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In DCIS, ER status is an important marker. The utility of concomitant PR testing remains unclear.A single-institution retrospective cohort study was performed with a comparative analysis of the NCDB to assess annual cost-savings with omission of routine PR testing. National Medicare payment standards determined PR staining costs to be $124.92.150 institutional DCIS cases with receptor data were identified. 104 (69%) were ER+/PR+, 16 (11%) were ER+/PR-, and none were ER-/PR+. Omission of routine PR testing would have resulted in $18,738 saved annually. Within the NCDB, 34,100 DCIS cases had receptor data: 29,277 (85.9%) patients were ER+, and 26,008 (76%) were both ER/PR+. 211 (0.6%) patients were ER-/PR+. Annual national cost-savings with omission of routine PR-testing would have been $4.3 million.PR testing for DCIS should be reserved only for patients with ER- DCIS undergoing breast conservation to determine the utility of adjuvant endocrine therapy.

The NCG triple immunodeficient mice on a NOD/Nju background lack functional/mature T, B, and NK cells, and have reduced macrophage and dendritic cell function. This study characterized the NCG mouse model for toxicity, engraftment and tumorigenicity assessments of cell therapies, using CD34+ hHSPC adult mobilized cells with two myeloablation regimens. Mice received sub-lethal irradiation or busulfan and were then injected intravenously with CD34+ hHSPCs (1.0 x 106 cells/mouse) or PBS (control), while positive control animals received 2 x 106 HL-60 cells/mouse. hCD34+ cell donors were treated with the mobilizing agent G-CSF prior to leukapheresis. Following injections, mouse blood samples were collected to assess engraftment rates by flow cytometry with body weights recorded periodically up to 20 weeks post-cell injection. No significant clinical signs or body weight changes were observed. At week 10 post-cell injection, the peripheral blood chimerism of hCD45+ cells was above 20%. While mCD45+ concentration was constant between week 10 and 17 in whole blood samples, hCD45+ concentration and chimerism slightly decreased at week 17. However, chimerism remained above 10%, with busulfan-treated mice presenting higher values. Chimerism was further assessed by quantifying human Alu sequences in blood and multiple organs using qPCR. Alu sequences were most abundant in the spleen and bone marrow, while lowest in the testes. In the positive control group, expected mortalities due to tumorigenesis were observed between days 27 and 40 post-cell injection. Overall, study results may be used to inform study design and potential toxicological endpoints relevant to non-clinical cell therapy development.

Nonionic surfactants are often used as general reagents for cell lysis enabling protein extraction, stabilization, and purification under nondenaturing conditions for downstream analysis in structural biology. However, the presence of surfactants in the sample matrix often has a deleterious effect on electrospray ionization (ESI)-mass spectrometry (MS) analysis of proteins and complexes. Here, we report a nonionic, cleavable surfactant, n-decyl-disulfide-β-D-maltoside (DSSM), for top-down proteomics. DSSM was designed to mimic the properties of one of the most common surfactants used in structural biology, n-dodecyl-β-D-maltoside (DDM), but contains a disulfide bond that allows for facile cleavage and surfactant removal before or during MS analysis. We have shown that DSSM is compatible with direct electrospray ionization (ESI)-MS analysis and reversed-phase liquid chromatography (RPLC)-MS analysis of proteins and protein complexes. We have demonstrated that DSSM can facilitate top-down proteomic characterization of membrane proteins such as a model ion channel protein and a G protein-coupled receptor as well as endogenous proteins from cell lysates for the determination of sequence variations and posttranslational modifications (PTMs). Conceivably, DSSM could serve as a general replacement for DDM in proteomic experiments and structural biology studies.

