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Group B streptococcus (GBS) is an increasing cause of disease in adults. We present long-term trends in incidence of overall infections and identify characteristics of patients with GBS cellulitis, bone and joint infections. Active, population-based surveillance was conducted from 1995-2012 in three California counties and the data were analysed retrospectively. All cases had isolation of GBS from a normally sterile site. Cases of cellulitis were classified based on clinical diagnosis. GBS bone or joint infection was defined as isolation of GBS from a bone or joint or a diagnosis of osteomyelitis or septic arthritis. Medical charts were reviewed for demographic and clinical information. There were 3917 cases of GBS; the incidence of disease increased from 5·8 to 8·3 cases/100 000 persons (P < 0·001) from 1995 to 2012. In adults aged ⩾40 years, the overall incidence of GBS increased from 8·5 to 14·2 cases/100 000 (P < 0·001) persons during the study period. The incidence of cellulitis increased from 1·6 to 3·8 cases/100 000 (P < 0·001), bone infection increased from 0·7 to 2·6 cases/100 000 (P < 0·001), and the incidence of joint infection remained approximately constant at an average rate of 1·0 case/100 000. The highest incidence rates were observed in men, persons aged ⩾80 years, non-Hispanic blacks and Hispanics. Diabetes was the most common underlying condition (51·2% cellulitis cases, 76·3% bone infections, 29·8% joint infections).

Tear production, evaluated every 2 hours from 8 AM to 8 PM by use of the Schirmer tear test over a 3-day period, was not significantly different between left and right eyes in 12 dogs. However, a significant diurnal pattern was evident. Tear production was lowest at midday and highest in the late afternoon/early evening. After pilocarpine HCl ophthalmic solution (0.25, 1.0, or 2.0%; 1 drop) was administered topically to the left eye of each dog at 7 AM on days 4, 6, and 8, respectively, tear production was determined for both eyes every 2 hours from 8 AM to 8 PM on the day of treatment. Analysis of tear values between eyes and between each eye's treatment and pretreatment values did not reveal significant change for the treated eye, but tear production was significantly less in the untreated eye, compared with its pretreatment values and with values in the treated eye. On day 10 (48 hours after the last treatment), tear production values were not significantly different between left and right eyes, and for both eyes, were not significantly different from the mean pretreatment tear production values. Topical application of 0.25, 1.0, or 2.0% pilocarpine HCl consistently caused blepharospasm, conjunctival hyperemia, and miosis of the treated eye, without significant increase in tear production. We concluded that topical application of pilocarpine, at the concentrations used, may have little value in treating disorders involving reduced tear production.

CONTEXT: The purpose of this case series study was to pilot test an evidence-based neuropathic pain (NP) treatment and referral algorithm for use by oncology nurses when managing cancer-related NP. OBJECTIVES: The primary study objective was to assess patient-reported outcomes (pain severity, changes in activities of daily living, and satisfaction) resulting from algorithm use. METHODS: Outpatients (n=20) with cancer-related NP scores >=4 on a 0-10 numeric rating scale participated in the study. NP assessment, treatment, and referral to ancillary providers were guided by an evidence-based NP algorithm that was implemented by oncology nurse practitioners. Based on efficacy evidenced through randomized clinical trials published at the time of study implementation, the following drugs were included in the algorithm: lidocaine patch, gabapentin, oxycodone, tramadol, morphine, methadone, duloxetine, pregabalin, and nortriptyline. Recommendations for starting dose, dose escalation, drug combinations, treatment duration, and contraindications were included for first-tier drugs. Patient-reported outcomes (pain severity, functional capacity, and satisfaction) were assessed monthly over 12 weeks. RESULTS: Average NP severity (P=0.001), general activity (P<0.001), mood (P=0.002), walking ability (P=0.01), ability to perform normal work (P=0.002), relationships (P=0.002), sleep (P=0.01), life enjoyment (P<0.001), and patient satisfaction (P=0.003) all improved by 12 weeks. CONCLUSION: Evidence from this pilot study suggests that NP evidence-based treatment may result in improved symptoms, function, and patient satisfaction. A randomized controlled trial is needed to further assess algorithm efficacy. [ABSTRACT FROM AUTHOR]

