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OBJECTIVE In the era of modern medicine with an armamentarium full of state-of-the art technologies at our disposal, the incidence of wrong-level spinal surgery remains problematic. In particular, the thoracic spine presents a challenge for accurate localization due partly to body habitus, anatomical variations, and radiographic artifact from the ribs and scapula. The present review aims to assess and describe thoracic spine localization techniques. METHODS The authors performed a literature search using the PubMed database from 1990 to 2020, compliant with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A total of 27 articles were included in this qualitative review. RESULTS A number of pre- and intraoperative strategies have been devised and employed to facilitate correct-level localization. Some of the more well-described approaches include fiducial metallic markers (screw or gold), metallic coils, polymethylmethacrylate, methylene blue, marking wire, use of intraoperative neuronavigation, intraoperative localization techniques (including using a needle, temperature probe, fluoroscopy, MRI, and ultrasonography), and skin marking. CONCLUSIONS While a number of techniques exist to accurately localize lesions in the thoracic spine, each has its advantages and disadvantages. Ultimately, the localization technique deployed by the spine surgeon will be patient-specific but often based on surgeon preference.

Peripheral monocyte-derived CX3C chemokine receptor 1 positive (CX3CR1(+)) cells play important roles in tissue homeostasis and gut repopulation. Increasing evidence also supports their role in immune repopulation of the brain parenchyma in response to systemic inflammation. Adoptive bone marrow transfer from CX3CR1 fluorescence reporter mice and high-resolution confocal microscopy was used to assess the time course of CX3CR1(+) cell repopulation of steady-state and dextran sodium sulfate (DSS)-inflamed small intestine/colon and the brain over 4 weeks after irradiation. CX3CR1(+) cell colonization and morphologic polarization into fully ramified cells occurred more rapidly in the small intestine than in the colon. For both organs, the crypt/mucosa was more densely populated than the serosa/muscularis layer, indicating preferential temporal and spatial occupancy. Repopulation of the brain was delayed compared with that of gut tissue, consistent with the immune privilege of this organ. However, DSS-induced colon injury accelerated the repopulation. Expression analyses confirmed increased chemokine levels and macrophage colonization within the small intestine/colon and the brain by DSS-induced injury. Early increases of transmembrane protein 119 and ionized calcium binding adaptor molecule 1 expression within the brain after colon injury suggest immune-priming effect of brain resident microglia in response to systemic inflammation. These findings identify temporal differences in immune repopulation of the gut and brain in response to inflammation and show that gut inflammation can impact immune responses within the brain.

Oncology nurse navigators (ONNs) rely on assessment tools to identify patient priorities so that care may be expedited along the cancer continuum. Few nonproprietary assessment tools exist for ONNs who work in rural and other resource-poor settings to reliably identify and track patient needs and barriers for seamless and timely oncology care.

Background To evaluate the prevalence of lifetime non-suicidal self-injury (NSSI) among U.S. military veterans, and identify sociodemographic, military, psychiatric, and clinical correlates associated with NSSI. Methods Data were analyzed from the 2019-2020 National Health and Resilience in Veterans Study, a contemporary, nationally representative survey of 4,069 US veterans. Outcomes measured included lifetime history of NSSI, trauma history, lifetime and current DSM-V mental disorders and lifetime and recent suicidal behaviors. Results The overall prevalence of lifetime NSSI was 4.2% (95% confidence interval=3.6%-4.9%). Multivariable analyses revealed that veterans who endorsed lifetime NSSI were more likely to be younger, female, non-Caucasian, unmarried or unpartnered, and to have a lower annual household income. Veterans who endorsed lifetime NSSI reported more adverse childhood experiences and lifetime traumas, and were more likely to have experienced military sexual trauma. They also were more likely to screen positive for lifetime posttraumatic stress disorder, major depressive disorder (MDD) and substance use disorders and to have attempted suicide. Finally, lifetime NSSI was associated with current MDD, generalized anxiety disorder, and substance use disorders, as well as past-year suicidal ideation. Conclusion Results of this study provide the first-known data on the epidemiology of NSSI in U.S. military veterans. They suggest that certain correlates can help identify veterans who may be at greater risk for engaging in NSSI, as well as the potential prognostic utility of lifetime NSSI in predicting current psychiatric problems and suicide risk in this population.

Natural killer (NK) cells are a promising cellular therapy for cancer, with challenges in the field including persistence, functional activity, and tumor recognition. Briefly, priming blood NK cells with recombinant human (rh)IL-12, rhIL-15, and rhIL-18 (12/15/18) results in memory-like NK cell differentiation and enhanced responses against cancer. However, the lack of available, scalable Good Manufacturing Process (GMP)–grade reagents required to advance this approach beyond early-phase clinical trials is limiting. To address this challenge, we developed a novel platform centered upon an inert tissue factor scaffold for production of heteromeric fusion protein complexes (HFPC). The first use of this platform combined IL-12, IL-15, and IL-18 receptor engagement (HCW9201), and the second adds CD16 engagement (HCW9207). This unique HFPC expression platform was scalable with equivalent protein quality characteristics in small- and GMP-scale production. HCW9201 and HCW9207 stimulated activation and proliferation signals in NK cells, but HCW9207 had decreased IL-18 receptor signaling. RNA sequencing and multidimensional mass cytometry revealed parallels between HCW9201 and 12/15/18. HCW9201 stimulation improved NK cell metabolic fitness and resulted in the DNA methylation remodeling characteristic of memory-like differentiation. HCW9201 and 12/15/18 primed similar increases in short-term and memory-like NK cell cytotoxicity and IFNγ production against leukemia targets, as well as equivalent control of leukemia in NSG mice. Thus, HFPCs represent a protein engineering approach that solves many problems associated with multisignal receptor engagement on immune cells, and HCW9201-primed NK cells can be advanced as an ideal approach for clinical GMP-grade memory-like NK cell production for cancer therapy.

Objective We leveraged the Massachusetts perinatal quality collaborative (PQC) to address the COVID-19 pandemic. Our goals were to: (1) implement perinatal practices thought to reduce mother-to-infant SARS-CoV-2 transmission while limiting disruption of health-promoting practices and (2) do so without inequities attributable to race/ethnicity, language status, and social vulnerability. Methods Main outcomes were cesarean and preterm delivery, rooming-in, and breastfeeding. We examined changes over time overall and according to race/ethnicity, language status, and social vulnerability from 03/20-07/20 at 11 hospitals. Results Of 255 mothers with SARS-CoV-2, 67% were black or Hispanic and 47% were non-English speaking. Cesarean decreased (49% to 35%), while rooming-in (55% to 86%) and breastfeeding (53% to 72%) increased. These changes did not differ by race/ethnicity, language, or social vulnerability. Conclusions Leveraging the Massachusetts PQC led to rapid changes in perinatal care during the COVID-19 crisis in a short time, representing a novel use of statewide PQC structures.