Methane (CH4) is a greenhouse gas associated with global warming that is released as a byproduct of rumen fermentation. Two experiments were conducted to determine if dietary inclusion of a novel high anthocyanin (Hi-A) containing corn cob meal [CCM; 4.99 mg anthocyanin×g-1 of dry matter (DM)] influences in vitro CH4 emissions relative to a conventional CCM (CNV; 0.04 mg anthocyanin×g-1 of DM). High-roughage starter (experiment 1) and low-roughage finisher (experiment 2) diets were formulated to contain 20% and0% total CCM (DM-basis), respectively. Treatments were based on the proportion of Hi-A to CNV CCM within each diet and consisted of 0% (0A), 25% (25A), 50% (50A), 75% (75A), and 100% Hi-A (100A) CCM. In experiments 1 and 2, ruminal fluid was collected from 4 cannulated steers offered traditional feedlot starter or finisher diets, respectively. Filter bags (F57; ANKOM; Macedon, NY) were loaded with 0.5 g of substrate and 2 bags per ANKOM RF system were incubated in buffer and rumen fluid for 48 h at 39°C. Cumulative gas production was recorded at 10-min intervals. The concentration of CH4 as a proportion of total gas production (%CH4) was measured using gas chromatography after 48 h. Total gas production was fit to the Ørskov model to determine asymptotic and fractional rates of gas production. In experiment 1, there was a cubic relationship between total gas production and Hi-A CCM inclusion for the intercept, asymptote, and fractional gas production rate (P ≤ 0.04). There was also a cubic relationship between %CH4 and Hi-A CCM inclusion (P = 0.04), where 50A had the largest reduction relative to 0A at -19.6% (P = 0.05). Total CH4 production (mL CH4×g DM-1) also exhibited a cubic relationship with Hi-A-CCM inclusion (P = 0.03), where 100A produced 20% less CH4 than 0A. In experiment 2, there was a cubic relationship between total gas production and Hi-A CCM inclusion for the intercept and asymptote (P ≤ 0.02) of the Ørskov model; however, fractional gas production rate expressed a quadratic relationship (P < 0.01). Furthermore, a cubic relationship existed between %CH4 and Hi-A CCM inclusion, where 100A had the largest reduction relative to 0A (17.4%; P = 0.03). Lastly, there was a tendency for a cubic relationship between Hi-A CCM inclusion and total CH4 production (P = 0.06); however, 100A reduced total CH4 production by 22% relative to 0A (P = 0.01). Collectively, the greatest level of Hi-A CCM inclusion reduced total CH4 production relative to 0A in both starter and finisher diets. These results indicate that dietary inclusion of anthocyanins through CCM decreased CH4 emissions in vitro. Further research is needed to determine if anthocyanins from Hi-A CCM are effective at mitigating CH4 emissions in vivo.

Class IC antiarrhythmics are generally considered a safe means of treating many common arrhythmias such as atrial fibrillation (a-fib), atrial flutter (a-flutter), and paroxysmal supraventricular tachycardia (PSVT). Essentially, flecainide works by binding and blocking sodium channels more effectively at higher heart rates. However, this class of drugs is known to exhibit use dependence which could predispose patients to the development of malignant arrhythmias during episodes of tachycardia. In this case, we present a patient who was being treated with flecainide for a-fib who ultimately developed a wide complex tachycardia after her metoprolol was held.

Autophagy is essential to maintaining cellular homeostasis in all eukaryotic cells and to tolerance of acute stressors such as starvation, heat, and recovery after exercise. Limited information exists regarding the exercise intensity-dependent autophagic response in humans, and it is unknown how environmental heat stress may modulate this response. Therefore, we evaluated autophagy and accompanying pathways of cellular stress [the heat-shock response (HSR), apoptosis, and acute inflammation] in peripheral blood mononuclear cells (PBMCs) from 10 young men (mean [SD]; 22 [2] years) before, immediately after and up to 6-h postexercise recovery from 30 min of low-, moderate-, and high-intensity semirecumbent cycling [40%, 55%, and 70% of maximal oxygen consumption (V̇o2max), respectively] in a temperate environment (25°C) and at 70% of V̇o2max in a hot environment (40°C). Changes in protein content were analyzed via Western blot. Each increase in exercise intensity was associated with elevations in mean body temperature. LC3-II increased after moderate-intensity exercise, with further increases after high-intensity exercise ( P < 0.05). However, an increase in beclin-2 and ULK1, with a decrease in p62 was only observed after high-intensity exercise, which was paralleled by elevated TNF-α and cleaved-caspase-3, with the HSR peaking at 6 h after exercise ( P < 0.05). When exercise was performed in the heat, greater LC3-II and cleaved-caspase-3 accumulation were observed; however, beclin-2 declined in recovery ( P < 0.05). Therefore, our findings indicate that autophagy in PBMCs during exercise may be associated with greater heat strain exhibited during increasing exercise intensities, which is modulated by exposure to heat.

Resistant Gram-negative bacteria are a growing concern in the United States, leading to significant morbidity and mortality. We identified a 72-year-old female patient who presented with unilateral vision loss.

