Genome scans for blood pressure and hypertension: the National Heart, Lung, and Blood Institute Family Heart Study.
This study presents genome scans for hypertension and blood pressures from 2959 individuals in 500 white families from the National Heart, Lung, and Blood Institute Family Heart Study. Genome scans were performed with different methods of handling the 27% of individuals taking antihypertensive medications. Variance components LOD scores were estimated by assigning medicated hypertensive individuals (1) to have a blood pressure of 140/90; (2) to be missing; and (3) to have a randomly assigned systolic blood pressure between 140 and 160 (N[150,5] distribution) and diastolic blood pressure between 90 and 100 mm Hg (N[95,2.5] distribution). There were 5 regions with heterogeneity LOD scores > or =2.0 for hypertension (unadjusted for multiple models): 2.8 on chromosome 1 (192 cM), 2.6 on chromosome 7 (58 cM), 2.0 on chromosome 7 (127 cM), 2.4 on chromosome 12 (83 cM), and 2.4 on chromosome 15 (103 cM). Diastolic blood pressure had no LOD scores > or =2.0. Only chromosome 6 showed linkage for systolic blood pressure, with a LOD score of 3.3 at 88.7 cM from the initial randomization. Multiple randomizations of medicated subjects' systolic blood pressures yielded a mean LOD score of 2.8+/-0.4, whereas setting medicated systolic blood pressures to 140 mm Hg yielded a LOD score of 3.3. Excluding the medicated individuals or using their treated blood pressures reduced the LOD scores to 0.8 and 1.3, respectively, indicating the importance of including the extremes of quantitative trait distributions in linkage analyses. These results overlap other published scans, particularly regions on chromosomes 1 and 6, which have been implicated in familial combined hyperlipidemia.


Genetic determinants of major blood lipids in Pakistanis compared with Europeans.
Evidence is sparse about the genetic determinants of major lipids in Pakistanis. Variants (n=45 000) across 2000 genes were assessed in 3200 Pakistanis and compared with 2450 Germans using the same gene array and similar lipid assays. We also did a meta-analysis of selected lipid-related variants in Europeans. Pakistani genetic architecture was distinct from that of several ethnic groups represented in international reference samples. Forty-one variants at 14 loci were significantly associated with levels of HDL-C, triglyceride, or LDL-C. The most significant lipid-related variants identified among Pakistanis corresponded to genes previously shown to be relevant to Europeans, such as CETP associated with HDL-C levels (rs711752; P<10(-13)), APOA5/ZNF259 (rs651821; P<10(-13)) and GCKR (rs1260326; P<10(-13)) with triglyceride levels; and CELSR2 variants with LDL-C levels (rs646776; P<10(-9)). For Pakistanis, these 41 variants explained 6.2%, 7.1%, and 0.9% of the variation in HDL-C, triglyceride, and LDL-C, respectively. Compared with Europeans, the allele frequency of rs662799 in APOA5 among Pakistanis was higher and its impact on triglyceride concentration was greater (P-value for difference <10(-4)). Several lipid-related genetic variants are common to Pakistanis and Europeans, though they explain only a modest proportion of population variation in lipid concentration. Allelic frequencies and effect sizes of lipid-related variants can differ between Pakistanis and Europeans.


Accuracy of two dental and one skeletal age estimation methods in 6-16 year old Gujarati children.
Age estimation is of immense importance not only for personal identification but also for treatment planning in medicine and dentistry. Chronologic age conveys only a rough approximation of the maturational status of a person, hence dental and skeletal ages have been explored as maturity indicators since decades. The tooth maturation provides a valuable indicator of dental age and serves as a better index of the maturation of a child as compared to other maturity indicators. To test the applicability of Demirjian's and Willem's dental age assessment methods as well as Greulich and Pyle skeletal age assessment method in children residing in Gandhinagar district. The study consisted of randomly selected 180 subjects (90 males and 90 females) ranging from 6 to 16 years age and residing in Gandhinagar district. Dental age estimation was performed from radiovisuograph (RVG) images of mandibular teeth of left quadrant by both Demirjian's and Willem's methods. Skeletal age estimation was done from right hand wrist radiograph by Greulich and Pyle method. The differences between the chronological age and the estimated dental and skeletal ages were statistically tested using paired 't' test. The correlation between chronological age, dental and skeletal age estimation methods was confirmed statistically by Pearson's correlation. The reproducibility of the estimations was statistically tested using the Pearson's Chi-square test. Amongst the age estimation methods used in this study, the Willem's dental age estimation method proved to be the most accurate and consistent. Although various age estimation methods do exist, the results are varied in different populations due to ethnic differences. However, till new tables are formulated, the Willem's method (Modified Demirjian method) can be accurately applied to estimate chronological age for the population residing in Gandhinagar district.


The microsphere method facilitates statistical assessment of regional blood flow.
When microspheres are injected into the circulation, they are trapped in the arteriolar or capillary system within various organs. It has been confirmed in animal experiments that the number of microspheres in a myocardial sample approximately follows a Poisson distribution, under adequate experimental conditions. On the basis of this result, we arrived at the following hypothesis: When regional blood flow is measured under a steady state by the reference sample method, the 95% relative error can be approximated by +/- 196 square root 1/v + 1/w, where v and w represent the number of microspheres in blood sample and myocardial sample, respectively. The equation is valid if v and w are greater than 400 and 49, respectively. We obtained an expression of the relation among the percent of increase or decrease in regional blood flow being verified, the probability of increase or decrease, as a statistically significant variation and the number of microspheres in a myocardial sample. An investigator can work out an approximate experimental design using this expression. For instance, when the increase in regional blood flow required for verification is expected to be 20% and he wants this increase to be verified by 90%-probability and as a statistically significant increase, he can predict from this expression that the number of microspheres in a myocardial sample should be 472 and 567 before and after the experimental intervention on the coronary circulation, respectively. The expression is useful as index for experiments involving use of the microsphere method.


Prognostic factors in canine acute leukaemias: a retrospective study.
Canine acute leukaemias (ALs) have a poor prognosis, with reported survival times (ST) of only a few weeks or months. Also, clinical studies assessing prognostic factors are lacking. This study aims to retrospectively assess variables that predict ST in dogs with AL, and to identify correlations between outcome and therapeutic protocols. Diagnosis and sub-classification into AL subtypes was made based on haematological findings, morphological assessment and flow cytometric immunophenotyping. Clinical-pathological features of AL subtypes at presentation concurred with those described in the literature. A normal neutrophil count at presentation significantly prolonged ST (P = 0.027). Additionally, there was a trend for anaemic dogs to have shorter survival compared with those without anaemia, and the incorporation of cytosine in the chemotherapy protocol produced a moderate but not significant increase in median ST for dogs with AL. Further prospective studies with standardized treatments are needed to confirm and improve our results.


Omega-3 fatty acids reduce lipopolysaccharide-induced abnormalities in expression of connexin-40 in aorta of hereditary hypertriglyceridemic rats.
Omega-3 fatty acids (omega3FA) are known to reduce hypertriglyceridemia- and inflammation-induced vascular wall diseases. However, mechanisms of their effects are not completely clear. We examined, whether 10-day omega3FA diet can reduce bacterial lipopolysaccharide-induced changes in expression of gap junction protein connexin40 (Cx40) in the aorta of hereditary hypertriglyceridemic (hHTG) rats. After administration of a single dose of lipopolysaccharide (LPS, 1 mg/kg, i.p.) to adult hHTG rats, animals were fed with omega3FA diet (30 mg/kg/day) for 10 days. LPS decreased Cx40 expression that was associated with reduced acetylcholine-induced relaxation of aorta. Omega3FA administration to LPS rats had partial anti-inflammatory effects, associated with increased Cx40 expression and improved endothelium dependent relaxation of the aorta. Our results suggest that 10-day omega3FA diet could protect endothelium-dependent relaxation of the aorta of hHTG rats against LPS-induced damage through the modulation of endothelial Cx40 expression.


Paratuberculosis in dairy goat flocks from southern Spain: risk factors associated with seroprevalence.
Paratuberculosis (PTB) is a chronic, enteric wasting disease of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP), with a worldwide distribution. Andalusia, located in southern Spain, is one of the European regions with the highest goat census and the highest milk production; however, current data on the prevalence of MAP in this species are not available. A cross-sectional study was performed to determine the seroprevalence and risk factors associated with PTB in dairy goat flocks from southern Spain. A total of 3312 serum samples were collected from 48 flocks located in three different geographical areas. Health and productive parameters were surveyed during the visit to the herds. A total of 511 goats were seropositive, with overall true seroprevalence of 22.54 per cent (95 per cent confidence interval (CI95) 21.12-23.97). Of the goat herds, 87.50 per cent (CI9578.14-96.98) were seropositive. The intraherd seroprevalence was 25.43±31.71, distributed as follows: 22 flocks with a seroprevalence under 10 per cent; 18 flocks between 10 per cent and 50 per cent; and eight flocks with a frequency over 50 per cent. Multivariate logistic regression showed significant association between PTB seropositivity and the following variables: intensive production system, lack of management by batches, inappropriate ventilationandseropositivity tocaprinearthritisencephalitisvirus (CAEV). The results indicate a widespread PTB infection in goat herds in southern Spain. Thus, control programmes must include management and sanitary measures to reduce the prevalence. Further experimental studies are necessary to determine the influence of CAEV-PTB coinfection on immune status.


Ancient steroids establish the Ediacaran fossil Dickinsonia as one of the earliest animals.
The enigmatic Ediacara biota (571 million to 541 million years ago) represents the first macroscopic complex organisms in the geological record and may hold the key to our understanding of the origin of animals. Ediacaran macrofossils are as "strange as life on another planet" and have evaded taxonomic classification, with interpretations ranging from marine animals or giant single-celled protists to terrestrial lichens. Here, we show that lipid biomarkers extracted from organically preserved Ediacaran macrofossils unambiguously clarify their phylogeny. Dickinsonia and its relatives solely produced cholesteroids, a hallmark of animals. Our results make these iconic members of the Ediacara biota the oldest confirmed macroscopic animals in the rock record, indicating that the appearance of the Ediacara biota was indeed a prelude to the Cambrian explosion of animal life.