Advanced physiological aging is associated with impaired cognitive performance and the inability to induce long-term potentiation (LTP), an electrophysiological correlate of memory. Here, we demonstrate in the physiologically aged, senescent mouse brain that scanning ultrasound combined with microbubbles (SUS+MB), by transiently opening the blood–brain barrier, fully restores LTP induction in the dentate gyrus of the hippocampus. Intriguingly, SUS treatment without microbubbles (SUSonly), i.e., without the uptake of blood-borne factors, proved even more effective, not only restoring LTP, but also ameliorating the spatial learning deficits of the aged mice. This functional improvement is accompanied by an altered milieu of the aged hippocampus, including a lower density of perineuronal nets, increased neurogenesis, and synaptic signaling, which collectively results in improved spatial learning. We therefore conclude that therapeutic ultrasound is a non-invasive, pleiotropic modality that may enhance cognition in elderly humans.

Acute Medicine is a specialty that is not defined by a single organ system and sits at the interface between primary and secondary care. In order to document improvements in the quality of care delivered a system of metrics is required. A number of frameworks for measurements exist to quantify quality of care at the level of patients, teams and organisations, such as measures of population health, patient satisfaction and cost per patient. Measures can capture whether care is safe, effective, patient-centred, timely, efficient and equitable. Measurement in Acute Medicine is challenged by the often-transient nature of the contact between Acute Medicine clinicians and patients, the lack of diagnostic labels, a low degree of standardisation and difficulties in capturing the patient experience in the context. In a time of increasing ecological and financial constraints, reflecting about the most appropriate metrics to document the impact of Acute Medicine is required.

Historically poor clinical results of tumor vaccines have been attributed to weakly immunogenic antigen targets, limited specificity, and vaccine platforms that fail to induce high-quality polyfunctional T cells, central to mediating cellular immunity. We show here that the combination of antigen selection, construct design, and a robust vaccine platform based on the Synthetically Modified Alpha Replicon RNA Technology (SMARRT), a self-replicating RNA, leads to control of tumor growth in mice. Therapeutic immunization with SMARRT replicon-based vaccines expressing tumor-specific neoantigens or tumor-associated antigen were able to generate polyfunctional CD4(+) and CD8(+) T cell responses in mice. Additionally, checkpoint inhibitors, or co-administration of cytokine also expressed from the SMARRT platform, synergized to enhance responses further. Lastly, SMARRT-based immunization of non-human primates was able to elicit high-quality T cell responses, demonstrating translatability and clinical feasibility of synthetic replicon technology for therapeutic oncology vaccines.

The cell cycle, over which cells grow and divide, is a fundamental process of life. Its dysregulation has devastating consequences, including cancer1-3. The cell cycle is driven by precise regulation of proteins in time and space, which creates variability between individual proliferating cells. To our knowledge, no systematic investigations of such cell-to-cell proteomic variability exist. Here we present a comprehensive, spatiotemporal map of human proteomic heterogeneity by integrating proteomics at subcellular resolution with single-cell transcriptomics and precise temporal measurements of individual cells in the cell cycle. We show that around one-fifth of the human proteome displays cell-to-cell variability, identify hundreds of proteins with previously unknown associations with mitosis and the cell cycle, and provide evidence that several of these proteins have oncogenic functions. Our results show that cell cycle progression explains less than half of all cell-to-cell variability, and that most cycling proteins are regulated post-translationally, rather than by transcriptomic cycling. These proteins are disproportionately phosphorylated by kinases that regulate cell fate, whereas non-cycling proteins that vary between cells are more likely to be modified by kinases that regulate metabolism. This spatially resolved proteomic map of the cell cycle is integrated into the Human Protein Atlas and will serve as a resource for accelerating molecular studies of the human cell cycle and cell proliferation.

Partnered gay, bisexual and other men who have sex with men (GBMSM) are less likely to engage in HIV and STI testing. We enrolled 51 male couples from a larger study of home HIV testing to test the feasibility of a dyadic home STI testing intervention delivered via telehealth, consisting of two telehealth sessions delivered via video-chat. In the first session, an interventionist demonstrated the specimen collection kits. In the second session, an interventionist delivered the STI results. Participants reported very high levels of acceptability of the intervention: 92% reported the telehealth calls quality as very good, 99% reported the sample collection instructions were clear, and 96% of respondents returned specimens for collection. 9% of participants tested positive for chlamydia or gonorrhea, and all were linked to care. The intervention has the potential to surmount economic, physical and stigma-related barriers to attending clinics for STI testing, but these results need to be further tested in more diverse samples of male couples.

Background Chronic lung disease remains a burden for extremely preterm infants. The changes in ventilation over time and optimal ventilatory management remains unknown. Newer, non-invasive technologies provide insight into these patterns. Methods This single-center prospective cohort study enrolled infants ≤32 0/7 weeks. We obtained epochs of transcutaneous carbon dioxide (TcCO2) measurements twice each week to describe the pattern of hypercarbia throughout their hospitalization. Results Patterns of hypercarbia varied based on birth gestational age and post-menstrual age (PMA) (p = 0.03), regardless of respiratory support. Infants receiving the most respiratory support had values 16–21 mmHg higher than those on room air (p

Sleep dysfunction and headaches are common and disabling conditions which are frequently comorbid with psychiatric disorders. Furthermore, there is a growing body of literature linking sleep dysfun...

The blood-brain barrier (BBB) is a dynamic diffusional barrier regulating the molecular and chemical flux between the blood and brain, thereby preserving cerebral homeostasis. Endothelial cells form the core anatomical component of the BBB based on properties such as specialized junctional complexes between cells, which restricts paracellular transport, and extremely low levels of vesicular transport, restricting transcytosis. In performing its protective function, the BBB also constrains the entry of therapeutics into the brain, hampering the treatment of various neurological disorders. Focused ultrasound is a novel therapeutic modality that has shown efficacy in transiently and non-invasively opening the BBB for the targeted delivery of therapeutics to the brain. Although the ability of ultrasound to disrupt the junctional assembly of endothelial cells has been partially investigated, its effect on the transcellular mode of transport has been largely neglected. In this study, we found that ultrasound induces a pronounced increase in the levels of the vesicle-forming protein caveolin-1. In order to investigate the role of vesicle-mediated transcytoplasmic transport, we compared the leakage of various cargo sizes between a mouse model that lacks caveolin-1 and wild-type mice following sonication of the hippocampus. The absence of caveolin-1 did not lead to overt abnormalities in the cerebral vasculature in the mice. We found that caveolin-1 has a critical role specifically in the transport of large (500 kDa), but not smaller (3 and 70 kDa) cargoes. Our findings indicate differential effects of therapeutic ultrasound on cellular transport mechanisms, with implications for therapeutic interventions.