Communicating information about health risks empowers individuals to make informed decisions. To identify effective communication strategies, we manipulated the specificity, self-relevance, and emotional framing of messages designed to motivate information seeking about COVID-19 exposure risk. In Study 1 (N=221,829), we conducted a large-scale social media field study. Using Facebook advertisements, we targeted users by age and political attitudes. Episodic specificity drove engagement: Advertisements that contextualized risk in specific scenarios produced the highest click-through rates, across all demographic groups. In Study 2, we replicated and extended our findings in an online experiment (N=4,233). Message specificity (but not self-relevance or emotional valence) drove interest in learning about COVID-19 risks. Across both studies, we found that older adults and liberals were more interested in learning about COVID-19 risks. However, message specificity increased engagement across demographic groups. Overall, evoking specific scenarios motivated information seeking about COVID-19, facilitating risk communication to a broad audience.

Synopsis Among extant great apes, orangutans are considered the most sexually dimorphic in body size. However, the expression of sexual dimorphism in orangutans is more complex than simply males being larger than females. At sexual maturity, some male orangutans develop cheek pads (flanges), while other males remain unflanged even after becoming reproductively capable. Sometimes flange development is delayed in otherwise sexually mature males for a few years. In other cases, flange development is delayed for many years or decades, with some males even spending their entire lifespan as unflanged adults. Thus, unflanged males of various chronological ages can be mistakenly identified as “subadults.” Unflanged adult males are typically described as “female-sized,” but this may simply reflect the fact that unflanged male body size has only ever been measured in peri-pubescent individuals. In this study, we measured the skeletons of 111 wild adult orangutans (Pongo spp.), including 20 unflanged males, 45 flanged males, and 46 females, resulting in the largest skeletal sample of unflanged males yet studied. We assessed long bone lengths (as a proxy for stature) for all 111 individuals and recorded weights-at-death, femoral head diameters, bi-iliac breadths, and long bone cross-sectional areas (CSA) (as proxies for mass) for 27 of these individuals, including seven flanged males, three adult confirmed-unflanged males, and three young adult likely-unflanged males. ANOVA and Kruskal–Wallis tests with Tukey and Dunn post-hoc pairwise comparisons, respectively, showed that body sizes for young adult unflanged males are similar to those of the adult females in the sample (all P ≥ 0.09 except bi-iliac breadth), whereas body sizes for adult unflanged males ranged between those of adult flanged males and adult females for several measurements (all P

Serum albumin is a prominent plasma protein that becomes modified in hyperglycemic conditions. In a process known as glycation, these modifications can change the structure and function of proteins, which decrease ligand binding capabilities and alter the bioavailability of ligands. C-peptide is a molecule that binds to the red blood cell (RBC) and stimulates the release of adenosine triphosphate (ATP), which is known to participate in the regulation of blood flow. C-peptide binding to the RBC only occurs in the presence of albumin, and downstream signaling cascades only occur when the albumin and C-peptide complex contains Zn

Background Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to over 170?million cases worldwide with over 33.2?million cases and 594,000 deaths in the US alone as of May 31st, 2021. The pandemic has also created severe shortages of personal protective equipment, particularly of filtering facepiece respirators (FFRs). The Centers for Disease Control and Prevention (CDC) has issued recommendations to help conserve FFRs, as well as crisis standards, including four criteria required for decontamination of the traditionally single use respirators. This review is designed to provide an overview of the current literature on vaporized hydrogen peroxide (vHP), hydrogen peroxide gas plasma (HPGP), and aerosolized hydrogen peroxide (aHP) with respect to each of the four CDC decontamination criteria. Methods PubMed and Medrxiv were queried for relevant articles. All articles underwent a title and abstract screen as well as subsequent full text screen by two blinded reviewers if indicated. Results Searches yielded 195 papers, of which, 79 were found to be relevant. Of those, 23 papers presented unique findings and 8 additional articles and technical papers were added to provide a comprehensive review. Overall, while there are potential concerns for all 3 decontamination methods, we found that vHP has the most evidence supporting its use in FFR decontamination consistent with CDC recommendation. Conclusions Future research is recommended to evaluate biological inactivation and real world fit failures after FFR reuse.