Tissue accumulation and urinary excretion of chromium in rats fed diets containing graded levels of chromium chloride or chromium picolinate.
To attempt a risk assessment of the excess intake of trivalent chromium (Cr), tissue Cr accumulation and urinary Cr excretion were examined in weanling rats fed experimental diets containing graded levels of Cr chloride (CrCl3) or Cr picolinate (CrPic). Thirty-six male weanling 4-weeks-old Wistar rats were divided into six groups and fed a casein-based semi-purified diet (Cr content: <0.02 microg/g) supplemented with 1, 10, or 100 microg Cr/g as CrCl3 or CrPic for 28 days. Among the experimental groups, no significant difference was observed in body weight; however, supplementation of 100 microg Cr/g to the diets caused a significant low liver weight irrespective of the chemical species of Cr. Activities of serum aspartate aminotransferase and alanine aminotransferase were significantly elevated in rats given CrPic at 100 microg Cr/g. In the liver, kidney and femur, Cr accumulation increased with elevation of the dietary Cr level. No influence of the difference in the chemical species of supplemented Cr was observed in the liver and kidney, but CrCl3 caused significantly higher Cr accumulation than CrPic in the femur of rats given 100 microg Cr/g. Daily urinary Cr excretion elevated with the increase of the dietary Cr level. Rats given CrPic showed significantly higher daily urinary Cr excretion than those given CrCl3, particularly at a dietary Cr level of 100 microg/g. The rate of urinary Cr excretion in rats given CrPic was constant, irrespective of the dietary Cr level, but that of rats given CrCl3 fell with the increase of the dietary Cr level. These results indicate that the lowest adverse effect level of dietary Cr is less than 100 microg/g, irrespective of the chemical species of Cr.


Antibacterial and antifungal activities of andrachne cordifolia muell.
The crude methanolic extract of Andrachne cordifolia Muell. (Euphorbiaceae) and its various fractions in different solvent systems (chloroform, ethyl acetate and n-butanol) were screened for antibacterial and antifungal activities. Crude extract and subsequent fractions demonstrated moderate to excellent antibacterial activities against the tested pathogens. Highest antibacterial activity was displayed by both chloroform and ethyl acetate fractions (100%) followed by the crude extract (68%) against Salmonella typhi. Similarly, crude extract and its subsequent fractions showed mild to excellent activities in antifungal bioassay with maximum (76%) antifungal activity against Microsporum canis by the chloroform fraction followed by the crude extract (65%).


Comparative efficacies of amphotericin B lipid complex and amphotericin B deoxycholate suspension against murine blastomycosis.
Amphotericin B as a lipid complex and as a deoxycholate suspension (Fungizone) was tested against murine blastomycosis. All doses of each form prolonged survival (P less than 0.05 to 0.001). Fungizone was more effective than lipid complex at doses of 0.8 mg/kg of body weight. However, lipid complex at 12.8 mg/kg was not toxic and superior in efficacy (P less than 0.001) to 2.0 mg of Fungizone per kg (a toxic dose), and it cleared all animals of infection. Lipid complex is an effective therapy for murine blastomycosis.


The unknown burden and cost of celiac disease in the U.S.
Celiac disease is an autoimmune disease that results from exposure to gluten in genetically susceptible individuals and leads to a range of gastrointestinal and extraintestinal symptoms. Areas covered: In order to evaluate the literature with respect to burden associated with celiac disease in the U.S. and identify any knowledge gaps, we performed a literature review of journal articles published between 2000-2016. We note that celiac disease is a prevalent condition associated with a significant burden of disease through its impact on morbidity, quality of life, as well as through increased costs associated with its diagnosis and management. At the same time, knowledge gaps exist in our understanding of the precise epidemiologic burden in the U.S.; the trade-offs between burden and benefit of a gluten-free diet; and better estimation of the costs of diagnosis, treatment and management.Expert commentary: Additional research is necessary to better understand these gaps to be able to reduce burden of celiac disease, particularly the impact on health-related quality of life and the costs associated with inaccurate or delayed diagnoses and insufficient treatment of disease.


TNFAIP3 rs2230926 polymorphisms in rheumatoid arthritis of southern Chinese Han population: a case-control study.
Polymorphism of tumor necrosis factor alpha-induced protein 3 (TNFAIP3) has been be related to various auto-immune diseases. Based on previous studies that the single nucleotide polymorphism (SNP) of rs2230926 was association with rheumatoid arthritis (RA) of Japanese, Caucasian population and the northern Chinese Han population, we tested the alleles and geno-type frequencies of rs2230926 in TNFAIP3 to investigate whether rs2230926 is susceptible to RA of southern Chinese Han population. In our case-control association study, 207 RA patients fulfilling the American College of Rheumatology (ACR) 1987 criteria were compared with 199 unrelated healthy subjects. After testing the alleles and genotype frequencies of rs2230926, the airwise linkage disequilibrium (LD) was computed and odd ration (OR) and 95% confidence intervals (95% CI) were used for evaluating the susceptibility to RA. The SNP of rs2230926 of the cases and control subjects were conformed to the Hardy-Weinberg equilibrium (P = 0.02257). The significantly statistical differences in alleles of T, G were founded in the cases and controls (P = 0.0027, OR 0.417, 95% CI 0.232-0.749); the genetic types of rs2230926 were associated with a susceptibility to RA, with OR 0.375 (95% CI 0.198-0.707, P = 0.0018). In the present study, our results indicated that the genetic polymorphism of rs2230926 in TNFAIP3 may be a susceptible factor conferring risk for RA in southern Chinese Han population.


Myelinated, synapsing cultures of murine spinal cord--validation as an in vitro model of the central nervous system.
Research in central nervous system (CNS) biology and pathology requires in vitro models, which, to recapitulate the CNS in vivo, must have extensive myelin and synapse formation under serum-free (defined) conditions. However, finding such a model has proven difficult. The technique described here produces dense cultures of myelinated axons, with abundant synapses and nodes of Ranvier, that are suitable for both morphological and biochemical analysis. Cellular and molecular events were easily visualised using conventional microscopy. Ultrastructurally, myelin sheaths were of the appropriate thickness relative to axonal diameter (G-ratio). Production of myelinated axons in these cultures was consistent and repeatable, as shown by statistical analysis of multiple experimental repeats. Myelinated axons were so abundant that from one litter of embryonic mice, myelin was produced in amounts sufficient for bulk biochemical analysis. This culture method was assessed for its ability to generate an in vitro model of the CNS that could be used for both neurobiological and neuropathological research. Myelin protein kinetics were investigated using a myelin fraction isolated from the cultures. This fraction was found to be superior, quantitatively and qualitatively, to the fraction recovered from standard cultures of dissociated oligodendrocytes, or from brain slices. The model was also used to investigate the roles of specific molecules in the pathogenesis of inflammatory CNS diseases. Using the defined conditions offered by this culture system, dose-specific, inhibitory effects of inflammatory cytokines on myelin formation were demonstrated, unequivocally. The method is technically quick, easy and reliable, and should have wide application to CNS research.


Operative illustrations of the Osborne's ligament.
The cubital tunnel syndrome is widely considered as the second most frequent compression neuropathy in the upper extremities although the existence of a compressive cause has not been determined conclusively. As far as we know, operational photography of compression of the ulnar nerve at the elbow is almost never found in the literature. In this paper, operational and pathological photographs of the Osborne's ligament as a cause of ulnar entrapment neuropathy at the elbow are presented. There is still an ambiguity as to whether compressive or tractional etiology or both of these factors may occur progressively to be a factor in the development of neuropathy. This report may be considered as concrete evidence for the compressive etiology for ulnar neuropathies.


MRI findings in the lumbar spines of asymptomatic, adolescent, elite tennis players.
To describe magnetic resonance imaging (MRI) findings in the lumbar spine in asymptomatic elite adolescent tennis players, to serve as the baseline for a future prospective longitudinal cohort study. Observational study. Institutional, national tennis centre. 33 asymptomatic elite adolescent tennis players, mean (SD) age, 17.3 (1.7) years (18 male, 15 female). Sagittal T1, T2, STIR, and axial T2 weighted MRI images were reviewed for the presence of abnormalities by two radiologists in consensus. Abnormalities included disc degeneration, disc herniation, pars lesions (fracture or stress reaction), and facet joint arthropathy. Five players (15.2%) had a normal MRI examination and 28 (84.8%) had an abnormal examination. Nine players showed pars lesions (10 lesions; one at two levels) predominately at the L5 level (9/10, L5; 1/10, L4). Three of the 10 lesions were complete fractures; two showed grade 1 and one grade 2 spondylolisthesis, both of which resulted in moderate narrowing of the L5 exit foramen. There were two acute and five chronic stress reactions of the pars. Twenty three patients showed signs of early facet arthropathy occurring at L5/S1 (15/29 joints) and L4/5 (12/29 joints). These were classified as mild degeneration (20/29) and moderate degeneration (9/29), with 20/29 showing sclerosis and 24/29 showing hypertrophy of the facet joint. Synovial cysts were identified in 14 of the 29 joints. Thirteen players showed disc desiccation and disc bulging (mild in 13; moderate in two) most often at L4/5 and L5/S1 levels (12 of 15 discs). Abnormalities were frequent, predominately in the lower lumbar spine, almost exclusively at L4/5 and L5/S1 levels. Pars injuries and facet joint arthroses were relatively common.


Microglial MT1 activation inhibits LPS-induced neuroinflammation via regulation of metabolic reprogramming.
Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Although its pathogenesis remains unclear, a number of studies indicate that microglia-mediated neuroinflammation makes a great contribution to the pathogenesis of PD. Melatonin receptor 1 (MT1) is widely expressed in glia cells and neurons in substantia nigra (SN). Neuronal MT1 is a neuroprotective factor, but it remains largely unknown whether dysfunction of microglial MT1 is involved in the PD pathogenesis. Here, we found that MT1 was reduced in microglia of SN in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. Microglial MT1 activation dramatically inhibited lipopolysaccharide (LPS)-induced neuroinflammation, whereas loss of microglial MT1 aggravated it. Metabolic reprogramming of microglia was found to contribute to the anti-inflammatory effects of MT1 activation. LPS-induced excessive aerobic glycolysis and impaired oxidative phosphorylation (OXPHOS) could be reversed by microglial MT1 activation. MT1 positively regulated pyruvate dehydrogenase alpha 1 (PDHA1) expression to enhance OXPHOS and suppress aerobic glycolysis. Furthermore, in LPS-treated microglia, MT1 activation decreased the toxicity of conditioned media to the dopaminergic (DA) cell line MES23.5. Most importantly, the anti-inflammatory effects of MT1 activation were observed in LPS-stimulated mouse model. In general, our study demonstrates that MT1 activation inhibits LPS-induced microglial activation through regulating its metabolic reprogramming, which provides a mechanistic insight for microglial MT1 in anti-inflammation.


