. The use of antipsychotic medications, both conventional and atypical, was not associated with either time to nursing home admission or time to death after adjustment for relevant covariates. Rather, it was the presence of psychiatric symptoms, including psychosis and agitation, that was linked to increased risk of institutionalization and death after adjustment for exposure to antipsychotics.


The emergence and evolution of the research fronts in HIV/AIDS research.
In this paper, we have identified and analyzed the emergence, structure and dynamics of the paradigmatic research fronts that established the fundamentals of the biomedical knowledge on HIV/AIDS. A search of papers with the identifiers "HIV/AIDS", "Human Immunodeficiency Virus", "HIV-1" and "Acquired Immunodeficiency Syndrome" in the Web of Science (Thomson Reuters), was carried out. A citation network of those papers was constructed. Then, a sub-network of the papers with the highest number of inter-citations (with a minimal in-degree of 28) was selected to perform a combination of network clustering and text mining to identify the paradigmatic research fronts and analyze their dynamics. Thirteen research fronts were identified in this sub-network. The biggest and oldest front is related to the clinical knowledge on the disease in the patient. Nine of the fronts are related to the study of specific molecular structures and mechanisms and two of these fronts are related to the development of drugs. The rest of the fronts are related to the study of the disease at the cellular level. Interestingly, the emergence of these fronts occurred in successive "waves" over the time which suggest a transition in the paradigmatic focus. The emergence and evolution of the biomedical fronts in HIV/AIDS research is explained not just by the partition of the problem in elements and interactions leading to increasingly specialized communities, but also by changes in the technological context of this health problem and the dramatic changes in the epidemiological reality of HIV/AIDS that occurred between 1993 and 1995.


Regulation of glucose production during exercise at 80% of VO2peak in untrained humans.
To determine whether alterations in insulin and/or glucagon secretion play an important role in stimulating glucose production (Ra) during intense but submaximal exercise, we studied six untrained subjects during 30 min of cycling at 80% of peak oxygen uptake on two occasions: once under control conditions and once when alterations in insulin and glucagon secretion were prevented with the use of the pancreatic islet clamp technique. In the latter experiments, glucose was infused during exercise to match glycemia with control levels. Glucose kinetics were measured in both trials using a primed, continuous infusion of [6,6-2H]glucose. In the control trial, glucose Ra rose from 11.9 +/- 0.8 mumol.min-1.kg-1 at rest to 42.5 +/- 4.3 mumol.min-1.kg-1 by the end of exercise. A similar increment was observed in the islet clamp experiments, with endogenous Ra peaking at 37.2 +/- 7.9 mumol.min-1.kg-1. This was true even through glucagon concentration did not change from basal and insulin concentration actually rose (the latter apparently due to a decrease in insulin clearance during intense exercise). Thus neither decrements in insulin or increments in glucagon are apparently required to stimulate glucose Ra under the present conditions. Because epinephrine levels rose only slightly, it appears that either neurally released norepinephrine or some other, as yet unidentified, factor is responsible for stimulating glucose Ra during intense but submaximal exercise.


Method in limbo? Theoretical and empirical considerations in using thematic analysis by veterinary and One Health researchers.
This article spans a number of theoretical, empirical and practice junctures at the intersection of human and animal medicine and the social sciences. We discuss the way thematic analysis, a qualitative method borrowed from the social sciences, is being increasingly used by veterinary and One Health researchers to investigate a range of complex issues. By considering theoretical aspects of thematic analysis, we expand our discussion to question whether this tool, as well as other social science methods, is currently being used appropriately by veterinary and human health researchers. We suggest that additional engagement with social science theory would enrich research practices and improve findings. We argue that considerations of 'big theory' - ontological and epistemological positionings of the researcher - and 'small(er)' theory, the specific social theory in which research is situated, are both necessary. Our point of departure is that scientific discourse is not merely construction or ideology but a unique and continuing arena of debate, in part at least because of the elevation of self-criticism to a central tenet of its practice. We argue for further engagement with the core ideas and concepts outlined above and discuss them in what follows. In particular, and by way of focusing the point, we suggest that for veterinary, One Health, and human medical researchers to use thematic analysis to its maximum potential they should be encouraged to engage with both broader socio-economic theories and with questions of ontology and epistemology.


