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Background: Risk factors for cardiovascular disease (CVD) and sleep health are well-known to be sex- and race-specific. To build on the established relationship between sleep duration and CVD risk, this cross-sectional study aimed to describe sex-specific associations between CVD risk and other sleep characteristics (sleep quality, sleep timing and sleep onset latency) in low-income adults of African descent. Methods: Self-reported sleep (Pittsburgh Sleep Quality Index [PSQI], Epworth Sleepiness Scale [ESS], Insomnia Severity Index [ISI]), demographic and lifestyle data were collected in 412 adults (56 % women, 35.0 ± 7.6y, 40 % employed) living in an informal settlement in South Africa. CVD risk was determined using the BMI-modified Framingham 10-year CVD risk formula. Results: Logistic regression analyses, adjusted for employment, alcohol use and physical activity, indicated that men reporting poor sleep quality (OR: 1.95[95 %CI: 1.07–3.51], p=0.025) and earlier bedtimes (0.54[0.39–0.74], p

Introduction: Drinking motives and neurocognition play significant roles in predicting alcohol use. There is limited research examining how relief-driven drinking motives interact with neurocognition in alcohol use, which would help to elucidate the neurocognitive-motivational profiles most susceptible to harmful drinking. This study investigated the interactions between neurocognition (response inhibition and cognitive flexibility) and relief-driven drinking, in predicting problem drinking. Methods: Participants completed the Alcohol Use Disorders Identification Test – Consumption items (AUDIT-C) to measure drinking behaviour, and online cognitive tasks, including the Value-Modulated Attentional Capture and Reversal Task (VMAC-R) and the Stop Signal Task (SST). The sample (N = 368) were individuals who drink alcohol, which included a subsample (N = 52) with problematic drinking, as defined by self-identifying as having a primary drinking problem. Drinking motives were assessed using a binary coping question in the overall sample, and the Habit, Reward, and Fear Scale (HRFS) in the subsample. Moderation analyses were conducted to investigate whether cognitive flexibility and response inhibition moderated relationships between relief-driven motives and drinking. Results: Cognitive flexibility moderated the relationship between relief-driven motives and drinking (overall sample: β = 13.69, p = 0.017; subsample: β = 1.45, p = 0.013). Greater relief-driven motives were associated with heavier drinking for individuals with low cognitive flexibility. There was no significant interaction between response inhibition and relief-driven motives. Conclusions: Relief-driven drinking motives interact with cognitive inflexibility to drive heavier drinking. Greater understanding of these neurocognitive-motivational mechanisms may help to develop more targeted and effective interventions for reducing harmful drinking.

Objective To understand barriers and facilitators for strengthening health systems for person-centred care of people with multiple long-term conditions-multimorbidity (MLTC-M) at the primary healthcare (PHC) level in low-income and middle-income countries (LMICs).Design A scoping review.Methods We adopted a systematic scoping review approach to chart literature guided by Arksey and O'Malley’s methodological framework. The review focused on studies conducted in LMICs’ PHC settings from January 2010 to December 2023. Papers were extracted from the following databases: PubMed, EBSCOhost and Google Scholar. Framework analysis was undertaken to identify barriers and facilitators for strengthening MLTC-M primary care according to the five health system pillars in the Lancet Global Health Commission on High-Quality Health Systems Framework.Results The literature search yielded 4322 citations, evaluated 202 studies and identified 36 for inclusion. Key barriers within the people pillar included poverty, low health education and low health literacy; within the platform pillar, fragmented services and lack of multimorbid care guidelines were mentioned; within the workforce pillar, lack of required skills and insufficient health workers; and in the tools pillar: a shortage of essential medicines and adverse polypharmacy effects were prominent. A lack of political will and the absence of relevant national health policies were identified under the governance pillar. Facilitators within the people pillar included enhancing self-management support; within the platforms, pillar included integration of services; within the tools pillar, included embracing emerging technologies and information and communication technology services; and governance issues included upscaling interventions to respond to multimorbid care needs through enhanced political commitment and financial support.Conclusions Potential solutions to strengthening the healthcare system to be more responsive to people with MLTC-M include empowering service users to self-manage, developing multimorbid care guidelines, incorporating community health workers into multimorbid care efforts and advocating for integrated person-centred care services across sectors. The need for policies and procedures in LMICs to meet the person-centred care needs of people with MLTC-M was highlighted.

Ecosystem functions such as biological pest control are mediated by the richness and abundance of service providers i.e., biological control agents (BCAs), relative contributions of individual taxa and community structure. This is especially relevant in the native range of agricultural herbivores, where a speciose community of co-evolved BCAs can prevent them from attaining pest status. Here, we use a powerful graphical approach to assess the functional structure of BCA communities of the fall armyworm (FAW) Spodoptera frugiperda (Lepidoptera: Noctuidae) on maize in the Neotropics. Drawing upon a curated database of all-time field and laboratory studies, we graphed patterns in the functional contribution, abundance and niche breadth for a respective 69, 53 and 3 taxa of resident parasitoids, predators and pathogens. Regardless of varying taxon coverage and rigor of the underlying studies, functional structure follows a saturating relationship in which the first three taxa account for 90–98% of aggregate biological control function. Abundance-functionality matrices prove critically incomplete, as more than 80% of invertebrate taxa miss empirically derived efficiency metrics while associated FAW infestation data are scarce. Despite its methodological shortfalls and data gaps, our work pinpoints Chelonus insularis, several taxa of egg parasitoids, Doru spp. and Orius spp. as taxa with outsized (average) functionality and conservation potential. This is also exemplified by the highly variable aggregate function across studies, with dispersion indices of 1.52 and 2.14 for invertebrate BCAs. Our work underlines the critical importance of functional ecology research, networked trials and standardized methodologies in advancing conservation biological control globally.

Sclerotherapy is the treatment of choice for telangiectasias and reticular veins. The most common side effects of this procedure are hyperpigmentation and matting, which are feared owing to their aesthetic damage and difficulty of treatment. Combined treatments with laser and hypertonic glucose sclerotherapy have been described with excellent results, but limited to treatment of veins of ≤2 mm in diameter. Cryo laser after foam sclerotherapy is a procedure to treat reticular veins in the lower extremities that utilizes first foam sclerotherapy with polidocanol than immediately followed by transdermal Nd:YAG 1064 laser treatment and we can treat veins ≤5 mm. This report presents a successful case of varicose vein treatment using combined transdermal laser and sclerotherapy with foam sclerotherapy with polidocanol to treat veins >2.5 mm in diameter.