The long-term (10 years) multimodality distributed phased archive for the Medical Information, Communication and Archive System (MICAS) is being implemented in three phases. The selection process took approximately 10 months. Based on the mandatory archive attributes and desirable features, Cemax-Icon (Fremont, CA) was selected as the vendor. The archive provides for an open-solution allowing incorporation of leading edge, 'best of breed' hardware and software and provides maximum flexibility and automation of workflow both within and outside of radiology. The solution selected is media-independent, provides expandable storage capacity, and will provide redundancy and fault tolerance in phase II at minimum cost. Other attributes of the archive include scalable archive strategy, virtual image database with global query, and an object-oriented database. The archive is seamlessly integrated with the radiology information system (RIS) and provides automated fetching and routing, automated study reconciliation using modality worklist manager, clinical reports available at any Digital Imaging and Communications in Medicine (DICOM) workstation, and studies available for interpretation whether validated or not. Within 24 hours after a new study is acquired, four copies will reside within different components of the archive including a copy that can be stored off-site. Phase II of the archive will be installed during 1999 and will include a second Cemax-Icon archive and database using archive manager (AM) Version 4.0 in a second computer room. Copyright (c) 1999 by W.B. Saunders Company [ABSTRACT FROM AUTHOR]

The Medical Information, Communication and Archive System (MICAS) is a multivendor incremental approach to picture archiving and communications system (PACS). It is a multimodality integrated image management system that is seamlessly integrated with the radiology information system (RIS). Phase II enhancements of MICAS include a permanent archive, automated workflow, study caches, Microsoft (Redmond, WA) Windows NT diagnostic workstations with all components adhering to Digital Information Communications in Medicine (DICOM) standards. MICAS is designed as an enterprise-wide PACS to provide images and reports throughout the Strong Health healthcare network. Phase II includes the addition of a Cemax-Icon (Fremont, CA) archive, PACS broker (Mitra, Waterloo, Canada), an interface (IDX PACSlink, Burlington, VT) to the RIS (IDXrad) plus the conversion of the UNIX-based redundant array of inexpensive disks (RAID) 5 temporary archives in phase I to NT-based RAID 0 DICOM modality-specific study caches (ImageLabs, Bedford, MA). The phase I acquisition engines and workflow management software was uninstalled and the Cemax archive manager (AM) assumed these functions. The existing ImageLabs UNIX-based viewing software was enhanced and converted to an NT-based DICOM viewer. Installation of phase II hardware and software and integration with existing components began in July 1998. Phase II of MICAS demonstrates that a multivendor open-system incremental approach to PACS is feasible, cost-effective, and has significant advantages over a single-vendor implementation. Copyright (c) 1999 by W.B. Saunders Company [ABSTRACT FROM AUTHOR]

The majority of the homeless population are people of color. There has been little study of racial differences among the homeless population, and racial findings have not been reported separately for homeless men and women. This study investigated the differences between white and nonwhite homeless people in a randomly selected sample of 600 homeless men and 300 homeless women in St. Louis. The 900 homeless people were interviewed using the Diagnostic Interview Schedule and Homeless Supplement. About three-fourths of the sample were African Americans. The homelessness of the white people was more often internally related, for example, substance abuse in men and non-substance abuse psychiatric illness in women. The homelessness of nonwhite people was more often externally related, for example, socioeconomic problems caused by lower incomes for men and reliance on a failing welfare system by women and their dependent families. These differences point to potentially divergent emphases for intervention with these subpopulations. Because of the diversity within racial subgroups, however, all need a variety of interventions for both external and internal problems. [ABSTRACT FROM AUTHOR]

This paper reviews the results of recent traffic systems research and concludes that the evidence shows that with sufficient ingenuity by farmers and their equipment suppliers to match operating and wheel track widths, the traffic management systems that reduce soil compaction should improve crop yield, reduce energy consumption and improve infiltration rates (which will reduce runoff, erosion and flooding). These together will improve agronomic, economic and environmental sustainability of agriculture. Low ground pressure alternatives may well be the option that best suits some farming enterprises and should not be discounted as viable traffic management methods. The paper also considers the implications for further work to improve the robustness of the experimental data.

Abstract Background Vitamin A supplementation of 6-59 month old children is currently recommended by the World Health Organization based on evidence that it reduces mortality. There has been considerable interest in determining the benefits of neonatal vitamin A supplementation, but the results of existing trials are conflicting. A technical consultation convened by WHO pointed to the need for larger scale studies in Asia and Africa to inform global policy on the use of neonatal vitamin A supplementation. Three trials were therefore initiated in Ghana, India and Tanzania to determine if vitamin A supplementation (50,000 IU) given to neonates once orally on the day of birth or within the next two days will reduce mortality in the period from supplementation to 6 months of age compared to placebo. Methods/Design The trials are individually randomized, double masked, and placebo controlled. The required sample size is 40,200 in India and 32,000 each in Ghana and Tanzania. The study participants are neonates who fulfil age eligibility, whose families are likely to stay in the study area for the next 6 months, who are able to feed orally, and whose parent(s) provide informed written consent to participate in the study. Neonates randomized to the intervention group receive 50,000 IU vitamin A and the ones randomized to the control group receive placebo at the time of enrolment. Mortality and morbidity information are collected through periodic home visits by a study worker during infancy. The primary outcome of the study is mortality from supplementation to 6 months of age. The secondary outcome of the study is mortality from supplementation to 12 months of age. The three studies will be analysed independent of each other. Subgroup analysis will be carried out to determine the effect by birth weight, sex, and timing of DTP vaccine, socioeconomic groups and maternal large-dose vitamin A supplementation. Discussion The three ongoing studies are the largest studies evaluating the efficacy of vitamin A supplementation to neonates. Policy formulation will be based on the results of efficacy of the intervention from the ongoing randomized controlled trials combined with results of previous studies. Trial Registration Ghana: Australian New Zealand Clinical Trials Registry (ANZCTR) - ACTRN12610000582055; India: CLINICALTRIALS.GOV - NCT01138449; Tanzania: Australian New Zealand Clinical Trials Registry (ANZCTR) - ACTRN12610000636055.

