Biblical Foundations for Interprofessional Collaboration in Nursing.

ABSTRACT: Interprofessional collaboration is an essential competency for nurses in today's complex healthcare environment. The Interprofessional Education Collaborative (IPEC) four competencies of values, teamwork, roles, and communication provide the organizing framework for effective interprofessional collaboration. In this article, the four competencies are used to explore biblical underpinnings and principles of collaboration for Christian nurses, showing how interprofessional collaboration helps achieve one's faith-based and professional commitments.

Three-dimensional geometric morphometric analyses of humerus ecomorphology: New perspectives for paleohabitat reconstruction in carnivorans and ungulates.

Long bone ecomorphology has proven effective for paleohabitat reconstructions across a wide range of mammalian clades. Still, there is no comprehensive framework to allow interpretation of long bone morphological variation within and between different monophyletic groups. Here, we investigated the use of humerus morphometry to classify living members of the orders Carnivora and ungulates based on their preferred habitats. Using geometric morphometrics, we extracted three different kinds of humerus shape data describing interspecific variation with and without accounting for evolutionary allometry and phylogenetic signal. The traditional a priori categorization of species in open, mixed, and closed habitats was employed in combination with selected subsets of shape variables to identify the best-predictive models for habitat adaptation. These were identified based on the statistical performance of phylogenetic and non-phylogenetic discriminant analyses and then applied to predict habitats on a subsample of fossil species. Size-free shape data combined with phylogenetic discriminant analyses showed the highest rate of accuracy in habitat classification for a combined sample of carnivorans and ungulates. Conversely, when the two groups were investigated separately, traditional shape data analyzed with phylogenetic discriminant function analyses provided models with the greatest predictive power. By combining carnivorans and ungulates within the same methodological framework we identified common adaptive features in closed habitat-adapted species that show compressed epiphyses, while open habitat-adapted species have expanded epiphyses. These morphologies evolved to allow significant degree of direction switches during locomotion in closed habitats compared to open habitat-adapted species whose forelimb joints evolved to stabilize articulations for increasing speed.

Computer-aided prognosis of tuberculous meningitis combining imaging and non-imaging data.

Tuberculous meningitis (TBM) is the most lethal form of tuberculosis. Clinical features, such as coma, can predict death, but they are insufficient for the accurate prognosis of other outcomes, especially when impacted by co-morbidities such as HIV infection. Brain magnetic resonance imaging (MRI) characterises the extent and severity of disease and may enable more accurate prediction of complications and poor outcomes. We analysed clinical and brain MRI data from a prospective longitudinal study of 216 adults with TBM; 73 (34%) were HIV-positive, a factor highly correlated with mortality. We implemented an end-to-end framework to model clinical and imaging features to predict disease progression. Our model used state-of-the-art machine learning models for automatic imaging feature encoding, and time-series models for forecasting, to predict TBM progression. The proposed approach is designed to be robust to missing data via a novel tailored model optimisation framework. Our model achieved a 60% balanced accuracy in predicting the prognosis of TBM patients over the six different classes. HIV status did not alter the performance of the models. Furthermore, our approach identified brain morphological lesions caused by TBM in both HIV and non-HIV-infected, associating lesions to the disease staging with an overall accuracy of 96%. These results suggest that the lesions caused by TBM are analogous in both populations, regardless of the severity of the disease. Lastly, our models correctly identified changes in disease symptomatology and severity in 80% of the cases. Our approach is the first attempt at predicting the prognosis of TBM by combining imaging and clinical data, via a machine learning model. The approach has the potential to accurately predict disease progression and enable timely clinical intervention.

Obstetric and perinatal outcomes in women with cerebrovascular accident vs. transient ischemic attack: an evaluation of a population database.