When replication forks encounter damaged DNA, cells utilize damage tolerance mechanisms to allow replication to proceed. These include translesion synthesis at the fork, postreplication gap filling, and template switching via fork reversal or homologous recombination. The extent to which these different damage tolerance mechanisms are utilized depends on cell, tissue, and developmental context-specific cues, the last two of which are poorly understood. To address this gap, we have investigated damage tolerance responses in Drosophila melanogaster. We report that tolerance of DNA alkylation damage in rapidly dividing larval tissues depends heavily on translesion synthesis. Furthermore, we show that the REV1 protein plays a multi-faceted role in damage tolerance in Drosophila. Larvae lacking REV1 are hypersensitive to methyl methanesulfonate (MMS) and have highly elevated levels of γ-H2Av (Drosophila γ-H2AX) foci and chromosome aberrations in MMS-treated tissues. Loss of the REV1 C-terminal domain (CTD), which recruits multiple translesion polymerases to damage sites, sensitizes flies to MMS. In the absence of the REV1 CTD, DNA polymerases eta and zeta become critical for MMS tolerance. In addition, flies lacking REV3, the catalytic subunit of polymerase zeta, require the deoxycytidyl transferase activity of REV1 to tolerate MMS. Together, our results demonstrate that Drosophila prioritize the use of multiple translesion polymerases to tolerate alkylation damage and highlight the critical role of REV1 in the coordination of this response to prevent genome instability.

Abstract South Africans living in low socioeconomic areas have self-reported unusually long sleep durations (approximately 9–10 h). One hypothesis is that these long durations may be a compensatory response to poor sleep quality as a result of stressful environments. This study aimed to investigate whether fear of not being safe during sleep is associated with markers of sleep quality or duration in men and women. South Africans (n = 411, 25–50 y, 57% women) of African-origin living in an urban township, characterised by high crime and poverty rates, participated in this study. Participants are part of a larger longitudinal cohort study: Modelling the Epidemiologic Transition Study (METS)–Microbiome. Customised questions were used to assess the presence or absence of fears related to feeling safe during sleep, and the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index were used to assess daytime sleepiness, sleep quality and insomnia symptom severity respectively. Adjusted logistic regression models indicated that participants who reported fears related to safety during sleep were more likely to report poor sleep quality (PSQI > 5) compared to participants not reporting such fears and that this relationship was stronger among men than women. This is one of the first studies outside American or European populations to suggest that poor quality sleep is associated with fear of personal safety in low-SES South African adults.

Since 2016, the fall armyworm (FAW) Spodoptera frugiperda has spread over extensive areas of the tropics and subtropics, imperiling food security, economic progress and the livelihoods of millions of cereal farmers. Although FAW has received long-standing scientific attention in its home range in the Americas, chemical inputs feature prominently in its mitigation and biological control uptake is globally lagging. Here, building upon a quantitative review of the global literature, we methodically dissect FAW biological control science. Of the known entomopathogens (46), parasitoids (304) and predators (215) of FAW, approx. 40% have been subject to laboratory- or field-level scrutiny. Laboratory-level performance has partially been assessed for 14–18% of the above invertebrate taxa. Yet, organismal, geographic, methodological and thematic biases hamper efforts to relate in-field biodiversity to actual ecosystem service delivery. Often, single-guild ‘snapshot’ surveys are preferred over comprehensive bio-inventories or population dynamics appraisals, trophic interactions are wrongly inferred from co-occurrence, standard pest infestation metrics are lacking and natural enemy censuses are performed arbitrarily. Diurnal biota receive inordinate attention, while egg and pupal predation - the main biotic sources of mortality - are routinely overlooked. Multiple microbial and invertebrate biota are investigated with a view towards mass-rearing and augmentative release, but the basis for agent selection is often unclear. Lastly, conservation biological control receives marginal attention and cross-disciplinary engagement with the agroecology domain is lagging. We lay out several steps, including standardized methodologies, smart use of biodemographic toolkits, networked field trials and a fortification of its ecological underpinnings, to sharpen the science of (FAW) biological control and urge further momentum in its global implementation.

Abstract Primary liver cancer arises either from hepatocytic or biliary lineage cells, giving rise to hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICCA). Combined hepatocellular- cholangiocarcinomas (cHCC-CCA) exhibit equivocal or mixed features of both, causing diagnostic uncertainty and difficulty in determining proper management. Here, we perform a comprehensive deep learning-based phenotyping of multiple cohorts of patients. We show that deep learning can reproduce the diagnosis of HCC vs. CCA with a high performance. We analyze a series of 405 cHCC-CCA patients and demonstrate that the model can reclassify the tumors as HCC or ICCA, and that the predictions are consistent with clinical outcomes, genetic alterations and in situ spatial gene expression profiling. This type of approach could improve treatment decisions and ultimately clinical outcome for patients with rare and biphenotypic cancers such as cHCC-CCA.

Abstract Background HIV has become a manageable chronic condition due to the success and scale-up of antiretroviral therapy (ART). Globally, South Africa has the highest number of people living with HIV (PLHIV) and research evidence indicates that countries with the highest burden of PLHIV have a substantial burden of obesity, hypertension (HPT) and type 2 diabetes (T2D). We sought to summarize the burden of these three common NCDs among PLHIV in South Africa. Methods In this systematic review, multiple databases were searched for articles reporting on the prevalence of obesity, HPT, and T2D among PLHIV in South Africa published since journal inception until March 2022. A meta-analysis was conducted using random-effects models to obtain pooled prevalence estimates of the three NCDs. Heterogeneity was assessed using X2 test on Cochran’s Q statistic. Results We included 32 studies, with 19, 22 and 18 studies reporting the prevalence of obesity, HPT, and T2D among PLHIV, respectively. The overall prevalence of obesity, HPT, and T2D was 23.2% [95% CI 17.6; 29.9], 25.5% [95% CI 15.6; 38.7], and 6.1% [95% CI 3.8; 9.7] respectively. The prevalence of obesity was significantly higher among women (P = 0.034) compared to men, however the prevalence of HPT and T2D did not differ by sex. The prevalence of each of the three NCDs did not differ significantly between rural, urban, and peri-urban areas. The prevalence of obesity and T2D was higher in studies conducted between 2013 and 2022 compared to studies conducted between 2000 and 2012, while the prevalence of HPT was higher between 2000 and 2012 compared to between 2013 and 2022. Conclusions These findings suggest that South Africa is experiencing a syndemic of NCDs among people PLHIV highlighting the need to increase cost-effective interventions and management strategies that involve integrated HIV and NCD care in the South African setting.

Aims A variety of the indicators have been the proposed method in-order to assist orthodontic diagnosis and treatment planning. This study aimed to appraise the applicability. the index of the Korkhaus to Iraqi persons, and to know if patients that having crowding of teeth have increase in arch length. Material and Methods: The sample consisted of (131) persons their age between (15-20) years, (64) boys and (67) girls, all of Iraqi origin, and live in the centre of Mosul city. All the individuals have Class I molar. relation. The sample consisted of three groups: Normal occlusion group with well aligned teeth (20) boys and (20) girls. Patients had moderate crowding, 2.5 - 4.5mm, (19) boys and (23) girls and severe crowding group, over 5mm, (23) boys and (26) girls. A linear distance was measured on a figure of the scanned study models for upper dental arches by Dimaxis program. statistical analysis with (SPSS) program at the level of P≤0.05 include: comparison between genders using in-depended t-test and, Pearson correlation coefficient among all the variables. Results: The results showed that the measurements (Sum of Incisors, Vertical, Measured Premolar value, measured molar value, Calculated Premolar Value, Calculated Molar Value) in normal occlusion had significantly higher mean Values in males than females. Also, there is a correlation coefficient between the sum of teeth width of four anterior and the posterior arch width which is significant for normal occlusion, but there is no such relation in the most crowding sample. Conclusions: Korkhaus index can be used to determine arch width in Iraqi individuals with normal occlusion, patients with crowded teeth had slight proclination of incisors that is not significant other than normal occlusion. So Korkhaus analysis is considered to be valid for Iraqi class I normal and crowded occlusion.