Abstract Background The first cases of influenza A/H1N1 (swine flu) were confirmed in the UK on 27th April 2009, after a novel virus first identified in Mexico rapidly evolved into a pandemic. The swine flu outbreak was the first pandemic in more than 40 years and for many, their first encounter with a major influenza outbreak. This study examines public understandings of the pandemic, exploring how people deciphered the threat and perceived they could control the risks. Methods Purposive sampling was used to recruit seventy three people (61 women and 12 men) to take part in 14 focus group discussions around the time of the second wave in swine flu cases. Results These discussions showed that there was little evidence of the public over-reacting, that people believed the threat of contracting swine flu was inevitable, and that they assessed their own self-efficacy for protecting against it to be low. Respondents assessed a greater risk to their health from the vaccine than from the disease. Such findings could have led to apathy about following the UK Governments recommended health protective behaviours, and a sub-optimal level of vaccine uptake. More generally, people were confused about the difference between seasonal influenza and swine flu and their vaccines. Conclusions This research suggests a gap in public understandings which could hinder attempts to communicate about novel flu viruses in the future. There was general support for the government's handling of the pandemic, although its public awareness campaign was deemed ineffectual as few people changed their current hand hygiene practices. There was less support for the media who were deemed to have over-reported the swine flu pandemic.

Objectives: Relative energy deficiency in sport (REDs) is a syndrome resulting from problematic low energy availability (LEA). Low areal bone mineral density (aBMD) is a primary indicator of LEA, measured by dual X-ray absorptiometry (DXA). High-resolution peripheral quantitative CT (HR-pQCT) is an advanced imaging device that provides measures of volumetric BMD (vBMD), bone microarchitecture, geometry and strength. This study aimed to assess the prevalence of REDs in elite winter sport athletes and to observe the associations in bone parameters using HR-pQCT in athletes identified as at-risk or not at-risk of REDs., Methods: Participants included 101 elite athletes (24.1±4.4 SD years; 52% female). The REDs Clinical Assessment Tool (CAT2) was used to determine REDs risk. HR-pQCT scans of the non-dominant radius and left tibia were analysed on REDs risk grouping., Results: 17 athletes (17%; 71% female) were at-risk based on the REDs CAT2. After covarying for lean mass, OR suggested a higher likelihood of REDs risk classification for athletes with low cortical thickness, cortical area, total vBMD and bone strength., Conclusions: Impaired total vBMD, bone strength and cortical bone parameters were approximately twice as likely (OR: 1.9-3.0) in athletes at-risk of REDs. Results agree with the consensus statement that HR-pQCT may identify impaired bone health in athletes at-risk of REDs. Future directions should use HR-pQCT to explore REDs risk longitudinally, using bone change over time, as this may provide greater insight. Using advanced imaging to explore REDs risk in a population of winter high-performance athletes is novel., Competing Interests: None declared., (Copyright © Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

RNase MRP and RNase P are evolutionarily related complexes that facilitate rRNA and tRNA biogenesis, respectively. The two enzymes share nearly all protein subunits and have evolutionarily related catalytic RNAs. Notably, RNase P includes a unique subunit, Rpp21, whereas no RNase MRP-specific proteins have been found in humans, limiting molecular analyses of RNase MRP function. Here, we identify the RNase MRP-specific protein, C18orf21/RMRPP1. RMRPP1 and Rpp21 display significant structural homology, but we identify specific regions that drive interactions with their respective complexes. Additionally, we reveal that RNase MRP is required for 40S, but not 60S, ribosome biogenesis uncovering an alternative pathway for ribosome assembly. Finally, we identify Nepro as an essential rRNA processing factor that associates with the RNase MRP complex. Together, our findings elucidate the molecular determinants of RNase MRP function and underscore its critical role in ribosome biogenesis., Competing Interests: Declaration of interests The authors declare no competing interests.