Hispanic women in the United States are disproportionately affected by intimate partner violence (IPV). One correlate of IPV among Hispanic women with important public health implications is substance misuse. However, limited research has identified culturally relevant factors that may impact the strength of the IPV-substance misuse association in this population. The present study examined the moderating role of acculturation in the relation between IPV types (i.e., physical, psychological, and sexual) and substance (i.e., alcohol and drug) misuse. Participants were 150 IPV-exposed Hispanic women in the community ( M age = 35.13). IPV types, substance misuse outcomes, and acculturation were significantly and positively correlated with each other at zero-order. Moderation analyses indicated that the relations between IPV and substance misuse were stronger among Hispanic women with higher (vs. lower) levels of acculturation. These findings suggest the potential utility of considering acculturation when assessing and treating substance misuse among IPV-exposed Hispanic women.

OBJECTIVE We evaluated the efficacy of a combined short-wavelength-enriched white light and exercise fatigue countermeasure during breaks for flight controllers working overnight shifts. METHODS Twenty NASA flight controllers were studied for two blocks of nightshifts in ISS mission control, randomized to either the control or countermeasure condition. The countermeasure constituted passive exposure to blue-enriched polychromatic lighting for three 20-minute intervals, which included 10 minutes of exercise and occurred before and twice during their shifts. Alertness, performance, and mood were evaluated. RESULTS Flight controllers reported being significantly more alert (P

Obesity is associated with numerous changes in skeletal muscle including greater muscle mass and muscle fiber cross sectional area (FCSA), yet fasted muscle protein synthesis is lower. Activation of the IGF-1/Akt/mTOR pathway is critical for muscle mass maintenance, muscle hypertrophy, and muscle protein regulation. Resistance exercise (RE) increases muscle mass, FCSA, and IGF-1. Persons with obesity have greater skeletal muscle mass and larger skeletal muscle fiber cross sectional area. The IGF-1/Akt/mTOR pathway is critical for the regulation of skeletal muscle mass. Our study found men and women with obesity have lower skeletal muscle IGF-1 mRNA and protein and higher expression of miR-206 an epigenetic regulator of IGF-1, at rest and following an acute bout of resistance exercise. Despite this, Akt mediated signaling was maintained and maintenance of phosphorylation does not appear to be accounted for by compensatory pathways. Our findings suggest a possible negative feedback mechanism via increased miR-206 and in turn decreased IGF-1 to limit further skeletal muscle hypertrophy in persons with obesity. The current work investigated if: (1) obesity dysregulates basal skeletal muscle IGF-1 pathways; and (2) obesity augments the muscle IGF-1 pathway responses to acute RE. Eight sedentary (no self-reported physical activity), lean (LN) and eight sedentary subjects with obesity (OB) had vastus lateralis biopsies taken at rest, and 15 min and 3 h post-acute RE for the measurement of the IGF-1 pathway and muscle FCSA. Type II FCSA was larger in OB vs. LN. Skeletal muscle IGF-1 mRNA and IGF-1 protein were lower in OB vs. LN at rest and post-exercise. Acute RE increased IGF-1 protein similarly in both groups. The expression of miR-206, a post-transcriptional inhibitor of IGF-1 expression, was higher in OB vs. LN and linked with lower IGF-1 mRNA (r = – 0.54). In spite of greater muscle FCSA, muscle IGF-1 expression was lower in obesity suggesting negative feedback may be limiting muscle mass expansion in obesity.

Practice patterns for the management of patent ductus arteriosus (PDA) in premature infants are changing with advances in medical management. We sought to determine the increased mortality for premature infants who had a PDA ligation with a co-existing diagnosis of intraventricular hemorrhage (IVH).Premature neonates (1 y old with known gestational week ≤36 wk) with a diagnosis of IVH were identified within the Kids' Inpatient Database (KID) for the years 2006, 2009, and 2012. Diagnoses and procedures were analyzed by ICD-9 codes and stratified by a diagnosis of PDA and procedure of ligation. Case weighting was used to make national estimations. Multivariable logistic regression was performed to adjust for confounders.We identified 7567 hospitalizations for premature neonates undergoing PDA ligation. The population was predominately male (51.6%), non-Hispanic white (41.1%), were from the lowest income quartile (33.1%), had a gestational week of 25-26 wk (34.0%), and a birthweight between 500 and 749 g (37.3%). There was an increased mortality (10.7% versus 6.3%, P 0.01) and an increased length of stay (88.2 d versus 74.4 d, P 0.01) in those with any diagnosis of IVH compared with those without. Adjusted multivariable logistic regression demonstrated that high-grade IVH (III or IV) was associated with a significantly increased risk of mortality in those undergoing PDA ligation (aOR 2.59, P 0.01). Specifically, grade III and IV were associated with an increased odds of in-hospital mortality (aOR 1.99 and 3.16, respectively, P 0.01).Attitudes regarding the need for surgical intervention for PDA have shifted in recent years. This study highlights that premature neonates with grade III or IV IVH are at significantly increased risk of mortality if undergoing PDA ligation during the same hospitalization.III.

Background: The cause of subsequent surgery after anterior cruciate ligament (ACL) reconstruction varies, but if risk factors for specific subsequent surgical procedures can be identified, we can better understand which patients are at greatest risk. Purpose: To report the incidence and types of subsequent surgery that occurred in a cohort of patients 6 years after their index ACL reconstruction and to identify which variables were associated with the incidence of patients undergoing subsequent surgery after their index ACL reconstruction. Study Design: Cohort study; Level of evidence, 2. Methods: Patients completed a questionnaire before their index ACL surgery and were followed up at 2 and 6 years. Patients were contacted to determine whether any underwent additional surgery since baseline. Operative reports were obtained, and all surgical procedures were categorized and recorded. Logistic regression models were constructed to predict which patient demographic and surgical variables were associated with the incidence of undergoing subsequent surgery after their index ACL reconstruction. Results: The cohort consisted of 3276 patients (56.3% male) with a median age of 23 years. A 6-year follow-up was obtained on 91.5% (2999/3276) with regard to information on the incidence and frequency of subsequent surgery. Overall, 20.4% (612/2999) of the cohort was documented to have undergone at least 1 subsequent surgery on the ipsilateral knee 6 years after their index ACL reconstruction. The most common subsequent surgical procedures were related to the meniscus (11.9%), revision ACL reconstruction (7.5%), loss of motion (7.8%), and articular cartilage (6.7%). Significant risk factors for incurring subsequent meniscus-related surgery were having a medial meniscal repair at the time of index surgery, reconstruction with a hamstring autograft or allograft, higher baseline Marx activity level, younger age, and cessation of smoking. Significant predictors of undergoing subsequent surgery involving articular cartilage were higher body mass index, higher Marx activity level, reconstruction with a hamstring autograft or allograft, meniscal repair at the time of index surgery, or a grade 3/4 articular cartilage abnormality classified at the time of index ACL reconstruction. Risk factors for incurring subsequent surgery for loss of motion were younger age, female sex, low baseline Knee injury and Osteoarthritis Outcome Score symptom subscore, and reconstruction with a soft tissue allograft. Conclusion: These findings can be used to identify patients who are at the greatest risk of incurring subsequent surgery after ACL reconstruction.

