The genome of Przewalski's horse (Equus ferus przewalskii).

The Przewalski's horse (Equus ferus przewalskii) is an endangered equid native to the steppes of central Asia. After becoming extinct in the wild multiple conservation efforts convened to preserve the species, including captive breeding programs, reintroduction and monitoring systems, protected lands, and cloning. Availability of a highly contiguous reference genome is essential to support these continued efforts. We used Oxford Nanopore sequencing to produce a scaffold-level 2.5 Gb nuclear assembly and 16,002 bp mitogenome from a captive Przewalski's mare. All assembly drafts were generated from 111 Gb of sequence from a single PromethION R10.4.1 flow cell. The mitogenome contained 37 genes in the standard mammalian configuration and was 99.63% identical to the domestic horse (Equus caballus). The nuclear assembly, EquPr2, contained 2,146 scaffolds with an N50 of 85.1 Mb, 43X mean depth, and BUSCO quality score of 98.92%. EquPr2 successfully improves upon the existing Przewalski's horse reference genome (Burgud), with 25-fold fewer scaffolds, a 166-fold larger N50, and phased pseudohaplotypes. Modified basecalls revealed 79.5% DNA methylation and 2.1% hydroxymethylation globally. Allele-specific methylation analysis between pseudohaplotypes revealed 226 differentially methylated regions (DMRs) in known imprinted genes and loci not previously reported as imprinted. The heterozygosity rate of 0.165% matches previous estimates for the species and compares favorably to other endangered animals. This improved Przewalski's horse assembly will serve as a valuable resource for conservation efforts and comparative genomics investigations.

You Cannot Function in "Overwhelm": Helping Primary Care Navigate the Slow End of the Pandemic.

GOAL: This study was developed to explicate underlying organizational factors contributing to the deterioration of primary care clinicians' mental health during the COVID-19 pandemic. METHODS: Using data from the Larry A. Green Center for the Advancement of Primary Health Care for the Public Good's national survey of primary care clinicians from March 2020 to March 2022, a multidisciplinary team analyzed more than 11,150 open-ended comments. Phase 1 of the analysis happened in real-time as surveys were returned, using deductive and inductive coding. Phase 2 used grounded theory to identify emergent themes. Qualitative findings were triangulated with the survey's quantitative data. PRINCIPAL FINDINGS: The clinicians shifted from feelings of anxiety and uncertainty at the start of the pandemic to isolation, lack of fulfillment, moral injury, and plans to leave the profession. The frequency with which they spoke of depression, burnout, and moral injury was striking. The contributors to this distress included crushing workloads, worsening staff shortages, and insufficient reimbursement. Consequences, both felt and anticipated, included fatigue and demoralization from the inability to manage escalating workloads. Survey findings identified responses that could alleviate the mental health crisis, namely: (1) measuring and customizing workloads based on work capacity; (2) quantifying resources needed to return to sufficient staffing levels; (3) promoting state and federal support for sustainable practice infrastructures with less administrative burden; and (4) creating patient visits of different lengths to rebuild relationships and trust and facilitate more accurate diagnoses. PRACTICAL APPLICATIONS: Attention to clinicians' mental health should be rapidly directed to on-demand, confidential mental health support so they can receive the care they need and not worry about any stigma or loss of license for accepting that help. Interventions that address work-life balance, workload, and resources can improve care, support retention of the critically important primary care workforce, and attract more trainees to primary care careers.

Deciphering the role of a SINE-VNTR-Alu retrotransposon polymorphism as a biomarker of Parkinson's disease progression.

SINE-VNTR-Alu (SVA) retrotransposons are transposable elements which represent a source of genetic variation. We previously demonstrated that the presence/absence of a human-specific SVA, termed SVA_67, correlated with the progression of Parkinson's disease (PD). In the present study, we demonstrate that SVA_67 acts as expression quantitative trait loci, thereby exhibiting a strong regulatory effect across the genome using whole genome and transcriptomic data from the Parkinson's progression markers initiative cohort. We further show that SVA_67 is polymorphic for its variable number tandem repeat domain which correlates with both regulatory properties in a luciferase reporter gene assay in vitro and differential expression of multiple genes in vivo. Additionally, this variation's utility as a biomarker is reflected in a correlation with a number of PD progression markers. These experiments highlight the plethora of transcriptomic and phenotypic changes associated with SVA_67 polymorphism which should be considered when investigating the missing heritability of neurodegenerative diseases.