Objective: Systemic lupus erythematosus (SLE) is a systemic autoimmune/inflammatory disease with a strong genetic component. Genetic burden is higher in children when compared to patients with adult-onset SLE, contributing to earlier disease expression and more severe phenotypes. The human leukocyte antigen (HLA) cluster on chromosome 6p21.3 is among the most variable genomic regions, representing a major risk-factor for SLE in adults. Its impact on juvenile-onset (j)SLE remains largely unstudied., Methods: High-resolution sequencing of HLA class I (A, B, C), class II (DRB1, DQA1, DQB1) and class III (complement C2 ) was undertaken in the multi-ancestral UK JSLE Cohort including participants of Caucasian (n = 151, 48.8 %), Asian (n = 108, 35.0 %) and African/Caribbean (n = 50, 16.2 %) descent. Considering ancestral variation, clinical associations were tested at the level of alleles (2-field resolution), associated HLA protein sequences (antigen binding domains, 4-field resolution), and extended haplotypes (DRh)., Results: Although important ancestral recombination was reported for HLA-DR2 and -DR3 haplotypes, risk associated with jSLE was conserved at related alleles (DR2h: DRB1∗15:01, DQA∗01:02, DQB1∗06:02; DR3h: C∗07:02 [Asian], B∗08:01, C2 rs9332730 [Asian], DRB1∗03:01). HLA-DR7 haplotypes (DRB1∗07:01, OR = 0.44, 95 % CI:0.27-0.72, p = 0.0004; DQA1∗02:01, OR = 0.34, 95 % CI:0.21-0.56, p = 1.8 × 10 -6 ) protect Asians from jSLE development. Among 23 clinical variables recorded, the main association was found between low levels of complement C4 in Caucasian carriers of HLA-DR3h. This was not the case in Asians due to recombination with HLA-C∗07:02 and integration of the C2 rs9332730 minor allele. Low C4 serum levels associated with HLA-DQA1∗01:02 (DR2h) in Caucasians after excluding HLA-DR3h carriers from the analysis. An association between low white blood cell counts and HLA-A∗03:01P was observed across ancestries., Conclusion: Genetic variation in the HLA cluster associates with organ domain involvement (hematological) and complement levels in jSLE. Lupus-associated HLA haplotypes vary between ancestral groups, underscoring the importance of multi-ancestral approaches to genetic studies in SLE and other autoimmune/inflammatory diseases., Competing Interests: The authors report no conflict of interest., (© 2025 The Authors.)

Background: Assistive technology is central to the realization of the rights of persons with disabilities. However, there remains limited access to assistive technology throughout much of the world, with particularly poor access in lower- and middle-income countries. Evaluating stakeholder engagement in assistive technology networks has been used as a successful strategy to understand and address gaps in the assistive technology ecosystem., Objective: The objective of this research was to provide an overview of the Kenyan Assistive Technology Ecosystem, including available assistive products and related services, and an understanding of the nature and strength of relationships between stakeholders., Methods: In this study, we employed an online qualitative stakeholder survey (2021) with representatives of organizations involved in assistive technology in Kenya., Results: The assistive technology network in Kenya is distributed, with Government Ministries and Agencies and Organizations of persons with disabilities central to the network. The strength of relationships is concentrated on awareness and communication, with fewer organizations actively collaborating. Innovation training organizations are not yet well integrated into the network., Conclusions: Improving access to assistive technology in Kenya will benefit from greater collaboration amongst all assistive technology stakeholders.

