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Summary: This case report concerns a 1‐day‐old, full‐term Quarter Horse colt presented due to a progressive inability to rise and nurse. Besides the general weakness, a marked bradycardia was evident, which was caused by a third‐degree atrioventricular (AV) block. Subsequently, the diagnosis of acute nutritional myodegeneration (NMD) was made based on clinical signs, elevated muscle enzymes, ECG findings, as well as low serum selenium and vitamin E values. Despite intensive care and supportive therapy, the foal´s condition deteriorated, and euthanasia was elected. Necropsy confirmed the diagnosis of NMD and revealed diffuse necrosis and inflammatory infiltration of the skeletal and myocardial musculature, as well as the cardiac conduction system which might have resulted in complete AV block. [ABSTRACT FROM AUTHOR]

The Friesian breed is quite popular nowadays: there are more than 70,000 Friesian horses registered worldwide. Based upon our research in the past, hiatal hernia is not a co-morbidity with "classical megaoesophagus" in the Friesian horse. Diaphragmatic defects leading to (diaphragmatic) herniation (DH) of an abdominal organ or bowel is an extremely rare condition in horses. The Friesian horse breed originally started its reason for existence as a working horse in agriculture. [Extracted from the article]

Background: Because of the serious disease sequelae associated with equine herpesvirus type 1 (EHV-1) infections, awareness and control measures used to control outbreaks are important issues for all horse populations. Objectives: Describe the occurrence and management of an outbreak of EHV-1 infection at a veterinary hospital. Animals: Horses hospitalized at a referral veterinary hospital. Methods: A horse with myeloencephalopathy associated with EHV-1 infection (EHM) was admitted for diagnostic evaluation and treatment under strict infection control procedures. We describe the occurrence and management of a nosocomial outbreak of EHV-1 infections associated with admission of this patient. Results: Despite institution of rigorous biosecurity precautions at the time of admission of the index case, EHV-1 infections spread to 6 other horses that were hospitalized at the James L. Voss Veterinary Teaching Hopsital, including 2 that served as sources of infection for horses on their home premises after discharge. Infection with EHV-1 was confirmed by polymerase chain reaction (PCR) and by seroconversion documented by glycoprotein G ELISA. A voluntary quarantine was imposed and admissions were restricted to prevent additional horses from being exposed. Quarantine duration was abbreviated by serial testing of all horses with PCR. Conclusions and Clinical Importance: These findings illustrate the contagious disease risk that can accompany management of horses with EHM. Horses with active nasal EHV-1 shedding should be isolated in an airspace that is separate from other horses by strictly enforced biosecurity and isolation procedures. Serial testing with PCR may be a useful adjunct to determine when the risk of transmission has been minimized. [ABSTRACT FROM AUTHOR]

Summary Reasons for performing study: The occurrence of unexpectedly high numbers of horses with neurological signs during two outbreaks of strangles required prompt in-depth researching of these cases, including the exploration of magnetic resonance imaging (MRI)as a possible diagnostic technique. Objectives: To describe the case series and assess the usefulness of MRI as an imaging modality for cases suspected of space-occupying lesions in the cerebral cavity. Methods: Four cases suspected of suffering from cerebral damage due to Streptococcus equi subsp. equi infection were examined clinically, pathologically, bacteriologically, by clinical chemistry (3 cases) and MRI (2 cases). In one case, MRI findings were compared to images acquired using computer tomography (CT). Results: In all cases, cerebral abscesses positive for Streptococcus equi subsp. equi were found, which explained the clinical signs. Although the lesions could be visualised with CT, MRI images were superiorin representing the exact anatomic reality of the soft tissue lesions. Conclusions: The diagnosis of bastard strangles characterised by metastatic brain abscesses was confirmed. MRI appeared to be an excellent tool for the imaging of cerebral lesions in the horse. Potential clinical relevance: The high incidence of neurological complications could not be explained but possibly indicated a change in virulence of certain strains of Streptococcus equi subsp. equi. MRI images were very detailed, permitting visualisation of much smaller lesions than demonstrated in this study and this could allow prompt clinical intervention in less advanced cases with a better prognosis. Further, MRI could assist in the surgical treatment of brain abscesses, as has been described earlier for CT. [ABSTRACT FROM AUTHOR]

