Engagement in Care, Awareness, and Interest in Long-Acting Injectable Anti-Retroviral Therapy.

Long Acting Injectable (LAI) therapy to treat HIV is an alternative to daily oral medications. The success of early roll-out of LAI to eligible patients requires a better understanding of patients' awareness and interest in this novel therapy. We administered an electronic survey to patients attending an urban HIV clinic in the US South. Eligible participants were 18 + years old with a most recent HIV-1 viral load < 200 copies/ml, without any evidence of genotypic resistance to LAI components or chronic hepatitis B. Survey recipients were asked about current treatment, engagement in care, and knowledge of LAI. Between January-April 2023, 480 patients were screened; 319 were eligible, and 155 (49%) completed the survey. The majority (119, 77%) were aware of, and 87 (56%) were interested in LAI. In regression analysis, only age was associated with interest in LAI (OR 0.95, 95% CI 0.92,0.99). Among proposed benefits of injectables, ease of travel without pills, lack of daily pill-taking, and fewer medication interactions were most appealing. Among proposed concerns with injectables, higher cost and insurance coverage of the new medicine were most worrisome. A large majority of people with HIV (PWH) are aware of the newest treatment available, and just over half of our sample expressed interest in LAI. Older age was associated with lower interest in LAI. LAI is appealing for its convenience, privacy, and avoidance of drug interactions, while the increased costs associated with LAI need to be addressed.

Anterior thalamic nucleus local field potentials during focal temporal lobe epileptic seizures.

Objective: To analyze the local field potentials (LFPs) in patients with focal drug-resistant epilepsy (DRE) from the anterior nucleus of the thalamus (ANT) during inter-ictal state and seizure state. Method: ANT stereotactic EEG (SEEG) recordings were studied in four patients with focal temporal lobe epilepsy. SEEG data was classified as inter-ictal and ictal state and sub-categorized into electrographic (ESz), focal aware seizure (FAS), focal with impaired awareness (FIA), or focal to bilateral tonic-clonic seizure (FBTC). LFP was analyzed at 4 Hz, 8 Hz, 16 Hz, 32 Hz, high gamma (100 Hz), and ripples (200 Hz) using spectrogram analysis and a statistical comparison of normalized power spectral density (PSD) averaged during seizures versus pre-ictal baseline segments. Result: The LFP recordings were analyzed for 162 seizures (127 ESz, 23 FAS, 6 FIA, and 6 FBTC). Based on time-frequency data (spectrogram), a broad band of activity, occurring between 2 and 6 Hz and centered at 4 Hz, and thin-band activity occurring specifically at 8 Hz on the frequency spectrogram were observed during the inter-ictal state. Statistically significant changes in LFP-PSD were seen for FAS, FIA, and FBTC. We observed a significant gain in LFP at the lower frequency band during FAS at 4 Hz, FIA, and FBTC at 4, 8, and 16 Hz while also observing increases at higher frequencies during FBTC at 100 and 200 Hz and a decrease during FAS seizures at 32 Hz. In contrast, no significant change in LFP power was seen for electrographic seizures. Interpretation: Our observations from a limited dataset indicate that all clinical seizure types, but not electrographic seizures, caused a change in ANT-LFP based on the magnitude of the associated power spectral density (PSD). Future work will be needed to validate the use of ANT-LFP at these frequencies as accurate measurements of seizure occurrence and severity. This work represents a first step toward understanding ANT thalamic LFP patterns during focal seizures and developing adaptive DBS strategies.

A novel murine model mimicking male genital Neisseria species infection using Neisseria musculi†.

With ~78 million cases yearly, the sexually transmitted bacterium Neisseria gonorrhoeae is an urgent threat to global public health due to continued emergence of antimicrobial resistance. In the male reproductive tract, untreated infections may cause permanent damage, poor sperm quality, and subsequently subfertility. Currently, few animal models exist for N. gonorrhoeae infection, which has strict human tropism, and available models have limited translatability to human disease. The absence of appropriate models inhibits the development of vital new diagnostics and treatments. However, the discovery of Neisseria musculi, a mouse oral cavity bacterium, offers much promise. This bacterium has already been used to develop an oral Neisseria infection model, but the feasibility of establishing urogenital gonococcal models is unexplored. We inoculated mice via the intrapenile route with N. musculi. We assessed bacterial burden throughout the male reproductive tract, the systemic and tissue-specific immune response 2-weeks postinfection, and the effect of infection on sperm health. Neisseria musculi was found in penis (2/5) and vas deferens (3/5) tissues. Infection altered immune cell counts: CD19+ (spleen, lymph node, penis), F4/80+ (spleen, lymph node, epididymus), and Gr1+ (penis) compared with noninfected mice. This culminated in sperm from infected mice having poor viability, motility, and morphology. We hypothesize that in the absence of testis infection, infection and inflammation in other reproductive is sufficient to damage sperm quality. Many results herein are consistent with outcomes of gonorrhoea infection, indicating the potential of this model as a tool for enhancing the understanding of Neisseria infections of the human male reproductive tract.

