Randomized trial of a patient decision aid for choice of surgical treatment for breast cancer.
A decision aid for the surgical treatment of early breast cancer was evaluated in a randomized controlled trial. The decision aid, a tape and workbook, includes explicit presentation of probabilities, photographs and graphics, and a values clarification exercise. Community surgeons were randomized to use the decision aid or a control pamphlet. Patients completed a questionnaire prior to using the decision aid, after reviewing it but prior to surgery, and 6 months after enrollment. There was no difference in anxiety, knowledge, or decisional regret across the 2 groups. There was a nonsignificant trend toward lower decisional conflict in the decision aid group. A subgroup of women who were initially leaning toward mastectomy or were unsure had lower decisional conflict. Although the decision aid had minimal impact on the main study outcomes, a subgroup may have benefited. Such subgroups should be identified, and appropriate decision support interventions should be developed and evaluated.


Principal Approaches to Understanding Occupation and Occupational Science Found in the Chilean Journal of Occupational Therapy (2001-2012).
The progression of occupational science in Chile is documented in the main scientific publication of the field, the Chilean Journal of Occupational Therapy (RChTO). Identify approaches to understanding and applying occupation and occupational science as elucidated in the RChTO. A systematic qualitative review of the journal (2001-2012) identified articles elucidating an approach to understanding and application operationally defined as references to specific authors, theories, models/paradigms, definitions, and other fields that support approaches to O/OS. The study identified two main approaches. The first considers occupation/occupational science from a practical perspective or as a means to explain human behavior; the second considers occupation/occupational science as an object of study. Each approach is further divided into categories. This study provides a novel perspective on regional use of occupational science concepts. These findings contribute to our understanding of this science in context and to recognition of the cultural relevance of these scientific concepts.


Skewed X-inactivation patterns in ageing healthy and myelodysplastic haematopoiesis determined by a pyrosequencing based transcriptional clonality assay.
Investigation of X-chromosome inactivation patterns (XCIP) by determination of differential CpG-methylation has been widely applied for investigation of female cell clonality. Using this approach the clonal origin of various tumours has been corroborated. Controversially, strong age-related increase of peripheral blood (PB) cell clonality in haematologically healthy female subjects was reported. Recently, transcriptional XCIP ratio analysis challenged these results and questioned the suitability of methylation based clonality assays. To reinvestigate XCIP-skewing in CD34, low-density mononuclear bone marrow (BM) as well as PB cells from healthy female subjects and patients with myelodysplastic syndromes (MDS), we established a transcriptional assay using pyrosequencing technique for quantification of single nucleotide polymorphism allele frequencies, representative for XCIP ratios. Our assay provides high sensitivity for XCIP ratio assessment as determined by standard curves, reproducibility, inter-marker correlation as well as correlation with the DNA-methylation based human androgen receptor (HUMARA) assay. Notably, in agreement with most studies investigating this issue, significant age-related increase of XCIP skewing in PB cells from healthy elderly female subjects was confirmed. Moreover, XCIP ratio analysis suggests even stronger clonal manifestation in BM and CD34 cells. In MDS, XCIP skewing levels were distinctively elevated as compared with controls of similar age and higher degrees were associated with poor clinical outcome. Transcriptional clonal profiling via pyrosequencing allows accurate assessment of XCIP ratios, confirms the validity of the DNA-methylation based HUMARA assay and reveals important insights into ageing healthy and myelodysplastic haematopoiesis.


Nucleotide sequence and expression of relaxin-like gonad-stimulating peptide gene in starfish Asterina pectinifera.
Starfish gonad-stimulating substance (GSS) is the only known invertebrate peptide hormone responsible for final gamete maturation, rendering it functionally analogous to gonadotropins in vertebrates. Because GSS belongs to the relaxin-like peptide family, we propose renaming for starfish gonadotropic hormone as relaxin-like gonad-stimulating peptide (RGP). This study examined the primary structure and expression regulation of the RGP gene in starfish Asterina pectinifera. RGP consisted of 3896 base pairs (bp) divided over two exons, exon 1 of 208 bp and exon 2 of 2277 bp, and one intron of 1411 bp. Promoter sequences, CAAT and TATA boxes, were present in the 5'-upstream region of the coding DNA sequence of RGP. The transcript was 2485 bases (b) in length. The AAUAAA polyadenylation signal was found in 3'-untranslated region over 2kb away from the stop codon. This showed that only 14% of the RGP mRNA was translated into the peptide, because a size of the open-reading frame was 351 b. Furthermore, an analysis by using real-time quantitative PCR with specific primers for RGP showed that mRNA of RGP was expressed at high levels in the radial nerves. Expression was also observed in the cardiac stomachs, although the level was low, and trace levels were detected in the gonads, pyloric caeca and tube feet. This result suggests that the RGP gene is transcribed mainly in the radial nerves of A. pectinifera.


Differential expression of Fos protein after transection of the rat infraorbital nerve in the trigeminal nucleus caudalis.
To determine the effects of nerve injury on Fos expression, temporal and spatial distributions of Fos-positive neurons in the trigeminal nucleus caudalis were examined after tissue injury for isolation of the infraorbital nerve as controls and transection of this nerve as well as noxious chemical stimulation by formalin injection in adult rats. Fos immunoreactivity was markedly elevated in laminae I and II of the only ipsilateral nucleus caudalis 2 h after these surgical procedures and noxious chemical stimulation. The distributions of Fos-positive neurons were restricted rostro-caudally following formalin injection and tissue injury compared to transection of the infraorbital nerve. One day after tissue injury and nerve transection, however, Fos-positive neurons were distributed bilaterally in laminae III and IV extending rostro-caudally and medio-laterally in this nucleus, and this persisted over the 2-week study period. The number of Fos-positive neurons in the side ipsilateral to nerve transection was markedly less than that in the contralateral side whereas positive neurons in the tissue injured rats were distributed symmetrically along the rostro-caudal axis. There was no difference in the contralateral sides between nerve transection and tissue injury groups. The rostro-caudal level showing reduction in Fos expression corresponded roughly to the sites of central termination of the injured nerve in this nucleus, suggesting a role for the primary afferents in the reduction of Fos expression in laminae III and IV neurons of the ipsilateral nucleus caudalis.


Obesity in children & adolescents.
Worldwide, obesity trends are causing serious public health concern and in many countries threatening the viability of basic health care delivery. It is an independent risk factor for cardiovascular diseases and significantly increases the risk of morbidity and mortality. The last two decades have witnessed an increase in health care costs due to obesity and related issues among children and adolescents. Childhood obesity is a global phenomenon affecting all socio-economic groups, irrespective of age, sex or ethnicity. Aetiopathogenesis of childhood obesity is multi-factorial and includes genetic, neuroendocrine, metabolic, psychological, environmental and socio-cultural factors. Many co-morbid conditions like metabolic, cardiovascular, psychological, orthopaedic, neurological, hepatic, pulmonary and renal disorders are seen in association with childhood obesity. The treatment of overweight and obesity in children and adolescents requires a multidisciplinary, multi-phase approach, which includes dietary management, physical activity enhancement, restriction of sedentary behaviour, pharmacotherapy and bariatric surgery. A holistic approach to tackle the childhood obesity epidemic needs a collection of activities including influencing policy makers and legislation, mobilizing communities, restructuring organizational practices, establishing coalitions and networks, empowering providers, imparting community education as well as enriching and reinforcing individual awareness and skills. The implications of this global phenomenon on future generations will be serious unless appropriate action is taken.


Embryonic MicroRNA-369 Controls Metabolic Splicing Factors and Urges Cellular Reprograming.
Noncoding microRNAs inhibit translation and lower the transcript stability of coding mRNA, however miR-369 s, in aberrant silencing genomic regions, stabilizes target proteins under cellular stress. We found that in vitro differentiation of embryonic stem cells led to chromatin methylation of histone H3K4 at the miR-369 region on chromosome 12qF in mice, which is expressed in embryonic cells and is critical for pluripotency. Proteomic analyses revealed that miR-369 stabilized translation of pyruvate kinase (Pkm2) splicing factors such as HNRNPA2B1. Overexpression of miR-369 stimulated Pkm2 splicing and enhanced induction of cellular reprogramming by induced pluripotent stem cell factors, whereas miR-369 knockdown resulted in suppression. Furthermore, immunoprecipitation analysis showed that the Argonaute complex contained the fragile X mental retardation-related protein 1 and HNRNPA2B1 in a miR-369-depedent manner. Our findings demonstrate a unique role of the embryonic miR-369-HNRNPA2B1 axis in controlling metabolic enzyme function, and suggest a novel pathway linking epigenetic, transcriptional, and metabolic control in cell reprogramming.


Protein C and Anti-Thrombin-III Deficiency in Children With Beta-Thalassemia.
Thromboembolic events (TEEs) are recently described complications in thalassemia patients. Many mechanisms were postulated for thrombosis. Conflicting results of natural anticoagulants values were reported in previous studies. Our aim was to investigate protein C and anti-thrombin-III (AT-III) levels in thalassemics and to detect risk factors for their decrement. A cross-sectional study for 60 beta-thalassemia patients (35 major and 25 intermedia) and 35 healthy children were tested for protein C and AT-III levels, liver function tests and Sr. ferritin. A significant reduction in protein C and AT-III levels was noticed in patient group compared to healthy children (82.50% (32 - 175) vs. 104% (60 - 204), P = 0.041 and 237.52 ± 53.19 mg/L vs. 322.99 ± 56.57 mg/L, P value ≤ 0.001, respectively). Protein C was lower among older patients (> 10 years) than younger patients (< 10 years), and splenectomized category than non-splenectomized one (P = 0.02 and 0.011, respectively). AT-III was significantly lower among splenectomized patients as compared to those who did not undergo splenectomy (P = 0.04). Significant correlations were found between protein C and AT-III with older age and liver functions. Protein C and AT-III were significantly lower among thalassemics with the main risk factors for their deficiencies being: splenectomy and increasing age. This allows establishment of early prophylactic policy against TEE for the vulnerable group.


