Northeast Conference on Andean Archaeology and Ethnohistory (NCAAE) Statement on Sexual harassment and Community Values

This is a statement on sexual harassment and community values signed by eight members of the Northeast Conference on Andean Archaeology and Ethnohistory (NCAAE)https://digitalcommons.library.umaine.edu/andean_past_special/1008/thumbnail.jp

Repurposing the HCV NS3-4A protease drug boceprevir as COVID-19 therapeutics

The rapid growth of COVID-19 cases is causing an increasing death toll and also paralyzing the world economy. De novo drug discovery takes years to move from idea and/or pre-clinic to market, and it is not a short-term solution for the current SARS-CoV-2 pandemic. Drug repurposing is perhaps the only short-term solution, while vaccination is a middle-term solution. Here, we describe the discovery path of the HCV NS3–4A protease inhibitors boceprevir and telaprevir as SARS-CoV-2 main protease (3CLpro) inhibitors. Based on our hypothesis that α-ketoamide drugs can covalently bind to the active site cysteine of the SARS-CoV-2 3CLpro, we performed docking studies, enzyme inhibition and co-crystal structure analyses and finally established that boceprevir, but not telaprevir, inhibits replication of SARS-CoV-2 and mouse hepatitis virus (MHV), another coronavirus, in cell culture. Based on our studies, the HCV drug boceprevir deserves further attention as a repurposed drug for COVID-19 and potentially other coronaviral infections as well

Genetic analysis of a major international collection of cultivated apple varieties reveals previously unknown historic heteroploid and inbred relationships

Domesticated apple (Malus x domestica Borkh.) is a major global crop and the genetic diversity held within the pool of cultivated varieties is important for the development of future cultivars. The aim of this study was to investigate the diversity held within the domesticated form, through the analysis of a major international germplasm collection of cultivated varieties, the UK National Fruit Collection, consisting of over 2,000 selections of named cultivars and seedling varieties. We utilised Diversity Array Technology (DArT) markers to assess the genetic diversity within the collection. Clustering attempts, using the software STRUCTURE revealed that the accessions formed a complex and historically admixed group for which clear clustering was challenging. Comparison of accessions using the Jaccard similarity coefficient allowed us to identify clonal and duplicate material as well as revealing pairs and groups that appeared more closely related than a standard parent-offspring or full-sibling relations. From further investigation, we were able to propose a number of new pedigrees, which revealed that some historically important cultivars were more closely related than previously documented and that some of them were partially inbred. We were also able to elucidate a number of parent-offspring relationships that had resulted in a number of important polyploid cultivars. This included reuniting polyploid cultivars that in some cases dated as far back as the 18th century, with diploid parents that potentially date back as far as the 13th century

Rumen-protected methionine supplementation alters lipid profile of preimplantation embryo and endometrial tissue of Holstein cows

Our objective is to evaluate the effects of feeding rumen-protected Met (RPM) throughout the transition period and early lactation on the lipid profile of the preimplantation embryos and the endometrial tissue of Holstein cows. Treatments consisted of feeding a total mixed ration with top-dressed RPM (Smartamine® M, Adisseo, Alpharetta, GA, United States; MET; n = 11; RPM at a rate of 0.08% of DM: Lys:Met = 2.8:1) or not (CON; n = 9, Lys:Met = 3.5:1). Endometrial biopsies were performed at 15, 30, and 73 days in milk (DIM). Prior to the endometrial biopsy at 73 DIM, preimplantation embryos were harvested via flushing. Endometrial lipid profiles were analyzed using multiple reaction monitoring-profiling and lipid profiles of embryos were acquired using matrix assisted laser desorption/ionization mass spectrometry. Relative intensities levels were used for principal component analysis. Embryos from cows in MET had greater concentration of polyunsaturated lipids than embryos from cows in CON. The endometrial tissue samples from cows in MET had lesser concentrations of unsaturated and monounsaturated lipids at 15 DIM, and greater concentration of saturated, unsaturated (specifically diacylglycerol), and monounsaturated (primarily ceramides) lipids at 30 DIM than the endometrial tissue samples from cows in CON. In conclusion, feeding RPM during the transition period and early lactation altered specific lipid classes and lipid unsaturation level of preimplantation embryos and endometrial tissue

Discordant antibiotic therapy and length of stay in children hospitalized for urinary tract infection

BACKGROUND: Urinary tract infections (UTIs) are a common reason for pediatric hospitalizations. OBJECTIVE: To determine the effect of discordant antibiotic therapy (in vitro nonsusceptibility of the uropathogen to initial antibiotic) on clinical outcomes for children hospitalized for UTI. DESIGN/SETTING: Multicenter retrospective cohort study in children aged 3 days to 18 years, hospitalized at 5 children's hospitals with a laboratory‐confirmed UTI. Data were obtained from medical records and the Pediatric Hospital Information System (PHIS) database. PARTICIPANTS: Patients with laboratory‐confirmed UTI. MAIN EXPOSURE: Discordant antibiotic therapy. MEASUREMENTS: Length of stay and fever duration. Covariates included age, sex, insurance, race, vesicoureteral reflux, antibiotic prophylaxis, genitourinary abnormality, and chronic care conditions. RESULTS: The median age of the 216 patients was 2.46 years (interquartile range [IQR]: 0.27, 8.89) and 25% were male. The most common causative organisms were E. coli and Klebsiella species. Discordant therapy occurred in 10% of cases and most commonly in cultures positive for Klebsiella species, Enterobacter species, and mixed organisms. In adjusted analyses, discordant therapy was associated with a 1.8 day (95% confidence interval [CI]: 1.5, 2.1) longer length of stay [LOS], but not with fever duration. CONCLUSIONS: Discordant antibiotic therapy for UTI is common and associated with longer hospitalizations. Further research is needed to understand the clinical factors contributing to the increased LOS and to inform decisions for empiric antibiotic selection in children with UTIs. Journal of Hospital Medicine 2012; © 2012 Society of Hospital MedicinePeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94298/1/1960_ftp.pd