Finger tip and nail bed injuries.
Damage to any of the anatomic structures of the finger tip can result in a change in use of the hand, even making some tasks impossible. Prevention is naturally most important; however, when an injury occurs, anatomic restoration should be the goal. Treatment should be the most direct and simple to reach the optimal structural and functional result. Caveats of treatment are: (1) save nails; (2) reapproximate nail matrix lacerations; (3) use wound contraction and epithelialization to advantage; (4) restore pulp when necessary with volar innervated flaps from the same finger; (5) reduce fracture angulation and displacement; (6) use skin grafts when subcutaneous tissue is sufficient; and (7) replace small noncrushed skin-pulp amputations and traumatic flaps.


The pain paradox: borderline personality disorder features, self-harm history, and the experience of pain.
Individuals with borderline personality disorder (BPD), compared to controls, report a relative absence of acute pain. In contrast, BPD is overrepresented among chronic pain patients, suggesting they experience a relative excess of chronic pain. To date, this "pain paradox" has been only partially explored; no study has examined both acute and chronic pain in the same sample. In addition, previous research has not fully examined the effect of nonsuicidal self-injury (NSSI) on either acute or chronic pain experience in BPD. Undergraduates (N = 206), oversampled for those high in BPD features, completed a Cold Pressor Task (CPT), rating their pain every 15 s over a maximum of 4 min. Following the CPT, participants completed measures of BPD features, NSSI history, past-year pain, and perceived pain tolerance. Results did not support the expected negative association between BPD features and acute pain. Multilevel modeling revealed an interaction of BPD features and NSSI history on CPT pain ratings: Among individuals in the no-NSSI group, BPD features were associated with greater acute pain. Among individuals in the NSSI group, BPD features were not significantly associated with acute pain. Results for past-year pain indicated that BPD features were associated with greater past-year pain regardless of NSSI history. This finding, coupled with the difference in the association of BPD features and acute pain between the NSSI and no-NSSI groups provides tentative evidence that the combination of BPD features and NSSI history, among nonclinical samples, is linked to a pain paradox.


Cortico-basal white matter alterations occurring in Parkinson's disease.
Magnetic resonance imaging studies typically use standard anatomical atlases for identification and analyses of (patho-)physiological effects on specific brain areas; these atlases often fail to incorporate neuroanatomical alterations that may occur with both age and disease. The present study utilizes Parkinson's disease and age-specific anatomical atlases of the subthalamic nucleus for diffusion tractography, assessing tracts that run between the subthalamic nucleus and a-priori defined cortical areas known to be affected by Parkinson's disease. The results show that the strength of white matter fiber tracts appear to remain structurally unaffected by disease. Contrary to that, Fractional Anisotropy values were shown to decrease in Parkinson's disease patients for connections between the subthalamic nucleus and the pars opercularis of the inferior frontal gyrus, anterior cingulate cortex, the dorsolateral prefrontal cortex and the pre-supplementary motor, collectively involved in preparatory motor control, decision making and task monitoring. While the biological underpinnings of fractional anisotropy alterations remain elusive, they may nonetheless be used as an index of Parkinson's disease. Moreover, we find that failing to account for structural changes occurring in the subthalamic nucleus with age and disease reduce the accuracy and influence the results of tractography, highlighting the importance of using appropriate atlases for tractography.


General management of depressive illness. Psychosocial issues.
This is a complex field of inquiry in which there has been research along several lines. There are as yet however, few generalizations that are widely accepted as applying to human depressive illness. Animal models that have been extensively studied are separation, learned helplessness, and stress. However, their relation to human depression is not conclusively established. Human studies suffer from greater methodological problems than animal studies. One of the few firm findings is that there is an excess of major life events prior to the onset of depressive illness, but the effect is not highly specific, and there is no consensus on what aspect of life events is important for the production of depression. With regard to vulnerability factors, there are contradictory findings. Surprisingly for clinicians in day-to-day practice, social support and self-esteem also lack conclusive evidence identifying them specifically as causing clinical depressive illness. It is not at present possible to draw definite conclusions in this field. There are, however, promising lines of inquiry which will require increasing complexity and sophistication of method in the future.


