Repurposing zidovudine and 5-fluoro-2'-deoxyuridine as antibiotic drugs made possible by synergy with both trimethoprim and the mitochondrial toxicity-reducing agent uridine.

Objectives: The increasing frequency of antibiotic-resistant bacterial infections is a major public health challenge, and new antibiotic drugs are urgently needed. A rapid solution to the problem is to repurpose clinically approved compounds with antibacterial properties, such as the nucleoside analogues zidovudine (azidothymidine) or 5-fluoro-2'-deoxyuridine. Here we report the in vitro and in vivo antibacterial properties of double and triple combinations of azidothymidine or 5-fluoro-2'-deoxyuridine with uridine and/or trimethoprim.

Reduced mTORC1-signaling in progenitor cells leads to retinal lamination deficits.

Background: Neuronal lamination is a hallmark of the mammalian central nervous system (CNS) and underlies connectivity and function. Initial formation of this tissue architecture involves the integration of various signaling pathways that regulate the differentiation and migration of neural progenitor cells.

Results: Here, we demonstrate that mTORC1 mediates critical roles during neuronal lamination using the mouse retina as a model system.

Hot metacognition: poorer metacognitive efficiency following acute but not traumatic stress.

Aberrations to metacognition-the ability to reflect on and evaluate self-performance-are a feature of poor mental health. Theoretical models of post-traumatic stress disorder propose that following severe stress or trauma, maladaptive metacognitive evaluations and appraisals of the event drive the development of symptoms. Empirical research is required in order to reveal whether disruptions to metacognition cause or contribute to symptom development in line with theoretical accounts, or are simply a consequence of ongoing psychopathology.

Effect of tebipenem pivoxil hydrobromide on the normal gut microbiota of a healthy adult population in Sweden: a randomised controlled trial.

Background: Antimicrobials cause perturbations in the composition and diversity of the host microbiome. We aimed to compare gut microbiome perturbations caused by oral tebipenem pivoxil hydrobromide (a novel carbapenem) and by amoxicillin-clavulanic acid (an orally administered β-lactam-β-lactam inhibitor combination widely used in clinical practice).

Methods: We did a phase 1, single-centre, randomised, parallel-group, active-control trial to evaluate the effect of tebipenem pivoxil hydrobromide on the human gut microbiota.

Cardiac psychophysiological tuning to socioaffective content is disrupted in aged rhesus monkeys (Macaca mulatta).

Aging ushers in numerous disruptions to autonomic nervous system (ANS) function. Although the effects of aging on ANS function at rest are well characterized, there is surprising variation in reports of age-related differences in ANS reactivity to psychosocial stressors, with some reports of decreases and other reports of increases in reactivity with age. The sources of variation in age-related differences are largely unknown.

A core component of psychological therapy causes adaptive changes in computational learning mechanisms.

Background: Cognitive distancing is an emotion regulation strategy commonly used in psychological treatment of various mental health disorders, but its therapeutic mechanisms are unknown.

Methods: 935 participants completed an online reinforcement learning task involving choices between pairs of symbols with differing reward contingencies. Half (49.

Estimates of life history parameters in a high latitude, arid-country vervet monkey population.

We present data on life history parameters from a long-term study of vervet monkeys in the Eastern Cape, South Africa. Estimates are presented of age at first conception for females and age at natal dispersal for males, along with the probability of survival to adulthood for infants born during the study, female reproductive life-span, reproductive output (including lifetime reproductive success for a subset of females), and inter-birth interval (IBI) duration. We also assess the effect of maternal age and infant survival on length of IBI.

Well-being of professional older adults' caregivers in Alberta's assisted living and long-term care facilities: a cross-sectional study.

Background: For the care need of older adults, long-term care (LTC) and assisted living (AL) facilities are expanding in Alberta, but little is known about the caregivers' well-being. The purpose of the study was to investigate the physical health conditions, mental and emotional health (MEH), health behaviour, stress levels, quality of life (QOL), and turnover and absenteeism (TAA) among professional caregivers in Alberta's LTC and AL facilities.

Methods: This cross-sectional survey involved 933 conveniently selected caregivers working in Alberta's LTC and AL facilities.

Perceived strategies for reducing staff-turnover and improving well-being and retention among professional caregivers in Alberta's continuing-care facilities: A qualitative study.

This qualitative study explored potential factors that lead to turnover and absenteeism and how to improve well-being and retention among professional older-adult-caregivers in Alberta's assisted living (AL) and long-term care (LTC) facilities. Four hundred and forty-seven participants aged 45-54 years were interviewed through a five-item, content-validated open-ended questionnaire. The questionnaire was self-administered in the English language and the soft copy of their responses was transferred into NVIVO version 12 software for coding.

A transdiagnostic meta-analysis of acute augmentations to psychological therapy.

At least half of all patients with mental health disorders do not respond adequately to psychological therapy. Acutely enhancing particular biological or psychological processes during psychological therapy may improve treatment outcomes. However, previous studies are confined to specific augmentation approaches, typically assessed within single diagnostic categories.

Quantitative 3D OPT and LSFM datasets of pancreata from mice with streptozotocin-induced diabetes.

Mouse models for streptozotocin (STZ) induced diabetes probably represent the most widely used systems for preclinical diabetes research, owing to the compound's toxic effect on pancreatic β-cells. However, a comprehensive view of pancreatic β-cell mass distribution subject to STZ administration is lacking. Previous assessments have largely relied on the extrapolation of stereological sections, which provide limited 3D-spatial and quantitative information.

Statistical power for cluster analysis.