Plasmon Reflections by Topological Electronic Boundaries in Bilayer Graphene.
Domain walls separating regions of AB and BA interlayer stacking in bilayer graphene have attracted attention as novel examples of structural solitons, topological electronic boundaries, and nanoscale plasmonic scatterers. We show that strong coupling of domain walls to surface plasmons observed in infrared nanoimaging experiments is due to topological chiral modes confined to the walls. The optical transitions among these chiral modes and the band continua enhance the local conductivity, which leads to plasmon reflection by the domain walls. The imaging reveals two kinds of plasmonic standing-wave interference patterns, which we attribute to shear and tensile domain walls. We compute the electronic structure of both wall varieties and show that the tensile wall contains additional confined bands which produce a structure-specific contrast of the local conductivity, in agreement with the experiment. The coupling between the confined modes and the surface plasmon scattering unveiled in this work is expected to be common to other topological electronic boundaries found in van der Waals materials. This coupling provides a qualitatively new pathway toward controlling plasmons in nanostructures.


Hemangiomas of the parotid gland in children.
Twenty-six cases of parotid hemangiomas seen at the Montreal Children's Hospital are reviewed. This lesion is by far the most common tumor of the parotid gland in children. In recent years, our treatment of this condition has gradually shifted toward conservatism, reserving surgical excision for the unusual case where the lesion does no show spontaneous resolution.


Approaches to conventional mechanical ventilation of the patient with acute respiratory distress syndrome.
To minimize ventilator-induced lung injury, attention should be directed toward avoidance of alveolar over-distention and cyclical opening and closure of alveoli. The most impressive study of mechanical ventilation to date is the Acute Respiratory Distress Syndrome (ARDS) Network study of higher versus lower tidal volume (V(T)), which reported a reduction in mortality from 39.8% to 31.0% with 6 mL/kg ideal body weight rather than 12 mL/kg ideal body weight (number-needed-to-treat of 12 patients). To achieve optimal lung protection, the lowest plateau pressure and V(T) possible should be selected. What is most important is limitation of V(T) and alveolar distending pressure, regardless of the mode set on the ventilator. Accumulating observational evidence suggests that V(T) should be limited in all mechanically ventilated patients-even those who do not have ALI/ARDS. Evidence does not support the use of pressure controlled inverse-ratio ventilation. Although zero PEEP is probably injurious, an area of considerable controversy is the optimal setting of PEEP. Available evidence does not support the use of higher PEEP, compared to lower PEEP, in unselected patients with acute lung injury (ALI)/ARDS. However, results of a meta-analysis using individual patients from 3 randomized controlled trials suggest that higher PEEP should be used for ARDS, whereas lower PEEP may be more appropriate in patients with ALI. PEEP should be set to maximize alveolar recruitment while avoiding over-distention. Many approaches for setting PEEP have been described, but evidence is lacking that any one approach is superior to any other. In most, if not all, cases of ALI/ARDS, conventional ventilation strategies can be used effectively to provide lung-protective ventilation strategies.


Clarifying proximal diaphyseal fifth metatarsal fractures. The acute fracture versus the stress fracture.
This article discusses the classification and treatment of proximal diaphyseal fifth metatarsal fractures. There are two types of proximal diaphyseal fracture of the fifth metatarsal: the acute proximal diaphyseal fracture and the proximal diaphyseal stress fracture. Confusion between the two types of fractures is probably due to their similar location and the historical practice of referring to all fractures in this location as Jones fractures. Both fractures are prone to delayed union and require long periods of nonweightbearing immobilization or internal fixation for healing. However, because the mechanism of injury is different for each fracture, the treatment plan may need to be tailored to the particular type of fracture.


A Community-Based Evaluation of a Culturally Grounded, American Indian After-School Prevention Program: The Value of Practitioner-Researcher Collaboration.
Programs serving American Indian (AI) youth are an important component of maintaining cultural identity and healthy lifestyles. The current research took a community-engaged approach to evaluate an urban AI youth after-school program that has transitioned into a culturally grounded prevention program. Ways to create a successful research collaboration between AI communities and academics is discussed as well as implications for understanding the importance of culturally-grounded programs for AI youth who reside in urban areas. Overall, the cultural and health components that are integrated into the after-school program were highlighted as primary strengths because they help foster a healthy lifestyle and deeper connection to the heritage/culture for the youth who participated.


The Tarsometatarsus of the Ostrich Struthio camelus: Anatomy, Bone Densities, and Structural Mechanics.
The ostrich Struthio camelus reaches the highest speeds of any extant biped, and has been an extraordinary subject for studies of soft-tissue anatomy and dynamics of locomotion. An elongate tarsometatarsus in adult ostriches contributes to their speed. The internal osteology of the tarsometatarsus, and its mechanical response to forces of running, are potentially revealing about ostrich foot function. Computed tomography (CT) reveals anatomy and bone densities in tarsometatarsi of an adult and a young juvenile ostrich. A finite element (FE) model for the adult was constructed with properties of compact and cancellous bone where these respective tissues predominate in the original specimen. The model was subjected to a quasi-static analysis under the midstance ground reaction and muscular forces of a fast run. Anatomy-Metatarsals are divided proximally and distally and unify around a single internal cavity in most adult tarsometatarsus shafts, but the juvenile retains an internal three-part division of metatarsals throughout the element. The juvenile has a sparsely ossified hypotarsus for insertion of the m. fibularis longus, as part of a proximally separate third metatarsal. Bone is denser in all regions of the adult tarsometatarsus, with cancellous bone concentrated at proximal and distal articulations, and highly dense compact bone throughout the shaft. Biomechanics-FE simulations show stress and strain are much greater at midshaft than at force applications, suggesting that shaft bending is the most important stressor of the tarsometatarsus. Contraction of digital flexors, inducing a posterior force at the TMT distal condyles, likely reduces buildup of tensile stresses in the bone by inducing compression at these locations, and counteracts bending loads. Safety factors are high for von Mises stress, consistent with faster running speeds known for ostriches. High safety factors suggest that bone densities and anatomy of the ostrich tarsometatarsus confer strength for selectively critical activities, such as fleeing and kicking predators. Anatomical results and FE modeling of the ostrich tarsometatarsus are a useful baseline for testing the structure's capabilities and constraints for locomotion, through ontogeny and the full step cycle. With this foundation, future analyses can incorporate behaviorally realistic strain rates and distal joint forces, experimental validation, and proximal elements of the ostrich hind limb.


Alogliptin: a new, highly selective dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes.
Alogliptin is a potent, highly selective dipeptidyl peptidase-4 inhibitor now undergoing clinical testing to support a new drug application for the treatment of type 2 diabetes. To provide an overview of the mechanism by which alogliptin reduces hyperglycemia and to summarize the pharmacology, efficacy and safety of the drug. A Medline search was conducted and abstracts and presentations from recent American Diabetes Association and European Association for the Study of Diabetes (EASD) meetings were reviewed. The results of Phase II and Phase III human studies were evaluated for clinical efficacy, safety and tolerability in patients with type 2 diabetes. Alogliptin is effective as a treatment for type 2 diabetes, either as monotherapy or in combination with metformin, thiazolidinediones, sulfonylureas and insulin. It is well tolerated and has an excellent safety profile. Additional studies are needed to evaluate the long-term safety and efficacy of alogliptin.


A study of occupational exposure to antineoplastic drugs and fetal loss in nurses.
In a case--control study, we examined the relation between fetal loss and occupational exposure to antineoplastic drugs in nurses in 17 Finnish hospitals. The pregnancies studied occurred in 1973 through 1980 and were identified using three national sources: the Central Register of Health Care Personnel, the Hospital Discharge Registry, and policlinic data. Each nurse with fetal loss was matched with three nurses who gave birth. Data on health and exposure were obtained by self-administered, mailed questionnaires; a response rate of 87 per cent was achieved after three mailings. A statistically significant association was observed between fetal loss and occupational exposure to antineoplastic drugs during the first trimester of pregnancy: odds ratio = 2.30 (95 per cent confidence interval, 1.20 to 4.39). Analyses suggested associations between fetal loss and cyclophosphamide, doxorubicin, and vincristine, although the independent effect of each individual drug could not be specifically identified, since many nurses reported handling more than one of these agents. The results of this study, combined with existing data on animals and human beings, suggest that caution be exercised in the handling of these valuable drugs.


An estimation of the minimum effective anesthetic volume of 2% lidocaine in ultrasound-guided axillary brachial plexus block.
Ultrasound guidance facilitates precise needle and injectate placement, increasing axillary block success rates, reducing onset times, and permitting local anesthetic dose reduction. The minimum effective volume of local anesthetic in ultrasound-guided axillary brachial plexus block is unknown. The authors performed a study to estimate the minimum effective anesthetic volume of 2% lidocaine with 1:200,000 epinephrine (2% LidoEpi) in ultrasound-guided axillary brachial plexus block. After ethical approval and informed consent, patients undergoing hand surgery of less than 90 min duration were recruited. A step-up/step-down study model was used with nonprobability sequential dosing based on the outcome of the previous patient. The starting dose of 2% LidoEpi was 4 ml per nerve. Block failure resulted in a dose increase of 0.5 ml; block success in a reduction of 0.5 ml.A blinded assistant assessed sensory and motor blockade at 5-min intervals up to 30 min. Block performance time and duration were measured. Two predetermined stopping points were used; a minimum of five consecutive block success/failures and five consecutive successful blocks at 1 ml per nerve. The study was terminated when five consecutive patients had successful blocks using 1 ml of 2% LidoEpi per nerve (overall group n = 11). All five patients had surgical anesthesia within 10 min. The mean (SD) block performance time was 445 (100) s, and block duration was 190 min (range 120-310 min). All surgical procedures were performed under regional anesthesia with anxiolytic sedation provided in 3 of 11 cases. Successful ultrasound-guided axillary brachial plexus block may be performed with 1 ml per nerve of 2% LidoEpi.