Abstract Equine herpesvirus-1 (EHV-1) infection remains a significant problem despite the widespread use of vaccines. The inability to generate a protective immune response to EHV-1 vaccination or infection is thought to be due to immunomodulatory properties of the virus, and the ORF1 and ORF2 gene products have been hypothesized as potential candidates with immunoregulatory properties. A pony infection study was performed to define immune responses to EHV-1, and to determine if an EHV-1 ORF1/2 deletion mutant (ΔORF1/2) would have different disease and immunoregulatory effects compared to wild type EHV-1 (WT). Infection with either virus led to cytokine responses that coincided with the course of clinical disease, particularly the biphasic pyrexia, which correlates with respiratory disease and viremia, respectively. Similarly, both viruses caused suppression of proliferative T-cell responses on day 7 post infection (pi). The ΔORF1/ORF2 virus caused significantly shorter primary pyrexia and significantly reduced nasal shedding, and an attenuated decrease in PBMC IL-8 as well as increased Tbet responses compared to WT-infected ponies. In conclusion, our findings are (i) that infection of ponies with EHV-1 leads to modulation of immune responses, which are correlated with disease pathogenesis, and (ii) that the ORF1/2 genes are of importance for disease outcome and modulation of cytokine responses.

BACKGROUND Injuries from falls are major contributors to complications and death in older adults. Despite evidence from efficacy trials that many falls can be prevented, rates of falls resulting in injury have not declined. METHODS We conducted a pragmatic, cluster-randomized trial to evaluate the effectiveness of a multifactorial intervention that included risk assessment and individualized plans, administered by specially trained nurses, to prevent fall injuries. A total of 86 primary care practices across 10 health care systems were randomly assigned to the intervention or to enhanced usual care (the control) (43 practices each). The participants were community-dwelling adults, 70 years of age or older, who were at increased risk for fall injuries. The primary outcome, assessed in a time-to-event analysis, was the first serious fall injury, adjudicated with the use of participant report, electronic health records, and claims data. We hypothesized that the event rate would be lower by 20% in the intervention group than in the control group. RESULTS The demographic and baseline characteristics of the participants were similar in the intervention group (2802 participants) and the control group (2649 participants); the mean age was 80 years, and 62.0% of the participants were women. The rate of a first adjudicated serious fall injury did not differ significantly between the groups, as assessed in a time-to-first-event analysis (events per 100 person-years of follow-up, 4.9 in the intervention group and 5.3 in the control group; hazard ratio, 0.92; 95% confidence interval [Cl], 0.80 to 1.06; P=0.25). The rate of a first participant-reported fall injury was 25.6 events per 100 person-years of follow-up in the intervention group and 28.6 events per 100 person-years of follow-up in the control group (hazard ratio, 0.90; 95% Cl, 0.83 to 0.99; P=0.004). The rates of hospitalization or death were similar in the two groups. CONCLUSIONS A multifactorial intervention, administered by nurses, did not result in a significantly lower rate of a first adjudicated serious fall injury than enhanced usual care. (Funded by the Patient-Centered Outcomes Research Institute and others; STRIDE ClinicalTrials.gov number, NCT02475850.). [ABSTRACT FROM AUTHOR]

Importance: Chronic rhinosinusitis (CRS) has been associated with anxiety and depression, but the association of socioeconomic factors and temporality has yet to be fully explored., Objective: To determine the bidirectional risk of anxiety and depression for patients with CRS., Design, Setting, and Participants: This retrospective cohort study of the National Institutes of Health All of Us database from January 1, 2008, to December 31, 2018, included 2 cohorts of adult patients with and without CRS. The data were analyzed from July 1, 2023, through April 1, 2024. Patients were classified as having CRS if they had at least 2 diagnoses during the study period. Those with a diagnosis of CRS before the study period were excluded. Patients were propensity score matched (1:5) with patients without CRS for age, sex, race, and annual household income., Main Outcomes and Measures: The primary outcome was the development of anxiety and depression. Patients with CRS were counted as having the primary outcome if it occurred after the criteria for CRS diagnosis were fulfilled. Multivariate logistic regression and survival analysis were performed to determine the odds ratios (ORs) and hazard ratios (HRs) of anxiety and depression. A secondary survival analysis determined the risk of developing CRS between patients with anxiety and depression and controls., Results: Among 33 732 patients (23 382 [69.3%] female individuals; 510 [1.5%] Asian, 6002 [17.9%] Black or African American, 576 [1.7%] multiracial, and 26 036 [77.2%] White individuals), there were 28 110 controls and 5622 patients with CRS. Along with higher odds of having anxiety (OR, 4.39; 95% CI, 3.95-4.87) and depression (OR, 2.04; 95% CI, 1.86-2.24), patients with CRS were at an increased risk of developing anxiety (HR, 2.79; 95% CI, 2.47-3.15) and depression (HR, 1.40; 95% CI, 1.27-1.55) compared with controls. Additionally, patients with anxiety (HR, 2.37; 95% CI, 2.18-2.57) and depression (HR, 1.59; 95% CI, 1.46-1.72) were at an increased risk of developing chronic rhinosinusitis compared with controls., Conclusions and Relevance: In this population-based cohort study of adults with and without CRS, a bidirectional association between common psychiatric disorders and CRS was observed. Physicians and health care clinicians who treat patients with anxiety, depression, and CRS should be vigilant regarding these risks and screen patients appropriately.