Alteration of histone acetylation pattern during long-term serum-free culture conditions of human fetal placental mesenchymal stem cells.
Increasing evidence suggests that the mesenchymal stem cells (MSCs) derived from placenta of fetal origin (fPMSCs) are superior to MSCs of other sources for cell therapy. Since the initial number of isolated MSCs is limited, in vitro propagation is often required to reach sufficient numbers of cells for therapeutic applications, during which MSCs may undergo genetic and/or epigenetic alterations that subsequently increase the probability of spontaneous malignant transformation. Thus, factors that influence genomic and epigenetic stability of MSCs following long-term expansions need to be clarified before cultured MSCs are employed for clinical settings. To date, the genetic and epigenetic stability of fPMSCs after long-term in vitro expansion has not been fully investigated. In this report, alterations to histone acetylation and consequence on the expression pattern of fPMSCs following in vitro propagation under serum-free conditions were explored. The results show that fPMSCs maintain their MSC characteristics before they reached a senescent state. Furthermore, acetylation modification patterns were changed in fPMSCs along with gradually increased global histone deacetylase (HDAC) activity and expression of HDAC subtypes HDAC4, HDAC5 and HDAC6, as well as a down-regulated global histone H3/H4 acetylation during in vitro culturing. In line with the acetylation alterations, the expression of oncogenes Oct4, Sox2 and TERT were significantly decreased over the propagation period. Of note, the down-regulation of Oct4 was strongly associated with changes in acetylation. Intriguingly, telomere length in fPMSCs did not significantly change during the propagating process. These findings suggest that human fPMSCs may be a safe and reliable resource of MSCs and can be propagated under serum-free conditions with less risk of spontaneous malignancy, and warrants further validation in clinical settings.


Early growth and coronary heart disease and type 2 diabetes: findings from the Helsinki Birth Cohort Study (HBCS).
A slow rate of intrauterine growth is a major risk factor for several common noncommunicable diseases, which include the following: coronary heart disease (CHD), hypertension, and type 2 diabetes. Likewise, growth patterns in infancy and childhood have been identified as important factors linked to the pathogenesis of these disorders. In this overview, patterns of growth associated with CHD, type 2 diabetes, and related metabolic traits in adult life are presented on the basis of findings from the Helsinki Birth Cohort Study (HBCS) 1934-1944. Later risk of CHD was associated with small body size at birth and during infancy, followed by an increase in body size later in childhood. This pattern of growth has been associated with dyslipidemia in later life, which offers an explanation for the observed findings. Type 2 diabetes and CHD share several risk factors. The early growth of persons who later develop type 2 diabetes includes a small body size at birth as well as a small body size during infancy. An early age at adiposity rebound was associated with a markedly increased risk of type 2 diabetes in adulthood. The patterns of growth associated with type 2 diabetes are also associated with alterations in body composition, which predisposes to insulin resistance and the metabolic syndrome. The presented findings suggest that to be able to understand the pathogenesis of several noncommunicable diseases, the diseases need to be studied from a life-course perspective, and prenatal and childhood growth as well as adult characteristics need to be taken into account.


[Organization of early detection of patients with tuberculosis in Moscow].
The tuberculosis mortality rate is largely determined by the organization of early identification of patients with this disease in the general population. At present the volume of prophylactic surveys has reduced, but, nevertheless, they are the method of choice in detecting tuberculosis in time. Since the prevalence of tuberculosis greatly differs in different populations, prophylactic examinations must be differential in relation to the risk of disease or epidemiological hazards. Increasing the coverage of prophylactic examinations of risk groups by 10% allows one to increase the identification of patients with tuberculosis by 1.6 times in them, that by 8.0% enhances it by 1.9 times. Since the socioeconomic conditions have changed and the logistics is poor, the most effective existing actions should be taken.


Work ability in nursing: relationship with psychological demands and control over the work.
to evaluate the association between psychological demands, control over the work and the reduction of work ability of nursing professionals. this cross-sectional study involved 498 nursing professionals of a university hospital in the State of Rio Grande do Sul, Brazil. Data collection was carried out in 2009 using the Brazilian versions of the Work Ability Index and Job Stress Scale, with logistic regression models used for the data analysis. the prevalence of 43.3% for reduced work ability and 29.7% for high-strain in the job (high psychological demand and low control) were observed. The chances for professionals presenting reduced work ability under high-strain were higher and significant when compared to those classified as being under low-strain, even after adjusting for potential confounders, except for age and gender. a high prevalence of reduced work ability was observed. This evidence indicates the need for investigation and detailed analysis of the psychosocial aspects of the professionals with regard to the health/disease process of nursing professionals.


Suspected Exposure to Filoviruses Among People Contacting Wildlife in Southwestern Uganda.
Human and filovirus host interactions remain poorly understood in areas where Ebola hemorrhagic fever outbreaks are likely to occur. In the Bwindi region of Uganda, a hot spot of mammalian biodiversity in Africa, human livelihoods are intimately connected with wildlife, creating potential for exposure to filoviruses. We tested samples from 331 febrile patients presenting to healthcare facilities near Bwindi Impenetrable Forest, Uganda, by polymerase chain reaction (PCR) analysis and Western blot, using recombinant glycoprotein antigens for Ebola virus (EBOV), Sudan virus (SUDV), Bundibugyo virus (BDBV), and Marburg virus. Behavioral data on contact with wildlife were collected to examine risk factors for filovirus seropositivity. All patients were negative for active filovirus infection, by PCR analysis. However, patients were seroreactive to SUDV (4.7%), EBOV (5.3%), and BDBV (8.9%), indicating previous exposure. Touching duikers was the most significant risk factor associated with EBOV seropositivity, while hunting primates and touching and/or eating cane rats were significant risk factors for SUDV seropositivity. People in southwestern Uganda have suspected previous exposure to filoviruses, particularly those with a history of wildlife contact. Circulation of filoviruses in wild animals and subsequent spillover into humans could be more common than previously reported.


Associations Among Psychologically Controlling Parenting, Autonomy, Relatedness, and Problem Behaviors During Emerging Adulthood.
The present study aimed to investigate the relations among perceived parental psychological control (PPC), autonomy and relatedness, and negative outcomes during emerging adulthood in two cultural contexts: Italy and the USA. More specifically, we explored the mechanisms through which dependency-oriented PPC (DPPC) and achievement-oriented PPC (APPC) are associated with both internalizing and externalizing difficulties, focusing on the mediating role of autonomy and relatedness. Participants were 418 European-American and 359 Italian college students. Results indicated that the expressions of PPC with regard to dependency and achievement were related to emerging adults' negative outcomes through different pathways, and these effects were moderated by the cultural group. The implications of the findings for future related empirical investigations and clinical interventions were discussed.


Prevalence and antibiogram study of Staphylococcus aureus isolated from clinical and selected drinking water of Dutsin-Ma, Katsina state, Nigeria.
Multidrug resistant Staphylococcus aureus in clinical and environmental samples is a global problem. Data comparing antibiogram of bacteria from these two sources in Nigeria is scarce. Therefore, this study compares antibiogram of isolates from both sources from Dutsin-Ma, Katsina State, Nigeria. A total of 120 and 150 clinical and aquatic samples respectively were collected for a five months period. Samples were analyzed for isolation of S. aureus using mannitol salt agar. Bacteria identification were carried out using standard biochemical characterization. Antibiogram of the isolates were determined using disc diffusion methods and comparison with Clinical Laboratory Standard Institute (CLSI)'s Standard. A total of 120 and 45 S. aureus were isolated from both clinical and aquatic samples respectively. Highest (100.0%) resistance to cloxacillin was observed among isolates from each source. Clinical and aquatic isolates showed least resistance of 20.0% and 48.0% respectively to gentamicin. All isolated S. aureus (165) from this studies were multidrug resistant with different antibiotic resistant pattern. This study revealed that multidrug resistance strains of S. aureus can be isolated from both clinical and drinking water sources, hence, a public health significance that calls for urgent attention by clinicians and public health workers.


Universal whole-sequence-based plasmid typing and its utility to prediction of host range and epidemiological surveillance.
Bacterial plasmids play a large role in allowing bacteria to adapt to changing environments and can pose a significant risk to human health if they confer virulence and antimicrobial resistance (AMR). Plasmids differ significantly in the taxonomic breadth of host bacteria in which they can successfully replicate, this is commonly referred to as 'host range' and is usually described in qualitative terms of 'narrow' or 'broad'. Understanding the host range potential of plasmids is of great interest due to their ability to disseminate traits such as AMR through bacterial populations and into human pathogens. We developed the MOB-suite to facilitate characterization of plasmids and introduced a whole-sequence-based classification system based on clustering complete plasmid sequences using Mash distances (https://github.com/phac-nml/mob-suite). We updated the MOB-suite database from 12 091 to 23 671 complete sequences, representing 17 779 unique plasmids. With advances in new algorithms for rapidly calculating average nucleotide identity (ANI), we compared clustering characteristics using two different distance measures - Mash and ANI - and three clustering algorithms on the unique set of plasmids. The plasmid nomenclature is designed to group highly similar plasmids together that are unlikely to have multiple representatives within a single cell. Based on our results, we determined that clusters generated using Mash and complete-linkage clustering at a Mash distance of 0.06 resulted in highly homogeneous clusters while maintaining cluster size. The taxonomic distribution of plasmid biomarker sequences for replication and relaxase typing, in combination with MOB-suite whole-sequence-based clusters have been examined in detail for all high-quality publicly available plasmid sequences. We have incorporated prediction of plasmid replication host range into the MOB-suite based on observed distributions of these sequence features in combination with known plasmid hosts from the literature. Host range is reported as the highest taxonomic rank that covers all of the plasmids which share replicon or relaxase biomarkers or belong to the same MOB-suite cluster code. Reporting host range based on these criteria allows for comparisons of host range between studies and provides information for plasmid surveillance.


