Genetic load and viability of a future restored northern white rhino population.

As biodiversity loss outpaces recovery, conservationists are increasingly turning to novel tools for preventing extinction, including cloning and in vitro gametogenesis of biobanked cells. However, restoration of populations can be hindered by low genetic diversity and deleterious genetic load. The persistence of the northern white rhino (Ceratotherium simum cottoni) now depends on the cryopreserved cells of 12 individuals. These banked genomes have higher genetic diversity than southern white rhinos (C. s. simum), a sister subspecies that successfully recovered from a severe bottleneck, but the potential impact of genetic load is unknown. We estimated how demographic history has shaped genome-wide genetic load in nine northern and 13 southern white rhinos. The bottleneck left southern white rhinos with more fixed and homozygous deleterious alleles and longer runs of homozygosity, whereas northern white rhinos retained more deleterious alleles masked in heterozygosity. To gauge the impact of genetic load on the fitness of a northern white rhino population restored from biobanked cells, we simulated recovery using fitness of southern white rhinos as a benchmark for a viable population. Unlike traditional restoration, cell-derived founders can be reintroduced in subsequent generations to boost lost genetic diversity and relieve inbreeding. In simulations with repeated reintroduction of founders into a restored population, the fitness cost of genetic load remained lower than that borne by southern white rhinos. Without reintroductions, rapid growth of the restored population (>20-30% per generation) would be needed to maintain comparable fitness. Our results suggest that inbreeding depression from genetic load is not necessarily a barrier to recovery of the northern white rhino and demonstrate how restoration from biobanked cells relieves some constraints of conventional restoration from a limited founder pool. Established conservation methods that protect healthy populations will remain paramount, but emerging technologies hold promise to bolster these tools to combat the extinction crisis.

Neuroinvasive Bacillus cereus Infection in Immunocompromised Hosts: Epidemiologic Investigation of 5 Patients With Acute Myeloid Leukemia.

Background: Bacillus cereus is a ubiquitous gram-positive rod-shaped bacterium that can cause sepsis and neuroinvasive disease in patients with acute leukemia or neutropenia. Methods: A single-center retrospective review was conducted to evaluate patients with acute leukemia, positive blood or cerebrospinal fluid test results for B cereus, and abnormal neuroradiographic findings between January 2018 and October 2022. Infection control practices were observed, environmental samples obtained, a dietary case-control study completed, and whole genome sequencing performed on environmental and clinical Bacillus isolates. Results: Five patients with B cereus neuroinvasive disease were identified. All patients had acute myeloid leukemia (AML), were receiving induction chemotherapy, and were neutropenic. Neurologic involvement included subarachnoid or intraparenchymal hemorrhage or brain abscess. All patients were treated with ciprofloxacin and survived with limited or no neurologic sequelae. B cereus was identified in 7 of 61 environmental samples and 1 of 19 dietary protein samples-these were unrelated to clinical isolates via sequencing. No point source was identified. Ciprofloxacin was added to the empiric antimicrobial regimen for patients with AML and prolonged or recurrent neutropenic fevers; no new cases were identified in the ensuing year. Conclusions: B cereus is ubiquitous in the hospital environment, at times leading to clusters with unrelated isolates. Fastidious infection control practices addressing a range of possible exposures are warranted, but their efficacy is unknown and they may not be sufficient to prevent all infections. Thus, including B cereus coverage in empiric regimens for patients with AML and persistent neutropenic fever may limit the morbidity of this pathogen.

Drug-resistant EGFR mutations promote lung cancer by stabilizing interfaces in ligand-free kinase-active EGFR oligomers.