PURPOSE: Cerebrovascular accidents (CVAs) and transient ischemic attacks (TIAs) are uncommon neurologic events in women of childbearing age. We aimed to compare pregnancy, delivery, and neonatal outcomes between women who suffered from a CVA and those who experienced a TIA. METHODS: A retrospective population-based cohort study was performed using the Healthcare Cost and Utilization Project, Nationwide Inpatient Sample. Included were all pregnant women who delivered or had a maternal death in the US between 2004 and 2014. We compared women with an ICD-9 diagnosis of a CVA before or during pregnancy to those diagnosed with a TIA before, during the pregnancy, or during the delivery admission. Pregnancy and perinatal outcomes were compared between the two groups, using multivariate logistic regression to control for confounders. RESULTS: Among 9,096,788 women in the database, 898 met the inclusion criteria. Of them, 706 women (7.7/100,000) had a CVA diagnosis, and 192 (2.1/100,000) had a TIA diagnosis. Women with a CVA, compared to those with a TIA, had a higher rate of pregnancy-induced hypertension (aOR 3.82,95%CI 2.14-6.81, p < 0.001); preeclampsia (aOR 2.6,95%CI 1.3-5.2, p = 0.007), eclampsia (aOR 13.78,95% CI 1.84-103.41, p < 0.001); postpartum hemorrhage (aOR 4.52,95%CI 1.31-15.56, p = 0.017), blood transfusion (aOR 5.57,95%CI 1.65-18.72, p = 0.006), and maternal death (54 vs. 0 cases, 7.6% vs. 0%), with comparable neonatal outcomes. CONCLUSION: Women diagnosed with a CVA before or during pregnancy had a higher incidence of myriad maternal complications, including hypertensive disorders of pregnancy, postpartum hemorrhage, and death, compared to women with a TIA diagnosis, with comparable neonatal outcomes, stressing the different prognoses of these two conditions, and the importance of these patients' diligent follow-up and care.

Inactivation of yellow fever virus by WHO-recommended hand rub formulations and surface disinfectants.

Despite continued outbreaks of yellow fever virus (YFV) in endemic regions, data on its environmental stability or guidelines for its effective inactivation is limited. Here, we evaluated the susceptibility of the YFV 17D vaccine strain to inactivation by ethanol, 2-propanol, World Health Organization (WHO)-recommended hand rub formulations I and II, as well as surface disinfectants. In addition, two pathogenic strains were tested to compare inactivation kinetics by WHO-recommended hand rub formulations I and II. Furthermore, environmental stability of the vaccine strain was assessed. YFV 17D particles displayed infectivity half-life decay profiles of ~13 days at room temperature. Despite this extended environmental stability, YFV was efficiently inactivated by alcohols, WHO-recommended hand formulations, and four out of five tested surface disinfectants. These results are useful in defining disinfection protocols to prevent non-vector borne YFV transmission.

ACR Appropriateness Criteria® Preprocedural Planning for Left Atrial Procedures in Atrial Fibrillation.

This document summarizes the relevant literature for the selection of preprocedural imaging in three clinical scenarios in patients needing endovascular treatment or cardioversion of atrial fibrillation. These clinical scenarios include preprocedural imaging prior to radiofrequency ablation; prior to left atrial appendage occlusion; and prior to cardioversion. The appropriateness of imaging modalities as they apply to each clinical scenario is rated as usually appropriate, may be appropriate, and usually not appropriate to assist the selection of the most appropriate imaging modality in the corresponding clinical scenarios. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

"Some distance between us": a UK mixed methods study exploring experiences of remote care for eating disorders during COVID-19.