Objective Assess evidence describing the effect of Sodium-Glucose Cotransporter-2 (SGLT2) inhibitors on total daily insulin (TDI) requirements in insulin-dependent patients with type 2 diabetes. Data sources A scoping review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Protocols and Scoping Reviews (PRISMA-ScR) guidelines. The search was conducted in PubMed; citation mapping was completed in Web of Science. Filters for human studies, English language, and a publication date, from January 1, 2005 to April 12, 2021, were applied. Study selection and data extraction Studies assessing insulin dose requirements with concurrent use of an SGLT2 inhibitor for patients with type 2 diabetes were included. Data synthesis Sixteen studies were included and demonstrated that addition of an SGLT2 inhibitor typically reduced TDI requirements. Insulin reductions were often statistically significant, occurring in studies evaluating (1) within subjects who received SGLT2 inhibitors, and (2) between subjects receiving SGLT2 inhibitors versus placebo. Compared with placebo, insulin dose reduction ranged from −0.72 to −19.2 units. However, studies were relatively small, not designed to assess TDI change, and some utilized fixed dose insulin protocols or empiric insulin dose reductions. Conclusions Lowering insulin requirements may have benefits, such as decreased hypoglycemia risk, insulin resistance, and cost. Addition of an SGLT2 inhibitor may modestly reduce TDI requirements for patients with type 2 diabetes. Evidence indicating SGLT2 inhibitor use reduces TDI may lead to additional implementation in practice and inform future research. Further research is needed to clarify insulin type (i.e., basal or prandial) and degree of TDI reduction expected with addition of an SGLT2 inhibitor.

Summary Background and aims Many critically ill patients experience increased blood glucose variability (BGV). The objective of the current pilot study was to assess the relationship between muscle composition (defined as average Hounsfield units (HU)) among ICU patients with an abdominal CT scan within seven days of intubation, and BGV (defined as coefficient of variation (CV)) calculated from blood glucose levels measured each morning while intubated. Methods The first serum blood glucose measurement obtained each day during intubation was recorded, blood glucose CV ((mean/SD)∗100) was calculated. Cross-sectional muscle area (CSA; cm2) at the third lumbar region was identified using the −29 to +150 HU range; muscle composition was calculated as the average HU. BGV predictors were determined using linear regression. Results Eighty-two patients were included (53% female), with a median age of 64 (25th, 75 percentile (IQR): 51, 70) years. The median CV was 29% (IQR: 20, 37); 40% of subjects required insulin. The median CSA was 100.4 cm2 (IQR: 84.0, 120.8) and muscle composition was 20.4 HU (IQR: 12.2, 29.4). Patients received only 36% of estimated calorie requirements. Insulin administration, history of diabetes, and muscle composition were significant BGV predictors. Conclusion Among these adult intubated ICU patients, higher muscle composition was associated with lower BGV. Future research is needed to corroborate these findings, determine other factors associated with poor muscle quality, and identify methods to describe muscle composition for all ICU patients.

Adrenocortical carcinoma (ACC) is a rare, but highly aggressive cancer with limited treatment options and poor survival for patients with advanced disease. Improved understanding of transcriptional programs engaged in ACC will help direct rational, targeted therapies. While activating mutations in Wnt/β-catenin signaling are frequently observed, the β-catenin-dependent transcriptional targets that promote tumor progression are poorly understood. To address this question, we used independent component analysis and identified a novel Wnt/β-catenin-associated signature in ACC predictive of poor survival. This signature was enriched for the extracellular matrix (ECM), suggesting a potential role for Wnt/β-catenin in regulating the ACC microenvironment. We further investigated the minor fibrillar collagen, collagen XI alpha 1 (COL11A1), and found thatCOL11A1expression strongly correlated with both Wnt/β-catenin activation and poor patient survival. Inhibition of constitutively active Wnt/β-catenin signaling in the human ACC cell line, NCI-H295R, significantly reduced expression ofCOL11A1and other ECM components, and decreased viability of cancer cellsin vitro. To investigate the preclinical potential of Wnt/β-catenin inhibitionin vivo, we developed and characterized a novel orthotopic xenograft model utilizing minimally invasive techniques. Treatment with the newly developed Wnt/β-catenin:TBL1 inhibitor Tegavivint significantly reduced tumor growth in this preclinical model. Together, our data supports that inhibition of aberrantly active Wnt/β-catenin disrupts transcriptional reprogramming of the microenvironment and reduces ACC growth and survival. Furthermore, this β-catenin-dependent oncogenic program can be therapeutically targeted with a newly developed Wnt/β-catenin inhibitor. These results show promise for further clinical development of Wnt/β-catenin inhibitors in ACC and unveil a novel Wnt/β-catenin-regulated transcriptome.Simple SummaryAdrenocortical carcinoma (ACC) is a rare, often deadly cancer arising from the adrenal gland. Mortality associated with ACC remains unchanged over the last several decades. The rarity of ACC, an incomplete understanding of its molecular basis, and limited availability of pre-clinical models have hampered the development of new effective therapies. The present work aims to address these gaps with a focus on the Wnt/β-catenin cell signaling pathway, which is aberrantly activated in ~40% of ACC tumors. We discover a novel ECM program activated in ACC that is associated with Wnt/β-catenin and poor survival. Wnt/β-catenin inhibition disrupts expression of ECM genes and induces loss of cancer cell viability. To extend these findings, we develop a rapid orthotopic mouse model of ACC and demonstrate that disruption of the Wnt/β-catenin axis with novel small molecule inhibitor Tegavivint is a potential effective therapeutic strategy to reduce ACC tumor burdenin vivo.