The cohesin complex is critical for genome organization and regulation, relying on specialized co-factors to mediate its diverse functional activities. Here, by analyzing patterns of similar gene requirements across cell lines, we identify PRR12 as a mediator of cohesin and genome integrity. We show that PRR12 interacts with NIPBL/MAU2 and the cohesin complex, and that the loss of PRR12 results in reduced cohesin localization and a substantial increase in DNA double-strand breaks in mouse NIH-3T3 cells. Additionally, PRR12 co-localizes with NIPBL to sites of DNA damage in a NIPBL and cohesin-dependent manner. We find that the requirement for PRR12 differs across cell lines, with human HeLa cells exhibiting reduced sensitivity to PRR12 loss compared with mouse NIH-3T3 cells, indicating context-specific roles. Together, our work identifies PRR12 as a regulator of cohesin and provides insight into how genome integrity is maintained across diverse cellular contexts., Competing Interests: Declaration of interests I.M.C. is a member of the Advisory Board of Developmental Cell., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Health promotion and growth-based interventions can effectively improve individual well-being; however, significant gaps in access and utilization still exist., Objective: This study aims to develop and test the effectiveness and implementation of a new, widely targeted conversational agent prevention program (Zenny) designed to enhance well-being., Methods: A total of 1345 individuals in the United States were recruited online and randomly assigned to either (1) a self-help program intervention delivered via an automated conversational agent on WhatsApp or (2) an active control group that had access to evidence-based wellness resources available online. The primary outcomes were well-being (measured using the 5-item World Health Organization Well-being Scale), psychosocial flourishing (assessed with the Flourishing Scale), and positive psychological health (evaluated with the Mental Health Continuum-Short Form). Outcome measures were collected at baseline and again 1 month postassessment. All analyses were conducted using an intention-to-treat approach., Results: Both groups showed significant improvements in well-being (self-help program intervention group effect size: Cohen d=0.26, P<.001; active control group effect size: d=0.24, P<.001), psychosocial flourishing (intervention: d=0.19, P<.001; active control: d=0.18, P<.001), and positive psychological health (intervention: d=0.17, P=.001; active control: d=0.24, P<.001) at postassessment. However, there were no significant differences in effectiveness between the 2 groups (P ranged from .56 to .92). As hypothesized a priori, a greater number of days spent actively engaging with the conversational agent was associated with larger improvements in well-being at postassessment among participants in the intervention group (β=.109, P=.04)., Conclusions: The findings from this study suggest that the free conversational agent wellness self-help program was as effective as evidence-based web resources. Further research should explore strategies to increase participant engagement over time, as only a portion of participants were actively involved, and higher engagement was linked to greater improvements in well-being. Long-term follow-up studies are also necessary to assess whether these effects remain stable over time., Trial Registration: ClinicalTrials.gov NCT06208566; https://clinicaltrials.gov/ct2/show/NCT06208566; OSF Registries osf.io/ahe2r; https://doi.org/10.17605/osf.io/ahe2r., (©Heather M Foran, Christian Kubb, Janina Mueller, Spencer Poff, Megan Ung, Margaret Li, Eric Michael Smith, Akinniyi Akinyemi, Melanie Kambadur, Franziska Waller, Mario Graf, Y-Lan Boureau. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 06.12.2024.)

The expression of a few key genes determines the body plan of the fruit fly. We show that the spatial expression patterns for several of these genes scale precisely with embryo size. Discrete positional markers such as the peaks in striped patterns or the boundaries of expression domains have positions along the embryo's major axis proportional to embryo length, accurate to within 1%. Further, the information (in bits) that graded patterns of expression provide about a cell's position can be decomposed into information about fractional or scaled position and information about absolute position or embryo length; all information available is about scaled position, with [Formula: see text]2% error. These findings imply that the underlying genetic network's behavior exhibits scale invariance in a more precise mathematical sense. We argue that models that can explain this scale invariance also have a "zero mode" in the dynamics of gene expression, and this connects to observations on the spatial correlation of fluctuations in expression levels., Competing Interests: Competing interests statement:The authors declare no competing interest.

Background: The enteric nervous system (ENS) is a complex network of interconnected ganglia within the gastrointestinal (GI) tract. Among its diverse functions, the ENS detects bowel luminal contents and coordinates the passing of stool. ENS defects predispose to GI motility disorders. Previously, distinct enteric neuron types were cataloged by dye-filling techniques, immunohistochemistry, retrograde labeling, and electrophysiology. Recent technical advances in single cell RNA-sequencing (scRNA-seq) have enabled transcriptional profiling of hundreds to millions of individual cells from the intestine. These data allow cell types to be resolved and compared to using their transcriptional profiles ("clusters") rather than relying on antibody labeling. As a result, greater diversity of enteric neuron types has been appreciated. Because each scRNA-seq study has relied on different methods for cell isolation and library generation, numbers of neuron clusters and cell types detected differs between analyses. Cell counts in each dataset are particularly important for characterization of rare cell types since small numbers of profiled cells may not sample rare cell types. Importantly, each dataset, depending on the isolation methods, may contain different proportions of cells that are not detected in other datasets. Aggregation of datasets can effectively increase the total number of cells being analyzed and can be helpful for confirming the presence of low-abundance neuron types that might be absent or observed infrequently in any single dataset., Results: Here we briefly systematically review each Mus musculus single cell or single nucleus RNA-sequencing enteric nervous system dataset. We then reprocess and computationally integrate these select independent scRNA-seq enteric neuron datasets with the aim to identify new cell types, shared marker genes across juvenile to adult ages, dataset differences, and achieve some consensus on transcriptomic definitions of enteric neuronal subtypes., Conclusions: Data aggregation generates a consensus view of enteric neuron types and improves resolution of rare neuron classes. This meta-atlas offers a deeper understanding of enteric neuron diversity and may prove useful to investigators aiming to define alterations among enteric neurons in disease states. Future studies face the challenge of connecting these deep transcriptional profiles for enteric neurons with historical classification systems., Competing Interests: Disclosures: Authors do not have any relevant conflicts of interest.