Correction to "ß-Phase Crystallinity, Printability, and Piezoelectric Characteristics of Polyvinylidene Fluoride (PVDF)/Poly(methyl methacrylate) (PMMA)/Cyclopentyl-polyhedral Oligomeric Silsesquioxane (Cp-POSS) Melt-Compounded Blends".

[This corrects the article DOI: 10.1021/acsapm.4c00468.].

Modulation of AAV9 Galactose Binding Yields Novel Gene Therapy Vectors and Predicts Cross-Species Differences in Glycan Avidity.

Effective use of adeno-associated viruses (AAVs) for clinical gene therapy is limited by their propensity to accumulate in and transduce the liver. This natural liver tropism is associated with severe adverse events at the high doses that can be necessary for achieving therapeutic transgene expression in extra-hepatic tissues. To improve the safety and cost of AAV gene therapy, capsid engineering efforts are underway to redirect in vivo AAV biodistribution away from the liver toward disease-relevant peripheral organs such as the heart. Building on previous work, we generated a series of AAV libraries containing variations at three residues (Y446, N470, and W503) of the galactose-binding pocket of the AAV9 VP1 protein. Screening of this library in mice identified the XRH family of variants (Y446X, N470R, and W503H), the strongest of which, HRH, exhibited a six-fold reduction in liver RNA expression and a ten-fold increase in cardiac RNA expression compared with wild-type AAV9 in the mouse. Screening of our library in a nonhuman primate (NHP) revealed reduced performance of AAV9 and two closely related vectors in the NHP liver compared with the mouse liver. Measurement of the galactose-binding capacity of our library further identified those same three vectors as the only strong galactose binders, suggesting an altered galactose presentation between the mouse and NHP liver. N-glycan profiling of these tissues revealed a 9% decrease in exposed galactose in the NHP liver compared with the mouse liver. In this work, we identified a novel family of AAV variants with desirable biodistribution properties that may be suitable for targeting extra-hepatic tissues such as the heart. These data also provide important insights regarding species- and tissue-specific differences in glycan presentation that may have implications for the development and translation of AAV gene therapies.

They all rock: A systematic comparison of conformational movements in LeuT-fold transporters.

Many membrane transporters share the LeuT fold-two five-helix repeats inverted across the membrane plane. Despite hundreds of structures, whether distinct conformational mechanisms are supported by the LeuT fold has not been systematically determined. After annotating published LeuT-fold structures, we analyzed distance difference matrices (DDMs) for nine proteins with multiple available conformations. We identified rigid bodies and relative movements of transmembrane helices (TMs) during distinct steps of the transport cycle. In all transporters, the bundle (first two TMs of each repeat) rotates relative to the hash (third and fourth TMs). Motions of the arms (fifth TM) to close or open the intracellular and outer vestibules are common, as is a TM1a swing, with notable variations in the opening-closing motions of the outer vestibule. Our analyses suggest that LeuT-fold transporters layer distinct motions on a common bundle-hash rock and demonstrate that systematic analyses can provide new insights into large structural datasets.

Outcomes and Performance Following Posteromedial Elbow Debridement in Major League Baseball Players.