The Epidermal Growth Factor Receptor (EGFR) is frequently found to be mutated in non-small cell lung cancer. Oncogenic EGFR has been successfully targeted by tyrosine kinase inhibitors, but acquired drug resistance eventually overcomes the efficacy of these treatments. Attempts to surmount this therapeutic challenge are hindered by a poor understanding of how and why cancer mutations specifically amplify ligand-independent EGFR auto-phosphorylation signals to enhance cell survival and how this amplification is related to ligand-dependent cell proliferation. Here we show that drug-resistant EGFR mutations manipulate the assembly of ligand-free, kinase-active oligomers to promote and stabilize the assembly of oligomer-obligate active dimer sub-units and circumvent the need for ligand binding. We reveal the structure and assembly mechanisms of these ligand-free, kinase-active oligomers, uncovering oncogenic functions for hitherto orphan transmembrane and kinase interfaces, and for the ectodomain tethered conformation of EGFR. Importantly, we find that the active dimer sub-units within ligand-free oligomers are the high affinity binding sites competent to bind physiological ligand concentrations and thus drive tumor growth, revealing a link with tumor proliferation. Our findings provide a framework for future drug discovery directed at tackling oncogenic EGFR mutations by disabling oligomer-assembling interactions.

Pen-Based Swine Oral Fluid Samples Contain Both Environmental and Pig-Derived Targets.

Laboratory methods for detecting specific pathogens in oral fluids are widely reported, but there is little research on the oral fluid sampling process itself. In this study, a fluorescent tracer (diluted red food coloring) was used to test the transfer of a target directly from pigs or indirectly from the environment to pen-based oral fluid samples. Pens of ~30, ~60, and ~125 14-week-old pigs (32 pens/size) on commercial swine farms received one of two treatments: (1) pig exposure, i.e., ~3.5 mL of tracer solution sprayed into the mouth of 10% of the pigs in the pen; (2) environmental exposure, i.e., 20 mL of tracer solution was poured on the floor in the center of the pen. Oral fluids collected one day prior to treatment (baseline fluorescence control) and immediately after treatment were tested for fluorescence. Data were evaluated by receiver operating characteristic (ROC) analysis, with Youden's J statistic used to set a threshold. Pretreatment oral fluid samples with fluorescence responses above the ROC threshold were removed from further analysis (7 of 96 samples). Based on the ROC analyses, oral fluid samples from 78 of 89 pens (87.6%), contained red food coloring, including 43 of 47 (91.5%) pens receiving pig exposure and 35 of 42 (83.3%) pens receiving environmental exposure. Thus, oral fluid samples contain both pig-derived and environmental targets. This methodology provides a safe and quantifiable method to evaluate oral fluid sampling vis-à-vis pen behavior, pen size, sampling protocol, and target distribution in the pen.

Generation of a Commercial-Scale Founder Population of Porcine Reproductive and Respiratory Syndrome Virus Resistant Pigs Using CRISPR-Cas.

Disease resistance genes in livestock provide health benefits to animals and opportunities for farmers to meet the growing demand for affordable, high-quality protein. Previously, researchers used gene editing to modify the porcine CD163 gene and demonstrated resistance to a harmful virus that causes porcine reproductive and respiratory syndrome (PRRS). To maximize potential benefits, this disease resistance trait needs to be present in commercially relevant breeding populations for multiplication and distribution of pigs. Toward this goal, a first-of-its-kind, scaled gene editing program was established to introduce a single modified CD163 allele into four genetically diverse, elite porcine lines. This effort produced healthy pigs that resisted PRRS virus infection as determined by macrophage and animal challenges. This founder population will be used for additional disease and trait testing, multiplication, and commercial distribution upon regulatory approval. Applying CRISPR-Cas to eliminate a viral disease represents a major step toward improving animal health.

A decade of clinical microbiology: top 10 advances in 10 years: what every infection preventionist and antimicrobial steward should know.

The past 10 years have brought paradigm-shifting changes to clinical microbiology. This paper explores the top 10 transformative innovations across the diagnostic spectrum, including not only state of the art technologies but also preanalytic and post-analytic advances. Clinical decision support tools have reshaped testing practices, curbing unnecessary tests. Innovations like broad-range polymerase chain reaction and metagenomic sequencing, whole genome sequencing, multiplex molecular panels, rapid phenotypic susceptibility testing, and matrix-assisted laser desorption ionization time-of-flight mass spectrometry have all expanded our diagnostic armamentarium. Rapid home-based testing has made diagnostic testing more accessible than ever. Enhancements to clinician-laboratory interfaces allow for automated stewardship interventions and education. Laboratory restructuring and consolidation efforts are reshaping the field of microbiology, presenting both opportunities and challenges for the future of clinical microbiology laboratories. Here, we review key innovations of the last decade.