Abstract The relationship between microbiota, short chain fatty acids (SCFAs), and obesity remains enigmatic. We employ amplicon sequencing and targeted metabolomics in a large (n = 1904) African origin cohort from Ghana, South Africa, Jamaica, Seychelles, and the US. Microbiota diversity and fecal SCFAs are greatest in Ghanaians, and lowest in Americans, representing each end of the urbanization spectrum. Obesity is significantly associated with a reduction in SCFA concentration, microbial diversity, and SCFA synthesizing bacteria, with country of origin being the strongest explanatory factor. Diabetes, glucose state, hypertension, obesity, and sex can be accurately predicted from the global microbiota, but when analyzed at the level of country, predictive accuracy is only universally maintained for sex. Diabetes, glucose, and hypertension are only predictive in certain low-income countries. Our findings suggest that adiposity-related microbiota differences differ between low-to-middle-income compared to high-income countries. Further investigation is needed to determine the factors driving this association.

Mycobacterium tuberculosis (M.tb.) infection leads to over 1.5 million deaths annually, despite widespread vaccination with BCG at birth. Causes for the ongoing tuberculosis endemic are complex and include the failure of BCG to protect many against progressive pulmonary disease. Host genetics is one of the known factors implicated in susceptibility to primary tuberculosis, but less is known about the role that host genetics plays in controlling host responses to vaccination against M.tb. Here, we addressed this gap by utilizing Diversity Outbred (DO) mice as a small animal model to query genetic drivers of vaccine-induced protection against M.tb. DO mice are a highly genetically and phenotypically diverse outbred population that is well suited for fine genetic mapping. Similar to outcomes in people, our previous studies demonstrated that DO mice have a wide range of disease outcomes following BCG vaccination and M.tb. challenge. In the current study, we used a large population of BCG-vaccinated/M.tb.-challenged mice to perform quantitative trait loci mapping of complex infection traits; these included lung and spleen M.tb. burdens, as well as lung cytokines measured at necropsy. We found sixteen chromosomal loci associated with complex infection traits and cytokine production. QTL associated with bacterial burdens included a region encoding major histocompatibility antigens that are known to affect susceptibility to tuberculosis, supporting validity of the approach. Most of the other QTL represent novel associations with immune responses to M.tb. and novel pathways of cytokine regulation. Most importantly, we discovered that protection induced by BCG is a multigenic trait, in which genetic loci harboring functionally-distinct candidate genes influence different aspects of immune responses that are crucial collectively for successful protection. These data provide exciting new avenues to explore and exploit in developing new vaccines against M.tb.

Background The development of strategies to better detect and manage patients with multiple long-term conditions requires estimates of the most prevalent condition combinations. However, standard meta-analysis tools are not well suited to synthesising heterogeneous multimorbidity data.Methods We developed a statistical model to synthesise data on associations between diseases and nationally representative prevalence estimates and applied the model to South Africa. Published and unpublished data were reviewed, and meta-regression analysis was conducted to assess pairwise associations between 10 conditions: arthritis, asthma, chronic obstructive pulmonary disease (COPD), depression, diabetes, HIV, hypertension, ischaemic heart disease (IHD), stroke and tuberculosis. The national prevalence of each condition in individuals aged 15 and older was then independently estimated, and these estimates were integrated with the ORs from the meta-regressions in a statistical model, to estimate the national prevalence of each condition combination.Results The strongest disease associations in South Africa are between COPD and asthma (OR 14.6, 95% CI 10.3 to 19.9), COPD and IHD (OR 9.2, 95% CI 8.3 to 10.2) and IHD and stroke (OR 7.2, 95% CI 5.9 to 8.4). The most prevalent condition combinations in individuals aged 15+ are hypertension and arthritis (7.6%, 95% CI 5.8% to 9.5%), hypertension and diabetes (7.5%, 95% CI 6.4% to 8.6%) and hypertension and HIV (4.8%, 95% CI 3.3% to 6.6%). The average numbers of comorbidities are greatest in the case of COPD (2.3, 95% CI 2.1 to 2.6), stroke (2.1, 95% CI 1.8 to 2.4) and IHD (1.9, 95% CI 1.6 to 2.2).Conclusion South Africa has high levels of HIV, hypertension, diabetes and arthritis, by international standards, and these are reflected in the most prevalent condition combinations. However, less prevalent conditions such as COPD, stroke and IHD contribute disproportionately to the multimorbidity burden, with high rates of comorbidity. This modelling approach can be used in other settings to characterise the most important disease combinations and levels of comorbidity.

BackgroundWhile several methodologies are available to measure adiposity, few have been validated in sub-Saharan African (SSA) and none in postpartum African women living with HIV (WLHIV). We compared bioelectrical impendence analysis (BIA) and air displacement plethysmography (ADP) against dual x-ray absorptiometry (DXA) in South African women and examined differences by HIV and body mass index (BMI) status.MethodsLin’s concordance correlation coefficient (CCC) test was used to examine fat mass (FM), fat free mass (FFM), and total body fat percent (%BF) difference between BIA vs. DXA, and ADP vs. DXA in women living with HIV (n = 57) and without HIV (n = 25). The Bland Altman test was used to assess mean differences and the direction of bias.ResultsThe median age was 31 years (IQR, 26–35) and months postpartum were 11 (IQR, 7–16), 44% of the women had obesity. Lin’s CCC for BIA and ADP vs. DXA were both 0.80 for %BF and 0.97 for FM, and 0.86 and 0.80 for FFM, respectively. Mean differences (DXA-BIA and ADP estimates) were 0.22 ± 4.54% (p = 0.54) and 3.35 ± 3.27% (p

Abstract Background Perihilar cholangiocarcinoma (pCCA) is a malignant tumor of the hepatobiliary system which is still associated with a challenging prognosis. Postoperative complications play a crucial role in determining the overall prognosis of patients with pCCA. Changes in body composition (BC) have been shown to impact the prognosis of various types of tumors. Therefore, our study aimed to investigate the correlation between BC, postoperative complications and oncological outcome in patients with pCCA. Methods All patients with pCCA who underwent curative‐intent surgery for pCCA between 2010 and 2022 were included in this analysis. BC was assessed using preoperative computed tomography and analyzed with the assistance of a 3D Slicer software. Univariate and multivariate binary logistic regression analyses were conducted to examine the relationship between BC and clinical characteristics including various measurements of postoperative complications and Cox regressions and Kaplan–Meier analysis to evaluate oncological risk factors in the study cohort. Results BC was frequently altered in patients undergoing curative‐intent liver resection for pCCA (n = 204) with 52.5% of the patients showing obesity, 55.9% sarcopenia, 21.6% sarcopenic obesity, 48.5% myosteatosis, and 69.1% visceral obesity. In multivariate analysis, severe postoperative complications (Clavien‐Dindo ≥3b) were associated with body mass index (BMI) (Odds ratio (OR) = 2.001, p = 0.024), sarcopenia (OR = 2.145, p = 0.034), and myosteatosis (OR = 2.097, p = 0.017) as independent predictors. Furthermore, sarcopenia was associated with reduced overall survival (OS) in pCCA patients (sarcopenia vs. no‐sarcopenia, 21 months vs. 32 months, p = 0.048 log rank). Conclusions BC is highly associated with severe postoperative complications in patients with pCCA and shows tendency to be associated impaired overall survival. Preoperative assessment of BC and interventions to improve BC might therefore be key to improve outcome in pCCA patients undergoing surgical therapy.