Comparative surgical outcomes of navigated vs non-navigated posterior spinal fusions in ankylosing spondylitis patients.

INTRODUCTION: Ankylosing Spondylitis (AS) patients with acute spinal fractures represent a challenge for practicing spine surgeons due to difficult operative anatomy and susceptibility to complications. RESEARCH QUESTION: Does intraoperative CT-navigation improve outcomes in patients with ankylosing spondylitis undergoing surgery? METHODS: A retrospective review was carried out at our centre from 05/2016-06/2021 to identify AS patients presenting with a traumatic spinal fracture, managed surgically with posterior spinal fusion (PSF). Cohorts were categorised and compared for outcomes based on those who underwent PSF with intraoperative CT-navigation versus those surgically managed with traditional intraoperative fluoroscopy. RESULTS: 37 AS patients were identified. 29/37 (78.4%) underwent PSF. Intraoperative navigation was used in 14 (48.3%) cases. Mean age of the entire cohort was 67.6 years. No difference existed between the navigated and non-navigated groups for mean levels fused (5.35 vs 5.07; p â€‹= â€‹0.31), length of operation (217.9mins vs 175.3mins; p â€‹= â€‹0.07), overall length-of-stay (12 days vs 21.9 days; p â€‹= â€‹0.16), patients requiring HDU (3/14 vs 5/15; p â€‹= â€‹0.09) or ICU (5/14 vs 9/15; p â€‹= â€‹0.10), postoperative neurological improvement (1/14 vs 1/15; p â€‹= â€‹0.48) or deterioration (1/14 vs 0/15; p â€‹= â€‹0.15), intraoperative complications (2/14 vs 3/15; p â€‹= â€‹0.34), postoperative complications 4/14 vs 4/15; p â€‹= â€‹0.46), revision surgeries (3/14 vs 1/15; p â€‹= â€‹0.16) and 30-day mortality (0/14 vs 0/15). CONCLUSION: This is the first study that compares surgical outcomes of navigated vs non-navigated PSFs for AS patients with an acute spinal fracture. Although limited by its retrospective design and sample size, this study highlights the non-inferiority of intraoperative navigation as a surgical aid in a challenging cohort.

The genome of Przewalski's horse (Equus ferus przewalskii).

The Przewalski's horse (Equus ferus przewalskii) is an endangered equid native to the steppes of central Asia. After becoming extinct in the wild, multiple conservation efforts convened to preserve the species including captive breeding programs, reintroduction and monitoring systems, protected lands, and cloning. Availability of a highly contiguous reference genome is essential to support these continued efforts. We used Oxford Nanopore sequencing to produce a scaffold-level 2.5 Gb nuclear assembly and 16,002 bp mitogenome from a captive Przewalski's mare. All assembly drafts were generated from 111 Gb of sequence from a single PromethION R10.4.1 flow cell. The mitogenome contained 37 genes in the standard mammalian configuration and was 99.63% identical to the domestic horse (Equus caballus). The nuclear assembly, EquPr2, contained 2,146 scaffolds with an N50 of 85.1 Mb, 43X mean depth, and BUSCO quality score of 98.92%. EquPr2 successfully improves upon the existing Przewalski's horse reference genome (Burgud), with 25-fold fewer scaffolds, a 166-fold larger N50, and phased pseudohaplotypes. Modified basecalls revealed 79.5% DNA methylation and 2.1% hydroxymethylation globally. Allele-specific methylation analysis between pseudohaplotypes revealed 226 differentially methylated regions (DMRs) in known imprinted genes and loci not previously reported as imprinted. The heterozygosity rate of 0.165% matches previous estimates for the species and compares favorably to other endangered animals. This improved Przewalski's horse assembly will serve as a valuable resource for conservation efforts and comparative genomics investigations.

Exploring SVA Insertion Polymorphisms in Shaping Differential Gene Expressions in the Central Nervous System.