The relationship between alcohol misuse and women’s use of IPV aggression has been well-studied; however, there has been no research to date on women’s self-reported motivations for use of IPV aggression (e.g., self-defense, control) as an underlying mechanism explaining this link. Accordingly, this study aims to examine whether the effects of alcohol misuse on IPV aggression vary as a function of women’s motivations for using aggression. Participants were 412 ethnically diverse community women, between the ages of 18 and 65, in intimate relationships characterized by bidirectional IPV. The Motives and Reasons for IPV Scale (Swan & Sullivan, 2002; Caldwell et al., 2009) was used to assess women’s reasons for using IPV aggression. Results revealed that the tough guise motive (i.e., wanting to appear tough, intimidating, and willing to harm one’s partner) explained the relationship between alcohol misuse and physical and sexual IPV aggression. Findings suggest the utility of incorporating the assessment of women’s motivations for IPV aggression in an effort to provide better informed intervention addressing the underlying reasons women use IPV aggression.

Background In 2011, the Accreditation Council for Graduate Medical Education (ACGME) instituted a 16-h limit on consecutive hours for first-year resident physicians. We sought to examine the effect of these work-hour regulations on physician safety. Methods All medical students matched to a US residency program from 2002 to 2007 and 2014 to 2017 were invited to participate in prospective cohort studies. Each month participants reported hours of work, extended duration shifts, and adverse safety outcomes, including motor vehicle crashes, percutaneous injuries, and attentional failures. The incidence of each outcome was compared before and after the 2011 ACGME work-hour limit. Hypotheses were tested using generalized linear models adjusted for potential confounders. Results Of all first-year resident physicians nationwide, 13% participated in the study, with 80,266 monthly reports completed by 15,276 first-year resident physicians. Following implementation of the 16-h 2011 ACGME work-hour limit, the mean number of extended duration (≥24-h) shifts per month decreased from 3.9 to 0.2. The risk of motor vehicle crash decreased 24% (relative risk [RR] 0.76; 0.67-0.85), percutaneous injury risk decreased more than 40% (relative risk 0.54; 0.48-0.61), and the rate of attentional failures was reduced 18% (incidence rate ratio [IRR] 0.82; 0.78-0.86). Extended duration shifts and prolonged weekly work hours were associated with an increased risk of adverse safety outcomes independent of cohort. Conclusions The 2011 ACGME work-hour limit was associated with meaningful improvements in physician safety and health. Surveillance is needed to monitor the ongoing impact of work hours on physician safety, health, and well-being.

Aims: Rodent cystometry has provided valuable insights into the impact of the disease, injury, and aging on the cellular and molecular pathways, neurologic processes, and biomechanics of lower urinary tract function. The purpose of this white paper is to highlight the benefits and shortcomings of different experimental methods and strategies and to provide guidance on the proper interpretation of results. Methods: Literature search, selection of articles, and conclusions based on discussions among a panel of workers in the field. Results: A range of cystometric tests and techniques used to explore biological phenomena relevant to the lower urinary tract are described, the advantages and disadvantages of various experimental conditions are discussed, and guidance on the practical aspects of experimental execution and proper interpretation of results are provided. Conclusions: Cystometric evaluation of rodents comprises an extensive collection of functional tests that can be performed under a variety of experimental conditions. Decisions regarding which approaches to choose should be determined by the specific questions to be addressed and implementation of the test should follow standardized procedures. (Less)

Light-absorbing aerosols emitted during open biomass burning (BB) events such as wildfires and agricultural burns have a strong impact on the Earth's radiation budget through both direct and indirect effects. Additionally, BB aerosols and gas-phase emissions can substantially reduce air quality at local, regional, and global scales, negatively affecting human health. South America is one of largest contributors to BB emissions globally. After Amazonia, the BB emissions from wildfires and agricultural burns in the grassland plains of northern South America (NSA) are the most significant in the region. However, few studies have analyzed the potential impact of NSA BB emissions on regional air quality. Recent evidence suggests that seasonal variations in air quality in several major cities in NSA could be associated with open biomass burning emissions, but it is still uncertain to what extent those sources impact air quality in the region. In this work, we report on 3 years of continuous equivalent black carbon (eBC) and brown carbon (BrC) observations at a hilltop site located upwind of the city of Bogotá, and we demonstrate its association with fires detected by the MODerate-resolution Imaging Spectroradiometer (MODIS) in a 3000 km × 2000 km domain. Offline PM2.5 filter samples collected during three field campaigns were analyzed to quantify water-soluble organic carbon (WSOC), organic and elemental carbon (OC∕EC), and biomass burning tracers such as levoglucosan, galactosan, and potassium. MODIS active fire data and HYSPLIT back trajectories were used to identify potential biomass burning plumes transported to the city. We analyzed the relationship between BrC, WSOC, water-soluble potassium, and levoglucosan to identify signals of the regional transport of BB aerosols. Our results confirm that regional biomass burning transport from wildfires occurs annually during the months of January and April. The seasonality of eBC closely followed that of PM2.5 at the city air quality stations; however, the observed seasonality of BrC is distinctly different to that of eBC and strongly associated with regional fire counts. The strong correlation between BrC and regional fire counts was observed at daily, weekly, and monthly timescales. WSOC at the measurement site was observed to increase linearly with levoglucosan during high BB periods and to remain constant at ∼2.5 µgC m−3 during the low BB seasons. Our findings show, for the first time in this region, that aged BB plumes can regularly reach densely populated areas in the Central Andes of northern South America. A source footprint analysis involving BrC observations, back trajectories, and remotely sensed fire activity shows that the eastern savannas in NSA are the main BB source region for the domain analyzed.