Introduction South Africa has a high prevalence of gestational diabetes mellitus (GDM; 15%) and many of these women (48%) progress to type 2 diabetes mellitus (T2DM) within 5 years post partum. A significant proportion (47%) of the women are not aware of their diabetes status after the index pregnancy, which may be in part to low postnatal diabetes screening rates. Therefore, we aim to evaluate a intervention that reduces the subsequent risk of developing T2DM among women with recent GDM. Our objectives are fourfold: (1) compare the completion of the nationally recommended 6-week postpartum oral glucose tolerance test (OGTT) between intervention and control groups; (2) compare the diabetes risk reduction between control and intervention groups at 12 months’ post partum; (3) assess the process of implementation; and (4) assess the cost-effectiveness of the proposed intervention package.Methods and analyses Convergent parallel mixed-methods study with the main component being a pragmatic, 2-arm individually randomised controlled trial, which will be carried out at five major referral centres and up to 26 well-baby clinics in the Western Cape and Gauteng provinces of South Africa. Participants (n=370) with GDM (with no prior history of either type 1 or type 2 diabetes) will be recruited into the study at 24–36 weeks’ gestational age, at which stage first data collection will take place. Subsequent data collection will take place at 6–8 weeks after delivery and again at 12 months. The primary outcome for the trial is twofold: first, the completion of the recommended 2-hour OGTT at the well-baby clinics 6–8 weeks post partum, and second, a composite diabetes risk reduction indicator at 12 months. Process evaluation will assess fidelity, acceptability, and dose of the intervention.Ethics and dissemination Ethics approval has been granted from University of Cape Town (829/2016), University of the Witwatersrand, Johannesburg (M170228), University of Stellenbosch (N17/04/032) and the University of Montreal (2019-794). The results of the trial will be disseminated through publication in peer-reviewed journals and presentations to key South African Government stakeholders and health service providers.Protocol version 1 December 2022 (version #2). Any protocol amendments will be communicated to investigators, Human Ethics Research Committees, trial participants, and trial registries.Trial registration number PAN African Clinical Trials Registry (https://pactr.samrc.ac.za) on 11 June 2018 (identifier PACTR201805003336174).

Background Sleep quality, quantity, and efficiency have all been demonstrated to be adversely affected by rotator cuff pathology. Previous measures of assessing the impact of rotator cuff pathology on sleep have been largely subjective in nature. The aim of the present study was to use an objective measure of sleep quality and to compare these findings to the patients’ Patte stage. Methods Patients with full-thickness rotator cuff tears at a single institution were prospectively enrolled between 2018 and 2020. Waist-worn accelerometers were provided for the patients to use each night for 14 days. Sleep efficiency was calculated using the ratio of the time spent sleeping to the total amount of time that was spent in bed. Retraction of the rotator cuff tear was classified using the Patte staging system. Results This study included 36 patients: 18 with Patte stage 1 disease, 14 with Patte stage 2 disease, and 4 patients with Patte stage 3 disease. During the study, 25 participants wore the monitor on multiple nights, and ultimately their data was used for the analysis. No difference in the median sleep efficiency was appreciated amongst these groups (P>0.1), with each cohort of patients demonstrating a generally high sleep efficiency. Conclusions The severity of retraction of the rotator cuff tear did not appear to correlate with changes in sleep efficiency for patients (P>0.1). These findings can better inform providers on how to counsel their patients who present with complaints of poor sleep in the setting of full-thickness rotator cuff tears. Level of evidenceLevel II.

AbstractBackground: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly utilized to reduce pain, inflammation, and fever. This study aimed to assess patterns of use and awareness of NSAID-related side-effects in an adult Jordanian. And the associations with sociodemographic factors. Methods: This cross-sectional study among a representative sample of 604 adults >18 years. A validated, self-administered questionnaire was used to collect basic sociodemographic data from the participants, as well as information regarding NSAID use. Results: Most respondents were NSAID users (65.7%), female (53.4%) and under 50 years of age (74.5%). Overall, 42.6% had been prescribed NSAIDs by a physician. Male gender and smoking were negatively correlated with NSAIDs use (multivariable odds ratio [OR]: 0.5, 95% confidence interval [CI]: 0.4–0.8, p = 0.001 and OR: 0.6, 95% CI 0.4–0.8, p = 0.003). In contrast, the Ministry of Health Insurance was associated with NSAIDs use with OR: 1.6, 95% CI: 1.1–2.6, p = 0.03. Overall, 65.1% were aware of kidney NSAID-related side-effects and 22.4% were aware of the increased risk of asthma and allergy. Conclusion: Despite the high frequency of NSAID use in the Jordanian general population, there is limited knowledge of their side-effects as well as drug interactions. This is cause for concern, particularly as many participants reported having been prescribed NSAIDs by physicians without adequate patient safety education.

Extrarenal clear cell renal cell carcinoma (eccRCC) is a rare type of RCC that arises in areas other than the kidney. Given its rarity, consensus guidelines for optimal treatment of eccRCC have not been established, and the literature is lacking any reports of patient response to systemic therapy and any reports of administration of immunotherapy to patients with ecRCC. Here, we present the case of a patient in their 60s with eccRCC arising in the spleen. The patient underwent splenic resection and then received systemic therapy, due to disease recurrence, with a combination of immunotherapy (IO) and tyrosine kinase inhibitor targeted therapy (VEGF-TKI). The patient had an excellent and durable response to this therapeutic regimen with minimal adverse effects, completing 2 years of therapy of nivolumab and cabozantinib. At the time of this report, the disease remains stable. This case demonstrates that combination therapy with IO+VEGF-TKI represents a reasonable and well-tolerated treatment option with activity in eccRCC and reveals interesting correlative data, including nests of stem-like CD8+T-cell infiltration in tumor tissue, which provide important biological context to this patient’s exceptional therapeutic response.