Planar fiber-optic chips for broadband spectroscopic interrogation of thin films.
A planar fiber-optic chip (FOC) has been developed using side-polished optical fibers and characterized for broadband absorbance and fluorescence detection of molecular films. FOC technology combines the sensitivity of an attenuated total reflection (ATR) element with the ease of use of fiber-optic-based spectrometers and light sources to create an improved platform for spectroscopic analysis of molecular adsorbates. A multi-mode optical fiber (core diameter = 50 mum, numerical aperture = 0.22, stepped refractive index profile) mounted in a glass V-groove block was side-polished to create a planar platform that allows access to the evanescent field escaping from the fiber core. For this generation of FOC technology, the exposed evanescent field has an interaction length of approximately 17.2 mm. The FOC platform was independently characterized through measurements of thin-film and bulk absorbing samples. The device performance was compared to the existing ATR technology and methods for increasing sensitivity of the FOC were investigated and validated. Additionally, we have demonstrated the ability of the FOC to both evanescently excite and collect fluorescence through guided modes of the optical fiber for a surface-confined luminescent semiconductor nanoparticle film (4 nm diameter, ligand capped, CdSe core). The FOC described here with a supported planar interface can facilitate the use of conventional planar deposition technologies and provide a robust planar platform that is amenable for incorporation into various sensor technologies.


Membrane Sterols Modulate the Binding Mode of Amphotericin B without Affecting Its Affinity for a Lipid Bilayer.
Membrane-active antibiotics are known to selectively target certain pathogens based on cell membrane properties, such as fluidity, lipid ordering, and phase behavior. These are in turn modulated by the composition of a lipid bilayer and in particular by the presence and type of membrane sterols. Amphotericin B (AmB), the golden standard of antifungal treatment, exhibits higher activity toward ergosterol-rich fungal membranes, which permits its use against systemic mycoses; however, the selectivity for fungal membranes is far from satisfactory leading to severe side effects. Despite decades of research, no consensus has emerged on the origin of AmB specificity for fungal cells and its actual mode of action at the molecular level. Previously, it has been proposed that the specific action of AmB is related to differences in its affinity for membranes of different composition. In this work, we investigate this relationship by employing molecular dynamics simulations to compare the free energy of insertion of AmB into three types of membranes: a pure DMPC bilayer and DMPC bilayers containing 30% of cholesterol or ergosterol. We analyze the orientation of AmB molecules within the bilayer in order to unambiguously establish their membrane binding mode and relate the orientational freedom to the sterol-dependent tightness of lipid packing. Our results strongly indicate that the membrane insertion of AmB proceeds virtually to completion independent of membrane type, and hence the higher toxicity against fungal membranes may rather result from differences in subsequent oligomerization in the membrane and assembly of monomers into functional transmembrane pores. In particular, the latter could be facilitated by sterol-induced ordering of AmB molecules along the membrane normal, revealed by our free energy profiles. Moreover--in contrast to certain claims--we find no stable binding mode corresponding to the horizontal adsorption of AmB on the membrane surface.


Personalized Atrophy Risk Mapping in Age-Related Macular Degeneration.
To develop and validate an automatic retinal pigment epithelial and outer retinal atrophy (RORA) progression prediction model for nonexudative age-related macular degeneration (AMD) cases in optical coherence tomography (OCT) scans. Longitudinal OCT data from 129 eyes/119 patients with RORA was collected and separated into training and testing groups. RORA was automatically segmented in all scans and additionally manually annotated in the test scans. OCT-based features such as layers thicknesses, mean reflectivity, and a drusen height map served as an input to the deep neural network. Based on the baseline OCT scan or the previous visit OCT, en face RORA predictions were calculated for future patient visits. The performance was quantified over time with the means of Dice scores and square root area errors. The average Dice score for segmentations at baseline was 0.85. When predicting progression from baseline OCTs, the Dice scores ranged from 0.73 to 0.80 for total RORA area and from 0.46 to 0.72 for RORA growth region. The square root area error ranged from 0.13 mm to 0.33 mm. By providing continuous time output, the model enabled creation of a patient-specific atrophy risk map. We developed a machine learning method for RORA progression prediction, which provides continuous-time output. It was used to compute atrophy risk maps, which indicate time-to-RORA-conversion, a novel and clinically relevant way of representing disease progression. Application of recent advances in artificial intelligence to predict patient-specific progression of atrophic AMD.


Electrochemical analyses of redox-active iron minerals: a review of nonmediated and mediated approaches.
Redox-active minerals are ubiquitous in the environment and are involved in numerous electron transfer reactions that significantly affect biogeochemical processes and cycles as well as pollutant dynamics. As a consequence, research in different scientific disciplines is devoted to elucidating the redox properties and reactivities of minerals. This review focuses on the characterization of mineral redox properties using electrochemical approaches from an applied (bio)geochemical and environmental analytical chemistry perspective. Establishing redox equilibria between the minerals and working electrodes is a major challenge in electrochemical measurements, which we discuss in an overview of traditional electrochemical techniques. These issues can be overcome with mediated electrochemical analyses in which dissolved redox mediators are used to increase the rate of electron transfer and to facilitate redox equilibration between working electrodes and minerals in both amperometric and potentiometric measurements. Using experimental data on an iron-bearing clay mineral, we illustrate how mediated electrochemical analyses can be employed to derive important thermodynamic and kinetic data on electron transfer to and from structural iron. We summarize anticipated methodological advancements that will further contribute to advance an improved understanding of electron transfer to and from minerals in environmentally relevant redox processes.


Endoscopic ultrasound-guided fine-needle aspiration for the diagnosis of peripancreatic tuberculous lymphadenitis.
The percentage of patients with atypical extrapulmonary forms of tuberculosis has been increasing. Among extrapulmonary tuberculosis cases, tuberculosis of the pancreas and peripancreatic lymph nodes is a rare clinical entity. Here, we present a case of peripancreatic tuberculous lymphadenitis diagnosed by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) both cytologically and microbiologically. A 23-year-old man had a 1-week history of epigastralgia and low-grade fever. Subsequently, he was found to have an abnormality on abdominal ultrasound. A computed tomography scan of the abdomen showed a solitary mass consisting of multiple cystic components with rim enhancement in the peripancreatic portion contiguous to the gall bladder. Endoscopic ultrasound-guided fine-needle aspiration was performed to confirm the diagnosis. The cytological examination revealed epithelioid cells with caseous necrosis, indicating tuberculosis. The aspirated fluid was positive by polymerase chain reaction (PCR) analysis and culture for Mycobacterium tuberculosis. Antituberculosis therapy with isoniazid, rifampicin, ethambutol, and pyrazinamide was started based on the PCR and cytology results, and a good response to the treatment was noted. Endoscopic ultrasound-guided fine-needle aspiration cytology with PCR analysis is very useful for the diagnosis of peripancreatic tuberculosis.


Preliminary results from an EIT breast imaging simulation system.
An electrical impedance tomography (EIT) simulation system for breast imaging has been developed using impedance data from a previous study and a finite-element model (FEM). This system has the functionality to construct various models of the breast, image the boundary voltages developed from any injection schema and provide parametric Cole-Cole modelling. Simulations indicate that breast carcinoma can be imaged and multi-frequency Cole-Cole dispersion data can be extracted. This is intended as the first stage towards providing an artificial intelligence based system capable of producing clinically relevant analytical data.


T-cell phenotypic profile and colony formation during recovery from cytotoxic therapy-induced marrow aplasia.
Lymphocytes which appeared in the peripheral blood early (approximately 4 weeks) after complete bone marrow aplasia were studied in two groups of patients. Twenty-two allogeneic bone marrow transplant recipients and 12 acute nonlymphocytic leukemia patients (entering remission) were compared to 70 healthy control subjects studied during the same time interval. Studies performed included phenotyping T-cells using monoclonal antibodies and T-cell colony formation in response to phytohemagglutinin. The phenotypic profile for the two patient groups differed from each other and from that of the healthy controls. The total number of circulating cells reactive with OKT4 were significantly depressed in marrow graft recipients while only mildly, but significantly, depressed in leukemic patients. The number of circulating cells reactive with OKT8 were depressed in leukemic patients but were essentially normal in marrow graft recipients. The number of circulating cells reactive with OKla1 and OKT10 were significantly elevated in marrow graft recipients while significantly depressed in leukemic patients. The T4:T8 ratio was significantly depressed for marrow transplant recipients and significantly elevated for leukemic patients. T-cell colony formation in agarose without and with added interleukin-2 was decreased for both groups, more so for marrow graft recipients who virtually lacked the ability to make colonies without exogenous interleukin 2. These phenotypic and functional data suggest that T-cell reconstitution after bone marrow aplasia and profound lymphopenia takes quite different pathways for leukemic patients recovering from remission induction therapy and for recipients of bone marrow transplants. We were unable to correlate T-cell functional response in T-cell colony formation with the phenotypic profile of peripheral blood T-cells.


Next-Generation Robotic Head and Neck Surgery.
Following the inception of transoral robotic surgery (TORS) in 2005, the field of robotic head and neck surgery has undergone refinement and innovation. Optimizing patient outcome, preserving function, and limiting morbidity are the key drivers. The next leap forward is another generation of flexible robotic surgical systems. Several such systems are under clinical and preclinical evaluation. A new single-port (Sp) robotic surgical architecture is now available integrating three fully articulating instruments and a flexible three-dimensional high-definition camera delivered through a 25-mm cannula. Preclinical feasibility studies of the Sp in human cadaver and porcine models suggest improved application compared to existing platforms for oropharyngeal and nasopharyngeal resection. With 3-handed manipulation of tissue, traction and countertraction may be used to deliver a more precise surgical dissection of head and neck anatomy than is currently possible. The single-port design permits greater access and maneuverability for the bedside surgical assistant. An alternative currently available in clinical use includes the Flex® system using a robotic camera and manually controlled endoscopic instruments. The Cambridge Medical Robotics Versius system is undergoing preclinical evaluation for TORS and may offer a novel modular approach. All of these systems allow the head and neck surgeon to reach further beyond the upper aerodigestive tract with greater agility and precision, expanding the boundaries of minimal access head and neck surgery.


Utilizing Telemedicine for Group Visit Provider Encounters: A Feasibility and Acceptability Study.
The value of telemedicine has been underscored during the coronavirus pandemic. Utilizing telemedicine could markedly enhance group visit scalability and sustainability. However, there are limited data demonstrating telemedicine use for group visits. To evaluate the feasibility and acceptability of provider encounters conducted via telemedicine in group visits. We conducted a 6-month diabetes group visit program and compared in-person (months 1-3) versus telemedicine (videoconferencing) (months 4-6) patient-provider encounters. Participants completed the Telehealth Usability Questionnaire (TUQ) at 6-months (primary outcome). To ensure telemedicine did not negatively affect clinical outcomes, we compared in-person versus telemedicine differences in HbA1c, blood pressure, body mass index (BMI), and attendance. The TUQ revealed that participants (N=19) found telemedicine useful and easy to use (4.9/5.0, 4.4/5.0, respectively) and with excellent interface (4.3/5.0), interaction (4.6/5.0), reliability (4.2/5.0), and satisfaction (4.4/5.0). There were no significant differences in clinical outcomes between arms: HbA1c (in-person: -0.60%, telemedicine: -0.52%, p=0.86), blood pressure (systolic: p=0.475, diastolic: p=0.683), weight (p=0.982), BMI (p=0.981), attendance (in-person: 75.44%, telemedicine: 70.12%, p=0.551). Provider telemedicine encounters in group visits are feasible and acceptable. This is a promising model to address provider limitations in group visits and increase access to care. Larger studies are needed to further evaluate these findings.