National survey of infectious disease fellowship program directors: A call for subspecialized training in infection prevention and control and healthcare epidemiology.

OBJECTIVE: The importance of infection prevention and control and healthcare epidemiology (IPC/HE) in healthcare facilities was highlighted during the COVID-19 pandemic. Infectious disease (ID) clinicians often hold leadership positions in IPC/HE teams; however, there is no standard for training or certification of ID physicians specializing in IPC/HE. We evaluated the current state of IPC/HE training in ID fellowship programs. DESIGN: A national survey of ID fellowship program directors was conducted to assess current IPC/HE training components in programs and plans for expanded offerings. SETTING AND PARTICIPANTS: All ID fellowship program directors in the United States and Puerto Rico. METHODS: Surveys were distributed using Research Electronic Data Capture (REDCap) to program directors in March 2023, with 2 reminder emails; the survey closed after 4 weeks. RESULTS: Of 166 program directors, 54 (32.5%) responded to the survey. Among respondent programs, 49 (90.7%) of 54 programs reported didactic training in IPC/HE averaging 4.4 hours over the course of the fellowship. Also, 18 (33.3%) of 54 reported a dedicated IPC/HE training track. Furthermore, 23 programs (42.6%) reported barriers to expanding training. There was support (n = 47, 87.0%) for formal IPC/HE certification from a professional society within the standard fellowship. CONCLUSIONS: Despite the COVID-19 pandemic highlighting the need for ID medical doctors with IPC/HE expertise, formal training in ID fellowship remains limited. Most program directors support formalization of IPC/HE training by a professional organization. Creation of standardized advanced curriculums for ID fellowship training in IPC/HE could be considered by the Society of Healthcare Epidemiology of America (SHEA) to grow, retain, and enhance the IPC/HE physician workforce.

Efficacy of three benznidazole dosing strategies for adults living with chronic Chagas disease (MULTIBENZ): an international, randomised, double-blind, phase 2b trial.

BACKGROUND: Treatment with benznidazole for chronic Chagas disease is associated with low cure rates and substantial toxicity. We aimed to compare the parasitological efficacy and safety of 3 different benznidazole regimens in adult patients with chronic Chagas disease. METHODS: The MULTIBENZ trial was an international, randomised, double-blind, phase 2b trial performed in Argentina, Brazil, Colombia, and Spain. We included participants aged 18 years and older diagnosed with Chagas disease with two different serological tests and detectable T cruzi DNA by qPCR in blood. Previously treated people, pregnant women, and people with severe cardiac forms were excluded. Participants were randomly assigned 1:1:1, using a balanced block randomisation scheme stratified by country, to receive benznidazole at three different doses: 300 mg/day for 60 days (control group), 150 mg/day for 60 days (low dose group), or 400 mg/day for 15 days (short treatment group). The primary outcome was the proportion of patients with a sustained parasitological negativity by qPCR during a follow-up period of 12 months. The primary safety outcome was the proportion of people who permanently discontinued the treatment. Both primary efficacy analysis and primary safety analysis were done in the intention-to-treat population. The trial is registered with EudraCT, 2016-003789-21, and ClinicalTrials.gov, NCT03191162, and is completed. FINDINGS: From April 20, 2017, to Sept 20, 2020, 245 people were enrolled, and 234 were randomly assigned: 78 to the control group, 77 to the low dose group, and 79 to the short treatment group. Sustained parasitological negativity was observed in 42 (54%) of 78 participants in the control group, 47 (61%) of 77 in the low dose group, and 46 (58%) of 79 in the short treatment group. Odds ratios were 1·41 (95% CI 0·69-2·88; p=0·34) when comparing the low dose and control groups and 1·23 (0·61-2·50; p=0·55) when comparing short treatment and control groups. 177 participants (76%) had an adverse event: 62 (79%) in the control group, 56 (73%) in the low dose group, and 59 (77%) in the short treatment group. However, discontinuations were less frequent in the short treatment group compared with the control group (2 [2%] vs 11 [14%]; OR 0·20, 95% CI 0·04-0·95; p=0·044). INTERPRETATION: Participants had a similar parasitological responses. However, reducing the usual treatment from 8 weeks to 2 weeks might maintain the same response while facilitating adherence and increasing treatment coverage. These findings should be confirmed in a phase 3 clinical trial. FUNDING: European Community's 7th Framework Programme.