Transposable elements (TEs) are repetitive elements which make up around 45% of the human genome. A class of TEs, known as SINE-VNTR-Alu (SVA), demonstrate the capacity to mobilise throughout the genome, resulting in SVA polymorphisms for their presence or absence within the population. Although studies have previously highlighted the involvement of TEs within neurodegenerative diseases, such as Parkinson's disease and amyotrophic lateral sclerosis (ALS), the exact mechanism has yet to be identified. In this study, we used whole-genome sequencing and RNA sequencing data of ALS patients and healthy controls from the New York Genome Centre ALS Consortium to elucidate the influence of reference SVA elements on gene expressions genome-wide within central nervous system (CNS) tissues. To investigate this, we applied a matrix expression quantitative trait loci analysis and demonstrate that reference SVA insertion polymorphisms can significantly modulate the expression of numerous genes, preferentially in the trans position and in a tissue-specific manner. We also highlight that SVAs significantly regulate mitochondrial genes as well as genes within the HLA and MAPT loci, previously associated within neurodegenerative diseases. In conclusion, this study continues to bring to light the effects of polymorphic SVAs on gene regulation and further highlights the importance of TEs within disease pathology.

CRISPR deletion of a SINE-VNTR-Alu (SVA_67) retrotransposon demonstrates its ability to differentially modulate gene expression at the MAPT locus.

Background: SINE-VNTR-Alu (SVA) retrotransposons are hominid-specific elements which have been shown to play important roles in processes such as chromatin structure remodelling and regulation of gene expression demonstrating that these repetitive elements exert regulatory functions. We have previously shown that the presence or absence of a specific SVA element, termed SVA_67, was associated with differential expression of several genes at the MAPT locus, a locus associated with Parkinson's Disease (PD) and frontotemporal dementia. However, we were not able to demonstrate that causation of differential gene expression was directed by the SVA due to lack of functional validation. Methods: We performed CRISPR to delete SVA_67 in the HEK293 cell line. Quantification of target gene expression was performed using qPCR to assess the effects on expression in response to the deletion of SVA_67. Differences between CRISPR edit and control cell lines were analysed using two-tailed t-test with a minimum 95% confidence interval to determine statistical significance. Results: In this study, we provide data highlighting the SVA-specific effect on differential gene expression. We demonstrate that the hemizygous deletion of the endogenous SVA_67 in CRISPR edited cell lines was associated with differential expression of several genes at the MAPT locus associated with neurodegenerative diseases including KANSL1, MAPT and LRRC37A. Discussion: This data is consistent with our previous bioinformatic work of differential gene expression analysis using transcriptomic data from the Parkinson's Progression Markers Initiative (PPMI) cohort. As SVAs have regulatory influences on gene expression, and insertion polymorphisms contribute to interpersonal differences in expression patterns, these results highlight the potential contribution of these elements to complex diseases with potentially many genetic components, such as PD.

Few Primary Care Physicians Lead Hospitals, Despite Their Immense Value: Systems Change and Delivery System Evolution Can Reverse This Trend.

Primary care physicians (PCPs) inherently offer a tremendous range of skills that would serve them well as chief executive officers in hospitals. Despite their immense value, very few serve in these top posts for a variety of reasons. Making changes in how we train, mentor, and support PCPs throughout their careers can reverse this trend.

Review of New Zealand Coastal Talitroids with description of three new genera (Crustacea, Amphipoda, Senticaudata).

A generic revision is provided for the New Zealand coastal talitroids, which reports two families, seven genera and thirteen species. Three new genera are described: Aotearorchestia gen. nov.; Subantarctorchestia gen. nov.; and Tatahipeke gen. nov. to accommodate seven known species, A. chathamensis (Hurley, 1956) comb. nov.; A. telluris (Spence Bate, 1862) comb. nov.; S. aucklandiae (Spence Bate, 1862) comb. nov.; S. bollonsi (Chilton, 1909) comb. nov.; Tatahipeke cookii (Filhol, 1885) comb. nov.; T. kirki (Hurley, 1956) comb. nov.; and T. tumida (G.M. Thomson, 1885) comb. nov. The three genera, Bellorchestia Serejo & Lowry, 2008, Protorchestia Bousfield 1982 and Transorchestia Bousfield, 1982 are revised to include additional information on morphology, growth stages and distributions for three New Zealand species: Bellorchestia quoyana (Milne Edwards, 1840); Transorchestia miranda (Chilton, 1916); and Trans. serrulata (Dana, 1852a). Lastly, a small commentary is given on four species of coastal talitroids where additional museum collections could not be located for study, B. spadix (Hurley, 1956), Pictonorchestia dentata (Filhol, 1885), Protorchestia campbelliana (Bousfield, 1964), and T. kirki (Hurley, 1956) gen. et comb. nov. A dichotomous key and pictorial field guide are provided to all New Zealand coastal talitroids.