Blue horizontal branch stars (BHBs), excellent distant tracers for probing the Milky Way’s halo density profile, are distinguished in the ${\left(g-r\right)}_{0}$ versus ( i − z ) _0 color space from another class of stars, blue straggler stars. We develop a Bayesian mixture model to classify BHBs using high-precision photometry data from the Dark Energy Survey Data Release 2 (DES DR2). We select ∼2100 highly probable BHBs based on their griz photometry and the associated uncertainties, and we use these stars to map the stellar halo over the Galactocentric radial range 20 kpc ≲ R ≲ 70 kpc. After excluding known stellar overdensities, we find that the number density n _⋆ of BHBs can be represented by a power-law density profile n _⋆ ∝ R ^− ^α with an index of $\alpha ={4.34}_{-0.12}^{+0.13}\pm 0.52$ , consistent with existing literature values. In addition, we examine the impact of systematic errors and the spatial inhomogeneity on the fitted density profile. Our work demonstrates the effectiveness of high-precision griz photometry in selecting BHBs. The upcoming photometric survey from the Rubin Observatory, expected to reach depths 2–3 mag greater than DES during its 10 yr mission, will enable us to investigate the density profile of the Milky Way’s halo out to the virial radius, unraveling the complex processes of formation and evolution in our Galaxy.

Abstract Introduction Shared decision‐making (SDM) is intended to increase patient‐centredness of medical decision‐making for patients with acute and chronic conditions. Concurrently, patient decision aids (PtDAs) can supplement SDM by providing information to guide communication between patients and healthcare providers. Because of the prevalence of chronic conditions, where decisions may be extended or recurring, we sought to explore how effectively these tools have been leveraged in this context. Methods We conducted a narrative review of the literature on both SDM and PtDAs, searching PubMed and Boston University's library database search tool for English‐language articles published from January 2005 until March 2021. Additional search terms focused on temporality. Drawing from our findings, we developed a combined framework to highlight areas for future research using the discussion of end‐of‐life decisions as an exemplar to illustrate its relevance to chronic care contexts. Results After screening 57 articles, we identified 25 articles that fulfilled the inclusion criteria on SDM, PtDA use and temporality for chronic care. The literature on SDM highlighted time outside of the medical visit and opportunity to include outside decision partners as important elements of the process. PtDAs were commonly evaluated for process‐related and proximal outcomes, but less often for distal outcomes. Early evidence points to the value of comparative outcome evaluation based on the timing of PtDA distribution. Conclusion Our review of the literature on SDM and PtDAs reveals less attention to the timing of PtDAs relative to that of SDM. We highlight the need for further study of timing in PtDA use to improve longitudinal SDM for chronic care. The model that we propose in our discussion provides a starting point for future research on PtDA efficacy. Patient or Public Contribution Five patient consultants provided input and feedback on the development and utility of our model.

Abstract The neutrophil-to-lymphocyte ratio (NLR) is used as biomarker in malignant diseases showing significant association with poor oncological outcomes. The main research question of the present study was whether NLR has also prognostic value in cholangiocarcinoma patients (CCA). A systematic review was carried out to identify studies related to NLR and clinical outcomes in CCA evaluating the literature from 01/2000 to 09/2021. A random-effects model, pooled hazard ratios (HR) and 95% confidence interval (CI) were used to investigate the statistical association between NLR and overall survival (OS) as well as disease-free survival (DFS). Subgroup analyses, evaluation of sensitivity and risk of bias were further carried out. 32 studies comprising 8572 patients were eligible for this systematic review and meta-analysis. The pooled outcomes revealed that high NLR prior to treatment is prognostic for poor OS (HR 1.28, 95% CI 1.18–1.38, p

Cognitive function in humans depends on the complex and interplay between multiple body systems, including the hypothalamic-pituitary-adrenal (HPA) axis. The gut microbiota, which vastly outnumbers human cells and has a genetic potential that exceeds that of the human genome, plays a crucial role in this interplay. The microbiota-gut-brain (MGB) axis is a bidirectional signalling pathway that operates through neural, endocrine, immune, and metabolic pathways. One of the major neuroendocrine systems responding to stress is the HPA axis which produces glucocorticoids such as cortisol in humans and corticosterone in rodents. Appropriate concentrations of cortisol are essential for normal neurodevelopment and function, as well as cognitive processes such as learning and memory, and studies have shown that microbes modulate the HPA axis throughout life. Stress can significantly impact the MGB axis via the HPA axis and other pathways. Animal research has advanced our understanding of these mechanisms and pathways, leading to a paradigm shift in conceptual thinking about the influence of the microbiota on human health and disease. Preclinical and human trials are currently underway to determine how these animal models translate to humans. In this review article, we summarize the current knowledge of the relationship between the gut microbiota, HPA axis, and cognition, and provide an overview of the main findings and conclusions in this broad field.

ABSTRACT Antituberculosis therapy (ATT) causes a rapid and distinct alteration in the composition of the intestinal microbiota that is long lasting in both mice and humans. This observation raised the question of whether such antibiotic-induced changes in the microbiome might affect the absorption or gut metabolism of the tuberculosis (TB) drugs themselves. To address this issue, we utilized a murine model of antibiotic-induced dysbiosis to assay the bioavailability of rifampicin, moxifloxacin, pyrazinamide, and isoniazid in mouse plasma over a period of 12 h following individual oral administration. We found that 4-week pretreatment with a regimen of isoniazid, rifampicin, and pyrazinamide (HRZ), a drug combination used clinically for ATT, failed to reduce the exposure of any of the four antibiotics assayed. Nevertheless, mice that received a pretreatment cocktail of the broad-spectrum antibiotics vancomycin, ampicllin, neomycin, and metronidazole (VANM), which are known to deplete the intestinal microbiota, displayed a significant decrease in the plasma concentration of rifampicin and moxifloxacin during the assay period, an observation that was validated in germfree animals. In contrast, no major effects were observed when similarly pretreated mice were exposed to pyrazinamide or isoniazid. Thus, the data from this animal model study indicate that the dysbiosis induced by HRZ does not reduce the bioavailability of the drugs themselves. Nevertheless, our observations suggest that more extreme alterations of the microbiota, such as those occurring in patients on broad-spectrum antibiotics, could directly or indirectly affect the exposure of important TB drugs and thereby potentially influencing treatment outcome. IMPORTANCE Previous studies have shown that treatment of Mycobacterium tuberculosis infection with first-line antibiotics results in a long-lasting disruption of the host microbiota. Since the microbiome has been shown to influence the host availability of other drugs, we employed a mouse model to ask whether the dysbiosis resulting from either tuberculosis (TB) chemotherapy or a more aggressive course of broad-spectrum antibiotics might influence the pharmacokinetics of the TB antibiotics themselves. While drug exposure was not reduced in animals previously described as exhibiting the dysbiosis triggered by conventional TB chemotherapy, we found that mice with other alterations in the microbiome, such as those triggered by more intensive antibiotic treatment, displayed decreased availability of rifampicin and moxifloxacin, which in turn could impact their efficacy. The above findings are relevant not only to TB but also to other bacterial infections treated with these two broader spectrum antibiotics.