Characterization of Novel Trypanosoma cruzi-Specific Antigen with Potential Use in the Diagnosis of Chagas Disease.

Chagas disease is caused by the parasite Trypanosoma cruzi. In humans, it evolves into a chronic disease, eventually resulting in cardiac, digestive, and/or neurological disorders. In the present study, we characterized a novel T. cruzi antigen named Tc323 (TcCLB.504087.20), recognized by a single-chain monoclonal antibody (scFv 6B6) isolated from the B cells of patients with cardiomyopathy related to chronic Chagas disease. Tc323, a ~323 kDa protein, is an uncharacterized protein showing putative quinoprotein alcohol dehydrogenase-like domains. A computational molecular docking study revealed that the scFv 6B6 binds to an internal domain of Tc323. Immunofluorescence microscopy and Western Blot showed that Tc323 is expressed in the main developmental forms of T. cruzi, localized intracellularly and exhibiting a membrane-associated pattern. According to phylogenetic analysis, Tc323 is highly conserved throughout evolution in all the lineages of T. cruzi so far identified, but it is absent in Leishmania spp. and Trypanosoma brucei. Most interestingly, only plasma samples from patients infected with T. cruzi and those with mixed infection with Leishmania spp. reacted against Tc323. Collectively, our findings demonstrate that Tc323 is a promising candidate for the differential serodiagnosis of chronic Chagas disease in areas where T. cruzi and Leishmania spp. infections coexist.

Assessing potential human health and ecological implications of PFAS from leave-in dental products.

Contaminated water and food are the main sources of documented per- and polyfluoroalkyl substances (PFAS) exposure in humans. However, other sources may contribute to the overall PFAS intake. While several studies documented the presence of PFAS in consumer products, PFAS evaluation in dental products has been limited to floss and tape to date. This study estimated PFAS exposures from a convenience sample of leave-in dental products (night guards and whitening trays), which remain in contact with the mouth for longer durations than previously evaluated dental products. This analysis evaluated whether consumer usage of these dental products meaningfully contributes to oral exposure of PFAS. Leaching of PFAS upon disposal of products was also considered. Out of 24 PFAS measured, perfluorobutanoic acid (PFBA; 3.24-4.17 ng/product or 0.67-0.83 ng/g) and perfluorooctanesulfonic acid (PFOS; 7.25-16.45 ng/product or 1.2-2.3 ng/g) were detected in night guards, and no PFAS were detected in whitening trays. Non-targeted analysis showed additional possible PFAS, which could not be characterized. The findings showed that PFOS and/or PFBA present in night guards were unlikely to pose a health concern. From an ecological perspective, the dental products examined were shown to constitute a negligible contribution to environmental PFAS. In conclusion, the examined dental products do not represent a significant source of exposure to PFAS for humans or the environment. The study demonstrates how risk assessment can be integrated by the industry into product stewardship programs to evaluate the potential health and environmental impacts of chemicals in consumer products.

Compositional Evolution of Individual CoNPs on Co/TiO2 during CO and Syngas Treatment Resolved through Soft XAS/X-PEEM.

The nanoparticle (NP) redox state is an important parameter in the performance of cobalt-based Fischer-Tropsch synthesis (FTS) catalysts. Here, the compositional evolution of individual CoNPs (6-24 nm) in terms of the oxide vs metallic state was investigated in situ during CO/syngas treatment using spatially resolved X-ray absorption spectroscopy (XAS)/X-ray photoemission electron microscopy (X-PEEM). It was observed that in the presence of CO, smaller CoNPs (i.e., ≤12 nm in size) remained in the metallic state, whereas NPs ≥ 15 nm became partially oxidized, suggesting that the latter were more readily able to dissociate CO. In contrast, in the presence of syngas, the oxide content of NPs ≥ 15 nm reduced, while it increased in quantity in the smaller NPs; this reoxidation that occurs primarily at the surface proved to be temporary, reforming the reduced state during subsequent UHV annealing. O K-edge measurements revealed that a key parameter mitigating the redox behavior of the CoNPs were proximate oxygen vacancies (Ovac). These results demonstrate the differences in the reducibility and the reactivity of Co NP size on a Co/TiO2 catalyst and the effect Ovac have on these properties, therefore yielding a better understanding of the physicochemical properties of this popular choice of FTS catalysts.