[Transformation of inpatient treatment by the introduction of Diagnosis-Related Groups (DRG)--the positive effects of health policy research results].
Empirical researches about the results of health policy are rare. Almost, these researches take a look to very special aspects. Researches about the results of health policy is not very often demanded from the policy. In contrast to most legislation, the implementation of "diagnosis related groups" (DRG) will be realised in several steps. In these steps, there are several possibilities to correct the implementation if something is going wrong. With this background, the policy demands the researches about the results of the implementation of the DRG. Now, we are standing at the beginning of the process of the DRG implementation. It is not yet the time to provide assured empirical results about all the consequences of DRG. In spite of this, we found first hints: the implementation of DRG increases the work stress of nurses. As a result the quality of nursing could decrease.


The role of osteopontin in the development of albuminuria.
Several gene array studies have suggested that osteopontin (Opn) expression strongly correlates with albuminuria and glomerular disease. Urinary Opn concentration and kidney Opn immunoreactivity were found to be increased in patients with steroid-sensitive nephrotic syndrome. In addition, renal Opn mRNA was increased in the Ins2(Akita) mouse model of type 1 diabetic nephropathy, in the LPS-induced albuminuria model, and in glomeruli of puromycin aminonucleotide-induced nephrotic rats. Opn knockout mice did not develop albuminuria in response to LPS injection, and Opn knockout mice were protected from diabetes-induced albuminuria and mesangial expansion. In the glomerulus, Opn immunostaining was increased specifically in podocytes. Treatment of podocytes with recombinant Opn activated the NF-kappaB pathway, increased expression of urokinase plasminogen activator and matrix metalloproteinases 2 and 9, and increased podocyte motility. Taken together, these results indicate that Opn plays an important role in the development of albuminuria, possibly by modulating podocyte signaling and motility.


Perioperative risk. Review of two guidelines for assessing older adults. American College of Cardiology and American Heart Association.
Elective in-patient surgery is a common occurrence among older persons and primary care physicians are routinely called on to provide preoperative assessment and perioperative risk management of these patients. Older patients undergoing noncardiac surgery may be at increased risk for cardiac or cardiovascular complications, thus perioperative assessment of risk in this population is prudent. Although the range of possible screens and diagnostic tools can make this task unwieldly, the clinical practice guidelines make it more manageable. Two guidelines in particular--one published jointly by the American College of Cardiology and American Heart Association, the other by the American College of Physicians--are particularly suited to perioperative assessment and risk management.


Simulation of a Novel Schedule for Intensivist Staffing to Improve Continuity of Patient Care and Reduce Physician Burnout.
Despite widespread adoption of in-house call for ICU attendings, there is a paucity of research on optimal scheduling of intensivists to provide continuous on-site coverage. Overnight call duties have traditionally been added onto 7 days of continuous daytime clinical service. We designed an alternative ICU staffing model to increase continuity of attending physician care for patients while also decreasing interruptions to attendings' nonclinical weeks. Computer-based simulation of a 1-year schedule. A simulated ICU divided into two daytime teams each covered by a different attending and both covered by one overnight on-call attending. Simulated patients were randomly admitted on different service days to assess continuity of care. A "shared service schedule" was compared to a standard "7 days on schedule." For the 7 days on schedule, an attending covered a team for 7 consecutive days and off-service attendings cross-covered each night. For the shared schedule, four attendings shared the majority of daytime and nighttime service for two teams over 2 weeks, with recovery periods built into the scheduled service time. Continuity of care as measured by the Continuity of Attending Physician Index increased by 9% with the shared schedule. Annually, the shared service schedule was predicted to increase free weekends by 3.4 full weekends and 1.3 weekends with either Saturday or Sunday off. Full weeks without clinical obligations increased by 4 weeks. Mean time between clinical obligations increased by 5.8 days. A shared service schedule is predicted to improve continuity of care while increasing free weekends and continuity of uninterrupted nonclinical weeks for attendings. Computer-based simulation allows assessment of benefits and tradeoffs of the alternative schedule without disturbing existing clinical systems.