Introduction: COVID-19 necessitated a rapid move from face-to-face services to remote care for eating disorders/eating distress (EDs). This study explores the advantages and challenges of remote care, identifying future implications for service provision. Remote care has been considered in the broadest of terms, including therapeutic care (e.g., Cognitive Behavioural Therapy, peer support, forums, one-to-one and group care options). Methods: Using a mixed methods approach, data were collected from 211 people with lived experience of EDs (PWLE), with and without formal diagnosis. 27 participants took part in semi-structured interviews/workshops and a further 184 participants took part via an online survey. Participants reported on their ED status, the impact of the pandemic on symptoms, the benefits, and challenges of remote care (and type of support accessed), and any reasons for not accessing support. Participants were invited to make future care recommendations. Results: ED symptoms were reported as worsening during the pandemic with contributing factors including isolation, lack of routine, negative emotions, and feeling like the external situation was outside of one's control. Remote care was positively attributed to increased flexibility and facilitation of social connection. Identified barriers to access included lack of awareness about support availability, digital access/literacy, and competing commitments. Further challenges included approaches being perceived as too clinical (e.g., ED information and support presented using clinical language and/or limited to support within medical care settings, without acknowledging the broader context of disordered eating), uncertainty around remote care quality, and concerns that remote platforms may facilitate masking of symptoms. Participants reported distress caused by online platforms where self-view is the default during video calls. They expressed a need for more holistic approaches to remote care, including: "real stories" of recovery, and hybrid (online and offline) options for greater flexibility and widening of access and choice. Participants also expressed a need for appropriate digital literacy training. Discussion: Future recommendations emphasise user-centred holistic and hybrid approaches to ED remote support, with training to address digital literacy barriers and facilitate user control of platform functionalities (e.g., self-view). This study underscores the need for continued remote care with a focus on inclusivity and user empowerment.

Intranasal insulin treatment ameliorates spatial memory, muscular strength, and frailty deficits in 5xFAD mice.

The 5xFAD mouse model shows age-related weight loss as well as cognitive and motor deficits. Metabolic dysregulation, especially impaired insulin signaling, is also present in AD. This study examined whether intranasal delivery of insulin (INI) at low (0.875 U) or high (1.750 U) doses would ameliorate these deficits compared to saline in 10-month-old female 5xFAD and B6SJL wildtype (WT) mice. INI increased forelimb grip strength in the wire hang test in 5xFAD mice in a dose-dependent manner but did not improve the performance of 5xFAD mice on the balance beam. High INI doses reduced frailty scores in 5xFAD mice and improved spatial memory in both acquisition and reversal probe trials in the Morris water maze. INI increased swim speed in 5xFAD mice but had no effect on object recognition memory or working memory in the spontaneous alternation task, nor did it improve memory in the contextual or cued fear memory tasks. High doses of insulin increased the liver, spleen, and kidney weights and reduced brown adipose tissue weights. P-Akt signaling in the hippocampus was increased by insulin in a dose-dependent manner. Altogether, INI increased strength, reduced frailty scores, and improved visual spatial memory. Hypoglycemia was not present after INI, however alterations in tissue and organ weights were present. These results are novel and important as they indicate that intra-nasal insulin can reverse cognitive, motor and frailty deficits found in this mouse model of AD.

The Uncontrollable Mortality Risk Hypothesis: Theoretical foundations and implications for public health.

The 'Uncontrollable Mortality Risk Hypothesis' employs a behavioural ecological model of human health behaviours to explain the presence of social gradients in health. It states that those who are more likely to die due to factors beyond their control should be less motivated to invest in preventative health behaviours. We outline the theoretical assumptions of the hypothesis and stress the importance of incorporating evolutionary perspectives into public health. We explain how measuring perceived uncontrollable mortality risk can contribute towards understanding socioeconomic disparities in preventative health behaviours. We emphasize the importance of addressing structural inequalities in risk exposure, and argue that public health interventions should consider the relationship between overall levels of mortality risk and health behaviours across domains. We suggest that measuring perceptions of uncontrollable mortality risk can capture the unanticipated health benefits of structural risk interventions, as well as help to assess the appropriateness of different intervention approaches.

The World Federation of Chiropractic Global Patient Safety Task Force: a call to action.