National Assistive Product Lists (APLs) play an important role in improving access to assistive products (APs). Assistive products are critical to enhancing the health, well-being, and quality of life of persons with disabilities and other functional limitations, including those associated with aging. Comparing national APL development across Malawi, Liberia, and Sierra Leone may provide insight into the differences between the resulting national APLs and how to enhance AP service delivery systems. The aim of this study was to compare how the World Health Organization's 5Ps model (people, personnel, policy, provision, products) influenced national APL development across Malawi, Liberia, and Sierra Leone. To achieve this aim, we conducted a series of qualitative interviews with representatives of key government and non-state organizations (n = 12) who had been involved in the development of the APL in each of the three countries. We used directed content analysis to review and analyze the resulting data, with the 5Ps representing the 5 areas of analysis. Our results found substantial differences between the APLs of the three countries, which were substantially influenced by the needs of assistive technology users in each of the respective countries (people). This was evident in the fact that product selection criteria differed across countries, with the most critical factor being population need. Provision systems were generally fragmented and depended heavily on donors, with a lack of coordination between the public and private sectors. None of the countries had or produced a standalone AT policy in the APL development process. County-specific factors also influenced the APL differences between countries. Our research concludes that national APLs will vary substantially if they are developed collaboratively, considering the needs of the population with consideration for the country's context and existing policies and systems.

Disruption of SYNGAP1 directly causes a genetically identifiable neurodevelopmental disorder (NDD) called SYNGAP1-related intellectual disability (SRID). Without functional SynGAP1 protein, individuals are developmentally delayed and have prominent features of intellectual disability (ID), motor impairments, and epilepsy. Over the past two decades, there have been numerous discoveries indicating the critical role of Syngap1. Several rodent models with a loss of Syngap1 have been engineered, identifying precise roles in neuronal structure and function, as well as key biochemical pathways key for synapse integrity. Homozygous loss of SYNGAP1/Syngap1 is lethal. Heterozygous mutations of Syngap1 result in a broad range of behavioral phenotypes. Our in vivo functional data, using the original mouse model from the Huganir laboratory, corroborated behaviors including robust hyperactivity and deficits in learning and memory in young adults. Furthermore, we described impairments in the domain of sleep, characterized using neurophysiological data that was collected with wireless, telemetric electroencephalography (EEG). Syngap1 +/- mice exhibited elevated spiking events and spike trains, in addition to elevated power, most notably in the delta power frequency. For the first time, we illustrated that primary neurons from Syngap1 +/- mice displayed: 1) increased network firing activity, 2) greater bursts, 3) and shorter inter-burst intervals between peaks, by utilizing high density microelectrode arrays (HD-MEA). Our work bridges in vitro electrophysiological neuronal activity and function with in vivo neurophysiological brain activity and function. These data elucidate quantitative, translational biomarkers in vivo and in vitro that can be utilized for the development and efficacy assessment of targeted treatments for SRID., (© 2024. The Author(s).)

Ovarian cancer remains a significant public health concern for women despite advancements in cancer management. Despite comprising only 2.5 % of cancers in women, ovarian cancer ranks as the fifth leading cause of cancer-related deaths among women, with patients frequently receiving late diagnoses. Chemotherapy, a primary treatment, frequently causes chemotherapy-induced peripheral neuropathy (CIPN), affecting over 60 % of patients and leading to severe sensory, motor, and autonomic nerve impairments. This often necessitates dosage reduction or discontinuation of treatment, thereby increasing mortality. While CIPN's impact on patients is well-documented, there is a paucity of knowledge of how structural and intermediary social determinants of health factors (SDOH), such as socioeconomic and political context, material circumstances such as living and walking conditions, area deprivation, and food availability, affect CIPN severity. The aim of this article was to explore the association between various SDOH and CIPN severity in ovarian cancer, identifying potential research gaps and future research directions. This article seeks to inform targeted interventions to mitigate CIPN's impact by elucidating these associations., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Inc.)

