Inappropriate medication use in hospitalised oldest old patients across transitions of care

Background: Oldest old patients aged 85 years and over are at risk of experiencing potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs) across transitions of care. Geriatricians also face enormous challenges in prescribing medications for these patients. Methods: A mixed-methods, sequential explanatory design was undertaken of electronic medical records and semi-structured interviews with geriatricians at a public teaching hospital. Data were collected at four time points using the Screening Tool of Older Persons' potentially inappropriate Prescriptions (STOPP) and Screening Tool to Alert doctors to the Right Treatment (START). Results: Of 249 patients, the prevalence of at least 1 PIM varied between 36.9 and 51.0%, while the prevalence of at least 1 PPO varied between 36.9 and 44.6%. The most common PIM was use of proton pump inhibitors while the most common PPO was omission of vitamin D supplements in housebound patients or patients experiencing falls. Poisson regression analysis showed that PIMs were significantly associated with use of mobility aids, 1.430 (95% CI 1.109–1.843, p = 0.006), and number of medications prescribed at admission, 1.083 (95% CI 1.058–1.108, p < 0.001). PPOs were significantly associated with comorbidities, 1.172 (95% CI 1.073–1.280, p < 0.001), medications prescribed at admission, 0.989 (95% CI 0.978–0.999, p = 0.035), and length of stay, 1.004 (95% CI 1.002–1.006, p < 0.001). Geriatrician interviews (N = 9) revealed medication-related, health professional-related and patient-related challenges with managing medications. Conclusions: Inappropriate prescribing is common in oldest old patients. Greater attention is needed on actively de-prescribing medications that are not beneficial and commencing medications that would be advantageous. Tailored strategies for improving prescribing practices are needed

New Records for the Arctic Shrew, Sorex arcticus and the Newly Recognized Maritime Shrew, Sorex maritimensis

We report the first record for the Arctic Shrew (Sorex arcticus) in the state of Montana, USA. We also report range extensions for the closely related Maritime Shrew (Sorex maritimensis) in New Brunswick and Nova Scotia, Canada. These collections augment our limited knowledge of the ranges and habitat associations of these rarely collected shrews, and highlight the need for a careful assessment of the status of S. maritimensis in Canada

Teamwork in an honours group writing assignment

Scientific practice is essentially collaborative. Most research publications list multiple authors making collaborative writing a key skill for scientists. This paper reports the student experience of a collaborative writing task for honours students in experimental science. Students were asked to work in groups of five to research and construct a scientific review suitable for publication in a peer-reviewed journal. Students submitted a piece of individual writing as well as the final group review and where also asked to assess the contribution of group members. Students found group work demanding and this appeared to overshadow the experience of collaborative writing. However, at the same time, students strongly agreed that teamwork skills and collaboration were essential for successful research. This dichotomy between the need for collaborative skills and the difficulty of putting this into practice argues for greater development of teamwork skills in the undergraduate curriculum in preparation for research training

Study of environmental enteropathy and malnutrition (SEEM) in Pakistan: protocols for biopsy based biomarker discovery and validation

Background: Environmental Enteropathy (EE), characterized by alterations in intestinal structure, function, and immune activation, is believed to be an important contributor to childhood undernutrition and its associated morbidities, including stunting. Half of all global deaths in children \u3c 5 years are attributable to under-nutrition, making the study of EE an area of critical priority. Methods: Community based intervention study, divided into two sub-studies, 1) Longitudinal analyses and 2) Biopsy studies for identification of EE features via omics analyses. Birth cohorts in Matiari, Pakistan established: moderately or severely malnourished (weight for height Z score (WHZ) \u3c − 2) children, and well-nourished (WHZ \u3e 0) children. Blood, urine, and fecal samples, for evaluation of potential biomarkers, will be collected at various time points from all participants (longitudinal analyses). Participants will receive appropriate educational and nutritional interventions; non-responders will undergo further evaluation to determine eligibility for further workup, including upper gastrointestinal endoscopy. Histopathological changes in duodenal biopsies will be compared with duodenal biopsies obtained from USA controls who have celiac disease, Crohn’s disease, or who were found to have normal histopathology. RNA-Seq will be employed to characterize mucosal gene expression across groups. Duodenal biopsies, luminal aspirates from the duodenum, and fecal samples will be analyzed to define microbial community composition (omic analyses). The relationship between histopathology, mucosal gene expression, and community configuration will be assessed using a variety of bioinformatic tools to gain better understanding of disease pathogenesis and to identify mechanism-based biomarkers. Ethical review committees at all collaborating institutions have approved this study. All results will be made available to the scientific community. Discussion: Operational and ethical constraints for safely obtaining intestinal biopsies from children in resource-poor settings have led to a paucity of human tissue-based investigations to understand and reverse EE in vulnerable populations. Furthermore, EE biomarkers have rarely been correlated with gold standard histopathological confirmation. The Study of Environmental Enteropathy and Malnutrition (SEEM) is designed to better understand the pathophysiology, predictors, biomarkers, and potential management strategies of EE to inform strategies to eradicate this debilitating pathology and accelerate progress towards the 2030 Sustainable Development Goals. Trial registration: Retrospectively registered; clinicaltrials.gov ID NCT03588013