BACKGROUND: The Global Patient Safety Action Plan, an initiative of the World Health Organization (WHO), draws attention to patient safety as being an issue of utmost importance in healthcare. In response, the World Federation of Chiropractic (WFC) has established a Global Patient Safety Task Force to advance a patient safety culture across all facets of the chiropractic profession. This commentary aims to introduce principles and call upon the chiropractic profession to actively engage with the Global Patient Safety Action Plan beginning immediately and over the coming decade. MAIN TEXT: This commentary addresses why the chiropractic profession should pay attention to the WHO Global Patient Safety Action Plan, and what actions the chiropractic profession should take to advance these objectives. Each strategic objective identified by WHO serves as a focal point for reflection and action. Objective 1 emphasizes the need to view each clinical interaction as a chance to improve patient safety through learning. Objective 2 urges the implementation of frameworks that dismantle systemic obstacles, minimizing human errors and strengthening patient safety procedures. Objective 3 supports the optimization of clinical process safety. Objective 4 recognizes the need for patient and family engagement. Objective 5 describes the need for integrated patient safety competencies in training programs. Objective 6 explains the need for foundational data infrastructure, ecosystem, and culture. Objective 7 emphasizes that patient safety is optimized when healthcare professionals cultivate synergy and partnerships. CONCLUSIONS: The WFC Global Patient Safety Task Force provides a structured framework for aligning essential considerations for patient safety in chiropractic care with WHO strategic objectives. Embracing the prescribed action steps offers a roadmap for the chiropractic profession to nurture an inclusive and dedicated culture, placing patient safety at its core. This commentary advocates for a concerted effort within the chiropractic community to commit to and implement these principles for the collective advancement of patient safety.

The association between attention deficit hyperactivity disorder and pregnancy, delivery and neonatal outcomes-an evaluation of a population database.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is one of the more common neuropsychiatric disorders in women of reproductive age. Our objective was to compare perinatal outcomes between women with an ADHD diagnosis and those without. METHODS: A retrospective population-based cohort study utilizing the Healthcare Cost and Utilization Project, Nationwide Inpatient Sample (HCUP-NIS) United States database. The study included all women who either delivered or experienced maternal death from 2004 to 2014. Perinatal outcomes were compared between women with an ICD-9 diagnosis of ADHD and those without. RESULTS: Overall, 9,096,788 women met the inclusion criteria. Amongst them, 10,031 women had a diagnosis of ADHD. Women with ADHD, compared to those without, were more likely to be younger than 25 years of age; white; to smoke tobacco during pregnancy; to use illicit drugs; and to suffer from chronic hypertension, thyroid disorders, and obesity (p < 0.001 for all). Women in the ADHD group, compared to those without, had a higher rate of hypertensive disorders of pregnancy (HDP) (aOR 1.36, 95% CI 1.28-1.45, p < 0.001), cesarean delivery (aOR 1.19, 95% CI 1.13-1.25, p < 0.001), chorioamnionitis (aOR 1.34, 95% CI 1.17-1.52, p < 0.001), and maternal infection (aOR 1.33, 95% CI 1.19-1.5, p < 0.001). Regarding neonatal outcomes, patients with ADHD, compared to those without, had a higher rate of small-for-gestational-age neonate (SGA) (aOR 1.3, 95% CI 1.17-1.43, p < 0.001), and congenital anomalies (aOR 2.77, 95% CI 2.36-3.26, p < 0.001). CONCLUSION: Women with a diagnosis of ADHD had a higher incidence of a myriad of maternal and neonatal complications, including cesarean delivery, HDP, and SGA neonates.

Targeting cellular cathepsins inhibits hepatitis E virus entry.