BACKGROUND: Overhead athletes are particularly susceptible to elbow valgus extension overload syndrome and development of pathologic changes in the posteromedial elbow. Though arthroscopic débridement/osteophyte resection is frequently performed, few studies have analyzed the outcomes of this procedure, and none have specifically addressed professional level athletes. HYPOTHESIS/PURPOSE: We hypothesized that following posteromedial elbow débridement, Major League Baseball (MLB) pitchers would exhibit a higher rate of ulnar collateral ligament (UCL) reconstruction than baseline incidence in the existing literature, along with a decline in pitching performance. METHODS: Using publicly accessible websites, MLB athletes undergoing posteromedial elbow débridement from 2007 to 2022 were identified. Demographic information, procedure details, return to play (RTP) information, return to the disabled/injured list (DL/IL), subsequent UCL reconstruction, and pitching statistics were analyzed. Pitching performance metrics included Earned Runs Average (ERA), Walks Plus Hits Per Innings Pitched (WHIP), innings pitched, and fastball velocity. RESULTS: A total of 39 MLB players, including 26 pitchers, were included. Within the first three seasons after surgery, 82.1% (n=32) of players returned to play at the MLB level at a mean time of 176.1 ± 69 days. Pitchers exhibited a return to play (RTP) rate of 76.9% (n=20) at 175.8 ± 16 days. A total of 38.5% (n=10) of pitchers returned to the DL/IL for elbow-related issues within three seasons. Subsequent UCL reconstruction was seen only in pitchers, with a frequency of 19.2% (n=5). No statistically significant differences between single season pre/postoperative pitching metrics were identified. A small but significant (p<0.05) decrease in fastball velocity (94.4 vs 92.84; p=0.02) was observed over a three-season comparison. CONCLUSION: Contrary to our hypothesis, this study demonstrates that posteromedial elbow débridement is a viable surgery in MLB athletes, with RTP rate of 82.1% and no increase in rate of UCL reconstruction. Furthermore, there was no significant difference in single season pre- and postoperative statistical pitching performance. However, over three years postoperatively, there was a 38.5% rate of return to the DL/IL for ongoing elbow ailment and a significant decrease in pitch velocity, raising some concern over the longevity of postoperative improvements.

Prior Teaching Experience and Barriers to Effective Resident Teaching: A Cross-Sectional Study.

INTRODUCTION: Resident physicians play an important role in teaching the next generation of health-care providers, yet limited research has explored factors influencing effective teaching, such as preresidency experiences or barriers within residency. This study examines residents' prior teaching experience, its correlation with teaching attitudes, and identifies potential barriers to sustained teaching engagement. METHODS: This cross-sectional study surveyed residents across multiple specialties at a single academic center. The survey assessed preresidency teaching experience, perceived barriers, and attitudes toward teaching. Univariate and multivariate analyses identified differences in teaching attitudes based on prior teaching experience and gender. RESULTS: Ninety-two residents across 11 specialties participated (52.2% female). Internal Medicine (28.3%) and General Surgery (26.1%) had the highest representation. Two-thirds of respondents (69.6%) had formal teaching experience before residency. After adjustment, prior teaching experience and male gender were associated with feeling prepared to teach medical students (P = 0.014 and P = 0.001). Male gender was also linked to confidence in teaching material on the wards (P = 0.015). Barriers identified included time constraints (73.9%), lack of content clarity (28.3%), and uncertainty about teaching methods (33.7%). CONCLUSIONS: Residents with prior teaching experience exhibit higher levels of preparedness, content clarity, and confidence in their teaching abilities, underscoring the importance of teaching experience before residency. This study also identified significant barriers to effective teaching, including time constraints, lack of content clarity, uncertainty about teaching methods, and perceived disinterest from medical students. Addressing these barriers is essential for optimizing medical student education.

Worsening of lymphopenia in patients with multiple sclerosis when switched from dimethyl fumarate to diroximel fumarate.

BACKGROUND: Diroximel fumarate (DRF) and dimethyl fumarate (DMF) are similar disease-modifying therapies (DMTs) that reduce disease activity in patients with relapsing-remitting multiple sclerosis (MS). We expect that patients on DRF would experience a similar incidence and severity of lymphopenia, given that it is a well-documented side effect of DMF treatment. METHODS: We utilized linear mixed-effects models to test for differences in white blood cell count (WBC), absolute lymphocyte count (ALC), absolute CD3+ count, absolute CD4+ count, and absolute CD8+ count over time in clinically stable patients with MS on DMF who switched to DRF. RESULTS: Twenty-two patients with MS who were clinically stable on DMF switched to DRF. Linear mixed-effects models showed a decrease in ALC when switching medications (ß = -225.70, p < 0.040). In addition, the models showed a decrease in absolute CD8+ counts after switches from DMF to DRF (ß = -85.59, p = 0.034). CONCLUSION: Patients with MS who are stable on DMF and switch to DRF may experience worsening of lymphopenia and lower absolute CD8+ counts, which may increase their risk of opportunistic infections. These findings indicate that close lymphocyte subset monitoring is clinically important when switching patients with MS from DMF to DRF.