Background & Aims: Enteric nervous system (ENS) development requires migration, proliferation, and appropriate neuronal diversification from progenitors to enable normal gastrointestinal (GI) motility. Sox10 deficit causes aganglionosis, modeling Hirschsprung disease, and disrupts ratios of postnatal enteric neurons in proximal ganglionated bowel. How Sox10 deficiency alters ratios of enteric neuron subtypes is unclear. Sox10's prominent expression in enteric neural crest-derived progenitors (ENCP) and lack of this gene in enteric neurons led us to examine Sox10 Dom effects ENS progenitors and early differentiating enteric neurons., Methods: ENS progenitors, developing neurons, and enteric glia were isolated from Sox10 +/+ and Sox10 Dom/+ littermates for single-cell RNA sequencing (scRNA-seq). scRNA-seq data was processed to identify cell type-specific markers, differentially expressed genes, cell fate trajectories, and gene regulatory network activity between genotypes. Hybridization chain reaction (HCR) validated expression changes detected in scRNA-seq., Results: scRNA-seq profiles revealed three neuronal lineages emerging from cycling progenitors via two transition pathways accompanied by elevated activity of Hox gene regulatory networks (GRN) as progenitors transition to neuronal fates. Sox10 Dom/+ scRNA-seq profiles exhibited a novel progenitor cluster, decreased abundance of cells in transitional states, and shifts in cell distributions between two neuronal trajectories. Hoxa6 was differentially expressed in the neuronal lineages impacted in Sox10 Dom/+ mutants and HCR identified altered Hoxa6 expression in early developing neurons of Sox10 Dom/+ ENS., Conclusions: Sox10 Dom/+ mutation shifts enteric neuron types by altering neuronal trajectories during early ENS lineage segregation. Multiple neurogenic transcription factors are reduced in Sox10 Dom/+ scRNA-seq profiles including multiple Hox genes. This is the first report that implicates Hox genes in lineage diversification of enteric neurons.

Enterococci are robust Gram-positive bacteria that pose a significant threat in healthcare settings due to antibiotic resistance, with vancomycin-resistant enterococci (VRE) most prominent. To tackle this issue, bacteriophages (bacterial viruses) can be exploited as they specifically and efficiently target bacteria. Here, we successfully isolated and characterised a set of novel phages: SHEF10, SHEF11, SHEF13, SHEF14, and SHEF16 which target E. faecalis (SHEF10,11,13), or E. faecium (SHEF13, SHEF14 & SHEF16) strains including a range of clinical and VRE isolates. Genomic analysis shows that all phages are strictly lytic and diverse in terms of genome size and content, quickly and effectively lysing strains at different multiplicity of infections. Detailed analysis of the broad host-range SHEF13 phage revealed the crucial role of the enterococcal polysaccharide antigen (EPA) variable region in its infection of E. faecalis V583. In parallel, the discovery of a carbohydrate-targeting domain (CBM22) found conserved within the three phage genomes indicates a role in cell surface interactions that may be important in phage-bacterial interactons. These findings advance our comprehension of phage-host interactions and pave the way for targeted therapeutic strategies against antibiotic-resistant enterococcal infections., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)

Female ticks deposit large egg clusters that range in size from hundreds to thousands. These clusters are restricted to a deposition site, usually under leaf litter and other debris. These sites can be exposed to periodic flooding, where the cluster of tick eggs can float to the surface or remain underneath organic debris entirely underwater. Here, we examined the viability of egg clusters from winter ticks, Dermacentor albipictus , and lone star ticks, Amblyomma americanum , when partially submerged or fully submerged in water in relation to the developmental stages of the eggs. In general, egg clusters that were older and partially submerged had a higher viability than fully submerged, young eggs in water. A. americanum was much more resistant to water exposure between the two species. These studies highlight that egg clusters for specific tick species can remain viable when exposed to water for at least two weeks, where eggs float on the surface. These studies also suggest that water-based distribution of egg clusters could occur for some species, and flooding will differentially impact tick egg survival based on the specific developmental stage of exposure and species.

We assess the strategic alignment of attitudes and the active construction of attitude-based identity across two studies. Study one assessed the twitter response (hashtags in English) to the war in Ukraine for five months after Russia's first invasion of Ukraine 2022 (N = 8149). Results demonstrated that individuals publicly expressed hashtags similar to others close to them in the followership network, showing their support for Ukraine and condemnation of the Russian invasion in qualitatively different ways. Study two was a preregistered Prolific experiment with geographical European participants ran in September, 2022 (N = 1368). Results demonstrated that attitude interaction with ingroup members motivated interactants towards attitude alignment, and attitude alignment strengthened the identification that motivated the alignment in the first place. Results suggest that attitude expression is performative and constrained by one's group relationship with one's audience and the definition of social identity can be constrained by opinion-based identity performance., (© 2024. The Author(s).)