Standardized Calcium Replacement in Massive Transfusion: A Quality Improvement Project.

BACKGROUND: Hypocalcemia is common in trauma patients receiving massive transfusion protocol and often leads to worsening coagulopathies. Despite the identified problem and recommendations for replacement, few institutions have implemented a standardized calcium replacement protocol. OBJECTIVE: This study aims to assess whether a revised massive transfusion protocol, including standardized calcium replacement, increases the incidence of calcium administration in trauma patients receiving massive transfusion protocol. METHODS: This quality improvement project used a retrospective pre-/postdesign to study the revision of the current facility's massive transfusion protocol to include calcium replacement and ionized calcium monitoring at an urban Level I academic trauma center. Pre- and postintervention data were collected from January 2022 through October 2022 to determine the number of times massive transfusion protocol was ordered, ionized calcium monitoring, and calcium administration rates. Feedback regarding the protocol was collected throughout the monitoring period and was utilized in the final analysis. RESULTS: A total of 40 patients received massive transfusion protocol, preintervention, 18 of 23 (78%) received calcium supplementation, postintervention, 15 of 16 (98%) were treated. The majority of protocol activations occurred in the trauma bay (79%) and postintervention; ionized calcium monitoring dropped by 14%. CONCLUSION: This study found that the addition of standardized calcium replacement improved administration rates of calcium in this patient population. Ongoing research will ensure the recommended changes improve the identified shortcomings and that patients maintain adequate ionized calcium levels with the current dosing parameters.

Filling the gaps: A community case study in using an interprofessional approach and community-academic partnerships to address COVID-19-related inequities.

Public health challenges rapidly escalated during the COVID-19 pandemic. In response to a severe lack of resources and support in the near western suburbs of Chicago, the COVID Equity Response Collaborative: Loyola (CERCL) was established by an interprofessional team of Loyola University Chicago students, staff, and faculty. CERCL sought to minimize the negative impact of COVID-19 on vulnerable communities, those that are largely Black, Hispanic, or low-income. From April 2020 to the present, the collaborative utilized community-academic partnerships and interdisciplinary collaborations to conduct programming. CERCL's programming included free community-based testing, screening for and assistance with social determinants of health, dissemination of relevant and reliable COVID-related information, provision of personal protective equipment, and facilitation of access to vaccines. With partners, the collaborative conducted 1,500 COVID-19 tests, trained 80 individuals in contact tracing, provided over 100 individuals with specifically tailored resources to address social and legal needs, distributed 5,000 resource bags, held 20 community conversations, canvassed 3,735 homes, and hosted 19 vaccine clinics. Community-academic partnerships with the health system, community and governmental agencies, and the local public health department have been critical to CERCL efforts. The interdisciplinary and interprofessional successes demonstrated in this case study lends the example of a relevant, sustainable, and practical intervention to address nuanced public health issues.

Examining the Psychometric Properties of the Revised Scale of Economic Abuse among Iranian Women.

Economic abuse, in the context of intimate relationships, is a pervasive form of violence that merits further empirical attention. We know from limited research that the rates of economic abuse appear to be high in Iran; however, there is a lack of culturally appropriate measures that can assess the extent to which women experience economic harm as a result of their partners' actions. The present study was conducted with the aims of (a) investigating the psychometric properties of the 14-item Revised Scale of Economic Abuse (SEA2) which was translated into Persian for this study and (b) examining the prevalence of economic abuse among a sample of 371 married housewives in Qazvin, Iran. Confirmatory factor analysis supports the two-factor structure of the SEA2, with the exception of one item. Composite reliability and Cronbach's alpha demonstrated good internal consistency. The average variance extracted method, along with correlations with other financial variables, demonstrated evidence of good convergent validity. Correlations with related, but distinct forms of abuse, support the scale's discriminant validity. Based on the collective findings, this measure can be used as a reliable and valid tool to study economic abuse among Iranian women which, within our sample, appears to be a common phenomenon. Implications for future research and practice are discussed.

