Influence of the intestinal microbiota on disease susceptibility in kittens with experimentally-induced carriage of atypical enteropathogenic Escherichia coli

Typical enteropathogenic E. coli (tEPEC) carries the highest hazard of death in children with diarrhea and atypical EPEC (aEPEC) was recently identified as significantly associated with diarrheal mortality in kittens. In both children and kittens there is a significant association between aEPEC burden and diarrheal disease, however the infection can be found in individuals with and without diarrhea. It remains unclear to what extent, under what conditions, or by what mechanisms aEPEC serves as a primary pathogen in individuals with diarrhea. It seems likely that a combination of host and bacterial factors enable aEPEC to cause disease in some individuals and not in others. The purpose of this study was to determine the impact of aEPEC on intestinal function and diarrhea in kittens following experimentally-induced carriage and the influence of a disrupted intestinal microbiota on disease susceptibility. Results of this study identify aEPEC as a potential pathogen in kittens. In the absence of disruption to the intestinal microbiota, kittens are resistant to clinical signs of aEPEC carriage but demonstrate significant occult changes in intestinal absorption and permeability. Antibiotic-induced disruption of the intestinal microbiota prior to infection increases subsequent intestinal water loss as determined by % fecal wet weight. Enrichment of the intestinal microbiota with a commensal member of the feline mucosa-associated microbiota, Enterococcus hirae, ameliorated the effects of aEPEC experimental infection on intestinal function and water loss. These observations begin to unravel the mechanisms by which aEPEC infection may be able to exploit susceptible hosts.Peer reviewe

Reply to Fischer et al

We welcome the correspondence from Fischer and colleagues regarding our recent paper on vocal learning in chimpanzee food grunts [1]. Fischer et al. make two challenges to our paper's conclusions, which we address here

Menopause induces changes to the stratum corneum ceramide profile, which are prevented by hormone replacement therapy

Abstract The menopause can lead to epidermal changes that are alleviated by hormone replacement therapy (HRT). We hypothesise that these changes could relate to altered ceramide production, and that oestrogen may have a role in keratinocyte ceramide metabolism. White Caucasian women were recruited into three groups: pre-menopausal (n = 7), post-menopausal (n = 11) and post-menopausal taking HRT (n = 10). Blood samples were assessed for hormone levels, transepidermal water loss was measured to assess skin barrier function, and stratum corneum lipids were sampled from photoprotected buttock skin. Ceramides and sphingomyelins were analysed by ultraperformance liquid chromatography with electrospray ionisation and tandem mass spectrometry. Post-menopausal stratum corneum contained lower levels of ceramides, with shorter average length; changes that were not evident in the HRT group. Serum oestradiol correlated with ceramide abundance and length. Ceramides had shorter sphingoid bases, indicating altered de novo ceramide biosynthesis. Additionally, post-menopausal women had higher sphingomyelin levels, suggesting a possible effect on the hydrolysis pathway. Treatment of primary human keratinocytes with oestradiol (10 nM) increased production of CER[NS] and CER[NDS] ceramides, confirming an effect of oestrogen on cutaneous ceramide metabolism. Taken together, these data show perturbed stratum corneum lipids post-menopause, and a role for oestrogen in ceramide production