Isolation of a human papillomavirus from a patient with epidermodysplasia verruciformis: presence of related viral DNA genomes in human urogenital tumors.
The DNA genome of a human papillomavirus (HPV), tentatively designated HPV-EV, was molecularly cloned from hand to leg lesions of a patient with epidermodysplasia verruciformis, a chronic skin disease associated with a 30% risk of developing cancer. Using stringent hybridization conditions, we observed less than 5% homology between HPV-EV and the cloned genomes of HPV-1, HPV-4, HPV-5, and HPV-5a. HPV-EV DNA showed approximately 6% homology with HPV-2 and 36% homology with HPV-3. These data suggest that HPV-EV is partially related to HPV-3. Using 32P-labeled cloned HPV-EV as probe in Southern blot hybridization experiments, we detected HPV-EV-related DNA in the carcinoma in situ (Bowenoid lesion) of the vulva of the patient from which HPV-EV was isolated. HPV-EV-related DNA was detected in 2 of 10 vulva carcinomas and in 2 of 31 cervical carcinomas. Related DNA sequences were found in papillomas from each of two patients with condyloma acuminata (anogenital warts), which is of interest considering that condylomas have been reported to convert occasionally to carcinomas. The positive vulva DNAs were also probed with other cloned HPV DNAs: HPV-1, HPV-4, and HPV-5a-related sequences were not detected; HPV-3 and HPV-2 DNA probes detected strong and weak DNA bands, respectively, of the same size as found with HPV-EV. The HPV DNA sequences were present in the positive tumors mainly as free viral DNA molecules; no evidence for integration into cellular DNA was found. The emerging biological picture with papillomaviruses is that cells transformed by these viruses are maintained in a transformed state by free episomal genomes. Thus, our findings are consistent with the idea, but by no means establish, that HPVs play a role in human cancer by a similar mechanism.


Determining organ weight toxicity with Bayesian causal models: Improving on the analysis of relative organ weights.
Regulatory authorities require animal toxicity tests for new chemical entities. Organ weight changes are accepted as a sensitive indicator of chemically induced organ damage, but can be difficult to interpret because changes in organ weight might reflect chemically-induced changes in overall body weight. A common solution is to calculate the relative organ weight (organ to body weight ratio), but this inadequately controls for the dependence on body weight - a point made by statisticians for decades, but which has not been widely adopted. The recommended solution is an analysis of covariance (ANCOVA), but it is rarely used, possibly because both the method of statistical correction and the interpretation of the output may be unclear to those with minimal statistical training. Using relative organ weights can easily lead to incorrect conclusions, resulting in poor decisions, wasted resources, and an ethically questionable use of animals. We propose to cast the problem into a causal modelling framework as it directly assesses questions of scientific interest, the results are easy to interpret, and the analysis is simple to perform with freely available software. Furthermore, by taking a Bayesian approach we can model unequal variances, control for multiple testing, and directly provide evidence of safety.


[Effects of double CO2 and O3 on growth and yields in soybean].
The effects of doubled CO2 and O3 interaction on growth and yields in soybean were investigated in the open top chamber for the first time. Increasing CO2 can promote roots growth. The ability of nitrogen fixation enhanced. Plant height and base diameter increased. There are a little effect on the development stage, green leaf number and leaf area. Double O3 concentration inhibited roots and stems growth. The ability of nitrogen fixation decreased. Green leaf number and leaf area decreased and advanced senescence course. This experiment also indicated that CO2 enhancement could relax the injury and inhibition by O3 to soybean seedling. The differences of growth and the ability of nitrogen fixation in soybean between lasted double CO2 and control are less than that of single O3 concentration. Stimulation and dose-effect of increasing CO2 and O3 concentrations to soybean gradually induced more serious damage in the development late. Green leaf number and leaf area decreased. The ability of nitrogen fixation increased markedly.


Effect of tea extracts, polyphenols, and epigallocatechin gallate on azoxymethane-induced colon cancer.
Studies were conducted to determine the chemopreventive efficacy of several types of tea extracts on azoxymethane-induced colon cancer in male F344 rats. After determining the maximally tolerated dosage of the tea products, their effect in a colon cancer model was investigated. Groups of 36 male F344 rats received 2 subcutaneous doses of 15 mg/kg azoxymethane (AOM) at Weeks 6 and 7. Experimental groups also received as drinking fluids 3600 ppm of black or green tea extracts, 1800 ppm of EGCG, or 1800 ppm of black or green tea polyphenols beginning at 5 weeks of age. Additional groups drank a lower dose of 360 ppm of the five tea products. The experiments were terminated 43 weeks after the first tea exposure. No evidence of toxicity was observed since the body weight gain of all groups was similar. The rats given AOM had carcinoma of the small intestine and of the colon, classified histologically as in situ carcinoma, exophytic, invasive, and Peyer's patch carcinoma. In the small intestine, most of the neoplasms were classified as invasive, but in the colon, most were exophytic. The various tea products failed to produce a significant difference in the incidence of the several types of colon and small intestine carcinoma. The multiplicity of colon cancers ranged from 1.2-2.8 in all groups. The group on 3600 ppm of green tea had a significantly higher tumor multiplicity than the control group on AOM and water. Also, the group on 3600 ppm of green tea had a significantly higher tumor multiplicity than the group on 360 ppm. The tea products did not affect the development aspects of the tumors in most groups. The mechanisms underlying these findings rest on the fact that azoxymethane is metabolized mainly by cytochrome P450 2E1, and this enzyme system is not affected by tea.


Shedding light on therapeutics in alopecia and their relevance to COVID-19.
As of July 9, 2020, there were more than 12 million confirmed cases of coronavirus disease 2019 (COVID-19) across the globe, with more than 550,000 deaths. Many European countries, including Belgium, the United Kingdom, Italy, and Spain, have had the highest numbers of fatalities per capita. This indicates the potential for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus to overwhelm even the most advanced health care systems despite extreme societal interventions. Since its emergence, SARS-CoV-2 has disseminated across the globe, affecting the structure of global societies, infrastructure, and economies. Patients with alopecia are a diverse group who, for various indications, are prescribed a number of antimicrobials and antiandrogen treatments in addition to immunomodulatory therapies such as hydroxychloroquine, oral corticosteroids, and a range of broad immunosuppressants. These drugs are being scrutinized for their capacity to potentially affect SARS-CoV-2 outcomes. We examine these treatments and highlight the critical role that patient registries will play in generating real-world evidence to assess their impact on COVID-19 outcomes.


An evaluation of nearly-extinct cohort methods for estimating the very elderly populations of australia and new zealand.
The rapid growth of very elderly populations requires accurate population estimates up to the highest ages. However, it is recognised that estimates derived from census counts are often unreliable. Methods that make use of death data have not previously been evaluated for Australia and New Zealand. The aim was to evaluate a number of nearly-extinct cohort methods for producing very elderly population estimates by age and sex for Australia and New Zealand. The accuracy of official estimates was also assessed. Variants of three nearly-extinct cohort methods, the Survivor Ratio method, the Das Gupta method and a new method explicitly allowing for falling mortality over time, were evaluated by retrospective application over the period 1976-1996. Estimates by sex and single years of age were compared against numbers derived from the extinct cohort method. Errors were measured by the Weighted Mean Absolute Percentage Error. It is confirmed that for Australian females the Survivor Ratio method constrained to official estimates for ages 90+ performed well. However, for Australian males and both sexes in New Zealand, more accurate estimates were obtained by constraining the Survivor Ratio method to official estimates for ages 85+. Official estimates in Australia proved reasonably accurate for ages 90+ but at 100+ they varied significantly in accuracy from year to year. Estimates produced by Statistics New Zealand in aggregate for ages 90+ proved very accurate. We recommend the use of the Survivor Ratio method constrained to official estimates for ages 85+ to create very elderly population estimates for Australia and New Zealand.


On the diversity of malaria parasites in African apes and the origin of Plasmodium falciparum from Bonobos.
The origin of Plasmodium falciparum, the etiological agent of the most dangerous forms of human malaria, remains controversial. Although investigations of homologous parasites in African Apes are crucial to resolve this issue, studies have been restricted to a chimpanzee parasite related to P. falciparum, P. reichenowi, for which a single isolate was available until very recently. Using PCR amplification, we detected Plasmodium parasites in blood samples from 18 of 91 individuals of the genus Pan, including six chimpanzees (three Pan troglodytes troglodytes, three Pan t. schweinfurthii) and twelve bonobos (Pan paniscus). We obtained sequences of the parasites' mitochondrial genomes and/or from two nuclear genes from 14 samples. In addition to P. reichenowi, three other hitherto unknown lineages were found in the chimpanzees. One is related to P. vivax and two to P. falciparum that are likely to belong to distinct species. In the bonobos we found P. falciparum parasites whose mitochondrial genomes indicated that they were distinct from those present in humans, and another parasite lineage related to P. malariae. Phylogenetic analyses based on this diverse set of Plasmodium parasites in African Apes shed new light on the evolutionary history of P. falciparum. The data suggested that P. falciparum did not originate from P. reichenowi of chimpanzees (Pan troglodytes), but rather evolved in bonobos (Pan paniscus), from which it subsequently colonized humans by a host-switch. Finally, our data and that of others indicated that chimpanzees and bonobos maintain malaria parasites, to which humans are susceptible, a factor of some relevance to the renewed efforts to eradicate malaria.


Direct cytotoxicity of Lentinula edodes mycelia extract on human hepatocellular carcinoma cell line.
Lentinula edodes mycelia (L.E.M.) is a dried powder extracted from shiitake mushrooms (Lentinula edodes). We previously demonstrated that it has immunomodulatory effects. In this paper, the direct cytotoxic effects of the polysaccharide-rich fraction of L.E.M. (L.E.M. ethanol precipitate; LEP) on HepG2 human hepatocellular carcinoma (HCC) cells were investigated. LEP directly killed the HepG2 cells efficaciously, but had only minor effects on normal rat hepatocytes and normal mouse dermal cells under the same conditions. Characteristic morphological changes associated with apoptosis such as shrinkage, rounding, and floating as well as chromatin condensation were confirmed; terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining was positive as determined by fluorescence microscopy analyses. The caspase-3 and -8 death receptor pathway was found largely responsible for the apoptotic death of HepG2 cells treated with LEP. In conclusion, LEP can directly induce apoptosis of HepG2 cells, and thus may have potential chemotherapeutic applications for the treatment of HCC.