Examining the Relations Between Social Competence, Autistic Traits, Anxiety and Depression in Autistic and Non-Autistic Children.

The current study examined whether social competence and autistic traits are related to anxiety and depression in autistic and non-autistic children. Parents of 340 children aged 6 to 12 years old, including 186 autistic and 154 non-autistic children completed the Autism Spectrum Quotient (AQ) to assess their child's autistic traits, the Multidimensional Social Competence Scale (MSCS) to assess their child's social competence, and the Behaviour Assessment Scale for Children 2 (BASC-2) to assess their child's internalizing symptoms of depression and anxiety, and children were administered the Wechsler Abbreviated Scale of Intelligence, Second Edition (WASI-II) to assess their intellectual abilities. Hierarchical multiple regression analyses were conducted to investigate the relations between social competence, autistic traits, anxiety, and depression. Social competence was related to anxiety and depression symptoms in autistic children, but only depression symptoms in non-autistic children, above and beyond the effects of autistic traits, IQ and age. Autistic children were also reported to experience more severe anxiety and depression symptoms, and more autistic traits were related to higher levels of anxiety and depression in both groups. These findings suggest that social competence and internalizing symptoms are intricately connected in autistic children and need to be jointly considered in both assessment and intervention. The social implications are discussed with an emphasis on acceptance of diverse social styles as a viable avenue to reduce children's internalizing symptoms.

Diversity Elements on Maternal Fetal Medicine (MFM) Fellowship Websites: Opportunity for Improvement in Recruitment and Representation.

Background: There has been a fundamental shift in recruitment of medical students and trainees into residency and fellowship programs during the Covid 19 pandemic.1 Historically, websites for medical trainees demonstrate a lack of explicit focus on diversity, equity, and inclusion. 2-7 Diversity has positive associations of improving healthcare team performance, patient care, and even financial goals.8 A lack of diversity may negatively impact patient care.9 Directed recruitment of underrepresented in medicine applicants has proven successful to increase diversity within training programs. Department websites have a more prominent role in virtual recruitment since the beginning of the COVID pandemic. Features on these websites may be utilized to attract underrepresented in medicine applicants and increase diversity in a field. Objective: To analyze Maternal Fetal Medicine fellowship websites for presence of diversity elements important to those people who are underrepresented in medicine. Study Design: Fellowship websites were accessed summer of 2021. They were analyzed for presence of twelve website elements that demonstrate commitment to diversity, including: 1) nondiscrimination statement; 2) diversity and inclusion message; 3) diversity specific language; 4) resources for trainees; 5) community demographics; 6-7) personalized biographies of faculty or fellows; 8-9) individual photographs of faculty or fellows; 10) photos or biographies of alumni; 11) diversity publications and; 12) department statistics. Program size, region, and location were collected. Self-reported underrepresented in medicine data on residency programs was extracted from the National Graduate Medical Education Survey from 2019. Programs were dichotomized into 6+ diversity elements. Nonparametric, chi-square and Fisher's exact were used for analysis. Results: Fellowship programs were analyzed (excluding military/fetal surgery, n = 91/94). Websites included a mean of 4.1± 2.5 diversity elements. Most featured fewer than 6 elements (n =75, 82.4%). When dichotomized to 6+ diversity elements, larger faculty size was the only significant factor (p=0.01). The majority of programs had fewer than 12 faculty members (n=54, 59.3%) and only 9.3% of those programs had 6 or more diversity elements. By contrast, among programs with more than 12 faculty, 29.7% had 6 or more diversity elements. Faculty photos, fellow photos, and diversity publications were the most commonly featured items (92.4%, 68.1%, and 49.5%, respectively). Mean rate of underrepresented in medicine was 18.8% ± 11.3% and no significant associations were noted. There was a non-significant difference in diversity elements in the West United States with a mean of 5.3±2.2 diversity elements, compared to 3.7±2 in the South. Conclusion: Fellowship websites convey information for trainees, especially in an era of virtual recruitment. This study highlights opportunities for directed improvements of websites for features which URIM medical trainees have identified as important.