BACKGROUND AND AIMS: HEV is estimated to be responsible for 70,000 deaths annually, yet therapy options remain limited. In the pursuit of effective antiviral therapies, targeting viral entry holds promise and has proven effective for other viruses. However, the precise mechanisms and host factors required during HEV entry remain unclear. Cellular proteases have emerged as host factors required for viral surface protein activation and productive cell entry by many viruses. Hence, we investigated the functional requirement and therapeutic potential of cellular protease during HEV infection. APPROACH AND RESULTS: Using our established HEV cell culture model and subgenomic HEV replicons, we found that blocking lysosomal cathepsins (CTS) with small molecule inhibitors impedes HEV infection without affecting replication. Most importantly, the pan-cathepsin inhibitor K11777 suppressed HEV infections with an EC 50 of ~0.02 nM. Inhibition by K11777, devoid of notable toxicity in hepatoma cells, was also observed in HepaRG and primary human hepatocytes. Furthermore, through time-of-addition and RNAscope experiments, we confirmed that HEV entry is blocked by inhibition of cathepsins. Cathepsin L (CTSL) knockout cells were less permissive to HEV, suggesting that CTSL is critical for HEV infection. Finally, we observed cleavage of the glycosylated ORF2 protein and virus particles by recombinant CTSL. CONCLUSIONS: In summary, our study highlights the pivotal role of lysosomal cathepsins, especially CTSL, in the HEV entry process. The profound anti-HEV efficacy of the pan-cathepsin inhibitor K11777, especially with its notable safety profile in primary cells, further underscores its potential as a therapeutic candidate.

TMPRSS2-mediated SARS-CoV-2 uptake boosts innate immune activation, enhances cytopathology, and drives convergent virus evolution.

The accessory protease transmembrane protease serine 2 (TMPRSS2) enhances severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uptake into ACE2-expressing cells, although how increased entry impacts downstream viral and host processes remains unclear. To investigate this in more detail, we performed infection assays in engineered cells promoting ACE2-mediated entry with and without TMPRSS2 coexpression. Electron microscopy and inhibitor experiments indicated TMPRSS2-mediated cell entry was associated with increased virion internalization into endosomes, and partially dependent upon clathrin-mediated endocytosis. TMPRSS2 increased panvariant uptake efficiency and enhanced early rates of virus replication, transcription, and secretion, with variant-specific profiles observed. On the host side, transcriptional profiling confirmed the magnitude of infection-induced antiviral and proinflammatory responses were linked to uptake efficiency, with TMPRSS2-assisted entry boosting early antiviral responses. In addition, TMPRSS2-enhanced infections increased rates of cytopathology, apoptosis, and necrosis and modulated virus secretion kinetics in a variant-specific manner. On the virus side, convergent signatures of cell-uptake-dependent innate immune induction were recorded in viral genomes, manifesting as switches in dominant coupled Nsp3 residues whose frequencies were correlated to the magnitude of the cellular response to infection. Experimentally, we demonstrated that selected Nsp3 mutations conferred enhanced interferon antagonism. More broadly, we show that TMPRSS2 orthologues from evolutionarily diverse mammals facilitate panvariant enhancement of cell uptake. In summary, our study uncovers previously unreported associations, linking cell entry efficiency to innate immune activation kinetics, cell death rates, virus secretion dynamics, and convergent selection of viral mutations. These data expand our understanding of TMPRSS2's role in the SARS-CoV-2 life cycle and confirm its broader significance in zoonotic reservoirs and animal models.

Efficacy and implementation of exercise-based smoking cessation treatment for adults with high anxiety sensitivity (STEP): Study protocol for a randomized controlled trial.

Anxiety sensitivity (AS), reflecting the fear of bodily sensations, is a transdiagnostic vulnerability factor that underpins both affective psychopathology and smoking. Phase II research supports the efficacy of a 15-week community-based intervention (STEP) that combines high-intensity exercise offered by the YMCA with standard smoking cessation treatment (tobacco quitline and nicotine replacement therapy) for sedentary smokers with elevated AS. This Phase III study aims to enroll 360 adults to evaluate whether STEP efficacy for achieving smoking abstinence generalizes to Black and Hispanic smokers with elevated AS.

The risk associated with organophosphorus nerve agents: from their discovery to their unavoidable threat, current medical countermeasures and perspectives.