Cryo-TEM Reveals the Influence of Multivalent Charge and PEGylation on Shape Transitions in Fluid Lipid Assemblies: From Vesicles to Discs, Rods, and Spheres.
Lipids, and cationic lipids in particular are of interest as delivery vectors for hydrophobic drugs such as the cancer therapeutic paclitaxel, and the structures of lipid assemblies affect their efficacy. We investigated the effect of incorporating the multivalent cationic lipid MVL5 (+5e) and poly(ethylene glycol)-lipids (PEG-lipids), alone and in combination, on the structure of fluid-phase lipid assemblies of the charge-neutral lipid 1,2-dioleoyl-sn-glycero-phosphocholine (DOPC). This allowed us to elucidate lipid-assembly structure correlations in sonicated formulations with high charge density, which are not accessible with univalent lipids such as the well-studied DOTAP (+1e). Cryogenic transmission electron microscopy (cryo-TEM) allowed us to determine the structure of the lipid assemblies, revealing diverse combinations of vesicles and disc-shaped, worm-like, and spherical micelles. Remarkably, MVL5 forms an essentially pure phase of disc micelles at 50 mol % MVL5. At a higher (75 mol %) content of MVL5, short- and intermediate-length worm-like micellar rods were observed, and in ternary mixtures with PEG-lipid, longer and highly flexible worm-like micelles formed. Independent of their length, the worm-like micelles coexisted with spherical micelles. In stark contrast, DOTAP forms mixtures of vesicles, disc micelles, and spherical micelles at all studied compositions, even when combined with PEG-lipids. The observed similarities and differences in the effects of charge (multivalent versus univalent) and high curvature (multivalent charge versus PEG-lipid) on the assembly structure provide insights into parameters that control the size of fluid lipid nanodiscs, relevant for future applications.


The Sur7 protein regulates plasma membrane organization and prevents intracellular cell wall growth in Candida albicans.
The Candida albicans plasma membrane plays important roles in cell growth and as a target for antifungal drugs. Analysis of Ca-Sur7 showed that this four transmembrane domain protein localized to stable punctate patches, similar to the plasma membrane subdomains known as eisosomes or MCC that were discovered in S. cerevisiae. The localization of Ca-Sur7 depended on sphingolipid synthesis. In contrast to S. cerevisiae, a C. albicans sur7Delta mutant displayed defects in endocytosis and morphogenesis. Septins and actin were mislocalized, and cell wall synthesis was very abnormal, including long projections of cell wall into the cytoplasm. Several phenotypes of the sur7Delta mutant are similar to the effects of inhibiting beta-glucan synthase, suggesting that the abnormal cell wall synthesis is related to activation of chitin synthase activity seen under stress conditions. These results expand the roles of eisosomes by demonstrating that Sur7 is needed for proper plasma membrane organization and cell wall synthesis. A conserved Cys motif in the first extracellular loop of fungal Sur7 proteins is similar to a characteristic motif of the claudin proteins that form tight junctions in animal cells, suggesting a common role for these tetraspanning membrane proteins in forming specialized plasma membrane domains.


School Health Services for Children With Special Health Care Needs in California.
Children with special health care needs (CSHCN) are at risk for school failure when their health needs are not met. Current studies have identified a strong connection between school success and health. This study attempted to determine (a) how schools meet the direct service health needs of children and (b) who provides those services. The study used the following two methods: (a) analysis of administrative data from the California Basic Educational Data System and (b) a cross-sectional online survey of 446 practicing California school nurses. Only 43% of California's school districts employ school nurses. Unlicensed school personnel with a variety of unregulated training provide school health services. There is a lack of identification of CSHCN, and communication barriers impair the ability to deliver care. Study results indicate that California invests minimally in school health services.


Single-Cell Landscape of Lungs Reveals Key Role of Neutrophil-Mediated Immunopathology during Lethal SARS-CoV-2 Infection.
Due to the limitation of human studies with respect to individual difference or the accessibility of fresh tissue samples, how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection results in pathological complications in lung, the main site of infection, is still incompletely understood. Therefore, physiologically relevant animal models under realistic SARS-CoV-2 infection conditions would be helpful to our understanding of dysregulated inflammation response in lung in the context of targeted therapeutics. Here, we characterized the single-cell landscape in lung and spleen upon SARS-CoV-2 infection in an acute severe disease mouse model that replicates human symptoms, including severe lung pathology and lymphopenia. We showed a reduction of lymphocyte populations and an increase of neutrophils in lung and then demonstrated the key role of neutrophil-mediated lung immunopathology in both mice and humans. Under severe conditions, neutrophils recruited by a chemokine-driven positive feedback produced elevated "fatal signature" proinflammatory genes and pathways related to neutrophil activation or releasing of granular content. In addition, we identified a new Cd177high cluster that is undergoing respiratory burst and Stfahigh cluster cells that may dampen antigen presentation upon infection. We also revealed the devastating effect of overactivated neutrophil by showing the highly enriched neutrophil extracellular traps in lung and a dampened B-cell function in either lung or spleen that may be attributed to arginine consumption by neutrophil. The current study helped our understanding of SARS-CoV-2-induced pneumonia and warranted the concept of neutrophil-targeting therapeutics in COVID-19 treatment. IMPORTANCE We demonstrated the single-cell landscape in lung and spleen upon SARS-CoV-2 infection in an acute severe disease mouse model that replicated human symptoms, including severe lung pathology and lymphopenia. Our comprehensive study revealed the key role of neutrophil-mediated lung immunopathology in SARS-CoV-2-induced severe pneumonia, which not only helped our understanding of COVID-19 but also warranted the concept of neutrophil targeting therapeutics in COVID-19 treatment.


Prediction of residual disease after primary cytoreductive surgery for advanced-stage ovarian cancer: accuracy of clinical judgment.
Treatment of patients with an advanced-stage epithelial ovarian cancer (EOC) is based on cytoreductive surgery and platinum-based chemotherapy. Amount of residual disease after primary cytoreductive surgery is an important prognostic factor. The objectives of the present study were to evaluate the accuracy and reproducibility of preoperative clinical judgment of residual disease after primary cytoreductive surgery and to compare the predictive performance of the offhand assessment to the predictive performance of prediction models. Fifteen observers (5 gynecologic oncologists, 5 gynecologists, and 5 senior residents) were offered preoperative data of 20 patients with advanced-stage EOC who underwent primary cytoreductive surgery. The observers were asked to predict residual disease after cytoreductive surgery (<or=1 or >1 cm). Their estimation was compared with the performance of 2 prediction models. Overall, suboptimal cytoreduction was predicted with a sensitivity of 50% and a specificity of 56%. The intraclass correlation coefficient was 0.27. chi(2) Test showed no significant difference in prediction of suboptimal cytoreduction between the different subgroups and prediction models. Clinical judgment of residual disease after primary cytoreductive surgery in patients with advanced-stage EOC shows limited accuracy. Given the poor interobserver reproducibility, prediction models could attribute to uniform treatment decisions and improve counseling.


Independent component analysis removing artifacts in ictal recordings.
Independent component analysis (ICA) is a novel algorithm able to separate independent components from complex signals. Studies in interictal EEG demonstrate its usefulness to eliminate eye, muscle, 50-Hz, electrocardiogram (ECG), and electrode artifacts. The goal of this study was to evaluate the usefulness of ICA in removing artifacts in ictal recordings with a known EEG onset. We studied 20 seizures of nine patients with focal epilepsy monitored in our video-EEG monitoring unit. ICA was applied to remove obvious artifacts in segments at the beginning of the seizure. The final EEGs were exported to the original format and were compared with the original EEG by two blinded examiners. We compared original recordings and the samples cleaned by digital filters (DFs), ICA and ICA plus digital filters (ICA + DFs), evaluating the possibility of finding an ictal pattern, the localization of the onset in area and time, and the global quality of the sample. All the recordings except one (95%) improved after the use of ICA for the elimination of blinking and other artifacts. Three seizures were found in which in the original recordings did not permit us to detect an ictal pattern, and after ICA + DFs, an ictal onset was evident; in two of them, ICA alone was able to show this pattern. The best results in all the scores were obtained with ICA + DF. ICA was better than DFs. The agreement between the two reviewers was highly significant. ICA is useful to remove artifacts from ictal recordings. When applied to ictal recordings, it increases the quality of the recording. In some cases, ICA may be useful to show ictal onsets obscured by artifacts. ICA + DFs obtained the best results regarding removal of the artifacts.


Variations of periphytic diatom sensitivity to the herbicide diuron and relation to species distribution in a contamination gradient: implications for biomonitoring.
Diatoms are commonly used as bioindicators of trophic and saprobic pollution in rivers. However, more knowledge is needed concerning their sensitivity to toxicants such as agricultural herbicides. In this study, seven species of periphytic diatoms were isolated from the Morcille River (Beaujolais area, France) which presents a streamward contamination gradient by pesticides and particularly diuron. The sensitivity of these species to diuron was assessed through ecotoxicological tests based on short-term growth inhibition of monospecific cultures. After application of an appropriate toxicological model, EC50 were determined and the species were ranked according to their tolerance. EC50 values ranged from 4.5 to 19 μg L(-1). Finally, the results were related to field periphyton samples from an upstream and a downstream site in order to check if variations in specific relative abundance between sites are consistent with differences in tolerance to diuron. Species distribution between sites was only partially in accordance with toxicological results suggesting that other factors (toxic or trophic) have an important influence on diatom communities in the river. Nevertheless, diatoms showed their potential to indicate water contamination by pesticides and toxic indices could be developed in complement to existing trophic indices.


Developing product label information to support evidence-informed use of vaccines in pregnancy.
Product labelling information describing the use of vaccines in pregnancy continues to contain cautionary language even after clinical and epidemiological evidence of safety becomes available. This language raises safety concerns among healthcare providers who may hesitate to recommend vaccines during pregnancy. To develop clear evidence-based language about vaccine safety and effectiveness in pregnancy for inclusion in vaccine product labels. We conducted a three-stage consensus-methods project with stakeholders, including: healthcare providers, vaccine regulators, industry representatives, and experts in public health, communication, law, ethics, and social sciences. Using qualitative and quantitative methods, we held a nominal group technique (NGT) meeting, followed by a Delphi survey, and then a consensus workshop with a subset of Delphi participants. We developed a methodological tool to analyse data for consensus. Stakeholders (N = 14) at the NGT meeting drafted product label statements for evaluation in the Delphi survey. Survey participants (N = 41) provided feedback on statements for five hypothetical vaccines. Workshop participants (N = 27) initiated discussions that demonstrated a lack of awareness that the regulatory purpose of product labels is to provide a scientific summary of product-specific pre-clinical and clinical trial data. Each stage of this project built on earlier stages until we achieved strong consensus on the language, structure, and types of data that stakeholders wanted to include in inactivated influenza vaccine (IIV) and tetanus-diphtheria-acellular pertussis (Tdap) vaccine product labels in Canada. The revised statements for IIV and Tdap aligned with workshop participants' goals that the product label be evidence-based, with a consistent structure and language that is easily understood by healthcare providers. Emergent methods uncovered stakeholder concerns about the regulatory purpose, content, and evidence used in product labels. Involving healthcare providers in the development and regular updating of product information could prevent interpretations of that information that contribute to vaccine hesitancy.