Cerebellar axonopathy in Shivers horses identified by spatial transcriptomic and proteomic analyses.

BACKGROUND: Shivers in horses is characterized by abnormal hindlimb movement when walking backward and is proposed to be caused by a Purkinje cell (PC) axonopathy based on histopathology. OBJECTIVES: Define region-specific differences in gene expression within the lateral cerebellar hemisphere and compare cerebellar protein expression between Shivers horses and controls. ANIMALS: Case-control study of 5 Shivers and 4 control geldings ≥16.2 hands in height. METHODS: Using spatial transcriptomics, gene expression was compared between Shivers and control horses in PC soma and lateral cerebellar hemisphere white matter, consisting primarily of axons. Tandem-mass-tag (TMT-11) proteomic analysis was performed on lateral cerebellar hemisphere homogenates. RESULTS: Differences in gene expression between Shivers and control horses were evident in principal component analysis of axon-containing white matter but not PC soma. In white matter, there were 455/1846 differentially expressed genes (DEG; 350 ↓DEG, 105 ↑DEG) between Shivers and controls, with significant gene set enrichment of the Toll-Like Receptor 4 (TLR4) cascade, highlighting neuroinflammation. There were 50/936 differentially expressed proteins (DEP). The 27 ↓DEP highlighted loss of axonal proteins including intermediate filaments (5), myelin (3), cytoskeleton (2), neurite outgrowth (2), and Na/K ATPase (1). The 23 ↑DEP were involved in the extracellular matrix (7), cytoskeleton (7), redox balance (2), neurite outgrowth (1), signal transduction (1), and others. CONCLUSION AND CLINICAL IMPORTANCE: Our findings support axonal degeneration as a characteristic feature of Shivers. Combined with histopathology, these findings are consistent with the known distinctive response of PC to injury where axonal changes occur without a substantial impact on PC soma.

An Exploratory Study of Financial Health as an Antecedent of Economic Abuse Among Women Seeking Help for Intimate Partner Violence.

Economic abuse is a common component of intimate partner violence (IPV). This study explored whether IPV victim and perpetrator financial health at relationship outset are associated with two types of economic abuse-restriction and exploitation-during the relationship. With a sample of 315 women seeking services for male-perpetrated IPV, the study showed increased use of economic restriction when perpetrators were advantaged in terms of assets or disadvantaged in terms of debt. There was increased use of economic exploitation when victims were advantaged in terms of assets or credit and when perpetrators were disadvantaged in terms of assets, debt, or credit. Implications for research and intervention are discussed.

If you don't test, they will not treat: Impact of stopping preoperative screening for asymptomatic bacteriuria.

Objective: Screening for asymptomatic bacteriuria (ASB) is not recommended outside of patients undergoing invasive urological procedures and during pregnancy. Despite national guidelines recommending against screening for ASB, this practice is prevalent. We present outcomes from a quality-improvement intervention targeting patients undergoing cardiac artery bypass grafting surgery (CABG) at Massachusetts General Hospital, a tertiary-care hospital in Boston, Massachusetts, where preoperative testing checklists were modified to remove routine urinalysis and urine culture. This was a before-and-after intervention study. Methods: Prior to the intervention, screening for ASB was included in the preoperative check list for all patients undergoing CABG. We assessed the proportion of patients undergoing screening for ASB in the 6 months prior to and after the intervention. We estimated cost savings from averted laboratory analyses, and we evaluated changes in antibiotic prescriptions. We additionally examined the incidence of postoperative surgical-site infections (SSIs), central-line-associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs) and Clostridioides difficile infections (CDIs). Results: Comparing the pre- and postintervention periods, urinalyses decreased by 76.5% and urine cultures decreased by 87.0%, with an estimated cost savings of $8,090.38. There were 50% fewer antibiotic prescriptions for bacteriuria after the intervention. Conclusions: Removal of urinalysis and urine culture from preoperative checklists for cardiac surgery led to a statistically significant decrease in testing without an increase in SSIs, CLABSIs, CAUTIs, or CDI. Challenges identified included persistence of checklists in templated order sets in the electronic health record.