Aim The aim of this study is to test the validity of the Organizational Learning in Hospitals model in the context of the COVID‐19 pandemic. Background Organizational learning is especially crucial in circumstances of intense, complex, enduring change, as with the COVID‐19 pandemic. Nurse managers need additional guidance for fostering organizational learning under such circumstances. The Organizational Learning in Hospitals model may be a helpful resource but requires additional validation. Methods Semi‐structured interviews were conducted to gather 19 nurses' first‐hand experiences of organizational learning during the COVID‐19 pandemic. Data were analysed using deductive thematic analysis. Results Nurses' experiences of organizational learning generally aligned with the tenets of the model. Specifically, effective organizational learning occurred when the contextual factors and mechanisms portrayed in the model converged. Model and contrary cases illustrate this phenomenon. Conclusions This study validates and adds context to the model. It offers practical examples of the contextual factors and mechanisms of organizational learning. Leaders can use the model to guide their efforts to foster organizational learning. Implications for Nursing Management This study reaffirms the importance of nurse leaders' central role in organizational learning. Nurse leaders can use the Organizational Learning in Hospitals model, and the practical examples provided, to foster organizational learning during challenging times.

BACKGROUND: The Ross procedure involves autograft transplantation of the native pulmonary valve into the aortic position and reconstruction of the right ventricular outflow tract (RVOT) with a homograft. The operation offers the advantages of a native valve with excellent hemodynamic performance, the avoidance of anticoagulation, and growth potential. Conversely, the operation is technically demanding and imposes the risk of turning single-valve disease into double-valve disease. This systematic review reports outcomes of pediatric patients undergoing the Ross procedure. METHODS: An electronic search identified studies reporting outcomes on pediatric patients (mean age

Distributed Stream Processing systems are becoming an increasingly essential part of Big Data processing platforms as users grow ever more reliant on their ability to provide fast access to new results. As such, making timely decisions based on these results is dependent on a system's ability to tolerate failure. Typically, these systems achieve fault tolerance and the ability to recover automatically from partial failures by implementing checkpoint and rollback recovery. However, owing to the statistical probability of partial failures occurring in these distributed environments and the variability of workloads upon which jobs are expected to operate, static configurations will often not meet Quality of Service constraints with low overhead. In this paper we present Khaos, a new approach which utilizes the parallel processing capabilities of virtual cloud automation technologies for the automatic runtime optimization of fault tolerance configurations in Distributed Stream Processing jobs. Our approach employs three subsequent phases which borrows from the principles of Chaos Engineering: establish the steady-state processing conditions, conduct experiments to better understand how the system performs under failure, and use this knowledge to continuously minimize Quality of Service violations. We implemented Khaos prototypically together with Apache Flink and demonstrate its usefulness experimentally.

Basal forebrain cholinergic neurons (BFCNs) represent the main source of cholinergic innervation to the cortex and hippocampus and degenerate early in Alzheimer's disease (AD) progression. Phenotypic maintenance of BFCNs depends on levels of mature nerve growth factor (mNGF) and mature brain-derived neurotrophic factor (mBDNF), produced by target neurons and retrogradely transported to the cell body. Whether a reciprocal interaction where BFCN inputs impact neurotrophin availability and affect cortical neuronal markers remains unknown. To address our hypothesis, we immunolesioned the nucleus basalis (nb), a basal forebrain cholinergic nuclei projecting mainly to the cortex, by bilateral stereotaxic injection of 192-IgG-Saporin (the cytotoxin Saporin binds p75ntr receptors expressed exclusively by BFCNs) in 2.5-month-old Wistar rats. At 6 months post-lesion, Saporin-injected rats (SAP) showed an impairment in a modified version of the 5-Choice Serial Reaction Time Task (5-choice task). Postmortem analyses of the brain revealed a reduction of Choline Acetyltransferase-immunoreactive neurons compared to wild-type controls. A diminished number of cortical vesicular acetylcholine transporter-immunoreactive boutons was accompanied by a reduction in BDNF mRNA, mBDNF protein levels, markers of glutamatergic (vGluT1), and GABAergic (GAD65) neurons in the SAP-group compared to the controls. NGF mRNA, NGF precursor, and mNGF protein levels were not affected. Additionally, cholinergic markers correlated with the attentional deficit and BDNF levels. Our findings demonstrate that while cholinergic nb loss impairs cognition and reduces cortical neuron markers, it produces differential effects on neurotrophin availability, affecting BDNF but not NGF levels.