Effect of intravenous silica on the course of Nocardia asteroides pneumonia.
Silica, a known toxin of mononuclear phagocytes, was administered intravenously to mice during Nocardia asteroides pneumonia. Mice that received silica had a sevenfold decrease in the number of peripheral blood monocytes and developed more severe N. asteroides pneumonia than control mice. Lung histology in mice that received silica resembled that of mice with impaired cell-mediated immunity. These results are most consistent with the explanation that silica injures blood monocytes and impairs their contributions to pulmonary host defense.


Phenanthroline and Schiff Base associated Cu(II)-coordinated compounds containing N, O as donor atoms for potent anticancer activity.
As an inherent metal ion, copper has been the subject of investigation for developing a novel antitumoral compound that exhibits fewer adverse effects. Copper serves as a cofactor in multiple enzymes, generates reactive oxygen species (ROS), facilitates tumour evolution, metastasis and angiogenesis and has been detected at elevated concentrations in the serum and tissues of various human cancer types. In the given setting, utilising two methodologies in developing novel Copper-based pharmaceuticals for anti-cancer applications is standard practice. These approaches involve either the sequestration of unbound Copper ions or the synthesis of Copper complexes that induce cellular apoptosis. In the past four decades, the latter system has been used, leading to numerous reviews that have examined the anticancer characteristics of a wide range of Copper complexes. These analyses have consistently demonstrated that multiple factors frequently influence the efficacy of these compounds. This review examines the possible anticancer properties of copper and Cu(II) complexes that incorporate Schiff base ligands containing 1,10-phenanthroline. The present study will comprehensively analyse the examined cell lines and mechanistic research associated with each complex.


Knowledge, attitude, and practice of bariatric surgery among adult Saudi community, Saudi Arabia, 2019.
The prevalence of overweight and obesity is higher in developed countries than in developing countries of all ages (data from 2013). This study is aimed at assessing the knowledge and attitudes of people in Saudi Arabia toward bariatric surgery. To do this, the specific objectives sought to determine the satisfaction of people who underwent bariatric surgery and to determine the importance of bariatric surgery among the community. The study is a cross-sectional, community-based study conducted among the Saudi adult population. The final sample size was 891 respondents from different regions of Saudi Arabia. Data collection was through online questionnaires that consisted of 26 questions to assess the perceived knowledge and attitudes toward obesity and bariatric surgery adopted from Abouhamda (2016). More than 70% of the study participants were aged between 18 and 25 years. There were more males than there were females 76.0% versus 24.0%, while most of the respondents were living single. The proportion of respondents across listed regions of Saudi Arabia significantly varied at a 5% level (P = 0.000). Sixty percent of the study respondents were within the normal weight range (BMI 18.5-25), 9% were marked as obese (BMI >30). Age group was not significantly associated with knowledge of quantization and perceived the knowledge that quantization can cause death (P > 0.05 in both cases). The knowledge about obesity in Saudi Arabia is generally good and most Saudis would rather take the approach of proper diet as opposed to surgery, with the bigger percentage being in the normal range (BMI 18.5-25).


[Combined operative interventions for locally-spread diseases of large bowel].
In the clinic of general surgery, based on The Rural coloproctological centre, in 2012-2013 yrs 469 patients were operated for various diseases of large bowel. There were analyzed the results of treatment in 51 (10.8%) patients, to whom the combined operative interventions (COI) were conducted. For the large bowel tumors 48 (94.1%) patients were operated, for nontumoral diseases--3 (5.9%). COI, as a palliative procedures for the large bowel tumors of various localization, were performed in 22 (13.1%) patients, in 34 (67%)--with resection and excision of one organ, and in 17 (33%)--of two organs and more. In 49 (96%) patients the operation was completed by formation of interintestinal anastomosis or using colonic descendence. In adequate conduction of diagnostic measures and preoperative preparations of patients the COI performance is expedient, because it do not compromise the indices of the patients quality of life. For estimation of the COI risk grade it is necessary to take into account the volume and severity of each stage, expressiveness of the disorders in the organs and systems function as well as the tumors resectability.


Community-led services for mental health care: a study.
This paper reports findings from a study into the effects of relocating untrained personnel from the hospital into the community, over a nine-month period. The study measured the dependent variables of hospital admissions, length of stay, resultant cost savings and community caseloads. Non-significant decreases occurred in bed occupancy as well as increases in bed occupancy, more demanding community psychiatric nurse (CPN) caseloads and an increasing use of the community services by females. Future studies will need to distinguish the most appropriate models of service delivery in a community setting. The findings, verified nationally, have major ramifications for mental health nurses if they are to provide effective care to the seriously mentally ill patient.


Cholecystokinin Switches the Plasticity of GABA Synapses in the Dorsomedial Hypothalamus via Astrocytic ATP Release.
Whether synapses in appetite-regulatory brain regions undergo long-term changes in strength in response to satiety peptides is poorly understood. Here we show that following bursts of afferent activity, the neuromodulator and satiety peptide cholecystokinin (CCK) shifts the plasticity of GABA synapses in the dorsomedial nucleus of the hypothalamus of male Sprague Dawley rats from long-term depression to long-term potentiation (LTP). This LTP requires the activation of both type 2 CCK receptors and group 5 metabotropic glutamate receptors, resulting in a rise in astrocytic intracellular calcium and subsequent ATP release. ATP then acts on presynaptic P2X receptors to trigger a prolonged increase in GABA release. Our observations demonstrate a novel form of CCK-mediated plasticity that requires astrocytic ATP release, and could serve as a mechanism for appetite regulation.SIGNIFICANCE STATEMENT Satiety peptides, like cholecystokinin, play an important role in the central regulation of appetite, but their effect on synaptic plasticity is not well understood. The current data provide novel evidence that cholecystokinin shifts the plasticity from long-term depression to long-term potentiation at GABA synapses in the rat dorsomedial nucleus of the hypothalamus. We also demonstrate that this plasticity requires the concerted action of cholecystokinin and glutamate on astrocytes, triggering the release of the gliotransmitter ATP, which subsequently increases GABA release from neighboring inhibitory terminals. This research reveals a novel neuropeptide-induced switch in the direction of synaptic plasticity that requires astrocytes, and could represent a new mechanism by which cholecystokinin regulates appetite.


Insights into gliadin supramolecular organization at digestive pH 3.0.
Alpha-gliadin is a highly immunogenic protein from wheat, which is associated with many human diseases, like celiac disease and non-celiac gluten sensitivity. Because of that, gliadin solution is subject to intense biomedical research. However, the physicochemical nature of the employed gliadin solution at physiological pH is not understood. Herein, we present a supramolecular evaluation of the alpha-gliadin protein in water at pH 3.0 by dynamic light scattering (DLS), cryo-transmission electron microscopy (cryo-TEM) and small-angle-.X-ray scattering (SAXS). We report that at 0.5 wt% concentration (0.1 mg/ml), gliadin is already a colloidal polydisperse system with an average hydrodynamic radius of 30 ± 10 nm. By cryo-TEM, we detected mainly large clusters. However, it was possible to visualise for the first time prolate oligomers of around 68 nm and 103 nm, minor and major axis, respectively. SAXS experiments support the existence of prolate/rod-like structures. At 1.5 wt% concentration gliadin dimers, small oligomers and large clusters coexist. The radius of gyration (Rg1) of gliadin dimer is 5.72 ± 0.23 nm with a dimer cross-section (Rc) of 1.63 nm, and an average length of around 19 nm, this suggests that gliadin dimers are formed longitudinally. Finally, our alpha-gliadin 3D model, obtained by ab initio prediction and analysed by molecular dynamics (MD), predicts that two surfaces prone to aggregation are exposed to the solvent, at the C-terminus. We hypothesise that this region may be involved in the dimerisation process of alpha-gliadin.


Cellular stress responses: cell survival and cell death.
Cells can respond to stress in various ways ranging from the activation of survival pathways to the initiation of cell death that eventually eliminates damaged cells. Whether cells mount a protective or destructive stress response depends to a large extent on the nature and duration of the stress as well as the cell type. Also, there is often the interplay between these responses that ultimately determines the fate of the stressed cell. The mechanism by which a cell dies (i.e., apoptosis, necrosis, pyroptosis, or autophagic cell death) depends on various exogenous factors as well as the cell's ability to handle the stress to which it is exposed. The implications of cellular stress responses to human physiology and diseases are manifold and will be discussed in this review in the context of some major world health issues such as diabetes, Parkinson's disease, myocardial infarction, and cancer.


Complete or Culprit-Only PCI in Older Patients with Myocardial Infarction.
The benefit of complete revascularization in older patients (≥75 years of age) with myocardial infarction and multivessel disease remains unclear. In this multicenter, randomized trial, we assigned older patients with myocardial infarction and multivessel disease who were undergoing percutaneous coronary intervention (PCI) of the culprit lesion to receive either physiology-guided complete revascularization of nonculprit lesions or to receive no further revascularization. Functionally significant nonculprit lesions were identified either by pressure wire or angiography. The primary outcome was a composite of death, myocardial infarction, stroke, or any revascularization at 1 year. The key secondary outcome was a composite of cardiovascular death or myocardial infarction. Safety was assessed as a composite of contrast-associated acute kidney injury, stroke, or bleeding. A total of 1445 patients underwent randomization (720 to receive complete revascularization and 725 to receive culprit-only revascularization). The median age of the patients was 80 years (interquartile range, 77 to 84); 528 patients (36.5%) were women, and 509 (35.2%) were admitted for ST-segment elevation myocardial infarction. A primary-outcome event occurred in 113 patients (15.7%) in the complete-revascularization group and in 152 patients (21.0%) in the culprit-only group (hazard ratio, 0.73; 95% confidence interval [CI], 0.57 to 0.93; P = 0.01). Cardiovascular death or myocardial infarction occurred in 64 patients (8.9%) in the complete-revascularization group and in 98 patients (13.5%) in the culprit-only group (hazard ratio, 0.64; 95% CI, 0.47 to 0.88). The safety outcome did not appear to differ between the groups (22.5% vs. 20.4%; P = 0.37). Among patients who were 75 years of age or older with myocardial infarction and multivessel disease, those who underwent physiology-guided complete revascularization had a lower risk of a composite of death, myocardial infarction, stroke, or ischemia-driven revascularization at 1 year than those who received culprit-lesion-only PCI. (Funded by Consorzio Futuro in Ricerca and others; FIRE ClinicalTrials.gov number, NCT03772743.).