The archival discovery of a strong Lyman-α\alpha and [CII] emitter at z = 7.677

We report the archival discovery of Lyman-$\alpha$ emission from the bright ultraviolet galaxy Y002 at $z=7.677$, spectroscopically confirmed by its ionized carbon [CII] 158$\mu$m emission line. The Ly$\alpha$ line is spatially associated with the rest-frame UV stellar emission ($M_{\rm UV}$~-22, 2x brighter than $M^\star_{\rm UV}$) and it appears offset from the peak of the extended [CII] emission at the current ~1" spatial resolution. We derive an estimate of the unobscured SFR(UV)=$(22\pm1)\,M_\odot$ yr$^{-1}$ and set an upper limit of SFR(IR)$<15\,M_\odot$ yr$^{-1}$ from the far-infrared wavelength range, which globally place Y002 on the SFR(UV+IR)-L([CII]) correlation observed at lower redshifts. In terms of velocity, the peak of the Ly$\alpha$ emission is redshifted by $\Delta v$(Ly$\alpha$)~500 km s$^{-1}$ from the systemic redshift set by [CII] and a high-velocity tail extends to up to ~1000 km s$^{-1}$. The velocity offset is up to ~3.5x higher than the average estimate for similarly UV-bright emitters at z~6-7, which might suggest that we are witnessing the merging of two clumps. A combination of strong outflows and the possible presence of an extended ionized bubble surrounding Y002 would likely facilitate the escape of copious Ly$\alpha$ light, as indicated by the large equivalent width EW(Ly$\alpha$)=$24^{+5}_{-6}$ \r{A}. Assuming that [CII] traces the neutral hydrogen, we estimate a HI gas fraction of $M({\rm HI})/M_\star\gtrsim8$ for Y002 as a system and speculate that patches of high HI column densities could contribute to explain the observed spatial offsets between Ly$\alpha$ and [CII] emitting regions. The low dust content, implied by the non-detection of the far-infrared continuum emission at rest-frame ~160 $\mu$m, would be sufficient to absorb any potential Ly$\alpha$ photons produced within the [CII] clump as a result of large HI column densities.Comment: 10 pages, 4 figures. Accepted for publication in The Astrophysical Journal Letter

Provider Perspectives on Rapid Treatment Initiation Among People Newly Diagnosed With HIV: A New Message of “Urgency”?

Background Early initiation of antiretroviral therapy improves human immunodeficiency virus (HIV) outcomes. However, achieving earlier treatment initiation is challenging for many reasons including provider awareness and clinic barriers; this study sought to understand perceptions of an early initiation program. Methods We interviewed 10 providers from 3 HIV clinics in North Carolina (October-November 2020). We asked providers about overall perceptions of early initiation and the pilot program. We developed narrative summaries to understand individual contexts and conducted thematic analysis using NVivo. Results Providers believed earlier initiation would signal an “extra sense of urgency” about the importance of antiretroviral therapy—a message not currently reflected in standard of care. Safety was a consistent concern. Cited implementation barriers included transportation assistance, medication sustainability, and guidance to address increased staff time and appointment availability. Conclusion Our qualitative findings highlight the need for training on the safety of early initiation and addressing staffing needs to accommodate quicker appointments.Plain Language Summary Doctor and clinic staff perspectives on a program to immediately start HIV treatment among patients newly diagnosed with HIV Treating human immunodeficiency virus (HIV) is easier than ever. Starting newly diagnosed persons on HIV medication as soon as possible is a now recommended goal. However, starting patients right away can be challenging. This study interviewed doctors and clinic staff to better understand their perspectives prior to implementing a program that would provide newly diagnosed patients with HIV treatment immediately. Results showed that some doctors are worried patients will not return after receiving their medications. Providers want support for linking patients to the clinic and ensuring they will be able to receive their next dose of medication when they come in. Other providers saw the benefits of reducing HIV stigma if the program can more quickly start patients on treatment. Some providers explained that when you go to the doctor and are sick you receive medications immediately, yet for newly diagnosed patients living with HIV, patients can be told to come back a month later to start treatment. Some providers believe shifting this messaging may also help patients take their medications better. Most providers saw the need for clinics to have more same-day appointment availability to meet the needs of the new program. Overall, providers were excited about the opportunity to improve the HIV care by offering HIV medications to newly diagnosed patients immediately

Are autistic children more vulnerable online? Relating autism to online safety, child wellbeing and parental risk management

Abstract Many autistic children are active online users. Research suggests that they are subject to distress and poor wellbeing following online safety threats. However, it is unclear if autistic children are more likely to experience online safety risks compared with non-autistic children. We conducted a parental online safety survey. Two groups of parents (autistic children, n=63; non-autistic children, n= 41) completed questionnaires about their child's online safety behaviours, wellbeing, and their own parental self-efficacy (PSE). Our results highlight that autistic children experience significantly more online safety risks than non-autistic children and poorer wellbeing than autistic children who did not experience online safety risks. Parents of autistic children reported carrying out significantly less risk management and reported poorer PSE than parents of non-autistic children. Having an autistic child and parental online safety knowledge were significant predictors of PSE. These results will help inform the co-design of interventions to protect autistic children online