Chlorhexidine skin antisepsis is frequently recommended for most surgical procedures; however, it is unclear if these recommendations should apply to surgery involving traumatic contaminated wounds where povidone-iodine has previously been preferred. We aimed to compare the effect of aqueous 10% povidone-iodine versus aqueous 4% chlorhexidine gluconate on the risk of surgical site infection in patients who required surgery for an open fracture.We conducted a multiple-period, cluster-randomised, crossover trial (Aqueous-PREP) at 14 hospitals in Canada, Spain, and the USA. Eligible patients were adults aged 18 years or older with an open extremity fracture treated with a surgical fixation implant. For inclusion, the open fracture required formal surgical debridement within 72 h of the injury. Participating sites were randomly assigned (1:1) to use either aqueous 10% povidone-iodine or aqueous 4% chlorhexidine gluconate immediately before surgical incision; sites then alternated between the study interventions every 2 months. Participants, health-care providers, and study personnel were aware of the treatment assignment due to the colour of the solutions. The outcome adjudicators and data analysts were masked to treatment allocation. The primary outcome was surgical site infection, guided by the 2017 US Centers for Disease Control and Prevention National Healthcare Safety Network reporting criteria, which included superficial incisional infection within 30 days or deep incisional or organ space infection within 90 days of surgery. The primary analyses followed the intention-to-treat principle and included all participants in the groups to which they were randomly assigned. This study is registered with ClinicalTrials.gov, NCT03385304.Between April 8, 2018, and June 8, 2021, 3619 patients were assessed for eligibility and 1683 were enrolled and randomly assigned to povidone-iodine (n=847) or chlorhexidine gluconate (n=836). The trial's adjudication committee determined that 45 participants were ineligible, leaving 1638 participants in the primary analysis, with 828 in the povidone-iodine group and 810 in the chlorhexidine gluconate group (mean age 44·9 years [SD 18·0]; 629 [38%] were female and 1009 [62%] were male). Among 1571 participants in whom the primary outcome was known, a surgical site infection occurred in 59 (7%) of 787 participants in the povidone-iodine group and 58 (7%) of 784 in the chlorhexidine gluconate group (odds ratio 1·11, 95% CI 0·74 to 1·65; p=0·61; risk difference 0·6%, 95% CI -1·4 to 3·4).For patients who require surgical fixation of an open fracture, either aqueous 10% povidone-iodine or aqueous 4% chlorhexidine gluconate can be selected for skin antisepsis on the basis of solution availability, patient contraindications, or product cost. These findings might also have implications for antisepsis of other traumatic wounds.US Department of Defense, Canadian Institutes of Health Research, McMaster University Surgical Associates, PSI Foundation.

This case report describes vision loss in a 72-year-old woman following use of EzriCare eye drops.

Through organizational learning, health care teams can consistently provide excellent patient care in a complex and changing environment. Nurse managers, educators, and other leaders can facilitate organizational learning within their teams by promoting certain contextual factors in the clinical work environment. This article provides an overview of contextual factors associated with organizational learning, includes practice-based examples of these factors, and offers evidence-based recommendations for creating a learning-focused work environment. [ J Contin Educ Nurs . 2021;52(6):281–285.]

Objectives: Suicide Awareness for Veterans Exiting Community Living Centers (SAVE-CLC) is a brief intervention to standardize suicide-risk screening and clinical follow-up after VA nursing home dis...