FMX101 4% topical minocycline foam has been shown to be an effective and safe treatment for acne vulgaris (AV).To further evaluate the efficacy and safety of FMX101 4% in treating moderate to severe acne vulgaris.A 12-week, multicenter, randomized (1:1), double-blind, vehicle-controlled study was conducted. Coprimary end points were the absolute change in inflammatory lesion count from baseline and the rate of treatment success (Investigator's Global Assessment score of 0 or 1 with a ≥2-grade improvement).There were 1488 participants in the intent-to-treat population. The FMX101 4% group had significantly greater reductions in the number of inflammatory lesions from baseline (P .0001) and a greater rate of treatment success based on Investigator's Global Assessment (P .0001) versus the foam vehicle group at week 12. FMX101 4% was generally safe and well tolerated.The efficacy and safety of FMX101 4% were not characterized in participants with mild AV.FMX101 4% topical minocycline foam was effective and safe for the treatment of moderate to severe AV.

Objectives To describe feasibility, adherence, acceptability, and outcomes of a cognitive-behavioral-based physical therapy (CBPT-ACLR) intervention for improving postoperative recovery after anterior cruciate ligament reconstruction (ACLR). Design Pilot study. Setting Academic medical center. Participants Eight patients (mean age [SD] = 20.1 [2.6] years, 6 females) participated in a 7-session telephone-based CBPT-ACLR intervention beginning preoperatively and lasting 8 weeks after surgery. Main outcome measures At 6 months, patients completed Knee Injury and Osteoarthritis Outcome Score (KOOS) sports/recreation and quality of life (QOL) subscales, International Knee Documentation Committee (IKDC), Tampa Scale of Kinesiophobia (TSK), Pain Catastrophizing Scale (PCS), and Knee Self-Efficacy Scale (K-SES), return to sport (Subjective Patient Outcome for Return to Sports), and satisfaction. Minimal clinically important difference (MCID) was used for meaningful change. Results Seven (88%) patients completed all sessions. Seven (88%) patients exceeded MCID on the TSK, 6 (75%) on the PCS, 5 (63%) on the KOOS sports/recreation subscale, 4 (50%) on the IKDC, and 3 (38%) on the KOOS QOL subscale. Three (38%) patients returned to their same sport at the same level of effort and performance. All patients were satisfied with their recovery. Conclusions A CBPT-ACLR program is feasible and acceptable for addressing psychological risk factors after ACLR.

OBJECTIVE: Evidence demonstrates sexual orientation disparities in physical and sexual victimization and alcohol misuse and consequences among female youth; however, most extant research has used variable-centered approaches. The current study used latent class analysis (LCA), a person-centered approach, to: (1) model female youths’ physical and sexual victimization; (2) examine sexual orientation disparities in physical and sexual victimization latent class membership; (3) and use physical and sexual victimization latent class membership to predict female youths’ engagement in alcohol misuse and related consequences. METHOD: Participants were 7,185 youth assigned female sex at birth (77.0% heterosexual, 12.8% bisexual, 2.3% gay or lesbian; 46.8% racial minority) in grades 9 – 12 who completed the 2017 Youth Risk Behavior Survey – a school-based, cross-sectional survey. RESULTS: LCA uncovered four classes: (1) “Poly-Victimization Class,” (2) “No Victimization Class,” (3) “Past-Year Sexual Victimization Class,” and (4) “Lifetime Rape Class.” Sexual orientation emerged as a significant predictor of class membership. Latent classes 3 and 4 were uniquely associated with alcohol misuse and consequences (i.e., binge drinking, riding with a drinking driver, and drinking and driving) among female youth. CONCLUSIONS: Our findings help to elucidate the patterns of physical and sexual victimization regarding timeline, tactic used, and context among female youth; sexual orientation disparities in latent class membership; and alcohol misuse correlates of class membership. Prevention efforts aimed at reducing physical and sexual victimization may ultimately reduce female youths’ risk of binge drinking, riding with drinking drivers, and drinking and driving.

A human hepatoma cell line synthesizes, as evidenced by metabolic labeling, an endothelial cell mitogen that is found to be mostly cell associated. The hepatoma-derived growth factor (HDGF) has been purified to homogeneity by a combination of Bio-Rex 70, heparin-Sepharose, and reverse-phase chromatography; it is a cationic polypeptide with a molecular weight of about 18,500-19,000. HDGF is structurally related to basic fibroblast growth factor (FGF). Immunological analysis demonstrates that antiserum prepared against a synthetic peptide corresponding to the amino-terminal sequence of basic FGF cross-reacts with HDGF when analyzed by electrophoretic blotting and by immunoprecipitation. Sequence analysis of tryptic fragments demonstrates that HDGF contains sequences that are homologous to both amino-terminal and carboxyl-terminal sequences of basic FGF.

Hispanic women in the United States experience disproportionate mental health impacts of intimate partner violence (IPV). Following the preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews guidelines, we synthesized the existing knowledge based on IPV and mental health outcomes among Hispanic women in the United States. In May 2020, we searched five electronic databases (i.e., MEDLINE, PILOTS, PSYCInfo, PSYCArticles, and EMBASE). From the initial 1,180 results, 13 articles met inclusion criteria for this review (written in English, empirical study, focus on the experiences of victimization from an intimate partner, focus on mental health outcomes occurring in the person experiencing IPV, included women who identify as Hispanic, and included participants residing in the United States), representing 4,060 women. Findings highlighted significant positive associations between IPV ( n = 13; 4,060 women) and general mental health outcomes ( n = 4; 759 women) as well as the specific outcomes of depression ( n = 12; 2,661 women), anxiety ( n = 1; 274 women), post-traumatic stress disorder ( n = 3; 515 women), and substance misuse ( n = 2; 1,673 women) among Hispanic women in the United States. Limitations included heterogeneity across Hispanic populations and methodological differences between studies. Key avenues for future research were identified, including the need to examine mental health outcomes understudied in relation to IPV among Hispanic women (e.g., personality, obsessive-compulsive, and eating disorders) and to identify cultural and demographic factors (e.g., nativity status, level of acculturation) that may influence relations between IPV and mental health outcomes among Hispanic women. Such research can inform prevention and intervention efforts aimed at improving mental health among Hispanic women in the Untied States experiencing IPV.

Sleep deficiency and undiagnosed or untreated sleep disorders are pervasive among employed adults, yet often ignored in the context of workplace health promotion programs among employers. Smartphone applications (app) are a promising, scalable approach to improving sleep among employees. In this randomized clinical trial, we evaluate the dayzz app, a personalized sleep training program that promotes healthy sleep and sleep disorders awareness through personalized, comprehensive sleep improvement solutions. In a sample of daytime employees affiliated with a large healthcare organization, we evaluated the dayzz app in a parallel-group, randomized, waitlist control trial. Participants were randomly assigned to either use the dayzz app throughout the study or the waitlist control condition where they would receive the dayzz app at the end of the study period. We collected data on employee sleep (e.g., sleep duration, sleep health behavioral changes); workplace outcomes (e.g., employee presenteeism, absenteeism, and performance); and healthcare utilization (e.g., mental health, ambulatory visits, and emergency room visits), throughout the study. Results show that those assigned to the experimental condition exhibited an increase in healthy sleep behaviors; an increase in sleep duration; a trend toward a more regular sleep schedule; and a significant increase in overall sleep quality. Regarding workplace outcomes, results showed that those in the experimental condition also demonstrated a trend toward less absenteeism and significantly lower presenteeism; and those in the experimental condition reported lower healthcare utilization. Results from this randomized clinical trial demonstrate that a workplace sleep wellness program can be beneficial to both the employee and employer.