Integrated care for older multimorbid heart failure patients:protocol for the ESCAPE randomized trial and cohort study

ESCAPE Evaluation of a patient-centred biopsychosocial blended collaborative care pathway for the treatment of multimorbid elderly patients. Therapeutic Area Healthcare interventions for the management of older patients with multiple morbidities. Aims Multi-morbidity treatment is an increasing challenge for healthcare systems in ageing societies. This comprehensive cohort study with embedded randomized controlled trial tests an integrated biopsychosocial care model for multimorbid elderly patients. Hypothesis A holistic, patient-centred pro-active 9-month intervention based on the blended collaborative care (BCC) approach and enhanced by information and communication technologies can improve health-related quality of life (HRQoL) and disease outcomes as compared with usual care at 9 months. Methods Across six European countries, ESCAPE is recruiting patients with heart failure, mental distress/disorder plus ≥2 medical co-morbidities into an observational cohort study. Within the cohort study, 300 patients will be included in a randomized controlled assessor-blinded two-arm parallel group interventional clinical trial (RCT). In the intervention, trained care managers (CMs) regularly support patients and informal carers in managing their multiple health problems. Supervised by a clinical specialist team, CMs remotely support patients in implementing the treatment plan—customized to the patients' individual needs and preferences—into their daily lives and liaise with patients' healthcare providers. An eHealth platform with an integrated patient registry guides the intervention and helps to empower patients and informal carers. HRQoL measured with the EQ-5D-5L as primary endpoint, and secondary outcomes, that is, medical and patient-reported outcomes, healthcare costs, cost-effectiveness, and informal carer burden, will be assessed at 9 and ≥18 months. Conclusions If proven effective, the ESCAPE BCC intervention can be implemented in routine care for older patients with multiple morbidities across the participating countries and beyond

A polymorphism near IGF1 is associated with body composition and muscle function in women from the Health, Aging, and Body Composition Study

Previous studies have reported associations of polymorphisms in the IGF1 gene with phenotypes of body composition (BC). The purpose of this study was to identify phenotypes of BC and physical function that were associated with the IGF1 promoter polymorphism (rs35767, −C1245T). Subjects from the Health, Aging, and Body Composition Study, white males and females (n = 925/836) and black males and females (533/705) aged 70–79 years were genotyped for the polymorphism. Phenotypes of muscle size and function, bone mineral density, and BC were analyzed for associations with this polymorphism. To validate and compare these findings, a cohort of young (mean age = 24.6, SD = 5.9) white men and women (n = 173/296) with similar phenotypic measurements were genotyped. An association with BC was identified in elderly females when significant covariates (physical activity, age, smoking status, body mass index) were included. White women with C/C genotype had 3% more trunk fat and 2% more total fat than those with C/T (P < 0.05). Black women with C/C genotype had 3% less total lean mass and 3% less muscle mass than their T/T counterparts (P < 0.05). Associations were identified with muscle strength in white women (P < 0.01) that were in agreement with the C/C genotype having lower muscle function. Thus, in an elderly population but not a young population, a polymorphism in the IGF1 gene may be predictive of differences in body composition, primarily in black females

Effects of Androgen Receptor and Androgen on Gene Expression in Prostate Stromal Fibroblasts and Paracrine Signaling to Prostate Cancer Cells

The androgen receptor (AR) is expressed in a subset of prostate stromal cells and functional stromal cell AR is required for normal prostate developmental and influences the growth of prostate tumors. Although we are broadly aware of the specifics of the genomic actions of AR in prostate cancer cells, relatively little is known regarding the gene targets of functional AR in prostate stromal cells. Here, we describe a novel human prostate stromal cell model that enabled us to study the effects of AR on gene expression in these cells. The model involves a genetically manipulated variant of immortalized human WPMY-1 prostate stromal cells that overexpresses wildtype AR (WPMY-AR) at a level comparable to LNCaP cells and is responsive to dihydrotestosterone (DHT) stimulation. Use of WPMY-AR cells for gene expression profiling showed that the presence of AR, even in the absence of DHT, significantly altered the gene expression pattern of the cells compared to control (WPMY-Vec) cells. Treatment of WPMY-AR cells, but not WPMY-Vec control cells, with DHT resulted in further changes that affected the expression of 141 genes by 2-fold or greater compared to vehicle treated WPMY-AR cells. Remarkably, DHT significantly downregulated more genes than were upregulated but many of these changes reversed the initial effects of AR overexpression alone on individual genes. The genes most highly effected by DHT treatment were categorized based upon their role in cancer pathways or in cell signaling pathways (transforming growth factor-β, Wnt, Hedgehog and MAP Kinase) thought to be involved in stromal-epithelial crosstalk during prostate or prostate cancer development. DHT treatment of WPMY-AR cells was also sufficient to alter their paracrine potential for prostate cancer cells as conditioned medium from DHT-treated WPMY-AR significantly increased growth of LNCaP cells compared to DHT-treated WPMY-Vec cell conditioned medium