Low total energy expenditure (TEE) has been a hypothesized risk factor for weight gain, but longitudinal repeatability of TEE is incompletely understood. Here the authors report that TEE is repeatable for adults, but not for children, and increases in TEE (adjusted for fat-free mass, fat mass, age and sex) are not associated with body composition changes in short-term longitudinal analyses.

IL-12p40 plays an important role in F. tularensis Live Vaccine Strain (LVS) clearance that is independent of its functions as a part of the heterodimeric cytokines IL-12p70 or IL-23. In contrast to WT, p35, or p19 knockout (KO) mice, p40 KO mice infected with LVS develop a chronic infection that does not resolve. Here, we further evaluated the role of IL-12p40 in F. tularensis clearance. Despite reduced IFN-γ production, primed splenocytes from p40 KO and p35 KO mice appeared functionally similar to those from WT mice during in vitro co-culture assays of intramacrophage bacterial growth control. Gene expression analysis revealed a subset of genes that were upregulated in re-stimulated WT and p35 KO splenocytes, but not p40 KO splenocytes, and thus are candidates for involvement in F. tularensis clearance. To directly evaluate a potential mechanism for p40 in F. tularensis clearance, we reconstituted protein levels in LVS-infected p40 KO mice using either intermittent injections of p40 homodimer (p80) or treatment with a p40-producing lentivirus construct. Although both delivery strategies yielded readily detectable levels of p40 in sera and spleens, neither treatment had a measurable impact on LVS clearance by p40 KO mice. Taken together, these studies demonstrate that clearance of F. tularensis infection depends on p40, but p40 monomers and/or dimers alone are not sufficient.

Abstract Background Cardiometabolic (CM) risk affects approximately 25% of adults globally, and is diagnosed by meeting 3 out of 5 of the following CM risk factors: elevated blood pressure, high triglycerides, elevated blood sugar, low high-density lipoprotein (HDL) level, and abdominal obesity. Adults with CM risk are approximately 22% more likely to have higher mortality rates, and alcohol consumption may be associated with higher CM risk. While previous studies have investigated this potential connection, the majority of them did not include African-origin adults. Therefore, the study aimed to explore the association between alcohol intake and CM risk in 5 African-origin cohorts, spanning the epidemiologic transition in Ghana, South Africa, Jamaica, Seychelles and the United States of America. Methods Measurements included clinical measures for CM risk and self-reported alcohol consumption. Each participant was categorized into one of three drinking categories: non-drinker, light drinker (1–3 drinks daily for men and 1–2 drinks daily for women) and heavy drinker (4 or more drinks every day for men and 3 or more drinks per day for women). Using non-drinker status as the reference, the association between alcohol consumption status and prevalence of each of the five CM risk factors and overall elevated CM risk (having 3 out of 5 risk factors) was explored, adjusting for site, age and sex. Associations were explored using logistic regression and significance was determined using odds ratios (OR) and 95% confidence intervals. Results Neither light nor heavy drinking was associated with increased odds for having higher CM risk compared to nondrinkers (OR = 1.05, p = 0.792 and OR = 1.11, p = 0.489, respectively). However, light drinking was associated with lower odds for having low high density lipoproteins (HDL) cholesterol (OR = 0.69, p = 0.002) and increased risk for high triglycerides (OR = 1.48, p = 0.030). Heavy drinking was associated with elevated blood pressure (OR = 1.59, p = 0.002), high triglycerides (OR = 1.73, p = 0.006) and decreased risk of low HDL-cholesterol (OR = 0.621, p

Summary: Lower ambient temperature (Ta) requires greater energy expenditure to sustain body temperature. However, effects of Ta on human energetics may be buffered by environmental modification and behavioral compensation. We used the IAEA DLW database for adults in the USA (n = 3213) to determine the effect of Ta (−10 to +30°C) on TEE, basal (BEE) and activity energy expenditure (AEE) and physical activity level (PAL). There were no significant relationships (p > 0.05) between maximum, minimum and average Ta and TEE, BEE, AEE and PAL. After adjustment for fat-free mass, fat mass and age, statistically significant (p

Abstract Background Metabolic reprogramming is a common phenomenon in tumorigenesis and tumor progression. Amino acids are important mediators in cancer metabolism, and their kinetics in tumor tissue are far from being understood completely. Mass spectrometry imaging is capable to spatiotemporally trace important endogenous metabolites in biological tissue specimens. In this research, we studied L-[ring-13C6]-labeled phenylalanine and tyrosine kinetics in a human non-small cell lung carcinoma (NSCLC) xenografted mouse model using matrix-assisted laser desorption/ionization Fourier-transform ion cyclotron resonance mass spectrometry imaging (MALDI-FTICR-MSI). Methods We investigated the L-[ring-13C6]-Phenylalanine (13C6-Phe) and L-[ring-13C6]-Tyrosine (13C6-Tyr) kinetics at 10 min (n = 4), 30 min (n = 3), and 60 min (n = 4) after tracer injection and sham-treated group (n = 3) at 10 min in mouse-xenograft lung tumor tissues by MALDI-FTICR-MSI. Results The dynamic changes in the spatial distributions of 19 out of 20 standard amino acids are observed in the tumor tissue. The highest abundance of 13C6-Phe was detected in tumor tissue at 10 min after tracer injection and decreased progressively over time. The overall enrichment of 13C6-Tyr showed a delayed temporal trend compared to 13C6-Phe in tumor caused by the Phe-to-Tyr conversion process. Specifically, 13C6-Phe and 13C6-Tyr showed higher abundances in viable tumor regions compared to non-viable regions. Conclusions We demonstrated the spatiotemporal intra-tumoral distribution of the essential aromatic amino acid 13C6-Phe and its de-novo synthesized metabolite 13C6-Tyr by MALDI-FTICR-MSI. Our results explore for the first time local phenylalanine metabolism in the context of cancer tissue morphology. This opens a new way to understand amino acid metabolism within the tumor and its microenvironment.

Abstract Chorioamnionitis, inflammation of fetal membranes, is an important cause of preterm birth and a risk factor for the development of adverse neonatal outcomes including sepsis and intestinal pathologies. Intestinal bile acids (BAs) accumulation and hepatic cytokine production are involved in adverse intestinal outcomes. These findings triggered us to study the liver and enterohepatic circulation (EHC) following intra-amniotic (IA) lipopolysaccharide (LPS) exposure. An ovine chorioamnionitis model was used in which circulatory cytokines and outcomes of the liver and EHC of preterm lambs were longitudinally assessed following IA administration of 10 mg LPS at 5, 12 or 24h or 2, 4, 8 or 15d before preterm birth. Hepatic inflammation was observed, characterized by increased hepatic cytokine mRNA levels (5h – 2d post IA LPS exposure) and increased erythropoietic clusters (at 8 and 15 days post IA LPS exposure). Besides, 12h after IA LPS exposure, plasma BA levels were increased, whereas gene expression levels of several hepatic BA transporters were decreased. Initial EHC alterations normalized over time. Concluding, IA LPS exposure induces significant time-dependent changes in the fetal liver and EHC. These chorioamnionitis induced changes have potential postnatal consequences and the duration of IA LPS exposure might be essential herein.