Background: Cluster algorithms are gaining in popularity in biomedical research due to their compelling ability to identify discrete subgroups in data, and their increasing accessibility in mainstream software. While guidelines exist for algorithm selection and outcome evaluation, there are no firmly established ways of computing a priori statistical power for cluster analysis. Here, we estimated power and classification accuracy for common analysis pipelines through simulation.

Interoceptive pathways to understand and treat mental health conditions.

An increasing recognition that brain and body are dynamically coupled has enriched our scientific understanding of mental health conditions. Peripheral signals interact centrally to influence how we think and feel, generating our sense of the internal condition of the body, a process known as interoception. Disruptions to this interoceptive system may contribute to clinical conditions, including anxiety, depression, and psychosis.

Causal analysis as a bridge between qualitative and quantitative research.

Yarkoni argues that one solution is to abandon quantitative methods for qualitative ones. While we agree that qualitative methods are undervalued, we argue that both are necessary for thoroughgoing psychological research, complementing one another through the use of causal analysis. We illustrate how directed acyclic graphs can bridge qualitative and quantitative methods, thereby fostering understanding between different psychological methodologies.

Activity of Omadacycline and Five Comparators against Contemporary Ribotypes of Clostridioides difficile in Stockholm, Sweden.

Clostridioides difficile infection represents a growing clinical challenge. The new compound omadacycline is a potential treatment alternative, as many antibiotics have limited activity or are rarely used due to costs and side effects. The activity of omadacycline and five comparators was assessed with agar dilution on a 2015-to-2018 collection of 65 C.

3D imaging of human organs with micrometer resolution - applied to the endocrine pancreas.

The possibility to quantitatively study specific molecular/cellular features of complete human organs with preserved spatial 3D context would have widespread implications for pre-clinical and clinical medicine. Whereas optical 3D imaging approaches have experienced a formidable revolution, they have remained limited due to current incapacities in obtaining specific labelling within large tissue volumes. We present a simple approach enabling reconstruction of antibody labeled cells within entire human organs with preserved organ context.

Distinct Opsin 3 () Expression in the Developing Nervous System during Mammalian Embryogenesis.

Opsin 3 () is highly expressed in the adult brain, however, information for spatial and temporal expression patterns during embryogenesis is significantly lacking. Here, an -eGFP reporter mouse line was used to monitor cell body expression and axonal projections during embryonic and early postnatal to adult stages. By applying 2D and 3D fluorescence imaging techniques, we have identified the onset of Opn3 expression, which predominantly occurred during embryonic stages, in various structures during brain/head development.

Avoiding monetary loss: A human habenula functional MRI ultra-high field study.

A number of convergent human neuroimaging and animal studies suggest that habenula neurons fire in anticipation of non-rewarding outcomes, and suppress their firing in anticipation of rewarding outcomes. This normative function of the habenula appears disrupted in depression, and may be critical to the anti-depressant effects of ketamine. However, studying habenula functionality in humans using standard 3 T MRI is inherently limited by its small size.

Disrupted Dorsal Mid-Insula Activation During Interoception Across Psychiatric Disorders.

Objective: Maintenance of bodily homeostasis relies on interoceptive mechanisms in the brain to predict and regulate bodily state. While altered neural activation during interoception in specific psychiatric disorders has been reported in many studies, it is unclear whether a common neural locus underpins transdiagnostic interoceptive differences.

Methods: The authors conducted a meta-analysis of neuroimaging studies comparing patients with psychiatric disorders with healthy control subjects to identify brain regions exhibiting convergent disrupted activation during interoception.

Liminal space and the negotiation of care work in extra-care housing.

This is a qualitative case study of care work in a liminal space, specifically the case of an extra-care housing residence, which is an innovative housing alternative for elderly people in need of care in Sweden. The study is an exploration of social care workers' perceptions about their workplaces and their understandings of themselves, which are shaped by their embeddedness in architectural space. The extra-care housing residence appeared as a liminal space in which two dominant spaces - home care services and residential care - underpinned the staff's perceptions of an unclear workplace and their identity work.

Selective Isolation of Multidrug-Resistant spp., Producers of Novel Antibacterial Peptides.

Twenty-eight multidrug-resistant bacterial strains closely related or identical to , and were isolated from soil samples by selection for multidrug-resistance. Approximately 3-30% of the selected isolates were identified as , whereas isolation without antibiotics did not yield any isolates of this genus. Next generation sequencing data showed to be on 69th place among the bacterial genera (0.

Predicting Response to Brain Stimulation in Depression: a Roadmap for Biomarker Discovery.

Purpose Of Review: Clinical response to brain stimulation treatments for depression is highly variable. A major challenge for the field is predicting an individual patient's likelihood of response. This review synthesises recent developments in neural predictors of response to targeted brain stimulation in depression.

Sustainability of an IPCP program within a federally qualified health center including interprofessional student team placements.

In an effort to improve teamwork and collaborative care at a Federally Qualified Health Center (FQHC), the Midwest Interprofessional Practice, Education, and Research Center (MIPERC) collaborated on the implementation of an interprofessional collaborative practice (IPCP) program that included placement of multidisciplinary student teams. The MIPERC IPCP program supported staff, preceptor and student teams through interprofessional education and structured interprofessional activities for students, including daily huddles, interprofessional student team visits, and nurse triage phone calls. Results from the project's first year were previously reported (Nagelkerk et al.

Neural effects of antidepressant medication and psychological treatments: a quantitative synthesis across three meta-analyses.

Background: Influential theories predict that antidepressant medication and psychological therapies evoke distinct neural changes.

Aims: To test the convergence and divergence of antidepressant- and psychotherapy-evoked neural changes, and their overlap with the brain's affect network.

Method: We employed a quantitative synthesis of three meta-analyses (n = 4206).