Liver X receptor-α activation enhances cholesterol secretion in lactating mammary epithelium

Liver X receptors (LXRs) are li-gand-dependent transcription factors activated by cholesterol metabolites. These receptors induce a suite of target genes required for de novo synthesis of triglycerides and cholesterol transport in many tissues. Two different isoforms, LXRβ and LXRβ, have been well characterized in liver, adipocytes, macrophages, and intestinal epithelium among others, but their contribution to cholesterol and fatty acid efflux in the lactating mammary epithelium is poorly understood. We hypothesize that LXR regulates lipogenesis during milk fat production in lactation. Global mRNA analysis of mouse mammary epithelial cells (MECs) revealed multiple LXR/RXR targets upregulated sharply early in lactation compared with midpregnancy. LXRβ is the primary isoform, and its protein levels increase throughout lactation in MECs. The LXR agonist GW3965 markedly induced several genes involved in cholesterol transport and lipogenesis and enhanced cytoplasmic lipid droplet accumulation in the HC11 MEC cell line. Importantly, in vivo pharmacological activation of LXR increased the milk cholesterol percentage and induced sterol regulatory element-binding protein 1c (Srebp1c) and ATP-binding cassette transporter a7 (Abca7) expression in MECs. Cumulatively, our findings identify LXRβ as an important regulator of cholesterol incorporation into the milk through key nodes of de novo lipogenesis, suggesting a potential therapeutic target in women with difficulty initiating lactation.Fil: Grinman, Diego Yair. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Careaga Quiroga, Valeria Pilar. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Wellberg, Elizabeth A.. University of Colorado; Estados UnidosFil: Dansey, Maria Virginia. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Kordon, Edith Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Anderson, Steven M.. University of Colorado; Estados UnidosFil: Maier, Marta Silvia. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Burton, Gerardo. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: MacLean, Paul S.. University of Colorado; Estados UnidosFil: Rudolph, Michael C.. University of Colorado; Estados UnidosFil: Pecci, Adali. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentin

Corrigendum: Increased Binding of Specificity Protein 1 to the IL21R Promoter in B Cells Results in Enhanced B Cell Responses in Rheumatoid Arthritis

B cells are implicated in rheumatoid arthritis (RA) based on the presence of autoantibodies and the therapeutic response to B cell depletion. IL-21 has a significant role in B cell development and function. Here we assess B cell responses to IL-21 and the mechanisms responsible for altered IL-21R expression in RA. Flow cytometry of PBMC and cultured B cells was used to quantify protein and mRNA levels of IL-21R, IL-21 signaling through pSTAT3, specificity protein 1 (SP1) and to determine cytokine production (IL-6) and maturation status of B cells in RA and healthy control subjects. SP1 binding to the IL21R promoter region in B cells was assessed with ChIP-qPCR. We demonstrate an increase in IL-21R expression in total and memory B cells from RA subjects, which correlated with responsiveness to IL-21 stimulation. Stimulation of naïve RA B cells with IL-21 and CD40L resulted in an increase in differentiation into plasmablasts and an increase in IL-6 production in comparison to healthy controls, which was dose dependent on IL-21 stimulation. IL-21R expression on memory B cells in RA synovial fluid was comparable to peripheral blood making our study pertinent to understanding B cell responses in the joint and site of inflammation. We identified an increase in SP1 protein and mRNA in RA B cells and demonstrate an increase in binding of SP1 to the IL21R promoter region, which suggests a mechanism by which IL-21R expression is enhanced on B cells in RA. Taken together, our results indicate a mechanism by which IL-21 enhances B cell development and function in RA through an SP1 mediated increase in IL-21R expression on B cells

Increased Binding of Specificity Protein 1 to the IL21R Promoter in B Cells Results in Enhanced B Cell Responses in Rheumatoid Arthritis

B cells are implicated in rheumatoid arthritis (RA) based on the presence of autoantibodies and the therapeutic response to B cell depletion. IL-21 has a significant role in B cell development and function. Here we assess B cell responses to IL-21 and the mechanisms responsible for altered IL-21R expression in RA. Flow cytometry of PBMC and cultured B cells was used to quantify protein and mRNA levels of IL-21R, IL-21 signaling through pSTAT3, specificity protein 1 (SP1) and to determine cytokine production (IL-6) and maturation status of B cells in RA and healthy control subjects. SP1 binding to the IL21R promoter region in B cells was assessed with ChIP-qPCR. We demonstrate an increase in IL-21R expression in total and memory B cells from RA subjects, which correlated with responsiveness to IL-21 stimulation. Stimulation of naïve RA B cells with IL-21 and CD40L resulted in an increase in differentiation into plasmablasts and an increase in IL-6 production in comparison to healthy controls, which was dose dependent on IL-21 stimulation. IL-21R expression on memory B cells in RA synovial fluid was comparable to peripheral blood making our study pertinent to understanding B cell responses in the joint and site of inflammation. We identified an increase in SP1 protein and mRNA in RA B cells and demonstrate an increase in binding of SP1 to the IL21R promoter region, which suggests a mechanism by which IL-21R expression is enhanced on B cells in RA. Taken together, our results indicate a mechanism by which IL-21 enhances B cell development and function in RA through an SP1 mediated increase in IL-21R expression on B cells