Combined inhibition of KRASG12C and mTORC1 kinase is synergistic in non-small cell lung cancer.

Current KRASG12C (OFF) inhibitors that target inactive GDP-bound KRASG12C cause responses in less than half of patients and these responses are not durable. A class of RASG12C (ON) inhibitors that targets active GTP-bound KRASG12C blocks ERK signaling more potently than the inactive-state inhibitors. Sensitivity to either class of agents is strongly correlated with inhibition of mTORC1 activity. We have previously shown that PI3K/mTOR and ERK-signaling pathways converge on key cellular processes and that inhibition of both pathways is required for inhibition of these processes and for significant antitumor activity. We find here that the combination of a KRASG12C inhibitor with a selective mTORC1 kinase inhibitor causes synergistic inhibition of Cyclin D1 expression and cap-dependent translation. Moreover, BIM upregulation by KRASG12C inhibition and inhibition of MCL-1 expression by the mTORC1 inhibitor are both required to induce significant cell death. In vivo, this combination causes deep, durable tumor regressions and is well tolerated. This study suggests that the ERK and PI3K/mTOR pathways each mitigate the effects of inhibition of the other and that combinatorial inhibition is a potential strategy for treating KRASG12C-dependent lung cancer.

Spectrotemporal profiling of ultrasonic vocalizations during neonatal opioid withdrawal reveals a kappa opioid receptor component in female mice.

Opioid use during pregnancy can lead to negative infant health outcomes, including neonatal opioid withdrawal syndrome(NOWS). NOWS comprises gastrointestinal, autonomic nervous system, and neurological dysfunction that manifest during spontaneous withdrawal. Current treatments involve non-pharmacological and pharmacological interventions, however, there is no one standardized approach, in part because of variability in NOWS severity. To effectively model NOWS traits in mice, we used a third trimester-approximate opioid exposure paradigm, where neonatal inbred FVB/NJ and outbred Carworth Farms White(CFW) pups were injected twice-daily with morphine(10-15mg/kg, s.c.) or saline(0.9%, 20 ul/g, s.c.) from postnatal day(P) one to P14. We observed reduced body weight gain, hypothermia, thermal hyperalgesia, and increased ultrasonic vocalizations(USVs). Neonatal USVs are emitted exclusively in isolation to communicate distress and thus serve as a model behavior for affective states. On P14, we observed altered USV syllable profiles during spontaneous morphine withdrawal, including an increase in Complex 3 syllables in FVB/NJ females(but not males) and in CFW mice of both sexes. Brainstem transcriptomics revealed an upregulation of the kappa opioid receptor(Oprk1), whose activation has previously been shown to contribute to withdrawal-induced dysphoria. Treatment with the kappa opioid receptor(KOR) antagonist, nor-BNI(30 mg/kg, s.c.), significantly reduced USV emission in FVB/NJ females, but not FVB/NJ males during spontaneous morphine withdrawal. Furthermore, treatment with the KOR agonist, U50,488h(0.625 mg/kg, s.c.), was sufficient to increase USV emission on P10(both sexes) and on P14(females only) in FVB/NJ mice. Together, these results indicate a female-specific recruitment of the dynorphin/KOR system in neonatal opioid withdrawal symptom severity.

Rare Case of Neuroendocrine Metastasis to the Left Ventricle.

Carcinoid syndrome is a constellation of signs and symptoms caused by different hormones produced by carcinoid tumors. Very rarely, those tumors can metastasize to the heart and cause cardiac involvement of the tumor. This study presents a very rare case of secondary cardiac tumor affecting the left ventricle from a metastatic carcinoid tumor originating from the small intestine without carcinoid valvular heart disease.

Failure to Rescue After Percutaneous Coronary Intervention: Insights From the National Cardiovascular Data Registry.