A CASE OF ADRENAL ADENOMATOID TUMOR DIAGNOSED BY IMMUNOHISTOCHEMICAL EVALUATION.
An adenomatoid tumor is a benign tumor of mesothelial derivation, typically found in the genital track. However, though extremely rare, an adenomatoid tumor can be found in the adrenal gland, making it difficult to clinically and radiologically differentiate it from an adrenocortical tumor or a pheochromocytoma prior to surgery. We encountered a-52-year old man with an adenomatoid tumor in the adrenal gland, who presented with an incidentally discovered left adrenal mass revealed by PET-CT from his regular health examinations. He had been diagnosed with paroxysmal hypertension two years before and was being treated with a hypolipidemic agent. Abdominal computed tomography revealed a left adrenal mass measuring 25 × 15 mm, and the findings were different from the typical adrenocortical adenoma or pheochromocytoma. Although laboratory examinations of his blood samples indicated normal adrenal function, 24-hour urine specimens revealed high levels of 17-OHCS, 17-KS, and catecholamine. Both 131I-MIBG scintigraphy and phentolamine tests showed negative findings. The patient underwent a laparoscopic left adrenalectomy. The cut surface of the left adrenal gland weighing 21 g contained a white, solid mass measuring 25 × 15 × 20 mm within the adrenocortical tissue. Histologically, the tumor was composed of small tubules lined by eosinophilic tumor cells. The tumor cells were immunohistochemically positive for cytokeratins and calretinin, but negative for steroidogenic factor-1. Therefore, based on these findings, we diagnosed this tumor as an adrenal adenomatoid tumor. Histopathologically, the adrenal adenomatoid tumor may be difficult to distinguish from an adrenocortical adenoma, carcinoma, lymphangioma, hemangioma, angiosarcoma, or metastatic adenocarcinoma. Under these conditions, immunohistochemical examination is useful for definite diagnosis.


Use of covered chimney stents for pararenal aortic pathologies is safe and feasible with excellent patency and low incidence of endoleaks.
To present the clinical experience of consecutive series with use of balloon-expandable and self-expanding chimney endografts (balloon-expandable covered stent group [BECS] vs self-expanding covered stent group [SECS]) in the endovascular treatment of challenging aortic pathologies requiring renal and/or visceral revascularization. Between January 2009 and May 2011, data for 37 high-risk patients from one center and 35 patients from another institution, with pararenal aortic pathologies treated by the chimney endovascular technique, were prospectively collected. The chimney-graft technique is based on the deployment of a covered or bare-metal stent parallel to the aortic endograft, thereby creating a conduit that runs outside the aortic main endograft, and has been proposed to ensure secure proximal fixation extending the sealing zones. Forty-six consecutive target vessels (43 renal arteries and 3 superior mesenteric arteries) were revascularized by the Advanta (Atrium, Hudson, NH) BECS (1.2 chimneys/patient); in contrast, 81 consecutive target vessels (64 renal arteries, 11 superior mesenteric arteries, and 6 celiac trunks) were revascularized by the Viabahn (Gore, Flagstaff, Ariz) SECS (2.3 chimneys/patient). The success rate for target vessel preservation was 97.8% for the BECS group and 100% for the SECS group in the entire follow up. There was one symptomatic left renal artery occlusion of the BECS group treated by open thrombectomy of the left renal artery and placement of 8-mm Dacron (BBraun, Aesculap AG, Tuttlingen, Germany) iliorenal bypass. Additionally, one patient underwent repeat balloon angioplasty with a 5-mm balloon due to high-grade in-stent stenosis of a 6 × 59 Advanta stent graft 12 months postoperatively. Overall, one perioperative (and not present in the computed tomography angiography at discharge) type Ia endoleak was detected in the BECS group. In contrast, five perioperative type Ia endoleaks were present in the SECS group; however, only one of them was persistent in the radiological imaging and was treated by proximal extension of a 5-mm cuff, 1 year postoperatively, due to continuous aneurismal sac increase. No patient of any subgroup developed postoperative persistent renal insufficiency with need of hemodialysis. Thirty-day and during the follow-up procedure-related mortality was 0% for both BECS and SECS groups. In summary, midterm results of use of covered chimney stents for pararenal aortic pathologies show safety and feasibility with excellent patency and low incidence of endoleaks.