Sleep deficiency is a hidden cost of our 24-7 society, with 70% of adults in the US admitting that they routinely obtain insufficient sleep. Further, it is estimated that 50-70 million adults in the US have a sleep disorder. Undiagnosed and untreated sleep disorders are associated with diminished health for the individual and increased costs for the employer. Research has shown that adverse impacts on employees and employers can be mitigated through sleep health education and sleep disorder screening and treatment programs. Smartphone applications (app) are increasingly commonplace and represent promising, scalable modalities for such programs. The dayzz app is a personalized sleep training program that incorporates assessment of sleep disorders and offers a personalized comprehensive sleep improvement solution. Using a sample of day workers affiliated with a large institution of higher education, we will conduct a single-site, parallel-group, randomized, waitlist control trial. Participants will be randomly assigned to either use the dayzz app throughout the study or receive the dayzz app at the end of the study. We will collect data on feasibility and acceptability of the dayzz app; employee sleep, including sleep behavioral changes, sleep duration, regularity, and quality; employee presenteeism, absenteeism, and performance; employee mood; adverse and safety outcomes; and healthcare utilization on a monthly basis throughout the study, as well as collect more granular daily data from the employee during pre-specified intervals. Our results will illuminate whether a personalized smartphone app is a viable approach for improving employee sleep, health, and productivity.

Botulinum neurotoxins (BoNTs) are the most potent toxins known and are also utilized to treat a wide range of disorders including muscle spasm, overactive bladder, and pain. BoNTs’ ability to target neurons determines their specificity, potency, and therapeutic efficacy. Homologous synaptic vesicle membrane proteins synaptotagmin-1 (Syt1) and synaptotagmin-2 (Syt2) have been identified as receptors for BoNT family members including BoNT/B, DC, and G, but their contributions at physiologically relevant toxin concentrations in vivo have yet to be validated and established. Here we generated two knockin mutant mouse models containing three designed point-mutations that specifically disrupt BoNT binding in endogenous Syt1 or Syt2, respectively. Utilizing digit abduction score assay by injecting toxins into the leg muscle, we found that Syt1 mutant mice showed similar sensitivity as the wild type mice, whereas Syt2 mutant mice showed reduced sensitivity to BoNT/B, DC, and G, demonstrating that Syt2 is the dominant receptor at skeletal neuromuscular junctions. We further developed an in vivo bladder injection assay for analyzing BoNT action on bladder tissues and demonstrated that Syt1 is the dominant toxin receptor in autonomic nerves controlling bladder tissues. These findings establish the critical role of protein receptors for the potency and specificity of BoNTs in vivo and demonstrate the differential contributions of Syt1 and Syt2 in two sets of clinically relevant target tissues., Author summary Establishing receptors that mediate binding and entry of toxins into host cells is fundamental to understanding the specificity of toxins. The in vivo contribution of candidate receptors can be difficult to elucidate if they are critical for survival. Such a limitation exists for botulinum neurotoxins (BoNTs), a family of bacterial toxins. They are potential bioterrorism agents and are also used to treat growing numbers of medical conditions. Previous studies identified synaptotagmin-1 (Syt1) and homologous synaptotagmin-2 (Syt2) as receptors for BoNT members including type B, G, and DC. However, as Syt1 and Syt2 are essential for survival of animals, there is no viable loss-of-function animal model to establish their role in vivo. Here we created and evaluated two mutant mouse lines containing designed point-mutations in endogenous Syt1 or Syt2, respectively, that specifically disrupt toxin binding. Using these tailor-made mouse models, we demonstrated that Syt2 is the dominant receptor for BoNT/B, DC, and G at skeletal muscle neuromuscular junctions, whereas Syt1 is the dominant receptor in autonomic nerves in bladder tissues. These findings validate the role of Syt1 and Syt2 as toxin receptors in animal models and reveal their differential contributions in two clinically relevant tissues.

INTRODUCTION AND OBJECTIVE:Neurogenic and idiopathic detrusor overactivity (DO) is currently treated with onabotulinumtoxin A (BoNT/A) as third line therapy. In cases of treatment failure, alternat...

Introduction: Neuropilin-1 (NRP1) is a transmembrane receptor present in vascular smooth muscle cells (VSMC) that mediates the inhibition of Rho signaling by binding the Class 3 Semaphorin (SEMA) ligand SEMA3A. Hypothesis: We hypothesize that loss of NRP1 in VSMC mitigates SEMA3A-induced Rho inhibition, thereby increasing vascular tone and blood pressure in vivo . Methods: Male and female adult mice (8-12 weeks) with inducible, smooth muscle cell-specific deletion of NRP1 (SM22a-Cre ERT2 X Nrp1 flox/flox ) were examined. Following recombination using 4-hydroxy tamoxifen (SM- NRP1 KO), systolic blood pressure (SBP) was measured using a tail cuff and compared to age- and sex-matched mice that did not receive tamoxifen (control). Aortic vascular reactivity and expression of key proteins in the Rho signaling cascade were measured using ex vivo tension myography and western blotting, respectively. Results: SBP was significantly increased in SM- NRP1 KO mice following recombination compared to control mice (SBP: 136.5 ± 10.9 vs 112.9 ± 5.6 mmHg; p=0.0006). Contractile responses in aortas of SM- NRP1 KO mice to phenylephrine (p=0.025), KCl (p=0.012), and the thromboxane agonist U44619 (p=0.019) were significantly enhanced compared to controls. Expression of total myosin light chain and LIMK-2 proteins were increased in SM- NRP1 KO compared to control aortas. In vitro , treatment of murine primary VSMC expressing NRP1 with SEMA3A decreased angiotensin II-induced Rho-GTP activation. Additionally, control and SM- NRP1 KO mice (starting at 2 weeks post-recombination) were administered angiotensin II (490 ng/kg/day) for 4 weeks. While there was no significant difference in SBP at weeks 1 and 2, SM- NRP1 KO mice had significantly lower SBP at weeks 3 and 4 following angiotensin II infusion compared to controls (Week 4 SBP: 150 ± 1.4 vs 130.5 ± 2.5 mmHg; p=0.02), suggesting a low ejection fraction and cardiac dysfunction in these mice. In support of this observation, mRNA expression of atrial natriuretic peptide was increased in hearts of angiotensin II-infused SM- NRP1 KO mice. Conclusion: Our data suggest that VSMC NRP1 regulates basal tone and blood pressure, and that loss of NRP1 causes hypertension and exacerbates cardiac dysfunction.