Implantable Systems for Stress Urinary Incontinence.
Stress urinary incontinence (SUI), the involuntary urine leakage due to failure of the urethral closure mechanism, is a global health challenge with substantial human suffering and socioeconomic costs. Approximately 167 million male and female patients are predicted to suffer from SUI in 2018, worldwide. A wide range of surgical interventions are available for the treatment of SUI. Severe cases, however, usually require the implantation of artificial urinary sphincter devices. This review comparatively presents and analyzes the working principles, as well as the challenges, associated with the current implantable SUI systems in clinical use. These include slings, urethral bulking agents, artificial urinary sphincters, and adjustable continence devices. It further reports on recent research progress and state-of-the-art in the field of SUI implants, including an original approach proposed by the authors with a pressure feedback sensory mechanism. The new emerging field of artificial muscle devices, including electroactive polymers, provides a promising innovative solution for replacing the weakened urethral sphincter in SUI patients.


Mediterranean diet is associated with better gastrointestinal health and quality of life, and less nutrient deficiency in children/adolescents with disabilities.
Children and adolescents with disabilities face various nutritional problems. This study aimed to examine dietary characteristics, nutritional status and problems, gastrointestinal health, and quality of life in children and adolescents with disabilities. This study included 5-18 years old children and adolescents (n = 1,991) with disabilities. We used the Mediterranean Diet Quality Index (KIDMED), the Gastrointestinal Symptom Rating Scale (GSRS), and the Pediatric Quality of Life Inventory (PedsQL) to assess diet characteristics, gastrointestinal problems, and life quality. We collected retrospective 24-h food record to assess energy and nutrient intakes. The rate of stunting in children with disabilities varies between 16.5% and 19.8%. When comparing disability types, more children with physical disabilities were underweight (8.8% vs. 6.7%) and stunted (19.8% vs. 16.5%), while more children with intellectual disabilities were tall (7.9% vs. 5.5%) and overweight/obese (21.1 vs. 17.2%; p < 0.05). Wasting (9.3%) and overweight/obesity (23.8%) were more common in children with disabilities aged 5-7 years (p < 0.001). Eating problems such as loss of appetite, food refusal, food neophobia, and food selectivity were more common in children aged 5-7 years, and problems with fast eating and overeating were more common in adolescents aged 13-18 years (p < 0.05). Among children and adolescents with disabilities, the nutrients with inadequate intakes were vitamin E, vitamin B1, folate, potassium, calcium, and iron, while the nutrients with intakes above the requirements were proteins, carbohydrates, vitamins A, B2, B6, B12, and C, phosphorus, zinc, and sodium. Participants with good Mediterranean diet quality had higher energy and nutrient intakes and higher percentages of meeting nutrient requirements (p < 0.05). KIDMED scores were negatively correlated with GSRS total (r = -0.14, p < 0.001) and subcomponent scores (abdominal pain, diarrhea, reflux, indigestion, and constipation; p < 0.05), and significantly and positively correlated with PedsQL total (r = 0.12, p < 0.001). A one-unit increase in the GSRS score resulted in a 14.4 times decrease in the PedsQL score, and a one-unit increase in the KIDMED score resulted in a 10.8 times increase in the PedsQL score (p = 0.001). Overweight/obesity, stunting/wasting, nutritional problems, and deficiencies are common among disabled children and adolescents. Mediterranean diet is associated with a better quality of life, and gastrointestinal health in children with disabilities.


Reversal of opioid-induced respiratory depression by BK-channel blocker GAL021: A pharmacokinetic-pharmacodynamic modeling study in healthy volunteers.
Opioid-induced respiratory depression (OIRD) is a serious and potentially life-threatening complication of opioid overdose, abuse, and misuse. An option to avert OIRD is to treat patients on strong opioids with respiratory stimulants that do not interact with the opioid system and consequently do not compromise opioid analgesic efficacy. The BK-channel blocker GAL021 is a respiratory stimulant acting at K(+) -channels expressed on type 1 carotid body cells. The authors performed a population pharmacokinetic-pharmacodynamic (PKPD) analysis on the ability of GAL021 to reverse alfentanil-induced respiratory depression in 12 male volunteers using an isohypercapnic experimental design. The analysis showed that (1) GAL021 interacts in a multiplicative fashion with alfentanil and GAL021, which predicts that GAL021 efficacy is reduced at low ventilation levels; (2) GAL021 has a rapid onset/offset with a blood-effect site equilibration half-life not different from zero; and (3) GAL021 displays ceiling in its efficacy to reverse OIRD.


The declining autopsy rate and clinicians' attitudes.
The autopsy rate has been declining worldwide for decades. This study determined the overall and differential autopsy rates for the Royal Victoria Hospital, Belfast for the years 1997-1999 inclusive. Trends were examined by comparison with previously collected data for the years 1990, 1991 and 1993. Reasons for the decline in autopsy rates as perceived by hospital clinicians were assessed by means of a questionnaire. Over the last decade, there has been a steady decline in the overall autopsy rate from 30.4% in 1990 to 18.4% in 1999. This is due to a decrease in the hospital autopsy rate from 21.6% in 1990 to 7.9% in 1999. The coroner's autopsy rate has remained comparatively unchanged at around 11%. The decline in the overall and hospital autopsy rates involves all of the principal bedholding directorates, but is most dramatic in medicine, surgery and intensive care, where hospital autopsy rates are currently 7% or less. The main reasons for this decline as perceived by clinicians are difficulty in obtaining consent from relatives and advances in modern diagnostic techniques. The findings of this enquiry are in keeping with trends elsewhere, despite repeated studies which clearly demonstrate the continuing value of the autopsy in clinical practice. Recent publicity concerning the retention of organs can only have an adverse affect. Pathologists and clinicians who value the autopsy must become actively engaged in both public and medical education. Renewed emphasis must be placed on the importance of the autopsy in teaching, training and clinically relevant research, and as a means of medical audit.


A large-scale study of differential gene expression in monocyte-derived macrophages infected with several strains of Mycobacterium avium subspecies paratuberculosis.
Mycobacterium avium subspecies paratuberculosis (MAP) is a significant concern to the American and European dairy industries and possibly to human health. MAP possesses the rare ability to survive and replicate in infected macrophages, cells that are typically able to destroy pathogens. Little is known about what changes occur in MAP-infected macrophages that prevent phagosome maturation and lead to intracellular survival of the bacteria. In this study, a bovine immunologically specific cDNA microarray was used to study genes whose expression was altered in monocyte-derived macrophages (MDM) when these cells were infected with 10 different strains of MAP bacteria. Although we used MAP strains isolated from four different host species, cluster analysis of each strains influence in infected MDMs showed no species of origin specific MAP alterations in the host transcriptome. However, MAP strain K10 was observed as a clear outlier in the cluster analysis. Additionally, we observed two SuperShedder MAP strains clustering very closely together compared to the other strains in this study. Overall, microarray analysis yielded 78 annotated genes whose expression was altered by MAP infection, regardless of strain. Few of these genes have been previously studied in the context of Johne's disease or other mycobacterium-caused diseases. Large groups of apoptosis genes, transcription factors and cytokines were found to be differentially expressed in infected monocyte-derived macrophages as well as several genes not previously linked to MAP-host interactions. Identifying novel host genes affected by MAP infection of macrophages may lead to a more complete picture of this complex host-pathogen interaction.


A multicenter survey of temporal changes in chemotherapy-induced hair loss in breast cancer patients.
Many breast cancer patients suffer from chemotherapy-induced hair loss. Accurate information about temporal changes in chemotherapy-induced hair loss is important for supporting patients scheduled to receive chemotherapy, because it helps them to prepare. However, accurate information, on issues such as the frequency of hair loss after chemotherapy, when regrowth starts, the condition of regrown hair, and the frequency of incomplete hair regrowth, is lacking. This study aimed to clarify the long-term temporal changes in chemotherapy-induced hair loss using patient-reported outcomes for chemotherapy-induced hair loss. We conducted a multicenter, cross-sectional questionnaire survey. Disease-free patients who had completed adjuvant chemotherapy consisting of anthracycline and/or taxanes for breast cancer within the prior 5 years were enrolled from 47 hospitals and clinics in Japan. Descriptive statistics were obtained in this study. The study is reported according to the STROBE criteria. The response rate was 81.5% (1511/1853), yielding 1478 questionnaires. Hair loss occurred in 99.9% of patients. The mean time from chemotherapy until hair loss was 18.0 days. Regrowth of scalp hair occurred in 98% of patients. The mean time from the completion of chemotherapy to the beginning of regrowth was 3.3 months. Two years after chemotherapy completion, the scalp-hair recovery rate was <30% in approximately 4% of patients, and this rate showed no improvement 5 years after chemotherapy. Eighty-four percent of the patients initially used wigs, decreasing to 47% by 1 year after chemotherapy and 15.2% after 2 years. The mean period of wig use was 12.5 months. However, a few patients were still using wigs 5 years after completing chemotherapy. Our survey focused on chemotherapy-induced hair loss in breast cancer patients. We believe these results to be useful for patients scheduled to receive chemotherapy.


Improved National Results With Simultaneous Liver-Kidney Transplantation Using Donation After Circulatory Death Donors.
Previous large registry studies have demonstrated inferior outcomes for simultaneous liver-kidney transplantation (SLKT) recipients of grafts from donation after circulatory death (DCD) donors compared with those from donation after brain death (DBD) donors in the era from 2000 to 2010. Given the improving national results in liver transplantation alone using grafts from DCD donors, the present study aimed to investigate if results with DCD-SLKT have improved in the modern era. Patients undergoing SLKT between 2000 and 2018 were obtained from the United Network for Organ Sharing Standard Analysis and Research file and divided into 2 eras based on the date of SLKT: era 1 (2000-2010) and era 2 (2011-2018). Improvement in DCD-SLKT patient, liver graft, and kidney graft survival rates was seen between era 1 and era 2 (P < 0.001). Concurrently, there was a decrease in the proportion of critically ill (P = 0.02) and retransplant (P = 0.006) candidates undergoing DCD-SLKT. When DCD-SLKT in era 2 was compared with a propensity-matched cohort of DBD-SLKT in era 2, no differences in patient (P = 0.99), liver graft (P = 0.19), or kidney graft (P = 0.90) survival were observed. In addition, both bilirubin (0.5 versus 0.5 mg/dL; P = 0.86) and creatinine (1.2 versus 1.2 mg/dL; P = 0.68) at last follow-up were not different between the DCD-SLKT and DBD-SLKT patients in era 2. In conclusion, in the most recent era, patients undergoing DCD-SLKT were able to achieve similar outcomes compared with matched patients undergoing DBD-SLKT. DCD-SLKT represents a viable option for appropriately selected recipients.