Long-Term Clinical Outcome After Alcohol Septal Ablation and Its Periprocedural Predictive Factors in Japan - A Retrospective Observational Study.
Evidence is limited regarding long-term clinical outcomes after alcohol septal ablation (ASA) for patients with hypertrophic obstructive cardiomyopathy and its periprocedural predictive factors in Japan.Methods and Results: This retrospective observational study included 44 patients who underwent ASA between 1998 and 2022 in a single center. We evaluated the periprocedural change in variables and long-term clinical outcomes after the procedure. The primary outcome was a composite of cardiovascular death or hospitalization for heart failure. The secondary outcome was all-cause death. Using multivariable Poisson regression with robust error variance, we predicted underlying periprocedural factors related to primary outcome development. ASA decreased the median pressure gradient at the left ventricular outflow tract from 88 to 33 mmHg and reduced moderate or severe mitral regurgitation (MR), present in 53% of patients before ASA, to 16%. Over a median 6-year follow-up, the cumulative incidence of the primary outcome at 5 and 10 years was 16.5% and 25.6%, respectively. After multivariable analysis, moderate or severe MR after ASA was significantly associated with the primary outcome (relative risk 8.78; 95% confidence interval 1.34-57.3; P=0.024). All-cause mortality after ASA was 15.1% and 28.9% at 5 and 10 years, respectively. This study presents long-term clinical outcomes after ASA in Japan. Moderate or severe MR after ASA was significantly associated with the composite of cardiovascular death or hospitalization for heart failure.


FDA Reported Use of Patient Experience Data in 2018 Drug Approvals.
"Patient experience data" (PED) refers to the systematic collection of meaningful data relating to the experiences, perspectives, needs, and priorities of patients. PED can augment traditional clinical trial data in the FDA's review of product applications. Section 3001 of the 2016 21st Century Cures Act requires the FDA to make a public statement about the PED considered in the approval of a drug application. Here, we present one of the first assessments of PED consideration during drug application approval, as reported by the FDA under Sec. 3001 of the Cures Act. FDA reported use of PED in the Review Documentation of the 59 new molecular entities (NMEs) approved in 2018 were collected, indexed, and cross-referenced against information regarding FDA review and product regulatory designation. The data reported in the PED tables were quantitatively described and visualized. Of the 59 approved NMEs in 2018, 48 include a table that summarized whether PED was or was not used during the FDA drug review. Thirty-four of those 48 approvals (70.8%) reported using PED in the drug review. Patient-reported outcomes (PROs) represented the most significant source of PED and were used in 60.4% of approved drug reviews. Additional findings, including PED use by FDA review division and by FDA regulatory designation, are described. This assessment is a first step to better understanding how FDA considers PED in regulatory decision making. This analysis should help develop a baseline regarding FDA use of PED and may inform decisions to ensure patients' experiences are adequately heard in future drug development.


Parentage exclusion of close relatives in haplodiploid species.
Parentage exclusion probability is usually calculated to evaluate the informativeness of a set of markers for, and the statistical power of, a parentage analysis. Equations for parentage exclusion probability have been derived in various scenarios such as paternity exclusion when maternity is known or unknown or when candidate males are unrelated or loosely related (being from the same subpopulation) to the father. All previous work assumes a diploid species. Although marker-based parentage analyses have been conducted in haploidiploid species (such as ants, bees and wasps) for diploid offspring at the individual level or haploid offspring at the class level, rigorously derived formulations of parentage exclusion probability for haploid offspring at the individual level are lacking, which prevents the precise evaluation of the informativeness for and the statistical power of a parentage analysis. In this study we derive equations for the exclusion probability of maternity of a haploid male when multiple mother candidates (workers or queens) are unrelated or fullsibs to the mother. The usefulness of the equations is exemplified by numerical examples, and the results are discussed in the context of the study of worker reproductivity in eusocial haplodiploid species. The results are especially valuable for an optimal experimental design in determining sampling intensities (e.g. number of markers and number of individuals) to achieve satisfactory statistical power of a parentage analysis in investigating workers' reproductivity in eusocial haplodiploid species.