The first organophosphorus nerve agent was discovered accidently during the development of pesticides, shortly after the first use of chemical weapons (chlorine, phosgene) on the battlefield during World War I. Despite the Chemical Weapons Convention banning these substances, they have still been employed in wars, terrorist attacks or political assassinations. Characterised by their high lethality, they target the nervous system by inhibiting the acetylcholinesterase (AChE) enzyme, preventing neurotransmission, which, if not treated rapidly, inevitably leads to serious injury or the death of the person intoxicated. The limited efficacy of current antidotes, known as AChE reactivators, pushes research towards new treatments. Numerous paths have been explored, from modifying the original pyridinium oximes to developing hybrid reactivators seeking a better affinity for the inhibited AChE. Another crucial approach resides in molecules more prone to cross the blood-brain barrier: uncharged compounds, bio-conjugated reactivators or innovative formulations. Our aim is to raise awareness on the threat and toxicity of organophosphorus nerve agents and to present the main synthetic efforts deployed since the first AChE reactivator, to tackle the task of efficiently treating victims of these chemical warfare agents.

Estrogen Receptor, Progesterone Receptor, and Human Epidermal Growth Factor Receptor 2 Expression Rates in Invasive Breast Carcinoma: A Study of 21 Institutions.

CONTEXT.­: Laboratories performing predictive marker testing for breast carcinoma are encouraged to compare patient results to published benchmarks. OBJECTIVE.­: To collect expression rates for estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) in invasive breast carcinoma from multiple laboratories. DESIGN.­: Participants submitted data from up to 50 primary cases during the study period. Participants reported ER, PgR, and HER2 results in addition to demographic and histologic information. Participants also provided annual institution-level expression rates. RESULTS.­: A total of 21 institutions submitted data for 687 cases. Aggregate positivity rates for ER and PgR were 85.6% and 75.1%, respectively. Receptor positivity rates were higher in well-differentiated (grade 1) tumors (ER, 97.4%; PgR, 88.0%) compared with moderately differentiated (grade 2) tumors (ER, 92.4%; PgR, 84.0%) and poorly differentiated (grade 3) tumors (ER, 61.8%; PgR, 48.0%). Expression rates were higher in postmenopausal women (ER, 87.2%) than premenopausal women (ER, 79.6%) and higher in lobular carcinomas (ER, 98.7%; PgR, 85.3%) than ductal carcinomas (ER, 84.1%; PgR, 74.5%). The aggregate HER2 positivity (score 3+) rate was 9.0%. The aggregate HER2 equivocal (score 2+) rate was 14.5%. Of 81 equivocal (score 2+) cases, 70 (86.4%) were nonamplified. CONCLUSIONS.­: The data from this study provide multi-institutional benchmark data to assist laboratories performing periodic comparisons as part of a quality management program. Overall expression rates were generally similar to those of other published reports, with the exception of the ER-negative and HER2-positive rates, both of which were somewhat lower.

Idiopathic intracranial hypertension and obstetric and neonatal outcomes: A 1:20 matched study from a population database.

OBJECTIVE: Idiopathic intracranial hypertension (IIH), also known as pseudotumor cerebri, is a common pathology in reproductive-aged women, although data regarding pregnancy outcomes are scarce. In the present study, we aimed to compare pregnancy and perinatal outcomes between women who suffered from IIH to those who did not. METHODS: A retrospective cohort study using the Healthcare Cost and Utilization Project, Nationwide Inpatient Sample. All pregnant women who delivered or had a maternal death in the US (2004-2014) were included. Women with an ICD-9 diagnosis of IIH before or during pregnancy were matched to controls without IIH according to age, race, insurance type, and income quartile, in a 1:20 ratio. Pregnancy, delivery, and neonatal outcomes were compared between the two groups. RESULTS: Overall, 9 096 788 deliveries were identified. Of these, 1454 women (0.016%) had a diagnosis of IIH (study group) and were compared to 29 080 women without IIH (control group). Women with IIH, compared to those without, were more likely to be obese (body mass index >30 kg/m2) and suffer from pregestational diabetes mellitus and chronic hypertension (P < 0.001, all). After adjusting for confounders, patients in the IIH group, compared to those without, had a higher rate of pregnancy-induced hypertension (aOR 1.82, 95% CI: 1.57-2.1, P < 0.001), pre-eclampsia (aOR 1.98, 95% CI: 1.61-2.45, P < 0.001), preterm delivery (aOR 1.88, 95% CI: 1.59-2.23, P < 0.001), CD (aOR 2.41, 95% CI: 2.12-2.73, P < 0.001), wound complications (aOR 3.2, 95% CI: 1.89-5.42, P < 0.001), and congenital anomalies (aOR 2.18, 95% CI: 1.4-3.4, P < 0.001). CONCLUSION: Women with IIH had a higher incidence of obstetrical complications, including preterm deliveries, hypertensive disorders of pregnancy, and congenital anomalies.

