Postmortem mitochondria function in longissimus lumborum of Angus and Brahman steers.

Mitochondria function and integrity may impact postmortem metabolism and meat quality development. Adaptations in heat tolerant Brahman may persist to limit cellular stress postmortem. Our objective was to evaluate glycolysis, pH decline, and mitochondria function in longissimus lumborum (LL) from Angus and Brahman steers (N = 28) early postmortem (1 to 6 h) and after rigor (24 h). We evaluated metabolites of anaerobic glycolysis, ATP, pH, and temperature, and determined mitochondria oxygen consumption rate (OCR) in permeabilized fibers. The main effects of breed (b) and time (t) and the interaction were tested. Brahman LL contained greater ATP during the first 6 h postmortem; Brahman also tended to exhibit a slower pH decline (b × t, P = 0.07) and more rapid temperature decline (b × t, P < 0.001), but metabolites of anaerobic glycolysis were not different. Mitochondria in Brahman and Angus LL were well-coupled and respired at 1 h postmortem. However, outer membrane integrity became increasingly compromised postmortem (t, P < 0.001). Brahman tended to exhibit greater electron transport system capacity (b, P < 0.1) and had greater capacity for oxidative phosphorylation (complex I and II substrates) at 6 h compared with Angus (P < 0.001). In totality, greater ATP, slower pH decline, and enhanced mitochondria capacity indicate that Brahman possess mitochondrial properties or cellular adaptations that help protect the cell during energy stress postmortem. Slower pH and more rapid temperature decline in LL from Brahman may also help preserve mitochondria function postmortem.

Peripheral quantitative computed tomography is a valid imaging technique for tracking changes in skeletal muscle cross-sectional area.

Peripheral quantitative computed tomography (pQCT) has recently expanded to quantifying skeletal muscle, however its validity to determine muscle cross-sectional area (mCSA) compared to magnetic resonance imaging (MRI) is unknown. Eleven male participants (age: 22 ± 3 y) underwent pQCT and MRI dual-leg mid-thigh imaging before (PRE) and after (POST) 6 weeks of resistance training for quantification of mid-thigh mCSA and change in mCSA. mCSA agreement at both time points and absolute change in mCSA across time was assessed using Bland-Altman plots for mean bias and 95% limits of agreement (LOA), as well as Lin's concordance correlation coefficients (CCC). Both pQCT and MRI mCSA increased following 6 weeks of resistance training (∆mCSApQCT: 6.7 ± 5.4 cm2, p < 0.001; ∆mCSAMRI: 6.0 ± 6.4 cm2, p < 0.001). Importantly, the change in mCSA was not different between methods (p = 0.39). Bland-Altman analysis revealed a small mean bias (1.10 cm2, LOA: -6.09, 8.29 cm2) where pQCT tended to overestimate mCSA relative to MRI when comparing images at a single time point. Concordance between pQCT and MRI mCSA at PRE and POST was excellent yielding a CCC of 0.982. For detecting changes in mCSA, Bland-Altman analysis revealed excellent agreement between pQCT and MRI (mean bias: -0.73 cm2, LOA: -8.37, 6.91 cm2). Finally, there was excellent concordance between pQCT and MRI mCSA change scores (CCC = 0.779). Relative to MRI, pQCT imaging is a valid technique for measuring both mid-thigh mCSA at a single time point and mCSA changes following a resistance training intervention.

Subnational Projections of Lymphatic Filariasis Elimination Targets in Ethiopia to Support National Level Policy.

