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Despite the ongoing interest in virus discovery, little is known about the factors that shape communities of viruses within individual hosts. Here, we address how virus communities might be impacted by the age of the hosts they infect, using total RNA sequencing to reveal the RNA viromes of different age groups of Ruddy Turnstones (Arenaria interpres). From oropharyngeal and cloacal swabs we identified 14 viruses likely infecting birds, 11 of which were novel, including members of the Reoviridae, Astroviridae, and Picornaviridae. Strikingly, 12 viruses identified were from juvenile birds sampled in the first year of their life, compared to only two viruses in adult birds. Both viral abundance and alpha diversity were marginally higher in juvenile than adult birds. As well as informing studies of virus ecology, that host age might be associated with viral composition is an important consideration for the future surveillance of novel and emerging viruses.The proper spatial organization of DNA, RNA, and proteins is critical for a variety of cellular processes. The genome is organized into numerous functional units, such as topologically associating domains (TADs), the formation of which is regulated by both proteins and RNA. In addition, a group of chromatin-bound proteins with the ability to undergo liquid-liquid phase separation (LLPS) can affect the spatial organization and compartmentalization of chromatin, RNA, and proteins by forming condensates, conferring unique properties to specific chromosomal regions. Although the regulation of DNA repair by histone modifications and chromatin accessibility is well established, the impacts of higher-order chromatin and protein organization on the DNA damage response (DDR) have not been appreciated until recently. In this review, we will focus on the movement of chromatin during the DDR, the compartmentalization of DDR proteins via LLPS, and the roles of membraneless nuclear bodies and transcription in DNA repair. With this backdrop, we will discuss the importance of the spatial organization of chromatin and proteins for the maintenance of genome integrity.

Persons experiencing homelessness (PEH) are known to be often excluded from primary health care and community prevention programmes leading to high use of hospital emergency departments (EDs). This study aimed to identify demographic features, clinical characteristics and attendance outcomes of PEH presenting to ED.

Analysis of routinely collected data set.

Clinical presentations and drug prescription data of PEH who presented a major ED in the West Midlands region of England from 2014 to 2019 were extracted and analysed using descriptive and inferential statistics.

During the study period, 3271 of 596,198 presentations were made by PEH; 74% PEH attendees were male. Drug- and alcohol-related conditions, as well as pain and injury constituted the most frequent reasons for presentation, contributing to over half of all presentations. A significantly higher proportion of males (n=481, 20.3%) presented with drug and alcohol problems than females (n=93, 11.2%) (P≤0.001). However, pain was the primary reasoe need of opioid analgesics constituted the majority of presentations made by PEH in ED. The observed rate of death of PEH in ED is 12 times higher than the general population. A very high proportion of PEH also leave the ED before being treated. Future research should focus on strengthening community interventions, particularly to improve access to those at risk of dual diagnoses of substance misuse and mental health problems. Interventions involving multisector collaborations are needed to improve seamless discharge from ED and minimise repeat attendance. Gender differences in the nature of presentations and ED outcomes needs to be investigated further.

The study aimed to investigate the misreporting number of positively tested individuals for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) succumbed or not to coronavirus disease 2019 (COVID-19) pandemic in Brazil at the city, state, and national scales using statistical forensic analysis.

This is a register-based study over public health data collected, organized, and maintained by the Ministry of Health covering the Brazilian population.

We evaluated the Brazilian notifications of positively tested cases for SARS-CoV-2 who have succumbed or not to COVID-19 between February 26th to September 7th of 2020at the city, state, and national scales for conformity to expected distribution provided by Benford's law (BL).

Statistical analyzes demonstrated a significant rejection of SARS-CoV-2 notification cases at the city and the number of deaths by COVID-19 in all regional levels according to the hypothesis of conformity to BL.

We demonstrated by BL, which has been widely applied to query thecare overload in some Brazilian regions.

This study aimed to provide evidence on the therapeutic prescribing activity by community optometrists in Scotland and to determine its impact on workload in general practice and ophthalmology clinics.

Scottish administrative healthcare data for a 53-month period (November 2013-April 2018) were used to analyse non-medical prescribing practice by optometrists.

Using interrupted time-series regression (Autoregressive Integrated Moving Average), we assessed the impact of optometrist prescribing on ophthalmology outpatient attendances and general practice prescribing for eye disorders.

A total of 54,246 items were prescribed by 205 optometrists over the study period. Since the commencement of data recording, optometrist prescribing activity increased steadily from a baseline of zero to 1.2% of all ophthalmic items prescribed. Neither the monthly number of items prescribed nor the size of optometric workforce were associated with a reduction in ophthalmology outpatient appointments over time.

Optometrists increasingly contribute to community ophthalmic prescribing in Scotland, releasing capacity and lessening general practice, but not secondary care workload. There appears to be an underutilisation of optometrists related to the management of dry eye, which represents an opportunity to release further capacity.