Current management of double-outlet left ventricle: towards biventricular repair in infancy.
Double-outlet left ventricle (DOLV) is an extremely rare type of ventriculoarterial connection, mostly reported anecdotally with wide variations in morphology, surgical strategy and clinical outcome. The aim of the present study was to define current morbidity and mortality of biventricular repair and discuss surgical management in infancy. Inclusion criteria were English literature publication; balanced ventricular development and completion of biventricular repair. Institutional experience was also reported. Study end points were survival and freedom from cardiovascular events. Univariate analysis to identify risk factors for complications was performed. During a 45-year interval, 37 cases of DOLV were identified. Median age at repair was 48 months (range 0.3-336); seven patients were infants. Extracardiac repair was performed in 21 (57%) patients, right ventricular outflow patch in seven, pulmonary translocation in six, and intraventricular repair in three. There were three (8%) hospital deaths, due to right heart failure, and seven (21%) patients experienced 10 perioperative complications. Univariate analysis showed year of operation (P = 0.02) and outflow patch technique (P = 0.003) as risk factors for hospital morbidity and mortality. During a median follow-up of 26 months (range 1-192), there was one death and seven reoperations. Ten-year survival and freedom from adverse cardiovascular events were 87 ± 6 and 70 ± 10%, respectively. Although seldom reported in the past, repair of DOLV in infancy does not increase surgical risk. Early and late morbidity are mostly due to right heart complications and more common after right ventricular outflow patch repair. Paucity of follow-up information may underestimate actual late adverse event rate.


The selenium levels of mothers and their neonates using hair, breast milk, meconium, and maternal and umbilical cord blood in Van Basin.
The objective of the present study is to calculate linear regressions between a mother and her child with respect to their selenium concentration (ng/g) in the following traits: maternal blood and umbilical cord blood, maternal and child hair, maternal milk and child umbilical cord blood, maternal milk and meconium, maternal blood plasma, and child meconium. The data were collected at Research Hospital of the University of Yüzüncü Yil from 30 pairs of mothers and their newborn baby. The mean maternal serum Se level in 30 mothers was 68.52 +/- 3.57 ng/g and cord plasma level was 119.90 +/- 18.08 ng/g. The Se concentration in maternal and neonatal hair was 330.84 +/- 39.03 and 1,124.76 +/- 186.84 ng/g, respectively. The Se concentration of maternal milk at day 14 after delivery was determined as 68.63 +/- 7.78 ng/g (n = 13) and the concentration of Se was 418.90 +/- 45.49 ng/g (n = 22) for meconium of neonatal. There was no significant difference between maternal blood and milk Se levels. However, hair Se concentration was significantly higher than milk and maternal blood Se level. For each trait comparison, the average absolute difference in log(10)-transformed Se concentration was calculated between a mother and her child. The observed average absolute difference was compared with a test distribution of 1,000 resampled bootstrap averages where the number of samples was maintained but the relationship between a mother and her child was randomized among samples (alpha = 0.05).


Mycobacterium tuberculosis, but not vaccine BCG, specifically upregulates matrix metalloproteinase-1.
Pulmonary cavitation is fundamental to the global success of Mycobacterium tuberculosis. However, the mechanisms of this lung destruction are poorly understood. The biochemistry of lung matrix predicts matrix metalloproteinase (MMP) involvement in immunopathology. We investigated gene expression of all MMPs, proteins with a disintegrin and metalloproteinase domain, and tissue inhibitors of metalloproteinases in M. tuberculosis-infected human macrophages by real-time polymerase chain reaction. MMP secretion was measured by zymography and Western analysis, and expression in patients with pulmonary tuberculosis was localized by immunohistochemistry. MMP-1 and MMP-7 gene expression and secretion are potently upregulated by M. tuberculosis, and no increase in tissue inhibitor of metalloproteinase expression occurs to oppose their activity. Dexamethasone completely suppresses MMP-1 but not MMP-7 gene expression and secretion. In patients with active tuberculosis, macrophages express MMP-1 and MMP-7 adjacent to areas of tissue destruction. MMP-1 but not MMP-7 expression and secretion are relatively M. tuberculosis specific, are not upregulated by tuberculosis-associated cytokines, and are prostaglandin dependent. In contrast, the vaccine M. bovis bacillus Calmette-Guérin (BCG) does not stimulate MMP-1 secretion from human macrophages, although M. tuberculosis and BCG do upregulate MMP-7 equally. BCG-infected macrophages secrete reduced prostaglandin E2 concentrations compared with M. tuberculosis-infected macrophages, and prostaglandin pathway supplementation augments MMP-1 secretion from BCG-infected cells. M. tuberculosis specifically upregulates MMP-1 in a cellular model of human infection and in patients with tuberculosis. In contrast, vaccine BCG, which does not cause lung cavitation, does not upregulate prostaglandin E2-dependent MMP-1 secretion.


Emergency Department Utilization by Adolescents Experiencing Homelessness in Massachusetts.
Adolescents who experience homelessness rely heavily on emergency departments (EDs) for their health care. This study estimates the relationship between homelessness and ED use and identifies the sociodemographic, clinical, visit-level, and contextual factors associated with multiple ED visits among adolescents experiencing homelessness in Massachusetts. We used the Healthcare Cost and Utilization Project State Emergency Department Databases on all outpatient ED visits in Massachusetts from 2011 to 2016. We included all adolescents who were 11-21 years old. We estimated the association between homelessness and ED utilization and investigated predictors of multiple ED visits among adolescents who experience homelessness using multivariate logistic and negative binomial regressions. Our study included 1,196,036 adolescents, of whom about 0.8% experienced homelessness and this subset of adolescents accounted for 2.2% of all ED visits. Compared with those with stable housing, adolescents who were homeless were mostly covered through Medicaid (P<0.001), diagnosed with 1 or more comorbidities (P<0.001), and visited the ED at least once for reasons related to mental health; substance and alcohol use; pregnancy; respiratory distress; urinary and sexually transmitted infections; and skin and subcutaneous tissue diseases (P<0.001). Homeless experience was associated with multiple ED visits (incidence rate ratio=1.18; 95% confidence intervals, 1.16-1.19) and frequent ED use (4 or more ED visits) (adjusted odds ratio=2.21; 95% confidence interval, 2.06-2.37). Factors related to clinical complexity and Medicaid compared with lack of coverage were also significant predictors of elevated ED utilization within the cohort experiencing homelessness. Adolescents who experience homelessness exhibit higher ED use compared with those with stable housing, particularly those with aggravated comorbidities and chronic conditions. Health policy interventions to integrate health care, housing, and social services are essential to transition adolescents experiencing homelessness to more appropriate community-based care.


Laparoscopic versus open resection of gastric gastrointestinal stromal tumors.
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. There is some controversy as to the effectiveness and feasibility of laparoscopic versus open resection of these tumors. We hypothesized that laparoscopic resection of gastric GISTs would offer better perioperative outcomes compared with the traditional open approach. A retrospective review was conducted of all GISTs treated at a tertiary care urban teaching hospital between January 1999 and August 2008. The medical records were examined for demographic and clinicopathological features. Forty-six gastric GISTs were identified (17 treated laparoscopically and 29 treated via laparotomy). The median age of patients in these groups were comparable at 62 and 60, respectively. Body mass index of these patients were also similar at 28.2 kg/m(2) for the laparoscopic and 29.9 kg/m(2) for the open group. The average size of tumor was slightly smaller in the laparoscopic group at 4.27 cm versus the open group at 6.39 cm (NS). The estimated blood loss for the laparoscopic group was lower at 94 mL versus 169 mL (P = 0.059). Operative times for the 2 surgical approaches were not significantly different at 135 minutes for laparoscopic and 157.4 minutes for open. Laparoscopic resection yielded a significantly shorter length of stay compared with open at 2.68 versus 6.25 days (P < 0.001). Laparoscopic resection of gastric GISTs offers a decreased length of stay, a trend to decreased blood loss, and comparable oncologic outcomes indicating that a laparoscopic approach should be considered in all patients with gastric GISTs who do not have a contraindication to this approach.


Development of Pretreatment Method for Analysis of Vitamin B12 in Cereal Infant Formula using Immunoaffinity Chromatography and High-Performance Liquid Chromatography.
Vitamin B12 deficiency may lead to serious health issues in both infants and adults. A simple analytical method involving sample pretreatment with enzyme, followed by cyanide addition under acidic conditions; separation on an immunoaffinity column; and high-performance liquid chromatography (HPLC) was developed for the rapid detection and quantitation of vitamin B12 in powdered milk. Detection limit and powdered milk recovery were determined by quantitative analysis. The limits of detection and quantitation were 2.71 and 8.21 μg/L, respectively. Relative standard deviations of the intra-day and inter-day precisions varied in the ranges of 0.98%-5.31% and 2.16%-3.90%, respectively. Recovery of the analysis varied in the range of 83.41%-106.57%, suggesting that the values were acceptable. Additionally, vitamin B12 content and recovery in SRM 1849a were 54.10 μg/kg and 112.24%, respectively. Our results suggested that the analytical method, including the sample pretreatment step, was valid. This analytical method can be implemented in many laboratory-scale experiments that seek to save time and labor. Therefore, this study shows that immunoaffinity-HPLC/ultraviolet is an acceptable technique for constructing a reliable database on vitamin B12 in powdered milk containing starch as well as protein and/or fat in high amounts.