Basal cell adenoma (BCA) and basal cell adenocarcinoma (BCAC) are uncommon basaloid biphasic salivary gland tumors composed of basal and ductal cells. BCAC is differentiated from BCA by the presence of invasion in BCAC. In this paper, an 82-year-old woman presented with a palpable 3 cm immobile mass in her right parotid gland. A computed tomography (CT) scan showed two separate right parotid masses. She underwent a right parotidectomy, and the pathology showed multiple membranous BCAs and BCAC, which were highly suspicious for Brooke-Spiegler syndrome (BSS). This paper discusses BCA, BCAC, and their relationship with BSS., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Goehring et al.)

The soft part of the Earth's surface - the ground beneath our feet - constitutes the basis for life and natural resources, yet a general physical understanding of the ground is still lacking. In this critical time of climate change, cross-pollination of scientific approaches is urgently needed to better understand the behavior of our planet's surface. The major topics in current research in this area cross different disciplines, spanning geosciences, and various aspects of engineering, material sciences, physics, chemistry, and biology. Among these, soft matter physics has emerged as a fundamental nexus connecting and underpinning many research questions. This perspective article is a multi-voice effort to bring together different views and approaches, questions and insights, from researchers that work in this emerging area, the soft matter physics of the ground beneath our feet. In particular, we identify four major challenges concerned with the dynamics in and of the ground: (I) modeling from the grain scale, (II) near-criticality, (III) bridging scales, and (IV) life. For each challenge, we present a selection of topics by individual authors, providing specific context, recent advances, and open questions. Through this, we seek to provide an overview of the opportunities for the broad Soft Matter community to contribute to the fundamental understanding of the physics of the ground, strive towards a common language, and encourage new collaborations across the broad spectrum of scientists interested in the matter of the Earth's surface.

Objective: The objective of this study is to explore the questions commonly asked online about biologic therapies for use in treatment of chronic sinusitis with nasal polyps (CRSwNP) and the quality of the available content. Methods: Most common search terms were identified via Google Trends. People Also Ask (PAA) questions were identified and extracted with their associated website using an online data-scraping program [Search Engine Optimization (SEO) Minion, Keywords Everywhere]. Sources were evaluated using Flesch Kincaid Grade Level (FKGL) and Flesch Reading Ease (FRE, higher number = better) score for readability; Journal of American Medical Association ( JAMA ) Benchmark criteria for quality assessment (0-4, 4 = all criteria met). Results: A total of 143 unique PAA questions and unique websites were identified. Questions were organized into 3 categories: questions about biologic therapies overall (38.46%), about CRSwNP (37.76%), and about treatment options for CRSwNP (23.78%). Websites answering PAA questions were from commercial (60.14%), medical practice (13.99%), academic (13.29%), and government (12.59%) sources. FKGL scores found the average reading level to be at approximately a 12th grade level (SD = 3.297) alongside a low reading ease FRE score of 37.6 (SD = 16.77). Mean JAMA criteria scores were 0.9895 (SD = 0.848), indicating largely low-quality materials. Conclusion: Biologic therapies are a novel treatment option for CRSwNP, and participants are seeking more information about these treatments and disease state. Online resources regarding biologics should be presented at a lower reading level. Sources with evidence-based information are needed. Physicians should be aware of these limitations in online material and counsel accordingly by curating and directing patients to good sources. Level of Evidence: Step 4., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: O.G.A. is a consultant for Medtronic and Aerin Medical. M.T. is a consultant for Aerin Medical, Medtronic, Acclarent, and LivaNova.