Background: In Spring 2020 many academic institutions transitioned to remote learning in response to the developing COVID-19 pandemic. These changes affected skills-based training, as schools of pharmacy were forced to transition traditionally in-person assessments to a remote setting. The purpose of this article is to describe the experience of pharmacy skills lab coordinators when transitioning summative skills-based assessments (SSBA). Methods: A web-based survey instrument administered through QualtricsXM was sent to all institutions in the Big Ten Academic Alliance-Performance Based Assessment Collaborative. Only one member from each institution completed the survey on behalf of the institution. The survey consisted of four sections: changes made to skills evaluated; changes made to the delivery of those evaluations; challenges to and strategies used by the skills lab program when switching to remote learning; and recommendations for incorporating remote learning within future SSBAs. Survey respondents were invited to participate in an optional unstructured interview regarding survey answers. Results: Nine of ten invited institutions responded to the survey. Of the nine respondents, three participated in the post-survey interview. Overall, 79.5% (93/117) of skills planned to be assessed were assessed with or without modification, with 8.5% (93/117) of skills canceled and 10.3% (12/117) of skills assessments postponed. The most common challenges mentioned were the lack of preparation time, inability to assess certain skills virtually, and student barriers. The most common recommendations made were to prioritize lab components and incorporate flexibility in planning and scheduling. Discussion: The results indicate that most skills were still assessed during the Spring 2020 semester. Though the transition to remote learning was challenging and unique for each institution, common strategies and recommendations identified here provide opportunities for academics to analyze and prioritize learning objectives and to rethink how to develop and deliver SSBAs as remote assessments.

Microbial infections are a threat to women’s reproductive health. Although reproductive cycles and pregnancy are controlled by sex hormones, the impact of hormones on host–pathogen interactions and immune function in the female reproductive tract are understudied. Furthermore, the changing endocrine environment throughout pregnancy may influence how and when women are susceptible to ascending infection. Because most intrauterine microbial infections originate in the lower reproductive tract, it is vital that future studies determine how different hormonal conditions influence the lower reproductive tract’s susceptibility to infection to understand temporal components of infection susceptibilities across pregnancy. These studies should also extend to nonpregnant women, as it is critical to establish how hormonal fluctuations across the menstrual cycle and hormonal contraceptives may influence disease susceptibility. This review summarizes current knowledge of how estrogen and progesterone impact vaginal and cervical mucosal immunity, barrier function, and interactions with microbial communities.

Why do many people believe that gun deaths are at an all-time high? This chapter explores the cognitive factors that support the acceptance of this and other incorrect beliefs. It highlights how people use heuristics to judge truth, relying on cues such as source credibility and ease of processing to decide whether something is true. Such heuristics develop because they often lead people to the correct answers, quickly and efficiently, but they can also cause mistakes. This chapter focuses on how people often make rapid decisions in complex situations that require simplification of incoming information. It also describes how having demonstrated knowledge is not always protective, with implications for interventions. Finally, it takes a deep dive into one cognitive process, namely the shifting accessibility of knowledge, to understand how activating one’s national identity can change the speed with which related information is retrieved.

The locus coeruleus (LC) is the main source of noradrenaline (NA) in the mammalian brain and has been found to degenerate during the initial stages of Alzheimer's disease (AD). Recent studies indicate that at late stages of the amyloid pathology, LC-pathological alterations accelerate AD-like pathology progression by interfering with the neuromodulatory and anti-inflammatory properties of NA. However, the impact of LC degeneration at the earliest stages of amyloidosis on the AD-like pathology is not well understood.The LC was lesioned in wild-type and McGill-R-Thy1-APP transgenic (APP tg) rats by administering N-(2-chloroethyl)-N-ethyl-bromo-benzylamine before amyloid plaque deposition. Cognitive deficits and AD-like neuropathological changes were measured after the LC lesion.Four months post-treatment, rats displayed a decrease in brain noradrenergic innervation. The LC lesion in APP tg-treated rats enhanced cognitive deficits and decreased hippocampal cholinergic innervation and neurotrophin expression. In addition, the APP tg-treated rats displayed an increased microglial and astroglial cell number in close vicinity to hippocampal amyloid-beta burdened neurons. The recruited microglia showed cellular alterations indicative of an intermediate activation state.Our results indicate that early LC demise aggravates the early neuroinflammatory process, cognitive impairments, cholinergic deficits and neurotrophin deregulation at the earliest stages of the human-like brain amyloidosis.

Culture plays a significant role in determining what people believe and claim to know. Here, we argue that, in addition to shaping what people come to know, culture influences the accessibility of that knowledge. In five studies, we examined how activating participants’ American identities (a cultural identity) influenced their ability to retrieve well-known information: the 50 U. S. states. Activating participants’ American identities—relative to other identities—led them to retrieve more U. S. states over brief periods of time; the effect disappeared over longer periods of time. Overall, our results suggest that the identity activated affects the speed with which relevant knowledge is retrieved, but that the effect is not large in magnitude (perhaps contributing to why we did not find the effect in Study 4). This work provides the first evidence that cultural identity influences not only what one knows but also its accessibility.