Optometrists increasingly contribute to community ophthalmic prescribing in Scotland, releasing capacity and lessening general practice, but not secondary care workload. There appears to be an underutilisation of optometrists related to the management of dry eye, which represents an opportunity to release further capacity.Loss-of-function mutations in Na+/H + exchanger 6 (NHE6) (also termed SLC9A6) cause the X-linked neurogenetic disorder Christianson syndrome (CS). Using peripheral blood mononuclear cells, we developed induced pluripotent stem cell (iPSC) lines from a patient with the NHE6 nonsense mutation c.1569G > A (p.(W523X)) and diagnosed with CS and from a biologically-related control. Using CRISPR/Cas9 gene editing, we generated two isogenic control lines in which the c.1569G > A mutation was corrected. All lines were verified by DNA sequencing and for NHE6 protein expression, pluripotency, and differentiation potential. These lines will serve as a valuable resource for both basic and translational studies in CS.Induced pluripotent stem cells (iPSCs) were generated from blood outgrowth endothelial cells (BOECs) obtained from a healthy donor and from a patient diagnosed with Hermansky Pudlak Syndrome type 2 (HPS2), caused by compound heterozygous AP3B1 mutations (c.177delA and c.1839-1842delTAGA). BOECs were reprogrammed with a hOKSM self-silencing polycistronic lentiviral vector, where the generated iPSCs showed normal karyotype, expression of pluripotency associated markers and in vitro spontaneous differentiation towards the three germ layers. The generated iPSCs can be used to study HPS2 pathophysiology and the basic functions of AP3B1 protein in different cell types.We have developed Joubert syndrome (JS)-derived induced pluripotent stem cell (iPSC) lines from dermal fibroblasts biopsied from a female patient harbouring novel compound heterozygous mutations in CC2D2A gene. The newly established iPSC lines provide tremendous promises for development of JS-derived neuronal cell lines to uncover the molecular and cellular mechanisms underlying the pathogenesis of JS and to develop therapeutic interventions for treatment of JS.Oxytocin receptors (OTRs) in the midbrain dorsal raphe (DR; the source of most forebrain serotonin) have recently been identified as a potential pharmacological target for treating numerous psychiatric disorders. However, almost all research on this topic has been conducted on males and the role of DR OTRs in female social and affective behaviors is mostly unknown. This may be particularly relevant during early motherhood, which is a time of high endogenous oxytocin signaling, but also a time of elevated risk for psychiatric dysfunction. To investigate whether OTRs in the DR are necessary for postpartum female social and affective behaviors, we constructed and then injected into the DR an adeno-associated virus permanently expressing an shRNA targeting OTR mRNA. We then observed a suite of social and affective behaviors postpartum. OTR knockdown in the maternal DR led to pup loss after parturition, decreased nursing, increased aggression, and increased behavioral despair. These effects of OTR knockdown in the DR may be due to disrupted neuroplasticity in the primary somatosensory cortex (S1), which mediates maternal sensitivity to the tactile cues from young, as we found significantly more plasticity-restricting perineuronal nets (PNNs) in the S1 rostral barrel field and fewer PNNs in the caudal barrel field of OTR-knockdown mothers. These results demonstrate that OTRs in the midbrain DR are essential for postpartum maternal social and affective behaviors, are involved in postpartum cortical plasticity, and suggest that pharmacotherapies targeting OTRs in the DR could be effective treatments for some peripartum affective disorders.Psychological treatments of posttraumatic stress disorder (PTSD) are associated with non-response rates of up to 50%. This fact highlights the need to identify characteristics of poorer treatment outcome. Among others, previous evidence focused on the role of dysfunctional cortisol secretion which has been related to the development, maintenance and treatment of PTSD. Particularly, promising evidence stems from research using hair cortisol analysis which allows for a reliable assessment of cortisol secretion over several months. Another variable that has been linked to both HCC and non-response to treatment is childhood maltreatment (CM). In order to examine the predictive value of pre-treatment hair cortisol concentrations (HCC), treatment-related changes in HCC as well as CM for changes in PTSD symptomatology, we set up a prospective study in which we followed 52 female PTSD patients over the course of a trauma-focused inpatient treatment. Specifically, 3-month integrated HCC were assessed at treatment entry, at discharge and on average five months later accompanied by assessments of PTSD, overall and depressive symptomatology. CM was measured at treatment entry. Self-report indices improved following inpatient treatment. No evidence for pre-treatment HCC to be associated with changes in PTSD symptoms was revealed. However, attenuated pre-treatment HCC predicted less improvement in overall symptomatology from treatment entry to discharge. This effect lost significance after adjusting for baseline dissociative symptoms. Neither changes in HCC nor CM were predictive of treatment response. Pre-treatment cross-sectional analyses revealed no association between HCC and CM. The current hair cortisol data provided little evidence for a predictive role of lower long-term integrated cortisol secretion for poorer inpatient treatment outcome. KT 474 datasheet If corroborated by further research in larger PTSD samples with much more methodological rigor, these data might be a valuable basis for future tailored research projects.

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