Bacteriophage therapy is a promising approach to address antimicrobial infections though questions remain regarding the impact of the immune response on clinical effectiveness. Here, we develop a mouse model to assess phage treatment using a cocktail of five phages from the Myoviridae and Siphoviridae families that target Vancomycin-Resistant Enterococcus gut colonization. Phage treatment significantly reduces fecal bacterial loads of Vancomycin-Resistant Enterococcus. We also characterize immune responses elicited following administration of the phage cocktail. While minimal innate responses are observed after phage administration, two rounds of treatment induces phage-specific neutralizing antibodies and accelerate phage clearance from tissues. Interestingly, the myophages in our cocktail induce a more robust neutralizing antibody response than the siphophages. This anti-phage immunity reduces the effectiveness of the phage cocktail in our murine model. Collectively, this study shows phage-specific immune responses may be an important consideration in the development of phage cocktails for therapeutic use., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Introduction: The prevalence of both obesity and gestational diabetes mellitus (GDM) has increased, and each is associated with adverse perinatal outcomes including fetal overgrowth, neonatal morbidity, hypertensive disorders of pregnancy and caesarean delivery. Women with GDM who are also overweight or obese have higher rates of pregnancy complications when compared with normal-weight women with GDM, which may occur in part due to suboptimal glycaemic control. The current recommendations for glycaemic targets in pregnant women with diabetes are based on limited evidence and exceed the mean fasting (70.9±7.8 mg/dL) and 1-hour postprandial (108.9±12.9 mg/dL) glucose values in pregnant individuals without diabetes. Our prior work demonstrated that the use of intensive (fasting <90 mg/dL and 1-hour postprandial <120 mg/dL) compared with standard (fasting <95 mg/dL and 1-hour postprandial <140 mg/dL) glycaemic targets resulted in improved glycaemic control without increasing the risk for hypoglycaemia in pregnant individuals with GDM, but the impact of intensive glycaemic targets on perinatal outcomes is unknown., Methods and Analysis: The Intensive Glycemic Targets in Overweight and Obese Women with Gestational Diabetes Mellitus: A Multicenter Randomized Trial (iGDM Trial) is a large, pragmatic randomised clinical trial designed to investigate the impact of intensive versus standard glycaemic targets on perinatal outcomes in women with GDM who are overweight and obese. During the 5-year project period, a multidisciplinary team of investigators from five medical centres representing regions of the USA with high rates of obesity will randomise 828 overweight and obese women with GDM to either intensive or standard glycaemic targets. We will test the central hypothesis that intensive glycaemic targets will result in lower rates of neonatal composite morbidity including large for gestational age birth weight, neonatal hypoglycaemia, respiratory distress syndrome and need for phototherapy when compared with standard glycaemic targets using the intention-to-treat approach to analysis., Ethics and Dissemination: The Institutional Review Board (IRB) at Indiana University School of Medicine approved this study (IRB# 11435; initial approval date 25 August 2021). We will submit the results of the trial for publication in peer-reviewed journals and presentations at international scientific meetings., Trial Registration Number: NCT05124808., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Acute hospital wards can be difficult places for many people living with dementia. Promoting comfort and wellbeing can be challenging in this environment. There is little evidence-based support for professionals working on acute care wards on how to respond to distress and maximise comfort and wellbeing among patients living with dementia., Objectives: Our overall aim was to codesign an evidence-based easy-to-use heuristic decision-support framework, which was acceptable and practical but acknowledges the complex and acute nature of caring for patients with dementia in the hospital. This paper presents the development process and resulting framework., Methods: A codesign study was informed by data from (1) a literature review of the care and management of people living with dementia in acute hospitals; (2) a cohort study of comfort and discomfort in people with dementia in acute hospitals; and (3) interviews with family carers and health care professionals. We synthesised evidence from these data sources and presented to key stakeholders through codesign meetings and workshops to produce our decision-support framework., Results: The framework consists of a series of flowcharts and operates using a three-stage process of: (1) assess comfort/discomfort; (2) consider causes of discomfort; and (3) address patient needs to manage the discomfort., Conclusion: Working with key stakeholders, synthesising diverse quantitative and qualitative evidence to build a clinical framework is a feasible approach to help address the needs of patients living with dementia in an acute hospital setting. The result is a framework which is now ready for evaluation and implementation., Patient and Public Contribution: We worked closely with people living with dementia and family carers throughout this study, including the development of the study protocol with input on study development and design, through to inclusion in stakeholder workshops and codesign of the decision support framework., (© 2023 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

The body plan of the fruit fly is determined by the expression of just a handful of genes. We show that the spatial patterns of expression for several of these genes scale precisely with the size of the embryo. Concretely, discrete positional markers such as the peaks in striped patterns have absolute positions along the anterior-posterior axis that are proportional to embryo length, with better than 1% accuracy. Further, the information (in bits) that graded patterns of expression provide about position can be decomposed into information about fractional or scaled position and information about absolute position or embryo length; all of the available information is about scaled position, again with ~ 1% accuracy. These observations suggest that the underlying genetic network exhibits scale invariance in a deeper mathematical sense. Taking this mathematical statement seriously requires that the network dynamics have a zero mode, which connects to many other observations on this system.