The establishment of large populations of yellow-legged gull Larus michahellis in coastal and urban areas can lead to strong changes in vegetation cover and composition through creating physical disturbance in the vegetation and impacting the soil quality through defecation. In this study, we evaluated the effects of breeding yellow-legged gull populations on tall and short vegetation cover and plant species composition in old (occupied for 13 years) and new (occupied for 3 years) colony sites in grey dunes of the Algarve, southern Portugal. In each site, sampling plots were used to measure the percentage of vegetation cover in areas with and without breeding gulls. In the old colony site, the cover by tall vegetation was substantially reduced and the cover by short vegetation substantially increased in the areas where gulls are breeding in comparison with the adjacent areas. In the new colony sites, there were only minor differences. The increase in cover of short vegetation in the breeding area of the old colony site was mostly by nitrophilous species (Paronychia argentea and Malcolmia littorea) and should be explained by the decrease in vegetation cover of tall plant species and by feces deposition. Tall and slow-growing species Suaeda maritima and Helichrysum italicum covers were negatively affected. Our results showed that yellow-legged gulls affected vegetation cover and composition of grey dunes after 3 years of consecutive breeding, and this should be considered in the management of these habitats where breeding yellow-legged gulls are increasing.

Abstract Background Globally, methamphetamine use has increased in prevalence in recent years. In Australia, there has been a dramatic increase in numbers of people seeking treatment, including residential rehabilitation, for methamphetamine use disorder (MUD). While residential rehabilitation is more effective for MUD than withdrawal treatment (i.e. “detoxification”) alone, relapse rates remain high, with approximately half of rehabilitation clients using methamphetamine within 3 months of rehabilitation. “Approach bias modification” (ABM) is a computerised cognitive training approach that aims to dampen automatically triggered impulses to approach drugs and drug-related stimuli. ABM has been demonstrated to reduce alcohol relapse rates, but no randomised controlled trials of ABM for MUD have yet been conducted. We aim to test whether a novel “personalised” form of ABM, delivered during rehabilitation, reduces post-treatment methamphetamine use, relative to a sham-training control condition. Secondary outcomes will include dependence symptoms, cravings, and approach bias. Methods We aim to recruit 100 participants attending residential rehabilitation for MUD at 3 sites in the Melbourne metropolitan area. Participants will complete baseline measures of methamphetamine use, craving, dependence severity, and approach bias before being randomised to receiving 6 sessions of ABM or “sham” training. In the active condition, ABM will be personalised for each participant, using those methamphetamine images that they rate as most relevant to their recent methods of methamphetamine use as “avoidance” images and using positive images representing their goals or healthy sources of pleasure as “approach” images. Approach bias and craving will be re-assessed following completion of training, and methamphetamine use, dependence, and craving will be assessed 4 weeks and 3 months following discharge from residential treatment. Discussion This study is the first randomised controlled trial of ABM for MUD and also the first ABM study to test using a personalised set of both approach and avoid images for ABM training. If effective, the low cost and easy implementation of ABM means it could be widely implemented as a standard part of MUD treatment. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12620000072910. Registered on 30 January 2020 (prospectively registered): https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378804&isReview=true

Abstract Background The prevalence of obesity among infants less than 2 years of age has increased by more than 60% over the last three decades. Obese infants and toddlers are at an increased risk for staying overweight into adolescence and adulthood. Metabolic programming has been demonstrated in animal models whereby early life feeding habits result in life-long changes in hormone balance and metabolism. Our study explores if newborn over-nutrition on the first day of life (DOL1) is associated with risk for future overweight and obesity in childhood. Methods Retrospective chart data was collected for full term formula-fed infants born between January 2008 and December 2012 who continued care at the same institution. Data included the volume of formula (ml) consumed on DOL1 as well, as subsequent yearly BMI measures from well child checkups (WCC). Overfeeding was categorized as any feed greater than or equal to 30 ml on any of the first seven feeds while controlling for birth weight. Results The final data set included 1106 infants (547 male; 559 female). 1023 of the 1106 newborns (93%) were overfed at least once during DOL1, while 789 of 1106 (71%) were overfed 3 or more times during their first 7 feeds. After adjusting for birth weight, infants who were overfed 5 of the first 7 feeds were 5 times as likely to be overweight or obese at their 4th year well child check-up (p

In the last four years, advances in Deep Learning technology have enabled the inference of selected mutational alterations directly from routine histopathology slides. In particular, recent studies have shown that genetic changes in clinically relevant driver genes are reflected in the histological phenotype of solid tumors and can be inferred by analysing routine Haematoxylin and Eosin (H&E) stained tissue sections with Deep Learning. However, these studies mostly focused on selected individual genes in selected tumor types. In addition, genetic changes in solid tumors primarily act by changing signaling pathways that regulate cell behaviour. In this study, we hypothesized that Deep Learning networks can be trained to directly predict alterations of genes and pathways across a spectrum of solid tumors. We manually outlined tumor tissue in H&E-stained tissue sections from 7,829 patients with 23 different tumor types from The Cancer Genome Atlas. We then trained convolutional neural networks in an end-to-end way to detect alterations in the most clinically relevant pathways or genes, directly from histology images. Using this automatic approach, we found that alterations in 12 out of 14 clinically relevant pathways and numerous single gene alterations appear to be detectable in tissue sections, many of which have not been reported before. Interestingly, we show that the prediction performance for single gene alterations is better than that for pathway alterations. Collectively, these data demonstrate the predictability of genetic alterations directly from routine cancer histology images and show that individual genes leave a stronger morphological signature than genetic pathways.

The Pulvers' silhouette showcards provide a non-invasive and easy-to-use way of assessing an individual's body size perception using nine silhouette shapes. However, their utility across different populations has not been examined. This study aimed to assess: 1) the relationship between silhouette perception and measured anthropometrics, i.e., body mass index (BMI), waist circumference (WC), waist-height-ratio (WHtR), and 2) the ability to predict with silhouette showcards anthropometric adiposity measures, i.e., overweight and obesity (BMI ≥ 25 kg/m2), obesity alone (BMI ≥ 30 kg/m2), elevated WC (men ≥ 94 cm; women ≥ 80 cm), and WHtR (> 0.5) across the epidemiological transition. 751 African-origin participants, aged 20-68 years old, from the United States (US), Seychelles, and Ghana, completed anthropometrics and selected silhouettes corresponding to their perceived body size. Silhouette performance to anthropometrics was examined using a least-squares linear regression model. A receiver operator curve (ROC) was used to investigate the showcards ability to predict anthropometric adiposity measures. The relationship between silhouette ranking and BMI were similar between sexes of the same country but differed between countries: 3.65 [95% CI: 3.34-3.97] BMI units/silhouette unit in the US, 3.23 [2.93-3.74] in Seychelles, and 1.99 [1.72-2.26] in Ghana. Different silhouette cutoffs predicted obesity differently in the three countries. For example, a silhouette ≥ five had a sensitivity/specificity of 77.3%/90.6% to predict BMI ≥ 25 kg/m2 in the US, but 77.8%/85.9% in Seychelles and 84.9%/71.4% in Ghana. Ultimately, silhouettes predicted BMI, WC, and WHtR similarly within each country and sex but not across countries. Our data suggest that Pulvers' silhouette showcards may be a helpful tool to predict anthropometric and adiposity measures in different populations when direct measurement cannot be performed. However, no universal silhouette cutoff can be used for detecting overweight or obesity status, and population-specific differences may stress the need to calibrate silhouette showcards when using them as a survey tool in different countries.