Voltage-regulated sodium channel molecules.
In summary, TTX and STX binding have been used to follow the purification of sodium channel proteins from electric organ, mammalian skeletal muscle, and brain. In each instance they were proteins somewhat larger than the acetylcholine receptor and exhibited stability properties that reflect an intimate interaction with membrane lipids. The principal peptide constituent seems to be a large glycopeptide of approximately 250,000 daltons. Because this is evidently the only constituent of the electroplax protein, it must contain the TTX receptor site, probably forming the ion pathway itself. Photo-labeling with ScTX and studies with Tityus gamma toxin (58a) indicate a site involved with gating processes, also associated with the large peptide of the neuronal and electroplax proteins. The smaller peptides are not consistent features of all of the preparations, but may contribute to the molecular ensemble. If, however, the entire channel were formed from a single extremely large peptide, there would be interesting mechanistic implications, because the ion transporting and voltage-sensing mechanisms would be accounted for by domains within the folded polypeptide chain. Clearly, the prospect for combining biochemical isolation and reconstitution with the new biophysical technology offers an exciting experimental conjunction.


Phylogenetic and morphological assessment of five new species of Thozetella from an Australian rainforest.
During an investigation of saprobic microfungi in leaf litter from an Australian rainforest, five new species of Thozetella, namely T. acerosa, T. boonjiensis, T. falcata, T. gigantea and T. queenslandica, were identified and these are described and illustrated here. The morphology of specimens derived from cultures grown under different conditions and from natural substrata was compared. DNA sequence data of ITS regions within nuclear rDNA confirmed the morphological species concept and indicated that Thozetella species are anamorphs of the ascomycete genus Chaetosphaeria.


Response reliability of demographic data: a longitudinal study in Sri Lanka.
Response consistency was examined by linking the records of women interviewed in the 1982 Sri Lanka Contraceptive Prevalence Survey with records from the same individuals followed up 3 years later. Seventy-eight percent of women reported identical year of birth in the two surveys, but only 58% were consistent for age at marriage. Data on sterilisation and number of children born were highly reliable, but wives' reports on husband's age and education were relatively weak. Multivariate analysis of the effects of socioeconomic factors on consistency in age reporting confirms that education is the most influential factor related to consistency, followed by religion and husband's occupation.


Of helping relationships: a concept paper.
As professionals engaged in the practice of nursing, our involvement with people in different situations provides us many opportunities to be of significant help to them. People are often motivated to enhance themselves. It is the aim of this paper to present a concept in helping relationships that may assist nurses towards a positive direction in helping other people, whether sick or well to improve themselves, to achieve growth, realize their potentials and/or limit their disabilities.


Encephalocraniocutaneous lipomatosis: a rare neurocutaneous syndrome.
Encephalocraniocutaneous lipomatosis is a congenital hamartomatous disorder with unique ocular, cutaneous and neurological features. A 13-year-old boy presented with history of mental retardation and delayed developmental milestones. Bulbar conjunctiva of left eye showed hypertrophy with a soft reddish limbal nodule encroaching on the cornea. Dermatological examination showed multiple patches of alopecia, soft papules in the left perioral and periorbital areas, soft masses over the right axilla, trunk and in the lumbosacral region suggestive of lipomas. The CT scan of the brain revealed well-defined, hypodense lesions in both the cerebellar hemispheres suggestive of lipomas. The constellation of these findings led us to a diagnosis of encephalocraniocutaneous lipomatosis.


Evidence that circulating proteins are more promising than miRNAs for identification of patients with squamous cell carcinoma of the tongue.
Despite intense research, squamous cell carcinoma of the tongue remains a devastating disease with a five-year survival of around 60%. Late detection and recurrence are the main causes for poor survival. The identification of circulating factors for early diagnosis and/or prognosis of cancer is a rapidly evolving field of interest, with the hope of finding stable and reliable markers of clinical significance. The aim of this study was to evaluate circulating miRNAs and proteins as potential factors for distinguishing patients with tongue squamous cell carcinoma from healthy controls. Array-based profiling of 372 miRNAs in plasma samples showed broad variations between different patients and did not show any evidence for their use in diagnosis of tongue cancer. Although one miRNA, miR-150, was significantly down-regulated in plasma from patients compared to controls. Surprisingly, the corresponding tumor tissue showed an up-regulation of miR-150. Among circulating proteins, 23 were identified as potential markers of squamous cell carcinoma of the tongue. These findings imply that circulating proteins are a more promising source of biomarkers for tongue squamous cell carcinomas than circulating miRNAs. The data also highlight that circulating markers are not always directly associated with tumor cell properties.


A microfluidic platform with digital readout and ultra-low detection limit for quantitative point-of-care diagnostics.
Quantitative assays are of great importance for point-of-care (POC) diagnostics because they can offer accurate information on the analytes. However, current POC devices often require an accessory instrument to give quantitative readouts for protein biomarkers, especially for those at very low concentration levels. Here, we report a microfluidic platform, the digital volumetric bar-chart chip (DV-chip), for quantitative POC diagnostics with ultra-low detection limits that are readable with the naked eye. Requiring no calibration, the DV-chip presents a digital ink bar chart (representing multiple bits composed of 0 and 1) for the target biomarker based on direct competition between O2 generated by the experimental and control samples. The bar chart clearly and accurately defines target concentration, allowing identification of disease status. For the standard PtNP solutions, the detection limit of the platform is approximately 0.1 pM and the dynamic range covers four orders of magnitude from 0.1 to 1000 pM. CEA samples with concentrations of 1 ng mL(-1) and 1.5 ng mL(-1) could be differentiated by the device. We also performed the ELISA assay for B-type natriuretic peptide (BNP) in 20 plasma samples from heart failure patients and the obtained on-chip data were in agreement with the clinical results. In addition, BNP was detectable at concentrations of less than 5 pM, which is three orders of magnitude lower than the detection limit of the previously reported readerless digital methods. By the integration of gas competition, volumetric bar chart, and digital readout, the DV-chip possesses merits of portability, visible readout, and ultra-low detection limit, which should offer a powerful platform for quantitative POC diagnostics in clinical settings and personalized detection.


Tumor targeting by a multivalent single-chain Fv (scFv) anti-Lewis Y antibody construct.
The use of single-chain variable fragment (scFv) constructs has been investigated in cancer radioimmunotherapy (RIT) and radioimmunodetection, as these molecules permit rapid tumor penetration and clearance from the serum relative to whole IgG. Multimerization of scFv constructs has demonstrated improvements in functional affinity (i.e., avidity) and maximal tumor uptake. In this paper, we report the first biodistribution and pharmacokinetics studies of a noncovalent, direct-linked scFv (V(L)-0-V(H)) trimeric/tetrameric "multimer" of the anti-Lewis Y monoclonal antibody, hu3S193. The in vitro binding and in vivo biodistribution of the hu3S193 multimer was characterized alongside the hu3S193 F(ab')(2) following radiolabeling with the Indium-111 ((111)In) radioisotope. Immunoreactivities of the radiolabeled multimer and F(ab')(2) were 73% and 53.2%, and binding affinities (K(a)) were 1.58 x 10(7) M(1) and 4.31 x 10(6) M (1) for the multimer and F(ab')(2), respectively. Maximal tumor uptake in Le(y)-positive MCF-7 breast cancer xenografted BALB/c nude mice was 12.6 +/- 2.5 percent injected dose/per gram (%ID/g) at 6 hours postinjection for the multimer and 15.7 +/- 2.1 %ID/g at 24 hours postinjection for the F(ab')(2). However, limited in vitro stability and high renal localization of radiolabeled constructs were observed, which, despite the observed tumor targeting of the hu3S193 multimer, most likely preclude its use in RIT and imaging modalities.


Identification of a tumor cell receptor for VGVAPG, an elastin-derived chemotactic peptide.
Extracellular matrix proteins and their proteolytic products have been shown to modulate cell motility. We have found that certain tumor cells display a chemotactic response to degradation products of the matrix protein elastin, and to an elastin-derived peptide, VGVAPG. The hexapeptide VGVAPG is a particularly potent chemotaxin for lung-colonizing Lewis lung carcinoma cells (line M27), with 5 nM VGVAPG eliciting maximal chemotactic response when assayed in 48-microwell chemotaxis chambers. Binding of the elastin-derived peptide to M27 cells was studied using a tyrosinated analog (Y-VGVAPG) to allow iodination. Scatchard analysis of [125I]Y-VGVAPG binding to viable M27 tumor cells at both 37 and 4 degrees C indicates the presence of a single class of high affinity binding sites. The dissociation constant obtained from these studies (2.7 X 10(-9) M) is equivalent to the concentration of VGVAPG required for chemotactic activity. The receptor molecule was identified as an Mr 59,000 species by covalent cross-linking of the radiolabeled ligand to the M27 tumor cell surface and subsequent analysis of the cross-linked material by electrophoresis and size-exclusion high performance liquid chromatography. These results suggest that M27 tumor cell chemotaxis to VGVAPG is initiated by high affinity binding of the peptide to a distinct cell surface receptor.