Eight-Centimeter Gallbladder Stone Post-Roux-en-Y Gastric Bypass: A Case Report.

Cholelithiasis occurs when a stone forms in the gallbladder; when symptoms develop, the condition is termed symptomatic cholelithiasis. The correlation between bariatric surgery and post-operative symptomatic cholelithiasis has long been established. Presented is a case of a 56-year-old female status post-Roux-en-Y gastric bypass who developed symptomatic cholelithiasis and subsequently underwent cholecystectomy with the removal of an 8-centimeter (cm) gallbladder stone. This case report explores the benefits and limitations of watchful waiting versus prophylactic concomitant cholecystectomy among bariatric surgery patients, noting the difference between the bariatric sleeve and bypass anatomy for managing biliary complications.

Perforated Duodenal Ulcer Post-Roux-en-Y Gastric Bypass: A Case Report.

Obesity is a growing health concern worldwide, with bariatric surgeries such as gastric bypass providing an effective treatment choice. However, a rare complication of gastric bypass is a duodenal ulcer. Currently, there is no exact incidence of this complication, and only a few case reports have been published in the literature. Presented is a case of a 32-year-old patient, eight years status post gastric bypass, who was evaluated for surgical repair of a large anterior perforated duodenal ulcer. This case report explores the relationship between patient history and gastric bypass surgery in the case of duodenal ulcer formation and perforation, as well as the diagnostic difficulty and modalities for duodenal ulcers in post-gastric bypass patients.

Partial ceratohyoidectomy as surgical treatment for horses with temporohyoid osteoarthropathy: 10 cases (2010-2021).

OBJECTIVE: To describe outcomes of horses with temporohyoid osteoarthropathy (THO) treated with partial ceratohyoidectomy. ANIMALS: 10 client-owned horses. PROCEDURES: Medical records from 2 institutions were examined for records of horses with THO treated with partial ceratohyoidectomy between 2010 and 2021. History, signalment, clinical signs, diagnostics, medications, and surgery-related details were recorded. Horses with a minimum of 6 months follow-up were recruited for neurologic and imaging examinations in the hospital or field where radiography of the basihyoid-ceratohyoid articulation were performed along with CT, when available. RESULTS: 10 horses with THO were included (9 unilateral; 1 bilateral). Nine planned partial ceratohyoidectomies were performed in 8 horses, whereas 2 horses had preoperatively planned complete ceratohyoidectomies transitioned to partial ceratohyoidectomies during surgery due to intraoperative complications. Postoperative complications occurred mostly in transitioned surgeries (obstructed airway, tongue mobility issues, and incisional hemorrhage), whereas only 1 horse with a planned ceratohyoidectomy had postoperative complication of rhabdomyolysis. All complications resolved before hospital discharge. Neurologic signs improved in all 10 horses, with 2 showing complete resolution. Nine horses were available for radiographic follow-up, 6 of which also had head CT scans. A space between the ceratohyoid and basihyoid bones was measurable on radiography in all 9 horses, and was confirmed on CT. Three horses demonstrated proliferation of either ceratohyoid or basihyoid bones. The 9 horses with unilateral disease returned to previous work, and the horse with bilateral disease was retired. CLINICAL RELEVANCE: Partial ceratohyoidectomy is a surgical option for treatment of THO that provides similar clinical outcomes to published reports on ceratohyoidectomy.

A weight of evidence approach for bioaccumulation assessment.