BACKGROUND: Failure to rescue (FTR) describes in-hospital mortality following a procedural complication and has been adopted as a quality metric in multiple specialties. However, FTR has not been studied for percutaneous coronary intervention (PCI) complications. METHODS: This is a retrospective study of patients undergoing PCI from the American College of Cardiology National Cardiovascular Data Registry's CathPCI Registry between April 1, 2018, and June 30, 2021. PCI complications evaluated were significant coronary dissection, coronary artery perforation, vascular complication, significant bleeding within 48 hours, new cardiogenic shock, and tamponade. Secular trends for FTR were evaluated with descriptive analysis, and hospital-level variation and clinical predictors were analyzed with logistic regression. RESULTS: Among 2 196 661 patients undergoing PCI at 1483 hospitals, 3.5% had at least 1 PCI complication. In-hospital mortality occurred more frequently following a complication compared with cases without a complication (19.7% versus 1.3%). FTR increased during the study period from 17.1% to 20.1% (P<0.001). The median odds ratio for FTR was 1.48 (95% CI, 1.44-1.53) indicating significant hospital-level variation. Spearman rank correlation demonstrated the modest correlation between FTR and in-hospital mortality, 0.525 (P<0.001). CONCLUSIONS: Major procedural complications during PCI are infrequent, but FTR occurs in roughly 1 in 5 patients following a PCI procedural complication with significant hospital-level variation. Improved understanding of practices associated with low FTR could meaningfully improve patient outcomes following a PCI complication.

Weather and leaf age separately contribute to temporal shifts in phyllosphere community structure and composition.

Microbial communities living on plant leaves can positively or negatively influence plant health and, by extension, can impact whole ecosystems. Most research into the leaf microbiome consists of snapshots, and little is known about how microbial communities change over time. Weather and host physiological characteristics change over time and are often collinear with other time-varying factors, such as substrate availability, making it difficult to separate the factors driving microbial community change. We leveraged repeated measures over the course of an entire year to isolate the relative importance of environmental, host physiological, and substrate age-related factors on the assembly, structure, and composition of leaf-associated fungal communities. We applied both culturing and sequencing approaches to investigate these communities, focusing on a foundational, widely-distributed plant of conservation concern: basin big sagebrush ( Artemisia tridentata subsp. tridentata ). We found that changes in alpha diversity were independently affected by the age of a community and the air temperature. Surprisingly, total fungal abundance and species richness were not positively correlated and responded differently, sometimes oppositely, to weather. With regard to beta diversity, communities were more similar to each other across similar leaf ages, air temperatures, leaf types, and δ 13 C stable isotope ratios. Nine different genera were differentially abundant with air temperature, δ 13 C, leaf type, and leaf age, and a set of 20 genera were continuously present across the year. Our findings highlight the necessity for longer-term, repeated sampling to parse drivers of temporal change in leaf microbial communities. Open Research Statement: All ITS DNA amplicon sequence raw data are deposited in the NCBI Sequence Read Archive (SRA), BioProject number PRJNA1107252, data will be released upon publication. All community data, metadata, taxonomic data, and R code necessary to reproduce these results are deposited in the GitHub repository archived on Zenodo: 10.5281/zenodo.11106439.

Propofol anesthesia destabilizes neural dynamics across cortex.

Every day, hundreds of thousands of people undergo general anesthesia. One hypothesis is that anesthesia disrupts dynamic stability-the ability of the brain to balance excitability with the need to be stable and controllable. To test this hypothesis, we developed a method for quantifying changes in population-level dynamic stability in complex systems: delayed linear analysis for stability estimation (DeLASE). Propofol was used to transition animals between the awake state and anesthetized unconsciousness. DeLASE was applied to macaque cortex local field potentials (LFPs). We found that neural dynamics were more unstable in unconsciousness compared with the awake state. Cortical trajectories mirrored predictions from destabilized linear systems. We mimicked the effect of propofol in simulated neural networks by increasing inhibitory tone. This in turn destabilized the networks, as observed in the neural data. Our results suggest that anesthesia disrupts dynamical stability that is required for consciousness.

A practical introduction to holo-omics.

Holo-omics refers to the joint study of non-targeted molecular data layers from host-microbiota systems or holobionts, which is increasingly employed to disentangle the complex interactions between the elements that compose them. We navigate through the generation, analysis, and integration of omics data, focusing on the commonalities and main differences to generate and analyze the various types of omics, with a special focus on optimizing data generation and integration. We advocate for careful generation and distillation of data, followed by independent exploration and analyses of the single omic layers to obtain a better understanding of the study system, before the integration of multiple omic layers in a final model is attempted. We highlight critical decision points to achieve this aim and flag the main challenges to address complex biological questions regarding the integrative study of host-microbiota relationships.

Effect of Qualifying Atherosclerotic Cardiovascular Disease Diagnosis Proximity on Cardiovascular Risk and Benefit of Empagliflozin in the EMPA-REG OUTCOME Trial.