BRCA2 is a tumor suppressor protein responsible for safeguarding the cellular genome from replication stress and genotoxicity, but the specific mechanism(s) by which this is achieved to prevent early oncogenesis remains unclear. Here, we provide evidence that BRCA2 acts as a critical suppressor of head-on transcription-replication conflicts (HO-TRCs). Using Okazaki-fragment sequencing (Ok-seq) and computational analysis, we identified origins (dormant origins) that are activated near the transcription termination sites (TTS) of highly expressed, long genes in response to replication stress. Dormant origins are a source for HO-TRCs, and drug treatments that inhibit dormant origin firing led to a reduction in HO-TRCs, R-loop formation, and DNA damage. Using super-resolution microscopy, we showed that HO-TRC events track with elongating RNA polymerase II, but not with transcription initiation. Importantly, RNase H2 is recruited to sites of HO-TRCs in a BRCA2-dependent manner to help alleviate toxic R-loops associated with HO-TRCs. Collectively, our results provide a mechanistic basis for how BRCA2 shields against genomic instability by preventing HO-TRCs through both direct and indirect means occurring at predetermined genomic sites based on the pre-cancer transcriptome., (© 2024. The Author(s).)

Herpesviruses establish a well-adapted balance with their host's immune system. Despite this co-evolutionary balance, infections can lead to severe disease including neurological disorders in their natural host. In horses, equine herpesvirus 1 (EHV-1) causes respiratory disease, abortions, neonatal foal death and myeloencephalopathy (EHM) in ~10 % of acute infections worldwide. Many aspects of EHM pathogenesis and protection from EHM are still poorly understood. However, it has been shown that the incidence of EHM increases to >70 % in female horses >20 years of age. In this study we used old mares as an experimental equine EHV-1 model of EHM to identify host-specific factors contributing to EHM. Following experimental infection with the neuropathogenic strain EHV-1 Ab4, old mares and yearling horses were studied for 21 days post-infection. Nasal viral shedding and cell-associated viremia were assessed by quantitative PCR. Cytokine/chemokine responses were evaluated in nasal secretions and cerebrospinal fluid (CSF) by Luminex assay and in whole blood by quantitative real-time PCR. EHV-1-specific IgG sub-isotype responses were measured by ELISA. All young horses developed respiratory disease and a bi-phasic fever post-infection, but only 1/9 horses exhibited ataxia. In contrast, respiratory disease was absent in old mares, but all old mares developed EHM that resulted in euthanasia in 6/9 old mares. Old mares also presented significantly decreased nasal viral shedding but higher viremia coinciding with a single fever peak at the onset of viremia. According to clinical disease manifestation, horses were sorted into an EHM group (nine old horses and one young horse) and a non-EHM group (eight young horses) for assessment of host immune responses. Non-EHM horses showed an early upregulation of IFN-α (nasal secretions), IRF7/IRF9, IL-1β, CXCL10 and TBET (blood) in addition to an IFN-γ upregulation during viremia (blood). In contrast, IFN-α levels in nasal secretions of EHM horses were low and peak levels of IRF7, IRF9, CXCL10 and TGF-β (blood) coincided with viremia. Moreover, EHM horses showed significantly higher IL-10 levels in nasal secretions, peripheral blood mononuclear cells and CSF and higher serum IgG3/5 antibody titres compared to non-EHM horses. These results suggest that protection from EHM depends on timely induction of type 1 IFN and upregulation cytokines and chemokines that are representative of cellular immunity. In contrast, induction of regulatory or TH-2 type immunity appeared to correlate with an increased risk for EHM. It is likely that future vaccine development for protection from EHM must target shifting this 'at-risk' immunophenotype.