Laryngopharyngeal reflux (LPR) symptoms are often present in patients with Gastroesophageal reflux disease (GERD). Whereas antireflux surgery (ARS) provides predictably excellent results in patients with typical GERD, those with atypical symptoms have variable outcomes. The goal of this study was to characterize the response of LPR symptoms to antireflux surgery. Patients who underwent ARS between January 2009 and May 2020 were prospectively identified from a single institutional database. Patient-reported information on LPR symptoms was collected at standardized time points (preoperative and 2 weeks, 8 weeks, and 1 year postoperatively) using a validated Reflux Symptom Index (RSI) questionnaire. Patients were grouped by preoperative RSI score: ≤ 13 (normal) and > 13 (abnormal). Baseline characteristics were compared between groups using chi-square test or t-test. A mixed effects model was used to evaluate improvement in RSI scores. One hundred and seventy-six patients fulfilled inclusion criteria (mean age 57.8 years, 70% female, mean BMI 29.4). Patients with a preoperative RSI ≤ 13 (n = 61) and RSI > 13 (n = 115) were similar in age, BMI, primary reason for evaluation, DeMeester score, presence of esophagitis, and hiatal hernia (p > 0.05). The RSI > 13 group had more female patients (80 vs 52%, p = 30) had the best response to ARS. When analyzing individual symptoms, the most likely to improve included heartburn, hoarseness, and choking. In our study population, patients with LPR symptoms achieved a rapid and durable response to antireflux surgery. Those with higher preoperative RSI scores experienced the greatest improvement. Our data suggest that antireflux surgery is a viable treatment option for this patient population.

PURPOSE OF REVIEW Patients admitted to the intensive care unit (ICU) often experience a significant decline in nutritional status due to a combination of the physiologic response to critical illness and insufficient calorie intake. The majority of research related to nutrition interventions for this population focuses on nutrition support during the acute phase. Minimal attention is given to the nutritional status of ICU patients during the recovery phase. This review will describe calorie intake when ICU care ends, provide an overview of barriers that limit intake, and possible interventions to improve nutritional status. RECENT FINDINGS Current evidence suggests patients are consuming

Background Candida spp. infective endocarditis (CIE) although rare is associated with high morbidity and mortality. Risk factors include prosthetic heart valves and injection drug use (IDU). We reviewed all cases of CIE at our institution to describe the microbiology, treatment and outcomes of patients focusing on IDU as a predisposing factor. Methods Retrospective cohort of patients with definite CIE between 2013 and 2019 at a university hospital was analysed. Demographic data collected included IDU, microbiologic, treatment and mortality. The primary outcome of interest was 12-month, all-cause mortality. Results Twenty patients were included (one had two separate episodes of CIE); CIE accounted for 4% of total infective endocarditis (IE) cases during the study period. The median (IQR) age was 38 (30-58) years, 10 (50%) had a previous history of IE, and 4 (20%) patients had prosthetic heart valves or an implanted cardiac device. Thirteen (65%) patients were IDU. The tricuspid valve was the primary valve involved (8/18, 44%), and C albicans was the most frequently isolated organism (8, 36%). Echinocandin was the most common treatment strategy (8, 40%). Only three (15%) patients underwent valve replacement during hospitalisation. There were no in-hospital fatalities, and 5 (25%) patients died at one year; all were IDU (39% to 0%, p = .11). Conclusion CIE is a rare infectious disease seen more commonly in the IDU population. Cardiac surgery was rarely performed, and long-term mortality was 25%. Additional data are needed to identify ideal management strategies in this population.

Our understanding of lipid peroxidation in biology and medicine is rapidly evolving, as it is increasingly implicated in various diseases but also recognized as a key part of normal cell function, signaling, and death (ferroptosis). Not surprisingly, the root and consequences of lipid peroxidation have garnered increasing attention from multiple disciplines in recent years. Here we "connect the dots" between the fundamental chemistry underpinning the cascade reactions of lipid peroxidation (enzymatic or free radical), the reactive nature of the products formed (lipid-derived electrophiles), and the biological targets and mechanisms associated with these products that culminate in cellular responses. We additionally bring light to the use of highly sensitive, fluorescence-based methodologies. Stemming from the foundational concepts in chemistry and biology, these methodologies enable visualizing and quantifying each reaction in the cascade in a cellular and ultimately tissue context, toward deciphering the connections between the chemistry and physiology of lipid peroxidation. The review offers a platform in which the chemistry and biomedical research communities can access a comprehensive summary of fundamental concepts regarding lipid peroxidation, experimental tools for the study of such processes, as well as the recent discoveries by leading investigators with an emphasis on significant open questions.