Effect of laser irradiation and cavity disinfectant application on the microtensile bond strength of different adhesive systems.
The aim of this study was to evaluate the effect of two different cavity disinfection procedures (chlorhexidine gluconate-based cavity disinfectant and Er,Cr:YSGG laser irradiation) on the bond strength of two different types of adhesive systems (Adper Single Bond 2 [SB] and Clearfil SE Bond [SE]). Thirty human third molars were ground flat to expose midcoronal dentin. After the dentin surfaces were polished with 600-grit silicon carbide paper, the teeth were randomly assigned to six groups (n = 5) according to the cavity disinfection procedure and the adhesive resin: Group I, etch and rinse adhesive (SB); Group II, self-etch adhesive (SE); Group III, cavity disinfectant application (cavity cleanser) + SB; Group IV, cavity disinfectant application + SE; Group V, laser irradiation (Er,Cr:YSGG laser, 20 Hz; 0.75 W; 15% water, 15% air) + SB; Group VI, laser irradiation + SE. For each group, the composite crown was incrementally fabricated with a composite resin. Following storage in distilled water at 37 degrees C for 24 h, the bonded specimens were serially sectioned into rectangular beams (n = 32). Bond strengths were determined using a microtensile tester at a crosshead speed of 0.5 mm/min. Data were analyzed using two-way ANOVA, and multiple comparisons were performed using post hoc Duncan's test (p < 0.05). Cavity disinfectant application and laser irradiation produced significantly higher bond strength values compared to the control group for SB. For SE, only laser irradiation improved the bond strength values compared to the control. There was a statistically significant decrease in the bond strength values of the specimens that were subjected to cavity disinfectant before SE application. The failure mode was mainly adhesive in all groups. Cavity disinfectant application and laser irradiation may influence bond strength, depending on the adhesive system used. As a cavity-disinfecting procedure, laser irradiation might enhance the bond strength of etch and rinse and self-etch adhesive systems.


Release of protein-bound residues of thiabendazole from liver.
Tissue-bound residues of thiabendazole (TBZ), a veterinary anthelmintic and postharvest fungicide, are formed when this compound is incubated with rabbit hepatocytes or administered to mice or pigs. Several pretreatment steps were investigated for removing free TBZ and metabolites prior to the release of bound residues, and three procedures were evaluated for the release of bound residues from solvent-extracted rabbit hepatocytes: incubation under acidic conditions, enzymatic action using cystathionine beta-lyase, and Raney nickel desulfurization. Immunoaffinity chromatography utilizes monoclonal antibodies capable of binding TBZ or its 5-hydroxy metabolite enabled isolation of crossreactive residue fractions. Residues released from incurred pig liver and isolated by immunoaffinity included TBZ, as determined by HPLC with photodiode array detection. The methodology described should facilitate food safety assessments of TBZ.


Team mental models: techniques, methods, and analytic approaches.
Effective team functioning requires the existence of a shared or team mental model among members of a team. However, the best method for measuring team mental models is unclear. Methods reported vary in terms of how mental model content is elicited and analyzed or represented. We review the strengths and weaknesses of vatrious methods that have been used to elicit, represent, and analyze individual and team mental models and provide recommendations for method selection and development. We describe the nature of mental models and review techniques that have been used to elicit and represent them. We focus on a case study on selecting a method to examine team mental models in industry. The processes involved in the selection and development of an appropriate method for eliciting, representing, and analyzing team mental models are described. The criteria for method selection were (a) applicability to the problem under investigation; (b) practical considerations - suitability for collecting data from the targeted research sample; and (c) theoretical rationale - the assumption that associative networks in memory are a basis for the development of mental models. We provide an evaluation of the method matched to the research problem and make recommendations for future research. The practical applications of this research include the provision of a technique for analyzing team mental models in organizations, the development of methods and processes for eliciting a mental model from research participants in their normal work environment, and a survey of available methodologies for mental model research.


Origins of house mice in ecological niches created by settled hunter-gatherers in the Levant 15,000 y ago.
Reductions in hunter-gatherer mobility during the Late Pleistocene influenced settlement ecologies, altered human relations with animal communities, and played a pivotal role in domestication. The influence of variability in human mobility on selection dynamics and ecological interactions in human settlements has not been extensively explored, however. This study of mice in modern African villages and changing mice molar shapes in a 200,000-y-long sequence from the Levant demonstrates competitive advantages for commensal mice in long-term settlements. Mice from African pastoral households provide a referential model for habitat partitioning among mice taxa in settlements of varying durations. The data reveal the earliest known commensal niche for house mice in long-term forager settlements 15,000 y ago. Competitive dynamics and the presence and abundance of mice continued to fluctuate with human mobility through the terminal Pleistocene. At the Natufian site of Ain Mallaha, house mice displaced less commensal wild mice during periods of heavy occupational pressure but were outcompeted when mobility increased. Changing food webs and ecological dynamics in long-term settlements allowed house mice to establish durable commensal populations that expanded with human societies. This study demonstrates the changing magnitude of cultural niche construction with varying human mobility and the extent of environmental influence before the advent of farming.


p53, p21(WAF1/CIP1), and MDM2 involvement in the proliferation and apoptosis in an in vitro model of conditionally immortalized human vascular smooth muscle cells.
Using an in vitro model of a conditionally immortalized cell line, we have investigated how human vascular smooth muscle cells (VSMCs) are affected by the expression of simian virus 40 (SV40) large T antigen (LT antigen), which binds to cell cycle regulators such as the tumor suppressor protein p53. Cells were obtained after infection of saphenous vein-derived VSMCs with a nonreplicative retroviral vector containing a temperature-sensitive mutant of SV40 LT antigen and were shown to have maintained some characteristics and responses of VSMCs. Under permissive-temperature conditions (36 degrees C), the increased rate of cell proliferation was shown to be associated with expression of LT antigen and with LT antigen binding to and inactivation of p53. p53 inactivation failed to block apoptosis induced by serum withdrawal or UV irradiation. Downregulation of LT antigen expression at a nonpermissive temperature (39 degrees C) was shown to be associated with growth arrest, increased expression of the cell cycle inhibitor p21(WAF1/CIP1), increased murine double minute-2 promoter activity, and differential expression of murine double minute-2 gene products, suggesting that p53-induced transcription/transactivation may be involved in VSMC cycle control but not necessarily in apoptosis. The established SMC line HVTs-SM1 may be a useful model for study of the processes involved in myointimal hyperplasia and cellular aging, as well as for the study of cell cycle control in general.


[Acute portal thrombosis and gas in the liver: a report of two cases].
The presence in adults of intrahepatic portal gas is a multifactorial event in which systemic inflammatory and prothrombotic factors coexist, it is common in patients with advanced liver cirrhosis and rare in those with a healthy liver, however its frequency increases with the presence of inflammatory abdominal disorders and hypercoagulability related to systemic inflammatory response, their manifestations are unspecific and varies according to severity. We study two cases with unspecific symptoms, where imaging studies reported intrahepatic portal gas, one secondary to diverticular disease and the second related to liver abscesses, which favorably response with surgical, antibiotic and anticoagulant treatment.


Cytogenotoxic potential and toxicity in adult Danio rerio (zebrafish) exposed to chloramine T.
Chloramine-T (CL-T) is a synthetic sodium salt used as a disinfectant in fish farms to combat bacterial infections in fish gills and skin. While its efficacy in pathogen control is well-established, its reactivity with various functional groups has raised concerns. However, limited research exists on the toxicity of disinfection by-products to aquatic organisms. Therefore, this study aims to assess the sublethal effects of CL-T on adult zebrafish by examining biomarkers of nucleus cytotoxicity and genotoxicity, acetylcholinesterase (AChE) inhibition, and histopathological changes. Male and female adult zebrafish (wildtype AB lineage) specimens were exposed to 70, 140, and 200 mg/L of CL-T and evaluated after 96 h. Cytotoxic and genotoxic effects were evaluated by estimating the frequencies of nuclear abnormalities (NA), micronuclei (MN), and integrated optical density (IOD) of nuclear erythrocytes. Histopathological changes in the gills and liver were assessed using the degree of tissue changes (DTC). AChE activity was measured in brain samples. At a concentration of 200 mg/L, NA increased, indicating the cytogenotoxic potential of CL-T in adult zebrafish. Morphological alterations in the nuclei were observed at both 70 and 200 mg/L concentrations. Distinct IOD profiles were identified across the three concentrations. There were no changes in AChE activity in adult zebrafish. The DTC scores were high in all concentrations, and histological alterations suggested low to moderate toxicity of CL-T for adult zebrafish.


Phenylsulfonylfuroxans as modulators of multidrug-resistance-associated protein-1 and P-glycoprotein.
A series of furoxan derivatives were studied for their ability to interact with P-gp and MRP1 transporters in MDCK cells overexpressing these proteins. 3-Phenylsulfonyl substituted furoxans emerged as the most interesting compounds. All of them were capable of inhibiting P-gp, and a few also were capable of inhibiting MRP1. Substituents at the 4-position of 3-phenylsulfonylfuroxan scaffold were able to modulate the selectivity and the intensity of inhibition. In some cases, they reverted MRP1 inhibitor activity, namely, they were capable of potentiating MRP1 dependent efflux. When compounds 16 and 17 were coadministered with doxorubicin, they restored a high degree of the activity of the antibiotic. Preliminary immunoblotting studies carried out on these two compounds indicate that they are capable of nitrating P-gp, which in this form is likely unable to efflux the antibiotic.


Risk factors of hemorrhagic and ischemic stroke among hospitalized patients in Bangladesh--A case control study.
The risk factor profiles, management and outcome have significant difference between stroke subsets. Aim of this study was to investigate the risk for the two most common subtypes of stroke in Bangladeshi population. Seventy cases of hemorrhagic stroke (HS) and 105 cases of confirmed ischemic stroke (IS) were recruited from the Shaheed Suhrawardy Medical College Hospital (ShSMCH) and Dhaka Medical College Hospital between January-June 2011. Total 171 age, sex matched controls were selected from the hospitalized patients with history of no stroke ever. Average hemorrhagic stroke patients (60.4 ± 12.3 years) were younger than both ischemic strokes (63.5 ± 13 years). Family history of premature cardiovascular death was found more in HS patients (p = 0.001). Multivariate logistic regression showed, in IS model 'less fruit consumption (OR 4.6), table salt intake (OR 8.15), psychosocial stress (OR 3.5), abnormal ECG (OR 3.6) and Increased WHR (OR 6.9) appeared as significant predictors adjusted for all potential candidate confounders. In HS model less fruit consumption (OR 5.0), table salt intake (OR 9.9), Stress (OR 4.1), family history of cardiovascular disease (CVD) death (OR 11.3), hypertension (OR 43), aspirin intake (OR 4.5) and increased WHR (OR 3.7) remained as significant predictors.