Vaccinia virus (VACV) is the causative agent of an emerging viral zoonosis called bovine vaccinia (BV). Several studies have documented characteristics of VACV infections in Brazil; however, the manner in which this virus is maintained in wildlife remains unknown. This work investigated the presence of viral DNA and anti-orthopoxvirus (OPXV) antibodies in samples collected from small mammals in a VACV-endemic area in Minas Gerais, Brazil, in the absence of current outbreaks. Samples did not show amplification of OPXV DNA in molecular tests. However, 5/142 serum samples demonstrated the presence of anti-OPXV neutralizing antibodies in serological tests. These data reinforce the involvement of small mammals in the natural cycle of VACV, highlighting the need for further ecological studies to better understand how this virus is maintained in nature and to develop measures to prevent BV outbreaks.

We present the first detailed comparison of populations of dwarf galaxy stellar streams in cosmological simulations and the Milky Way. In particular, we compare streams identified around 13 Milky Way analogs in the FIRE-2 simulations to streams observed by the Southern Stellar Stream Spectroscopic Survey ( S ^5 ). For an accurate comparison, we produce mock Dark Energy Survey (DES) observations of the FIRE streams and estimate the detectability of their tidal tails and progenitors. The number and stellar mass distributions of detectable stellar streams is consistent between observations and simulations. However, there are discrepancies in the distributions of pericenters and apocenters, with the detectable FIRE streams, on average, forming at larger pericenters (out to >110 kpc) and surviving only at larger apocenters (≳40 kpc) than those observed in the Milky Way. We find that the population of high-stellar-mass dwarf galaxy streams in the Milky Way is incomplete. Interestingly, a large fraction of the FIRE streams would only be detected as intact satellites in DES-like observations, since their tidal tails have too low surface brightness to be detectable. We thus predict a population of yet-undetected tidal tails around Milky Way satellites, as well as a population of fully undetected low-surface-brightness stellar streams, and estimate their detectability with the Rubin Observatory. Finally, we discuss the causes and implications of the discrepancies between the stream populations in FIRE and the Milky Way, and explore future avenues for tests of satellite disruption in cosmological simulations.

Translocation-associated renal cell carcinoma (tRCC) is a rare, aggressive malignancy that primarily affects children and young adults. There is no clear consensus on the most effective treatment for tRCC and there are no biomarkers of response to treatments in these patients. We present a case of a 23 year-old female with metastatic tRCC to the lungs who was started on treatment with nivolumab and ipilimumab. She had a complete radiographic response to treatment and has been progression-free for over 18 months. Immunofluorescence imaging performed on the baseline primary tumor sample showed significant intratumoral immune infiltration. Importantly, these cells are present in niches characterized by TCF1+ CD8+ T cells. Histopathologic investigation showed the presence of lymphocytes in the fibrovascular septae and foci of lymphovascular invasion. Furthermore, lymphovascular invasion and intratumor niches with TCF1+ CD8+ T cells may predict a favorable response to treatment with nivolumab and ipilimumab. These findings have significant clinical relevance given that immune checkpoint inhibitors are approved for several malignancies and predictive biomarkers for response to treatment are lacking. Importantly, the identification of these TCF1+ CD8+ T cells may guide treatment for patients with tRCC, which is a rare malignancy without a consensus first-line treatment option.

E. coli is one of the etiological agents responsible for pyometra in female dogs, with conventional treatment involving ovariohysterectomy. Here, we report the isolation and full characterization of two novel lytic phages, viz. vB_EcoM_Uniso11 (ph0011) and vB_EcoM_Uniso21 (ph0021). Both phages belong to the order Caudovirales and present myovirus-like morphotypes, with phage ph0011 being classified as Myoviridae genus Asteriusvirus and phage ph0021 being classified as Myoviridae genus Tequatrovirus, based on their complete genome sequences. The 348,288 bp phage ph0011 and 165,222 bp phage ph0021 genomes do not encode toxins, integrases or antimicrobial resistance genes neither depolymerases related sequences. Both phages were shown to be effective against at least twelve E. coli clinical isolates in in vitro antibacterial activity assays. Based on their features, both phages have potential for controlling pyometra infections caused by E. coli. Phage ph0011 (reduction of 4.24 log CFU/mL) was more effective than phage ph0021 (reduction of 1.90 log CFU/mL) after 12 h of incubation at MOI 1000. As a cocktail, the two phages were highly effective in reducing the bacterial load (reduction of 5.57 log CFU/mL) at MOI 100, after 12 h of treatment. Both phages were structurally and functionally stabilized in vaginal egg formulations.

Abstract Coronavirus 2019 (COVID‐19) disease has been a public health emergency of international concern with millions of confirmed cases globally. Closed environments with reduced ventilation contribute to the spread of COVID‐19, including superspreading events. Exercising in closed places further increases the risk for transmission. Therefore, many fitness facilities were closed as part of mandated shutdowns early in the pandemic. Evidence‐based safety protocols have now emerged and substantially reduce the risk of transmission. We report three positive cases of SARS‐CoV‐2 identified at a Dojo exercise facility in Manlius, NY, at three distinct time points. All cases were present in the Dojo 2 days prior to symptoms, a time period considered to be highly infectious. The safety protocols included universal mask wearing (no valves), multiple high‐efficiency particulate air (HEPA) filters, and reduced capacity which resulted in no known spread of COVID‐19.

Abstract Background The prevalence of pediatric allergic diseases has increased rapidly in the United States over the past few decades. Recent studies suggest an association between the increase in allergic disease and early disturbances to the gut microbiome. The gut microbiome is a set of intestinal microorganisms that begins to form during birth and is highly susceptible to disturbance during the first year of life. Early antibiotic exposure may negatively impact the gut microbiota by altering the bacterial composition and causing dysbiosis, thus increasing the risk for developing childhood allergic disease. Methods We performed a retrospective chart review of data in Loyola University Medical Center’s (LUMC) Epic system from 2007 to 2016. We defined antibiotic exposure as orders in both the outpatient and inpatient settings. Inclusion criteria were being born at LUMC with at least two follow up visits. Asthma and allergic rhinitis diagnoses were obtained using ICD 9 and ICD 10 codes. We controlled for multiple confounding factors. Using Stata, bivariate logistic regression was performed between antibiotics from 0 to 12 months of life and development of disease. This analysis was repeated for total lifetime antibiotics. We defined statistically significant as p