Cystic fibrosis population carrier screening: 2004 revision of American College of Medical Genetics mutation panel

Group recommended a panel of mutations and variants that should be tested to determine carrier status within the CFTR gene as a part of population screening programs.1,2 This was initially done in response to the recommendations of an NIH CF Consensus Conference that CF carrier screening be consid-ered by all couples for use before conception or prenatally.3 At that time, the Working Group recognized limitations in our understanding of the population frequencies of several CF al-leles and proposed to review mutation distribution data after the first two years of the program. In 2002, as part of an ongo-ing effort to ensure that the cystic fibrosis carrier screening programs are current with respect to the scientific literature and other available data and practices, we initiated a second review of data on the distribution of mutations in different ethnic groups and we began to assess whether providers wer

Global no net loss of natural ecosystems

A global goal of no net loss of natural ecosystems or better has recently been proposed, but such a goal would require equitable translation to country-level contributions. Given the wide variation in ecosystem depletion, these could vary from net gain (for countries where restoration is needed), to managed net loss (in rare circumstances where natural ecosystems remain extensive and human development imperative is greatest). National contributions and international support for implementation also must consider non-area targets factors such as the capacity to conserve and the imperative for human development

Establishing a distributed national research infrastructure providing bioinformatics support to life science researchers in Australia

EMBL Australia Bioinformatics Resource (EMBL-ABR) is a developing national research infrastructure, providing bioinformatics resources and support to life science and biomedical researchers in Australia. EMBL-ABR comprises 10 geographically distrib- uted national nodes with one coordinating hub, with current funding provided through Bioplatforms Australia and the University of Melbourne for its initial 2-year development phase. The EMBL-ABR mission is to: (1) increase Australia’s capacity in bioinformatics and data sciences; (2) contribute to the development of training in bioinformatics skills; (3) showcase Australian data sets at an international level and (4) enable engagement in international programs. The activities of EMBL-ABR are focussed in six key areas, aligning with comparable international initiatives such as ELIXIR, CyVerse and NIH Commons. These key areas—Tools, Data, Standards, Platforms, Compute and Training—are described in this article

Non-randomised feasibility study testing a primary care intervention to promote engagement in an online health community for adults with troublesome asthma: protocol

Introduction: In the UK, approximately 4.3 million adults have asthma, with one-third experiencing poor asthma control, affecting their quality of life, and increasing their healthcare use. Interventions promoting emotional/behavioural self-management can improve asthma control and reduce comorbidities and mortality. Integration of online peer support into primary care services to foster self-management is a novel strategy. We aim to co-design and evaluate an intervention for primary care clinicians to promote engagement with an asthma online health community (OHC). Our protocol describes a ‘survey leading to a trial’ design as part of a mixed-methods, non-randomised feasibility study to test the feasibility and acceptability of the intervention. Methods and analysis: Adults on the asthma registers of six London general practices (~3000 patients) will be invited to an online survey, via text messages. The survey will collect data on attitudes towards seeking online peer support, asthma control, anxiety, depression, quality of life, information on the network of people providing support with asthma and demographics. Regression analyses of the survey data will identify correlates/predictors of attitudes/receptiveness towards online peer support. Patients with troublesome asthma, who (in the survey) expressed interest in online peer support, will be invited to receive the intervention, aiming to reach a recruitment target of 50 patients. Intervention will involve a one-off, face-to-face consultation with a practice clinician to introduce online peer support, sign patients up to an established asthma OHC, and encourage OHC engagement. Outcome measures will be collected at baseline and 3 months post intervention and analysed with primary care and OHC engagement data. Recruitment, intervention uptake, retention, collection of outcomes, and OHC engagement will be assessed. Interviews with clinicians and patients will explore experiences of the intervention. Ethics and dissemination: Ethical approval was obtained from a National Health Service Research Ethics Committee (reference: 22/NE/0182). Written consent will be obtained before intervention receipt and interview participation. Findings will be shared via dissemination to general practices, conference presentations and peer-reviewed publications. Trial registration number: NCT05829265