Safety of etanercept and methotrexate in patients with rheumatoid arthritis and hepatitis C virus infection: a multicenter randomized clinical trial.
To evaluate the safety and efficacy of therapy with etanercept and methotrexate (MTX) in patients with active rheumatoid arthritis (RA) and mild hepatitis C virus (HCV) infection. In this prospective open study, 29 patients with active RA were randomly assigned to receive therapy with MTX alone, etanercept alone, or a combination of MTX and etanercept, and monitored up to 54 weeks. The primary endpoint was safety; secondary aims were efficacy as defined by the 44-joint Disease Activity Score (DAS44) and health assessment questionnaire (HAQ). Serum liver enzymes and HCV viral load were serially measured. In the whole cohort, aspartate aminotransferase (AST) serum levels were (mean ± SD) 35 ± 3 at entry, 39 ± 5, 41 ± 7, and 38 ± 4 at 14, 30, and 54 weeks, respectively; alanine aminotransferase (ALT) serum levels were 43 ± 5 at entry, 47 ± 5, 53 ± 9, and 50 ± 6 at 14, 30, and 54 weeks, respectively. HCV viral load was 5.6 ± 0.5 at entry, 5.9 ± 0.6, 5.7 ± 0.3, and 5.6 ± 0.6 at 14, 30, and 54 weeks, respectively. AST and ALT did not significantly change in all 3 arms of treatment, nor did HCV viral load. A significant reduction of DAS44 (p < 0.01) and HAQ (p < 0.04) was detected at 54 weeks compared to baseline. No patient discontinued the therapy because of worsening of liver disease. This study showed that patients with RA and chronic HCV and mild hepatitis may be successfully treated with etanercept and MTX without increasing the risk of hepatotoxicity and HCV replication. ClinicalTrials.gov Identifier NCT01543594.


The efficacy of bariatric surgery performed in the public sector for obese patients with comorbid conditions.
To determine the efficacy of bariatric surgery in the public sector for the treatment of complicated obesity. A longitudinal observational study of obese participants with comorbid conditions, aged 21-73 years, who underwent publicly funded bariatric surgery. Data were extracted from clinical databases (1 October 2009 to 1 September 2013) and recorded at seven time points. Participants are from an ongoing public obesity program. Postoperative weight loss and partial or full resolution of: type 2 diabetes mellitus (T2DM), hypertension (HTN), dyslipidaemia and obstructive sleep apnoea (OSA). The 65 participants in the cohort lost a mean weight of 22.6 kg (SD, 9.5 kg) by 3 months, 34.2.kg (SD, 20.1 kg) by 12 months and 39.9 kg (SD, 31.4 kg) by 24 months (P < 0.001). Body mass index (BMI) decreased from a preoperative mean of 48.2 kg/m(2) (SD, 9.5 kg/m(2)) to 35.7 kg/m(2) (SD, 7.7 kg/m(2)) by 24 months (P < 0.001). Full resolution of comorbid conditions by 18 months (P < 0.001) was achieved by almost half of those with baseline T2DM, nearly two-thirds with HTN and three-quarters of those with OSA, with continued improvements beyond 24 months. Bariatric surgery performed in the public sector is efficacious in the treatment of obese patients with comorbid conditions. Our findings parallel similar studies suggesting that there is equal benefit in publicly funded and privately performed procedures. This study highlights that obese patients reliant on public health care maintain sufficient intrinsic motivation in the absence of payment and supposed value-driven incentive. Improved access to bariatric surgery in the public sector can justifiably reduce the health inequities for those most in need.


Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1 alpha.
Hypoxia is an essential developmental and physiological stimulus that plays a key role in the pathophysiology of cancer, heart attack, stroke, and other major causes of mortality. Hypoxia-inducible factor 1 (HIF-1) is the only known mammalian transcription factor expressed uniquely in response to physiologically relevant levels of hypoxia. We now report that in Hif1a-/- embryonic stem cells that did not express the O2-regulated HIF-1alpha subunit, levels of mRNAs encoding glucose transporters and glycolytic enzymes were reduced, and cellular proliferation was impaired. Vascular endothelial growth factor mRNA expression was also markedly decreased in hypoxic Hif1a-/- embryonic stem cells and cystic embryoid bodies. Complete deficiency of HIF-1alpha resulted in developmental arrest and lethality by E11 of Hif1a-/- embryos that manifested neural tube defects, cardiovascular malformations, and marked cell death within the cephalic mesenchyme. In Hif1a+/+ embryos, HIF-1alpha expression increased between E8.5 and E9.5, coincident with the onset of developmental defects and cell death in Hif1a-/- embryos. These results demonstrate that HIF-1alpha is a master regulator of cellular and developmental O2 homeostasis.


Mobile Aid to Assist with Care Decisions in Children with Autism Spectrum Disorder (ASD).
MyHeifer is an autism spectrum disorder (ASD) intervention application aimed at better understanding patients' behavioral patterns and informing healthcare decisions, easing caregiver burden, and providing an emotional outlet for patients. Children with ASD often struggle with the complexity of human communication because of the array of verbal and nonverbal communication methods at play. Because of this, technological interventions can be a valuable tool for communicating with children with ASD because of their simplicity. Hence the MyHeifer application seeks to provide an uncomplicated environment for children with ASD to express and explore their emotions. Children perform "actions" or "interactions" which are classified as either positive or negative behaviors. Through these interactions, children learn various ways to react to situations. The choices children make are collected and serve as a basis for future healthcare decisions. Because communication is often difficult for children with ASD, utilizing data from past actions or interactions helps caregivers anticipate and understand the challenges to make better emotional and behavioral connections in individual patients in order to address personalized care needs.


An infective cause for the limping child.
A 7-year-old girl presented with left hip pain and a limp, in the absence of any other systemic features, having recently been treated for a urinary tract infection. Examination revealed limited active hip movements on the left, with a tendency to weight bear on the contralateral side. Biochemical investigations were significant for raised inflammatory markers, and subsequent MRI imaging revealed osteomyelitis of the left pubis and ischium with an associated large soft tissue collection. Treatment was bimodal with surgical drainage and long-term antibiotics. The patient consequently recovered, without significant effect on either growth or mobility.


Bone morphogenetic protein-7 (OP1) and transforming growth factor-beta1 modulate 1,25(OH)2-vitamin D3-induced differentiation of human osteoblasts.
Bone morphogenetic proteins (BMPs) and transforming growth factor-beta (TGFbeta) are potent regulators of osteoblast differentiation and proliferation, processes that are crucial in bone remodeling. BMPs and TGFbeta act in concert with other local factors and hormones, among them 1,25(OH)2-vitamin D3 and insulin. Here we show that BMP7 inhibits 1,25(OH)2-vitamin D3-induced differentiation of human osteoblasts, whereas TGFbeta1 stimulates it, as assessed by assays for alkaline phosphatase (ALP) induction, matrix mineralization, and morphology changes. BMP7 or TGFbeta1 alone affects the differentiation of human osteoblasts. Similar results were obtained in assays for ALP induction using conditionally immortalized human osteoblasts (hFOB) and primary osteoblasts obtained from trabecular bone of the femoral head after hip replacement surgery. BMP7 stimulation led to a decrease of 1,25(OH)2-vitamin D3-induced binding of nuclear proteins to a vitamin D response element, as shown by electrophoretic mobility shift assay. Our results suggest that 1,25(OH)2-vitamin D3 modulates in opposite ways the effects of BMP7 and TGFbeta1 on osteoblast differentiation.


Prevalence of allergic diseases among Korean school-age children: a nationwide cross-sectional questionnaire study.
The purpose of this study was to investigate the nationwide prevalence of childhood asthma, eczema and other allergic diseases in Korean school-age children (8-11 yr old) and to assess the difference between residential areas. Among 6,279 elementary schools, 427 schools were randomly selected according to residential area (metropolitan, provincial, rural, and industrial area) by the cluster sampling method. Parents of students completed a modified Korean version of a questionnaire formulated by the International Study of Asthma and Allergies in Childhood (ISAAC). Among 50,200 subjects, 31,026 (61.8%) responded, and 30,893 (99.6%) were analyzed. The 12-month prevalence of wheeze, flexural rash, and allergic rhinitis symptoms were 4.8%, 15.3%, and 32.9%, respectively. The prevalence of diagnosis of allergic diseases in boys was higher than that in girls, with the exception of eczema. In both boys and girls, the difference of the prevalence of allergic diseases among industrial, metropolitan and provincial areas was not statistically significant, but the differences between rural area and other areas were significant. Our results support the importance of contextual effect associated with residential area as causative agents of allergic diseases among Korean school-age children.


Identification of Two Missense Mutations in DUOX1 (p.R1307Q) and DUOXA1 (p.R56W) That Can Cause Congenital Hypothyroidism Through Impairing H2O2 Generation.
Context: The DUOX/DUOXA systems play a key role in H2O2 generation in thyroid cells, which is required for iodine organification and thyroid hormone synthesis. DUOX2/DUOXA2 defects can cause congenital hypothyroidism (CH), but it is unknown whether DUOX1/DUOXA1 mutations can also cause CH. Objective: We aimed to identify DUOX1/DUOXA1 mutations and explore their role in the development of CH by investigating their functional impacts on H2O2 generation. Patients and Methods: Forty-three children with CH with goiter were enrolled, in whom all exons and flanking intronic regions of DUOX1/DUOXA1 were directly sequenced. We characterized the functional effects of identified mutations on the expression of DUOX1 and DUOXA1 and H2O2 generation. Results: We identified a heterozygous DUOX1 missense mutation (G > A base substitution at nucleotide 3920 in exon 31) that changed a highly conserved arginine to glutamine at residual 1307 (p.R1307Q) in patient 1. A heterozygous-missense mutation (c.166 C>T; p.R56W) was identified in DUOXA1 in patient 2. Functional studies demonstrated that both p.R1307Q mutant or p.R56W mutant decreased the DUOX1 expression at mRNA and protein levels, with a corresponding impairment in H2O2 generation (P < 0.01). The results also showed that intact DUOXA1 was required for full activity of DUOX1 and H2O2 generation. Conclusions: We have identified two heterozygous missense mutations in DUOX1 and DUOXA1 in two patients that can cause CH through disrupting the coordination of DUOX1 and DUOXA1 in the generation of H2O2. This study for the first time demonstrates that the DUOX1/DUOXA1 system, if genetically defective, can cause CH.