Background: In patients with type 2 diabetes mellitus (T2DM), a history of an ischemic event is associated with increased risk for cardiovascular (CV) disease. Whether patients with T2DM and a recent atherothrombotic diagnosis benefit from early intervention with a sodium-glucose co-transporter 2 inhibitor is unknown. Methods: This study is a secondary analysis of the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME), which compared empagliflozin to placebo in adults with T2DM and atherosclerotic CV disease (ASCVD). Participants were categorized based on the time since their last qualifying ASCVD diagnosis (≤ 1 year vs > 1 year). Qualifying ASCVD diagnoses included ischemic or hemorrhagic stroke, myocardial infarction, coronary artery disease, and peripheral artery disease. The primary outcome was a composite of CV death, nonfatal myocardial infarction, or nonfatal stroke. Results: A total of 6796 participants (n = 4547 empagliflozin, n = 2249 placebo) were included. Median time since the last qualifying ASCVD diagnosis was 3.8 years (quartile 1-quartile 3: 1.5-7.6), and most qualifying diagnoses occurred > 1 year before randomization (≤ 1 year, n = 1214; > 1 year, n = 5582). Empagliflozin reduced the incidence of the primary outcome irrespective of the time since the last qualifying ASCVD diagnosis (≤ 1 year: hazard ratio 0.82, 95% confidence interval: 0.57-1.16; vs > 1 year: hazard ratio 0.85, 95% confidence interval: 0.72-1.00; P for interaction = 0.84). Results were similar for the composite of CV death or hospitalization for heart failure. Conclusions: Empagliflozin improved CV outcomes in participants with T2DM, irrespective of the time since the last qualifying ASCVD diagnosis at randomization. Prospective trials are necessary to investigate the use of sodium-glucose co-transporter 2 inhibitors at the time of an acute ASCVD event. Trial Registration: EMPA-REG OUTCOME (Clinicaltrials.gov identifier: NCT01131676).

Contexte: Chez les patients atteints de diabète de type 2 (DT2), des antécédents d'accidents ischémiques sont associés à un risque accru de maladie cardiovasculaire (CV). On ignore si une intervention précoce par un inhibiteur du cotransporteur sodium-glucose de type 2 pourrait être bénéfique pour les patients atteints de DT2 ayant récemment reçu un diagnostic d'athérothrombose. Méthodologie: Cette étude est une analyse secondaire de l'essai EMPA-REG OUTCOME ( Empa gliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients­ R emoving E xcess G lucose), qui visait à comparer l'empagliflozine à un placebo chez des adultes atteints de DT2 et d'une maladie CV athéroscléreuse. Les participants ont été répartis selon le temps écoulé depuis leur plus récent diagnostic de maladie CV athéroscléreuse admissible (≤ 1 an vs > 1 an). Les diagnostics de maladies CV athéroscléreuses admissibles comprenaient un accident vasculaire cérébral ischémique ou hémorragique, un infarctus du myocarde, une coronaropathie et une artériopathie périphérique. Le critère d'évaluation principal était composé des décès d'origine CV, des infarctus du myocarde non mortels et des accident vasculaire cérébral non mortels. Résultats: Au total, 6796 participants (n = 4547 pour l'empagliflozine, n = 2249 pour le placebo) ont été inclus. Le temps écoulé médian depuis le diagnostic le plus récent de maladie CV athéroscléreuse admissible était de 3,8 ans (quartile 1-quartile 3 : 1,5-7,6). La plupart des diagnostics admissibles avaient été posés plus de 1 an avant la répartition aléatoire (≤ 1 an, n = 1214; > 1 an, n = 5582). L'empagliflozine a réduit la fréquence des événements constituant le critère d'évaluation principal, sans égard au temps écoulé depuis le plus récent diagnostic de maladie CV athéroscléreuse admissible (≤ 1 an : rapport des risques instantanés 0,82, intervalle de confiance à 95 % : 0,57-1,16; vs > 1 an : rapport des risques instantanés 0,85, intervalle de confiance à 95 % : 0,72-1,00; p pour l'interaction = 0,84). Les résultats étaient comparables à ceux observés pour le critère composé des décès d'origine CV et des hospitalisations pour insuffisance cardiaque. Conclusions: L'empagliflozine a amélioré les issues CV chez les patients atteints de DT2 sans égard au temps écoulé depuis le plus récent diagnostic de maladie CV admissible au moment de la répartition aléatoire. Des essais prospectifs sont nécessaires pour étudier l'utilisation des inhibiteurs du cotransporteur sodium-glucose de type 2 lorsqu'une manifestation de maladie CV athéroscléreuse aiguë survient. Inscription de l'essai: EMPA-REG OUTCOME (numéro d'identification dans clinicaltrials.gov : NCT01131676).