Host determinants and responses underlying SARS-CoV-2 liver tropism.

Hepatic sequelae are frequently reported in coronavirus disease 2019 cases and are correlated with increased disease severity. Therefore, a detailed exploration of host factors contributing to hepatic impairment and ultimately infection outcomes in patients is essential for improved clinical management. The causes of hepatic injury are not limited to drug-mediated toxicity or aberrant host inflammatory responses. Indeed, multiple studies report the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in liver autopsies and the susceptibility of explanted human hepatocytes to infection. In this review, we confirm that hepatic cells express an extensive range of factors implicated in SARS-CoV-2 entry. We also provide an overview of studies reporting evidence for direct infection of liver cell types and the infection-induced cell-intrinsic processes that likely contribute to hepatic impairment.

Age-related changes in species-typical behaviours in the 5xFAD mouse model of Alzheimer's disease from 4 to 16 months of age.

Alzheimer's disease (AD) patients show age-related decreases in the ability to perform activities of daily living and the decline in these activities is related to the severity of neurobiological deterioration underlying the disease. The 5xFAD mouse model of AD shows age-related impairments in sensory- motor and cognitive function, but little is known about changes in species-typical behaviours that may model activities of daily living in AD patients. Therefore, we examined species-typical behaviours used as indices of exploration (rearing) and compulsivity (grooming) across six tests of anxiety-like behaviour or motor function in female 5xFAD mice from 3 to 16 months of age. Robust decreases in rearing were found in 5xFAD mice across all tests after 9 months of age, although few differences were observed in grooming. A fine-scale analysis of grooming, however, revealed a previously unresolved and spatially restricted pattern of grooming in 5xFAD mice at 13-16 months of age. We then examined changes in species-typical behaviours in the home-cage, and show impaired nest building in 5xFAD mice at all ages tested. Lastly, we examined the relationship between reduced species typical behaviours in 5xFAD mice and the presentation of freezing behaviour, a commonly used measure of memory for conditioned fear. These results showed that along with cognitive and sensory-motor behaviour, 5xFAD mice have robust age-related impairments in species-typical behaviours. Therefore, species typical behaviours in 5xFAD mice may help to model the decline in activities of daily living observed in AD patients, and may provide useful behavioural phenotypes for evaluating the pre-clinical efficacy of novel therapeutics for AD.

Measuring the replicability of our own research.

In the study of transgenic mouse models of neurodevelopmental and neurodegenerative disorders, we use batteries of tests to measure deficits in behaviour and from the results of these tests, we make inferences about the mental states of the mice that we interpret as deficits in "learning", "memory", "anxiety", "depression", etc. This paper discusses the problems of determining whether a particular transgenic mouse is a valid mouse model of disease X, the problem of background strains, and the question of whether our behavioural tests are measuring what we say they are. The problem of the reliability of results is then discussed: are they replicable between labs and can we replicate our results in our own lab? This involves the study of intra- and inter- experimenter reliability. The variables that influence replicability and the importance of conducting a complete behavioural phenotype: sensory, motor, cognitive and social emotional behaviour are discussed. Then the thorny question of failure to replicate is examined: Is it a curse or a blessing? Finally, the role of failure in research and what it tells us about our research paradigms is examined.