Opioid-related respiratory and gastrointestinal adverse events in patients with acute postoperative pain: prevalence, predictors, and burden.
Opioid-induced respiratory depression (OIRD) and postoperative nausea and vomiting (PONV) are challenging, resource-intensive, and costly opioid-related adverse events (ORAEs). Utilizing the Premier Healthcare Database, we identified patients > 18 years old, who underwent at least one surgical procedure of interest (i.e., cardiothoracic/vascular, general/colorectal, obstetric/gynecologic, orthopedic, or urologic), and received at least one dose of intravenous morphine, hydromorphone, or fentanyl for acute postoperative pain. The incidence of OIRD and PONV using ICD-9 codes, factors influencing these AEs, length of stay (LOS) and related costs were analyzed. Among 592,127 inpatient stays, rates of respiratory depression ranged from 3% (obstetric/gynecologic) to 17% (cardiothoracic/vascular) and nausea/vomiting from 44% (obstetric/gynecologic) to 72% (general/colorectal). Increased odds of OIRD were associated with older age (cardiothoracic/vascular, general/colorectal, obstetric/gynecologic); obesity, respiratory conditions, and sleep apnea (all surgery groups); opioid dose (cardiothoracic/vascular, general/colorectal, orthopedic); and sedative use after day 1. Increased odds of PONV were associated with younger age, female sex, and major disease severity. When respiratory depression or nausea/vomiting was present versus absent, LOS was significantly longer, and hospital costs were higher. In this analysis, OIRD and PONV were more prevalent than previously reported, were associated with identifiable risk factors, and had substantial effects on resource utilization and costs.


Organizational and individual factors associated with breakdown of residential placements for people with intellectual disabilities.
People with intellectual disabilities (IDs) whose behaviour challenges services are at increased risk of placement breakdown. Most previous research has tended to focus on the role of individual characteristics in predicting breakdown. A small number of studies have suggested that service variables may impact on intervention effectiveness and hence placement breakdown. This study used a non-experimental group comparison design to investigate potential differences between two groups of residential homes, one of which had experienced placement breakdown, and one of which had successfully maintained placements in the community. More residents in the breakdown group had inappropriate sexual behaviours but there were no other differences. Services in the breakdown group had more limited procedural guidance for staff, weaker training, supervision and team meetings and less external professional support. Placement characteristics may be an important determinant of community placement success for people with IDs and challenging behaviour. Those selecting and funding residential placements for such people should attend to the technical competence of the placement (in terms of its use of procedural guidance, training and professional advice) and to the extent of support for staff (in terms of training, supervision and team meetings).


Regulation of Brn3b by DLX1 and DLX2 is required for retinal ganglion cell differentiation in the vertebrate retina.
Regulated retinal ganglion cell (RGC) differentiation and axonal guidance is required for a functional visual system. Homeodomain and basic helix-loop-helix transcription factors are required for retinogenesis, as well as patterning, differentiation and maintenance of specific retinal cell types. We hypothesized that Dlx1, Dlx2 and Brn3b homeobox genes function in parallel intrinsic pathways to determine RGC fate and therefore generated Dlx1/Dlx2/Brn3b triple-knockout mice. A more severe retinal phenotype was found in the Dlx1/Dlx2/Brn3b-null retinas than was predicted by combining features of the Brn3b single- and Dlx1/Dlx2 double-knockout retinas, including near total RGC loss with a marked increase in amacrine cells in the ganglion cell layer. Furthermore, we discovered that DLX1 and DLX2 function as direct transcriptional activators of Brn3b expression. Knockdown of Dlx2 expression in primary embryonic retinal cultures and Dlx2 gain of function in utero strongly support that DLX2 is both necessary and sufficient for Brn3b expression in vivo We suggest that ATOH7 specifies RGC-committed progenitors and that Dlx1 and Dlx2 function both downstream of ATOH7 and in parallel, but cooperative, pathways that involve regulation of Brn3b expression to determine RGC fate.


Isolation and characterization of polymorphic microsatellite loci in yellowtail catfish, Pangasius pangasius (Hamilton, 1822).
A total of nine polymorphic microsatellite loci were obtained from a genomic library of Pangasius pangasius (order Siluriformes, family Pangasiidae). Samples from rivers Bhagirathi (n = 22) and Mahanadi (n = 20) were genotyped for each of the nine microsatellite loci to determine genetic variation. The mean number of alleles per locus was 5.22 in Bhagirathi and 5.78 in Mahanadi; and expected heterozygosity ranged from 0.567 (Bhagirathi) to 0.578 (Bhagirathi). Significant deviation (P < 0.003) from Hardy-Weinberg expectations was evident at three loci, Ppa2 (Bhagirathi), Ppa14 (Mahanadi) and Ppa28 (Bhagirathi and Mahanadi). The identified microsatellite loci were found to be promising for population genetics studies of P. pangasius.


Extended sleep (hypersomnia) in young depressed patients.
To test the hypothesis that young depressed patients have prolonged rather than shortened sleep, 14 depressed patients aged 17-25 and age-matched normal control subjects were allowed to sleep as long as they wanted. All subjects increased their sleep over baseline values, but the extended sleep period of the depressed patients was almost twice as long as that of the control subjects. The distribution of sleep stages in the extended period did not differ. The depressed patients had changes in the length of REM periods similar to those of older subjects. The findings suggest an interaction between age, sleep, and depression.


Microarray analysis reveals marked intestinal microbiota aberrancy in infants having eczema compared to healthy children in at-risk for atopic disease.
Deviations in composition and diversity of intestinal microbiota in infancy have been associated with both the development and recurrence of atopic eczema. Thus, we decided to use a deep and global microarray-based method to characterize the diversity and temporal changes of the intestinal microbiota in infancy and to define specific bacterial signatures associated with eczema. Faecal microbiota at 6 and 18 months of age were analysed from 34 infants (15 with eczema and 19 healthy controls) selected from a prospective follow-up study based on the availability of faecal samples. The infants were originally randomized to receive either Lactobacillus rhamnosus GG or placebo. Children with eczema harboured a more diverse total microbiota than control subjects as assessed by the Simpson's reciprocal diversity index of the microarray profiles. Composition of the microbiota did not differ between study groups at age of 6 months, but was significantly different at age of 18 months as assessed by MCPP (p=0.01). At this age healthy children harboured 3 -fold greater amount of members of the Bacteroidetes (p=0.01). Microbiota of children suffering from eczema had increased abundance of the Clostridium clusters IV and XIVa, which are typically abundant in adults. Probiotic Lactobacillus rhamnosus GG supplementation in early infancy was observed to have minor long-term effects on the microbiota composition. A diverse and adult-type microbiota in early childhood is associated with eczema and it may contribute to the perpetuation of eczema.


Physician Burnout and Barriers to Care on Professional Applications.
We surveyed New York physicians to study their perceptions of reporting requirements related to their own mental health care on professional applications, including whether they were experiencing symptoms of burnout. Over half of the responding physicians reported experiencing symptoms of burnout and these physicians were at increased odds of perceiving a barrier to seeking mental health care if they had to report such care on professional applications and renewals for medical licensure, malpractice, and hospital privileges and credentialing compared to physicians not experiencing symptoms of burnout. As state medical boards, hospitals, and insurers seek information to help assess risks posed by physicians, it is essential to strike an appropriate balance between their duty to protect the public and the physician's right to confidentiality. This balance can be assessed based on the questions that are asked on various professional applications and how information gleaned through physician responses is used. Overly intrusive questions, though well intentioned to protect the public, may run counter to current interpretations of federal law and may inhibit care-seeking among physicians, which is critical to both patient safety and physician health.


The role of anti-EGFR therapies in EGFR-TKI-resistant advanced non-small cell lung cancer.
Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are the current recommended option for the first-line treatment of patients with EGFR-mutant non-small cell lung cancer (NSCLC). Resistance to first-generation TKIs led to the development of second- and third-generation TKIs with improved clinical outcomes. However, sequential administration of TKIs has led to the emergence of new EGFR resistance mutations and persistent tumor cell survival. This evidence highlights the potential role of EGFR in transducing growth signals in NSCLC tumor cells. Therefore, dual inhibition of EGFR using combinations of anti-EGFR monoclonal antibodies (mAbs) and EGFR-TKIs may offer a unique treatment strategy to suppress tumor cell growth. Several clinical studies have demonstrated the benefits of dual blockade of EGFR using anti-EGFR mAbs coupled with EGFR-TKIs in overcoming treatment resistance in patients with EGFR-mutated NSCLC. However, a single treatment option may not result in the same clinical benefits in all patients with acquired resistance. Biomarkers, including EGFR overexpression, EGFR gene copy number, EGFR and KRAS mutations, and circulating tumor DNA, have been associated with improved clinical efficacy with anti-EGFR mAbs in patients with NSCLC and acquired resistance. Further investigation of biomarkers may allow patient selection for those who could benefit from anti-EGFR mAbs in combination with EGFR-TKIs. This review summarizes findings of recent studies of anti-EGFR mAbs in combination with EGFR-TKIs for the treatment of patients with EGFR-mutated NSCLC, as well as clinical evidence for potential biomarkers towards personalized targeted medicine.


Near-roadway air quality: synthesizing the findings from real-world data.
Despite increasing regulatory attention and literature linking roadside air pollution to health outcomes, studies on near roadway air quality have not yet been well synthesized. We employ data collected from 1978 as reported in 41 roadside monitoring studies, encompassing more than 700 air pollutant concentration measurements, published as of June 2008. Two types of normalization, background and edge-of-road, were applied to the observed concentrations. Local regression models were specified to the concentration-distance relationship and analysis of variance was used to determine the statistical significance of trends. Using an edge-of-road normalization, almost all pollutants decay to background by 115-570 m from the edge of road; using the more standard background normalization, almost all pollutants decay to background by 160-570 m from the edge of road. Differences between the normalization methods arose due to the likely bias inherent in background normalization, since some reported background values tend to underpredict (be lower than) actual background. Changes in pollutant concentrations with increasing distance from the road fell into one of three groups: at least a 50% decrease in peak/edge-of-road concentration by 150 m, followed by consistent but gradual decay toward background (e.g., carbon monoxide, some ultrafine particulate matter number concentrations); consistent decay or change over the entire distance range (e.g., benzene, nitrogen dioxide); or no trend with distance (e.g., particulate matter mass concentrations).