BACKGROUND: Lymphatic filariasis (LF) is a debilitating, poverty-promoting, neglected tropical disease (NTD) targeted for worldwide elimination as a public health problem (EPHP) by 2030. Evaluating progress towards this target for national programmes is challenging, due to differences in disease transmission and interventions at the subnational level. Mathematical models can help address these challenges by capturing spatial heterogeneities and evaluating progress towards LF elimination and how different interventions could be leveraged to achieve elimination by 2030. METHODS: Here we used a novel approach to combine historical geo-spatial disease prevalence maps of LF in Ethiopia with 3 contemporary disease transmission models to project trends in infection under different intervention scenarios at subnational level. RESULTS: Our findings show that local context, particularly the coverage of interventions, is an important determinant for the success of control and elimination programmes. Furthermore, although current strategies seem sufficient to achieve LF elimination by 2030, some areas may benefit from the implementation of alternative strategies, such as using enhanced coverage or increased frequency, to accelerate progress towards the 2030 targets. CONCLUSIONS: The combination of geospatial disease prevalence maps of LF with transmission models and intervention histories enables the projection of trends in infection at the subnational level under different control scenarios in Ethiopia. This approach, which adapts transmission models to local settings, may be useful to inform the design of optimal interventions at the subnational level in other LF endemic regions.

An Ensemble Framework for Projecting the Impact of Lymphatic Filariasis Interventions Across Sub-Saharan Africa at a Fine Spatial Scale.

BACKGROUND: Lymphatic filariasis (LF) is a neglected tropical disease targeted for elimination as a public health problem by 2030. Although mass treatments have led to huge reductions in LF prevalence, some countries or regions may find it difficult to achieve elimination by 2030 owing to various factors, including local differences in transmission. Subnational projections of intervention impact are a useful tool in understanding these dynamics, but correctly characterizing their uncertainty is challenging. METHODS: We developed a computationally feasible framework for providing subnational projections for LF across 44 sub-Saharan African countries using ensemble models, guided by historical control data, to allow assessment of the role of subnational heterogeneities in global goal achievement. Projected scenarios include ongoing annual treatment from 2018 to 2030, enhanced coverage, and biannual treatment. RESULTS: Our projections suggest that progress is likely to continue well. However, highly endemic locations currently deploying strategies with the lower World Health Organization recommended coverage (65%) and frequency (annual) are expected to have slow decreases in prevalence. Increasing intervention frequency or coverage can accelerate progress by up to 5 or 6 years, respectively. CONCLUSIONS: While projections based on baseline data have limitations, our methodological advancements provide assessments of potential bottlenecks for the global goals for LF arising from subnational heterogeneities. In particular, areas with high baseline prevalence may face challenges in achieving the 2030 goals, extending the "tail" of interventions. Enhancing intervention frequency and/or coverage will accelerate progress. Our approach facilitates preimplementation assessments of the impact of local interventions and is applicable to other regions and neglected tropical diseases.

Macrophage Ontogeny, Phenotype, and Function in Ischemia Reperfusion-Induced Injury and Repair.

AKI is characterized by a sudden, and usually reversible, decline in kidney function. In mice, ischemia-reperfusion injury (IRI) is commonly used to model the pathophysiologic features of clinical AKI. Macrophages are a unifying feature of IRI as they regulate both the initial injury response as well as the long-term outcome following resolution of injury. Initially, macrophages in the kidney take on a proinflammatory phenotype characterized by the production of inflammatory cytokines, such as CCL2 (monocyte chemoattractant protein 1), IL-6, IL-1 ß , and TNF- α . Release of these proinflammatory cytokines leads to tissue damage. After resolution of the initial injury, macrophages take on a reparative role, aiding in tissue repair and restoration of kidney function. By contrast, failure to resolve the initial injury results in prolonged inflammatory macrophage accumulation and increased kidney damage, fibrosis, and the eventual development of CKD. Despite the extensive amount of literature that has ascribed these functions to M1/M2 macrophages, a recent paradigm shift in the macrophage field now defines macrophages on the basis of their ontological origin, namely monocyte-derived and tissue-resident macrophages. In this review, we focus on macrophage phenotype and function during IRI-induced injury, repair, and transition to CKD using both the classic (M1/M2) and novel (ontological origin) definition of kidney macrophages.

Intra-Articular Injectable Biomaterials for Cartilage Repair and Regeneration.