Molecular Signatures of Membrane Protein Complexes Underlying Muscular Dystrophy.
Mutations in genes encoding components of the sarcolemmal dystrophin-glycoprotein complex (DGC) are responsible for a large number of muscular dystrophies. As such, molecular dissection of the DGC is expected to both reveal pathological mechanisms, and provides a biological framework for validating new DGC components. Establishment of the molecular composition of plasma-membrane protein complexes has been hampered by a lack of suitable biochemical approaches. Here we present an analytical workflow based upon the principles of protein correlation profiling that has enabled us to model the molecular composition of the DGC in mouse skeletal muscle. We also report our analysis of protein complexes in mice harboring mutations in DGC components. Bioinformatic analyses suggested that cell-adhesion pathways were under the transcriptional control of NFκB in DGC mutant mice, which is a finding that is supported by previous studies that showed NFκB-regulated pathways underlie the pathophysiology of DGC-related muscular dystrophies. Moreover, the bioinformatic analyses suggested that inflammatory and compensatory mechanisms were activated in skeletal muscle of DGC mutant mice. Additionally, this proteomic study provides a molecular framework to refine our understanding of the DGC, identification of protein biomarkers of neuromuscular disease, and pharmacological interrogation of the DGC in adult skeletal muscle https://www.mda.org/disease/congenital-muscular-dystrophy/research.


t-BuOK mediated oxidative coupling amination of 1,4-naphthoquinone and related 3-indolylnaphthoquinones with amines.
The transition-metal free amination of 1,4-naphthoquinone and related 3-indolylnaphthoquinones with amines, such as various (hetero)aromatic amine and aliphatic amine via t-BuOK-mediated oxidative coupling at room temperature has been developed. This reaction provides efficient access to the biologically important and synthetically useful 2-amino-1,4-naphthoquinones and 2-amino-3-indolylnaphthoquinones with good yields under mild conditions. The present protocol is simple, practical and shows good functional group tolerance. In addition, the obtained 2-amino-3-indolylnaphthoquinones were further transformed to synthesize polycyclic N-heterocycles.


Spatial dynamics in model plant communities: what do we really know?
A variety of models have shown that spatial dynamics and small-scale endogenous heterogeneity (e.g., forest gaps or local resource depletion zones) can change the rate and outcome of competition in communities of plants or other sessile organisms. However, the theory appears complicated and hard to connect to real systems. We synthesize results from three different kinds of models: interacting particle systems, moment equations for spatial point processes, and metapopulation or patch models. Studies using all three frameworks agree that spatial dynamics need not enhance coexistence nor slow down dynamics; their effects depend on the underlying competitive interactions in the community. When similar species would coexist in a nonspatial habitat, endogenous spatial structure inhibits coexistence and slows dynamics. When a dominant species disperses poorly and the weaker species has higher fecundity or better dispersal, competition-colonization trade-offs enhance coexistence. Even when species have equal dispersal and per-generation fecundity, spatial successional niches where the weaker and faster-growing species can rapidly exploit ephemeral local resources can enhance coexistence. When interspecific competition is strong, spatial dynamics reduce founder control at large scales and short dispersal becomes advantageous. We describe a series of empirical tests to detect and distinguish among the suggested scenarios.


Biogenic amines determination in some traditional cheeses in West Azerbaijan province of Iran.
Biogenic amines (BA) are nitrogenous compounds that possess biological activity. The source of production is the microbial decarboxylation of amino acids. This compounds are found in various types of cheese. The aim of this work was to evaluate the BA content of some traditional cheeses in West Azerbaijan province Iran. For this purpose, 70 samples of Koopeh, 10 samples of Lighvan and 5 samples of Red Salmas cheeses were obtained from local supermarkets of different cities of West Azerbaijan province. After preparation of samples, biogenic amines content was evaluated by modified HPLC method. The presence of histamine, cadaverine, putrescine and tyramine in tested cheeses were observed. Total amount of biogenic amines was highest in Red Salmas cheese with 1426.91 ppm. It followed by Lighvan cheese and Koopeh cheese with 1008.98 and 517.71 ppm, respectively. Putrescine, cadaverine, histamine and tyramine were detected in Koopeh cheese at levels up to 156.09, 282.34, 70.80, 8.48 ppm respectively. These amines were detected also in Lighvan cheese at levels up to 277.53, 342.74, 37.58, 351.12 ppm and in Red Salmas cheese samples at levels up to 438.03, 701.05, 105.21, 182.62 ppm, respectively. Large amounts of biogenic amines can indicate non hygienic conditions and contamination of used milk for cheese production.


An intervention for nonsuicidal self-injury in young adults: A pilot randomized controlled trial.
Nonsuicidal self-injury (NSSI) is prevalent among young adults and associated with negative medical and psychological consequences, necessitating its treatment. However, few treatments have been developed to treat NSSI specifically, or to treat the behavior among individuals without borderline personality disorder. The purpose of this study was to investigate the Treatment for Self-Injurious Behaviors (T-SIB), a brief, behavioral intervention specifically developed to treat NSSI among young adults, in a pilot randomized controlled trial (RCT). Young adults (N = 33; age: M = 22.36 years, SD = 3.40) meeting inclusion and exclusion criteria were randomly assigned to the treatment (T-SIB; n = 15) or treatment as usual (n = 18) condition. The sample was 93.9% female, 42.4% Caucasian, and 30.3% Hispanic/Latino. Feasibility and acceptability of the study and intervention were supported, and medium effects were found for decreased NSSI frequency in the T-SIB group using intent-to-treat analyses. Results of this study support the further evaluation of T-SIB in a larger RCT. (PsycINFO Database Record


Combination of ivabradine and sacubitril/valsartan in patients with heart failure and reduced ejection fraction.
Ivabradine and sacubitril/valsartan are second-line therapies for patients with heart failure and reduced ejection fraction (HFrEF) based on guideline recommendations. We aimed to evaluate the synergistic effects of these two medications. Patients' data were extracted from a multicentre database between 2016 and 2018. Patients were classified into (1) Simultaneous group: simultaneous prescription of ivabradine and sacubitril/valsartan within 6 weeks; (2A) Sequential group, ivabradine-first: ivabradine was prescribed first, followed by sacubitril/valsartan; and (2B) Sequential group, sacubitril/valsartan-first: sacubitril/valsartan was prescribed first, followed by ivabradine. A total of 464 patients with HFrEF were enrolled. Cardiovascular death and/or unplanned re-hospitalizations for HF were less frequent (28.6% vs. 44.8%, P = 0.01), and the improvement of left ventricular ejection fraction (LVEF) was significantly greater in patients from the Simultaneous group than those from the Sequential group (∆LVEF 12.8 ± 12.9% vs. 9.3 ± 12.6%, P = 0.007). Among Sequential subgroups, the ivabradine-first treatment decreased heart rate and increased systolic blood pressure (SBP) compared with sacubitril/valsartan-first treatment (∆heart rate -9.1 ± 12.9 b.p.m. vs. 2.6 ± 16.0 b.p.m., P < 0.001; ∆SBP 4.6 ± 16.5 mmHg vs. -4.8 ± 17.2 mmHg, P < 0.001), whereas sacubitril/valsartan-first treatment showed a higher degree of LVEF improvement (∆LVEF 3.6 ± 7.8% vs. 0.7 ± 7.7%, P = 0.002) than ivabradine-first treatment. At the end of follow-up, SBP, LVEF, and left ventricular volume were comparable between two Sequential subgroups. Among patients with HFrEF, simultaneous rather than sequential treatment with sacubitril/valsartan and ivabradine was a better strategy to reduce adverse events and achieve left ventricular reverse remodelling. Ivabradine treatment had a more significant benefit on improving haemodynamic stability, whereas sacubitril/valsartan treatment showed a more significant effect on improving LVEF.


Moderate renal impairment and risk of dementia among older adults: the Cardiovascular Health Cognition Study.
Renal impairment is associated with an increased risk of carotid atherosclerosis and stroke, determinants of cognitive dysfunction and dementia. The purpose of this study was to determine whether moderate renal impairment is associated with incident dementia among community-dwelling older adults. Participants in the Cardiovascular Health Cognition Study without prevalent dementia (n = 3349) were included in the analysis. Incident dementia was confirmed through neurologic testing. Renal function at baseline was estimated by the inverse of serum creatinine (1/SCr); moderate renal impairment was defined as SCr > or = 1.3 mg/dl for women and > or = 1.5 mg/dl for men. Cox regression models were used to estimate the association of renal impairment with incident dementia. Because SCr is also a function of muscle mass, the authors determined whether the relationship between SCr and dementia was particularly strong among individuals without severe co-morbidity at baseline, as reflected by self-reported general health status. There were 477 incident dementia cases over a median 6 yr follow-up. After adjustment for potential confounders, moderate renal insufficiency was associated with a 37% increased risk of dementia (95% CI = 1.06 to 1.78). Similarly, a 0.5-unit decrement in 1/SCr (equivalent to an increase in SCr from 1.0 to 2.0 mg/dl) was associated with a 26% increased risk (95% CI = 1.02 to 1.60). These associations were present only among the 84% of older adults who reported good-excellent health. Among those in good-excellent health, higher SCr was associated with vascular-type dementia but not Alzheimer-type dementia. Moderate renal impairment, reflected by a higher SCr, is associated with an excess risk of incident dementia among individuals in good-excellent health. Strategies to prevent or delay the onset of dementia in patients with moderate renal impairment are needed.


Enforced expression of GATA3 allows differentiation of IL-17-producing cells, but constrains Th17-mediated pathology.
The zinc-finger transcription factor GATA3 serves as a master regulator of T-helper-2 (Th2) differentiation by inducing expression of the Th2 cytokines IL-4, IL-5 and IL-13 and by suppressing Th1 development. Here, we investigated how GATA3 affects Th17 differentiation, using transgenic mice with enforced GATA3 expression. We activated naïve primary T cells in vitro in the presence of transforming growth factor-beta and IL-6, and found that enforced GATA3 expression induced co-expression of Th2 cytokines in IL-17-producing T cells. Although the presence of IL-4 hampered Th17 differentiation, transforming growth factor-beta/IL-6 cultures from GATA3 transgenic mice contained substantial numbers of IL-17(+) cells, partially because GATA3 supported Th17 differentiation by limiting IL-2 and IFN-gamma production. GATA3 additionally constrained Th17 differentiation in vitro through IL-4-independent mechanisms, involving downregulating transcription of STAT3, STAT4, NFATc2 and the nuclear factor RORgammat, which is crucial for Th17 differentiation. Remarkably, upon myelin oligodendrocyte glycoprotein immunization in vivo, GATA3 transgenic mice contained similar numbers of IL-17-producing T cells in their lymph nodes as wild-type mice, but were not susceptible to autoimmune encephalomyelitis, possibly due to concomitant production of IL-4 and IL-10 induction. We therefore conclude that although GATA3 allows Th17 differentiation, it acts as an inhibitor of Th17-mediated pathology, through IL-4-dependent and IL-4-independent pathways.