The microbial populations in the gut microbiome have recently been associated with COVID-19 disease severity. However, a causal impact of the gut microbiome on COVID-19 patient health has not been established. Here we provide evidence that gut microbiome dysbiosis is associated with translocation of bacteria into the blood during COVID-19, causing life-threatening secondary infections. Antibiotics and other treatments during COVID-19 can potentially confound microbiome associations. We therefore first demonstrate that the gut microbiome is directly affected by SARS-CoV-2 infection in a dose-dependent manner in a mouse model, causally linking viral infection and gut microbiome dysbiosis. Comparison with stool samples collected from 97 COVID-19 patients at two different clinical sites also revealed substantial gut microbiome dysbiosis, paralleling our observations in the animal model. Specifically, we observed blooms of opportunistic pathogenic bacterial genera known to include antimicrobial-resistant species in hospitalized COVID-19 patients. Analysis of blood culture results testing for secondary microbial bloodstream infections with paired microbiome data obtained from these patients suggest that bacteria translocate from the gut into the systemic circulation of COVID-19 patients. These results are consistent with a direct role for gut microbiome dysbiosis in enabling dangerous secondary infections during COVID 19.

Hypoxia-inducible factors (HIFs) are activated in parenchymal cells in response to low oxygen and as such have been proposed as therapeutic targets during hypoxic insult, including myocardial infarction (MI). HIFs are also activated within macrophages, which orchestrate the tissue repair response. Although isoform-specific therapeutics are in development for cardiac ischemic injury, surprisingly, the unique role of myeloid HIFs, and particularly HIF-2α, is unknown. Using a murine model of myocardial infarction and mice with conditional genetic loss and gain of function, we uncovered unique proinflammatory roles for myeloid cell expression of HIF-1α and HIF-2α during MI. We found that HIF-2α suppressed anti-inflammatory macrophage mitochondrial metabolism, while HIF-1α promoted cleavage of cardioprotective MerTK through glycolytic reprogramming of macrophages. Unexpectedly, combinatorial loss of both myeloid HIF-1α and HIF-2α was catastrophic and led to macrophage necroptosis, impaired fibrogenesis, and cardiac rupture. These findings support a strategy for selective inhibition of macrophage HIF isoforms and promotion of anti-inflammatory mitochondrial metabolism during ischemic tissue repair.

Pre-exposure prophylaxis (PrEP) affords an opportunity to significantly reduce the risk of HIV infection among male couples. We used cross-sectional dyadic data from 382 concordant-negative male couples to examine demographic and relationship characteristics associated with current PrEP use, willingness to use PrEP in the future, and perceived ability to adhere to PrEP using Actor–Partner Independence Models. Few partnered men reported currently using PrEP (16.4%) and 57.7% of non-users reported being unlikely to use PrEP in the future. Actor and partner perceptions of PrEP stigma significantly reduced PrEP use and perceptions of willingness to use PrEP or the ability to adhere to PrEP, while perceiving a higher prevalence of HIV among men was associated with significant increases in PrEP use, willingness and perceived ability to adhere. Perceptions that more friends would support PrEP use were also significantly associated with increases in willingness and perceived ability to adhere to PrEP. Dyadic interventions are needed to provide couples the skills to communicate about HIV risk and prevention, and address myths around the protective effect of relationships against HIV acquisition.

The microbial populations in the gut microbiome have recently been associated with COVID-19 disease severity. However, a causal impact of the gut microbiome on COVID-19 patient health has not been established. Here we provide evidence that gut microbiome dysbiosis is associated with translocation of bacteria into the blood during COVID-19, causing life-threatening secondary infections. Antibiotics and other treatments during COVID-19 can potentially confound microbiome associations. We therefore first demonstrate in a mouse model that SARS-CoV-2 infection can induce gut microbiome dysbiosis, which correlated with alterations to Paneth cells and goblet cells, and markers of barrier permeability. Comparison with stool samples collected from 96 COVID-19 patients at two different clinical sites also revealed substantial gut microbiome dysbiosis, paralleling our observations in the animal model. Specifically, we observed blooms of opportunistic pathogenic bacterial genera known to include antimicrobial-resistant species in hospitalized COVID-19 patients. Analysis of blood culture results testing for secondary microbial bloodstream infections with paired microbiome data obtained from these patients indicates that bacteria may translocate from the gut into the systemic circulation of COVID-19 patients. These results are consistent with a direct role for gut microbiome dysbiosis in enabling dangerous secondary infections during COVID-19.

This paper presents data from an online sample of U.S gay, bisexual, and other men who have sex with men (GBMSM), to explore the factors associated with three dimensions of vaccine beliefs: perception of the likelihood of a COVID-19 vaccine becoming available, perception of when a COVID-19 vaccine would become available, and the likelihood of taking a COVID-19 vaccine. Data are taken from the Love and Sex in the Time of COVID-19 study, collected from November 2020 to January 2021. A sample of 290 GBMSM is analyzed, modeling three binary outcomes: belief that there will be a COVID-19 vaccine, belief that the COVID-19 vaccine will be available in 6 months, and being very likely to take the COVID-19 vaccine. In contrast to other studies, Black/African Americans and GBMSM living with HIV had higher levels of pandemic optimism and were more likely to be willing to accept a vaccine. Men who perceived a higher prevalence of COVID-19 among their friends and sex partners, and those who had reduced their sex partners, were more likely to be willing to take a COVID-19 vaccine. There remained a small percentage of participants (14%) who did not think the pandemic would end, that there would not be a vaccine and were unlikely to take a vaccine. To reach the levels of vaccination necessary to control the pandemic, it is imperative to understand the characteristics of those experiencing vaccine hesitancy and then tailor public health messages to their unique set of barriers and motivations.

The function of endothelial cell IQGAP1 during diapedesis requires its actin-binding domain and IQ motifs to recruit the lateral border recycling compartment. Genetic ablation of endothelial cell IQGAP1 expression in vivo causes significant disruption of diapedesis in two models of inflammation., Transendothelial migration (TEM) of leukocytes across the endothelium is critical for inflammation. In the endothelium, TEM requires the coordination of membrane movements and cytoskeletal interactions, including, prominently, recruitment of the lateral border recycling compartment (LBRC). The scaffold protein IQGAP1 was recently identified in a screen for LBRC-interacting proteins. Knockdown of endothelial IQGAP1 disrupted the directed movement of the LBRC and substantially reduced leukocyte TEM. Expression of truncated IQGAP1 constructs demonstrated that the calponin homology domain is required for IQGAP1 localization to endothelial borders and that the IQ domain, on the same IQGAP1 polypeptide, is required for its function in TEM. This is the first reported function of IQGAP1 requiring two domains to be present on the same polypeptide. Additionally, we show for the first time that IQGAP1 in the endothelium is required for efficient TEM in vivo. These findings reveal a novel function for IQGAP1 and demonstrate that IQGAP1 in endothelial cells facilitates TEM by directing the LBRC to the site of TEM.