Background: Equine herpesvirus type 1 (EHV-1) infection is associated with upper respiratory disease, EHM, abortions, and neonatal death., Research Questions: Are nasal secretions a more sensitive biological sample compared to blood for the detection of EHV-1 infection? How long is EHV-1 detectable after primary infection by PCR?, Methods: MedLine and Web of Science searches identified original peer-reviewed reports evaluating nasal shedding and viremia using virus isolation methods or PCR published in English before October 9, 2023., Results: Sixty experimental and 20 observational studies met inclusion criteria. EHV-1 detection frequency by qPCR in nasal secretions and blood from naturally-infected horses with fever and respiratory signs were 15% and 9%, respectively; qPCR detection rates in nasal secretions and blood from horses with suspected EHM were 94% and 70%, respectively. In experimental studies the sensitivity of qPCR matched or exceeded that seen for virus isolation from either nasal secretions or blood. Detection of nasal shedding typically occurred within 2 days after EHV-1 inoculation with a detection period of 3 to 7 days. Viremia lasted 2 to 7 days and was usually detected ≥1 days after positive identification of EHV-1 in nasal secretions. Nasal shedding and viremia decreased over time and remained detectable in some horses for several weeks after inoculation., Conclusions and Clinical Importance: Under experimental conditions, blood and nasal secretions have similar sensitivity for the detection of EHV-1 when horses are sampled on multiple consecutive days. In contrast, in observational studies detection of EHV-1 in nasal secretions was consistently more successful., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Equine herpes virus type 1 (EHV-1) infection in horses is associated with upper respiratory disease, neurological disease, abortions, and neonatal death., Review Question: Does pharmacological therapy decrease either the incidence or severity of disease or infection caused by EHV-1 in domesticated horses?, Methods: A systematic review was preformed searching AGRICOLA, CAB Abstracts, Cochrane, PubMed, Web of Science, and WHO Global Health Index Medicus Regional Databases to identify articles published before February 15, 2021. Selection criteria were original research reports published in peer reviewed journals, and studies investigating in vivo use of therapeutic agents for prevention or treatment of EHV-1 in horses. Outcomes assessed included measures related to clinical outcomes that reflect symptomatic EHV-1 infection or virus infection. We evaluated risk of bias and performed a GRADE evaluation of the quality of evidence for interventions., Results: A total of 7009 unique studies were identified, of which 9 met the inclusion criteria. Two studies evaluated valacyclovir or small interfering RNAs, and single studies evaluated the use of a Parapoxvirus ovis-based immunomodulator, human alpha interferon, an herbal supplement, a cytosine analog, and heparin. The level of evidence ranged between randomized controlled studies and observational trials. The risk of bias was moderate to high and sample sizes were small. Most studies reported either no benefit or minimal efficacy of the intervention tested., Conclusions and Clinical Importance: Our review indicates minimal or limited benefit either as a prophylactic or post-exposure treatment for any of the studied interventions in the mitigation of EHV-1-associated disease outcome., (© 2024 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Equine herpes virus type 1 (EHV-1) infection in horses is associated with upper respiratory disease, neurological disease, abortions, and neonatal death., Objective: To determine if there is an association between the level and duration of EHV-1 viremia and either abortion or equine herpesvirus myeloencephalopathy (EHM) in domesticated horses?, Methods: A systematic review was performed searching numerous databases to identify peer reviewed reports that evaluated viremia and EHM, or viremia and abortion published before January 19, 2021. Randomized controlled trials and observational studies were assessed for risk of bias or publication quality., Results: A total of 189 unique studies were identified, of which 34 met the inclusion criteria. Thirty studies evaluated viremia and neurologic outcomes including 4 observational studies. Eight experimental studies examined viremia and abortion, which used the Ab4 and OH03 virus strains or recombinant Ab4 derivatives. Incidence rates for both EHM and abortion in experimental studies varied among the studies as did the level of evidence. Viremia was generally detectable before the onset of either EHM or abortion. Risk of bias was generally low to moderate, sample sizes were small, and multiple studies reported negative outcome data., Conclusions and Clinical Importance: The results of this study support that viremia is regularly present before EHM or abortion occurs. However, no inferences could be made about the relationship between the occurrence of either neurological signs or abortion and the magnitude or duration of viremia., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Colloidal suspensions are the basis of a wide variety of coatings, prepared as liquids and then dried into solid films. The processes at play during film formation, however, are difficult to observe directly. Here, we demonstrate that optical coherence tomography (OCT) can provide fast, non-contact, precise profiling of the dynamics within a drying suspension. Using a scanning Michelson interferometer with a broadband laser source, OCT creates cross-sectional images of the optical stratigraphy of a sample. With this method, we observed the drying of colloidal silica in Hele-Shaw cells with 10 μm transverse and 1.8 μm depth resolution, over a 1 cm scan line and a 15 s sampling period. The resulting images were calibrated to show how the concentration of colloidal particles varied with position and drying time. This gives access to important transport properties, for example, of how collective diffusion depends on particle concentration. Looking at early-time behaviours, we also show how a drying front initially develops, and how the induction time before the appearance of a solid film depends on the balance of diffusion and evaporation-driven motion. Pairing these results with optical microscopy and particle tracking techniques, we find that film formation can be significantly delayed by any density-driven circulation occurring near the drying front.