Bioaccumulation assessments conducted by regulatory agencies worldwide use a variety of methods, types of data, metrics, and categorization criteria. Lines of evidence (LoE) for bioaccumulation assessment can include bioaccumulation metrics such as in vivo bioconcentration factor (BCF) and biomagnification factor (BMF) data measured from standardized laboratory experiments, and field (monitoring) data such as BMFs, bioaccumulation factors (BAFs), and trophic magnification factors (TMFs). In silico predictions from mass-balance models and quantitative structure-activity relationships (QSARs) and a combination of in vitro biotransformation rates and in vitro-in vivo extrapolation (IVIVE) models can also be used. The myriad bioaccumulation metrics and categorization criteria and underlying uncertainty in measured or modeled data can make decision-making challenging. A weight of evidence (WoE) approach is recommended to address uncertainty. The Bioaccumulation Assessment Tool (BAT) guides a user through the process of collecting and generating various LoE required for assessing the bioaccumulation of neutral and ionizable organic chemicals in aquatic (water-respiring) and air-breathing organisms. The BAT includes data evaluation templates (DETs) to critically evaluate the reliability of the LoE used in the assessment. The DETs were developed from standardized testing guidance. The approach used in the BAT is consistent with OECD and SETAC WoE principles and facilitates the implementation of chemical policy objectives in chemical assessment and management. The recommended methods are also iterative and tiered, providing pragmatic methods to reduce unnecessary animal testing. General concepts of the BAT are presented and case study applications of the tool for hexachlorobenzene (HCB) and ß-hexachlorocyclohexane (ß-HCH) are demonstrated. The BAT provides a consistent and transparent WoE framework to address uncertainty in bioaccumulation assessment and is envisaged to evolve with scientific and regulatory developments. Integr Environ Assess Manag 2023;19:1235-1253. © 2022 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Impact of the COVID-19 pandemic on anaesthesia specialty training: a single-centre quantitative analysis.

Background: The COVID-19 pandemic disrupted healthcare services worldwide, with a consequent impact on the delivery of medical education and training in all acute care specialties. Anaesthesia training has been challenged by a combination of reduced elective theatre activity, redeployment of trainees to critical care units, and changes in standard anaesthetic practices. Methods: The aim of this study was to quantify the impact of COVID-19 on specialist anaesthesia training at a tertiary level teaching hospital in Ireland via a retrospective analysis of data captured by electronic anaesthesia records. The anaesthetic caseloads of trainees in periods before and during the pandemic were analysed along with airway management practices, core procedural skills performed, and critical care rostering. Data relating to 145 anaesthesia trainees were captured during the study periods: pre-pandemic (January 2018 to January 2020) and pandemic (January 2020 to January 2022). Results: The mean number of theatre cases logged per trainee in a 6-month period reduced from 156.8 pre-pandemic to 119.2 during the pandemic (23.9% reduction; P<0.0001). Although theatre caseload was reduced, trainees gained additional critical care experience with a significant increase in overall days spent staffing critical care wards. In the theatre setting, the number of arterial lines, central lines, neuraxial blocks, and peripheral nerve blocks performed were significantly reduced during the pandemic. Conclusions: Although the COVID-19 pandemic significantly reduced anaesthesia training exposure and increased critical care exposure over an extended period, the overall long-term significance of this alteration in the anaesthesia training experience remains uncertain.

In pursuit of high-quality primary care: A call to action to implement the objectives of the 2021 NASEM report.

A seminal National Academies of Sciences, Engineering, and Medicine consensus report released in May 2021-Implementing High-Quality Primary Care: Rebuilding the Foundation of Health Care-emphasizes the importance of ensuring that high-quality primary care is accessible to all people, regardless of whether they have paid for it and in spite of its limited availability. This report outlines five recommendations for primary care stakeholders seeking to transform the health care landscape. This article summarizes these recommendations; identifies progress made toward high-quality primary care implementation since the report's publication; and outlines examples of policies, operational approaches, and advocacy strategies we believe are necessary to implement high-quality primary care. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Strengthening Primary Care to Improve Health Outcomes in the US-Creating Oversight to Address Invisibility.

This Viewpoint discusses how the lack of a comprehensive national primary care approach creates gaps and confusion in federal policy and proposes solutions.

Intero-External Hemorrhoids Complicated by Ischio-Anal Infection Coexisting with Tubo-Ovarian Abscesses: A Case for Early Surgical Intervention.

Hemorrhoids are abnormal collections of engorged blood vessels and tissue within the anal canal or surrounding the anus. Management consists of conservative treatment or a hemorrhoidectomy, dependent on disease severity, duration, and physician discretion. Reported is a case of a 44-year-old, African American female initially treated conservatively for intero-external hemorrhoids, that later abscessed into the ischio-anal fossa and was further complicated by an infection of the deep pelvic space. This report explores conservative and surgical management of hemorrhoids, and offers recommendations for symptom management, and reducing disease progression and complications.