Outcomes of Total Hip Arthroplasty in Patients Who Have Ehlers-Danlos Syndrome: A Matched Cohort Study.

INTRODUCTION: Total hip arthroplasty (THA) is an effective surgical treatment for severe osteoarthritis of the hip. While THA is considered a reliable and safe procedure, outcome data on patients who have Ehlers-Danlos syndrome (EDS) is limited. The purpose of this study was to compare rates of postoperative complications after primary THA in patients who have EDS against matched controls. METHODS: A large national database was searched to identify patients who underwent THA between 2009 and 2020. Patients younger than 18 years, who had a history of prior THA, and who were undergoing THA for a hip fracture were excluded from analysis. Propensity score matching was utilized to match patients who had EDS with patients who did not have EDS at a 1:4 ratio. Rates of medical and surgical complications at 90 days and 2 years were queried and compared between the cohorts using multivariable logistic regression. We identified 118 patients who had EDS and underwent primary THA, who were then matched with 418 controls. RESULTS: At 90 days, the EDS cohort had greater rates of dislocation (8.5 versus 3.8%, P = 0.038). At 2 years, the EDS cohort had greater odds of dislocation (OR [odds ratio] 2.47, P = 0.018), aseptic loosening (OR 6.91, P = 0.002), and aseptic revision (OR 2.66, P = 0.02). CONCLUSION: Patients who have EDS possess significantly higher odds of complications after THA compared to matched controls, including dislocation, aseptic loosening, and aseptic revision. Careful surgical planning in these patients should be made to prevent dislocation and potentially minimize the risk of other prosthesis-related complications leading to revision.

Domestication and evolutionary histories of specialized gut symbionts across cephalotine ants.

The evolution of animals and their gut symbionts is a complex phenomenon, obscured by lability and diversity. In social organisms, transmission of symbionts among relatives may yield systems with more stable associations. Here, we study the history of a social insect symbiosis involving cephalotine ants and their extracellular gut bacteria, which come predominantly from host-specialized lineages. We perform multi-locus phylogenetics for symbionts from nine bacterial orders, and map prior amplicon sequence data to lineage-assigned symbiont genomes, studying distributions of rigorously defined symbionts across 20 host species. Based on monophyly and additional hypothesis testing, we estimate that these specialized gut bacteria belong to 18 distinct lineages, of which 15 have been successfully isolated and cultured. Several symbiont lineages showed evidence for domestication events that occurred later in cephalotine evolutionary history, and only one lineage was ubiquitously detected in all 20 host species and 48 colonies sampled with amplicon 16S rRNA sequencing. We found evidence for phylogenetically constrained distributions in four symbionts, suggesting historical or genetic impacts on community composition. Two lineages showed evidence for frequent intra-lineage co-infections, highlighting the potential for niche divergence after initial domestication. Nearly all symbionts showed evidence for occasional host switching, but four may, more often, co-diversify with their hosts. Through our further assessment of symbiont localization and genomic functional profiles, we demonstrate distinct niches for symbionts with shared evolutionary histories, prompting further questions on the forces underlying the evolution of hosts and their gut microbiomes.

Strategies for Improving Firefighter Health On-Shift: A Review.

The fire service suffers from high rates of cardiovascular disease and poor overall health, and firefighters often suffer fatal and non-fatal injuries while on the job. Most fatal injuries result from sudden cardiac death, while non-fatal injuries are to the musculoskeletal system. Previous works suggest a mechanistic link between several health and performance variables and injury risk. In addition, studies have suggested physical activity and nutrition can improve overall health and occupational performance. This review offers practical applications for exercise via feasible training modalities as well as nutritional recommendations that can positively impact performance on the job. Time-efficient training modalities like high-intensity interval training and feasible modalities such as resistance training offer numerous benefits for firefighters. Also, modifying and supplementing the diet and can be advantageous for health and body composition in the fire service. Firefighters have various schedules, making it difficult for planned exercise and eating while on shift. The practical training and nutritional aspects discussed in this review can be implemented on-shift to improve the overall health and performance in firefighters.