There are strong individual differences in performance during sleep deprivation. We assessed whether baseline features of Psychomotor Vigilance Test (PVT) performance can be used for classifying participants’ relative attentional vulnerability to total sleep deprivation. In a laboratory, healthy adults (n = 160, aged 18–30 years) completed a 10-min PVT every 2 h while being kept awake for ≥24 hours. Participants were categorized as vulnerable (n = 40), intermediate (n = 80), or resilient (n = 40) based on their number of PVT lapses during one night of sleep deprivation. For each baseline PVT (taken 4–14 h after wake-up time), a linear discriminant model with wrapper-based feature selection was used to classify participants’ vulnerability to subsequent sleep deprivation. Across models, classification accuracy was about 70% (range 65–76%) using stratified 5-fold cross validation. The models provided about 78% sensitivity and 86% specificity for classifying resilient participants, and about 70% sensitivity and 89% specificity for classifying vulnerable participants. These results suggest features derived from a single 10-min PVT at baseline can provide substantial, but incomplete information about a person’s relative attentional vulnerability to total sleep deprivation. In the long term, modeling approaches that incorporate baseline performance characteristics can potentially improve personalized predictions of attentional performance when sleep deprivation cannot be avoided.

Exposure to air pollution from solid-fuel cookstoves is a leading risk factor for premature death; however, the effect of fuel moisture content on air pollutant emissions from solid-fuel cookstoves remains poorly constrained. The objective of this work was to characterize emissions from a rocket-elbow cookstove burning wood at three different moisture levels (5%, 15%, and 25% on a dry mass basis). Emissions of carbon dioxide (CO2), carbon monoxide (CO), methane, fine particulate matter (PM2.5), PM2.5 elemental carbon (EC), PM2.5 organic carbon, formaldehyde, acetaldehyde, benzene, toluene, ethylbenzene, and xylenes were measured. Emission factors (EFs; g·MJdelivered–1) for all pollutants, except CO2 and EC, increased with increasing fuel moisture content: CO EFs increased by 84%, PM2.5 EFs increased by 149%, formaldehyde EFs increased by 216%, and benzene EFs increased by 82%. Both modified combustion efficiency and the temperature at the combustion chamber exit decreased with increasing fuel moisture, su...

Converging evidence from human and animal studies support an association between vitamin D deficiency and cognitive impairment. Previous studies have shown that hippocampal volume is reduced in adults with vitamin D deficiency as well as in a range of disorders, such as schizophrenia. The aim of the current study was to examine the effect of adult vitamin D (AVD) deficiency on hippocampal-dependent spatial learning, and hippocampal volume and connectivity in healthy adult mice. Ten-week-old male BALB/c mice were fed a control (vitamin D 1500 IU/kg) or vitamin D-depleted (vitamin D 0 IU/kg) diet for a minimum of 10 weeks. The mice were then tested for hippocampal-dependent spatial learning using active place avoidance (APA) and on tests of muscle and motor coordination (rotarod and grip strength). The mice were perfused and brains collected to acquire ex vivo structural and diffusion-weighted images using a 16.4 T MRI scanner. We also performed immunohistochemistry to quantify perineuronal nets (PNNs) and parvalbumin (PV) interneurons in various brain regions. AVD-deficient mice had a lower latency to enter the shock zone on APA, compared to control mice, suggesting impaired hippocampal-dependent spatial learning. There were no differences in rotarod or grip strength, indicating that AVD deficiency did not have an impact on muscle or motor coordination. AVD deficiency did not have an impact on hippocampal volume. However, AVD-deficient mice displayed a disrupted network centred on the right hippocampus with abnormal connectomes among 29 nodes. We found a reduction in PNN positive cells, but no change in PV, centred on the hippocampus. Our results provide compelling evidence to show that AVD deficiency in otherwise healthy adult mice may play a key role in hippocampal-dependent learning and memory formation. We suggest that the spatial learning deficits could be due to the disruption of right hippocampal structural connectivity.

Acute Medicine is a specialty that is not defined by a single organ system and sits at the interface between primary and secondary care. In order to document improvements in the quality of care delivered a system of metrics is required. A number of frameworks for measurements exist to quantify quality of care at the level of patients, teams and organisations, such as measures of population health, patient satisfaction and cost per patient. Measures can capture whether care is safe, effective, patient-centred, timely, efficient and equitable. Measurement in Acute Medicine is challenged by the often-transient nature of the contact between Acute Medicine clinicians and patients, the lack of diagnostic labels, a low degree of standardisation and difficulties in capturing the patient experience in the context. In a time of increasing ecological and financial constraints, reflecting about the most appropriate metrics to document the impact of Acute Medicine is required.

Background The demographic of Northern Territory prison population differs than elsewhere in Australia and the prevalence of hepatitis B and hepatitis C may therefore be somewhat different from other jurisdictions. There has been no study which has specifically described the serological results of a large proportion of prisoners in Northern Territory correctional facilities over an extended period of time. Methods This retrospective longitudinal study reviewed serological results and testing rates for hepatitis B, and hepatitis C performed in correctional facilities in the Northern Territory of Australia between July 1st, 2003 and June 30th, 2017. Results The proportion of positive records over 14 years for hepatitis B surface antigen (HBsAg) was 641/12,066 (5.3, 95% CI 4.9–5.7), for hepatitis B core antibody (anti-HBc) 4937/12,138 (40.1, 95%CI 39.8–41.6), for hepatitis B surface antibody (anti-HBs) 6966/13,303 (52.4, 95% CI 51.5–53.2), and for hepatitis C antibody 569/12,153 (4.7, 95% CI 4.3–5.1). The proportion of prisoners tested for hepatitis B and hepatitis C has decreased since 2015, while a high proportion of prisoners remain non-immune to hepatitis B. Conclusion There is a relatively high proportion of positive serological markers of hepatitis B, and a lower proportion of positive hepatitis C serology in the Northern Territory’s correctional facilities compared to overall Australian rates. As the proportion of prisoners tested for hepatitis B and C has decreased recently, and a high proportion of prisoners remain non-immune to hepatitis B, there are opportunities to increase testing and vaccination rates in this population.