Osteoarthritis is a degenerative joint disease characterized by cartilage deterioration and subsequent inflammatory changes in the underlying bone. Injectable hydrogels have emerged as a promising approach for controlled drug delivery in cartilage therapies. This review focuses on the latest developments in utilizing injectable hydrogels as vehicles for targeted drug delivery to promote cartilage repair and regeneration. The pathogenesis of osteoarthritis is discussed to provide a comprehensive understanding of the disease progression. Subsequently, the various types of injectable hydrogels used for intra-articular delivery are discussed. Specifically, physically and chemically crosslinked injectable hydrogels are critically analyzed, with an emphasis on their fabrication strategies and their capacity to encapsulate and release therapeutic agents in a controlled manner. Furthermore, the potential of incorporating growth factors, anti-inflammatory drugs, and cells within these injectable hydrogels are discussed. Overall, this review offers a comprehensive guide to navigating the landscape of hydrogel-based therapeutics in osteoarthritis.

Determination of psilocybin and psilocin content in multiple Psilocybe cubensis mushroom strains using liquid chromatography - tandem mass spectrometry.

A method for clinical potency determination of psilocybin and psilocin in hallucinogenic mushroom species Psilocybe cubensis was developed using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Five strains of dried, intact mushrooms were obtained and analyzed: Blue Meanie, Creeper, B-Plus, Texas Yellow, and Thai Cubensis. An extraction protocol was developed; this included an evaluation of sample milling technique, extraction solvents, and recovery/stability. Reversed phase chromatography on fused-core particle phases was developed for the determination of the two analytes using internal standard calibration with deuterated isotopologues of each analyte. The separation takes less than 5 min. Matrix effects were investigated by comparing signal response of calibration samples in neat solution and several mushroom matrices; no significant matrix effects were observed. The limit of detection for psilocybin was 1.5 ng/mL (1.5 pg on-column; 300 ng/g mushroom) and for psilocin was 0.15 ng/mL (0.15 pg on-column; 30 ng/g mushroom) using a Shimadzu LCMS-8050 triple quadrupole mass spectrometer. Assessment of the accuracy and precision of the method indicated percent error and RSD were <6 % at all concentration levels. Three whole, intact mushrooms from each strain were analyzed individually to obtain average content differences both between strains and between mushrooms of the same strain. From most to least potent, the study found that the average total psilocybin and psilocin concentrations for the Creeper, Blue Meanie, B+, Texas Yellow, and Thai Cubensis strains were 1.36, 1.221, 1.134, 1.103, and 0.879 % (w/w), respectively. A subset of these mushrooms was also tested in a separate non-affiliated laboratory, and the results were comparable between the two laboratories. Results from the secondary laboratory showed improved precision when multiple mushrooms were homogenized together, prior to extraction.

Family presence during resuscitation: Perceptions and confidence of intensive care nurses in an Australian metropolitan hospital.

BACKGROUND: While literature supporting family presence during resuscitation (FPDR) was first published over three decades ago, the practice remains controversial. Benefits have been confirmed, and barriers to practice identified through international research. The extent that FPDR is practised in Australian intensive care units (ICUs) is currently unknown. OBJECTIVES: To examine ICU nurses' previous exposure and experiences with FPDR To establish their perceptions of the risks and benefits of the practice, as well as their confidence participating. METHODS: A descriptive, cross-sectional study design, using validated FPDR risk-benefits and confidence scales, was distributed electronically to registered nurses working within a single adult ICU in Australia. RESULTS: Fifty-six percent (n = 45) of respondents had never witnessed FPDR. Respondents were divided on whether families had the right to be present or should be given the option. ICU nurses perceived benefits for families but not for the patients involved or for the nurses participating. Nurses indicated they felt conflicted between the needs of the family, preserving the quality of the care delivered to a deteriorating patient, and protecting the safety of all stakeholders. Support for FPDR was often dependent on the availability of resources such as a family-support person. CONCLUSION: This research establishes that ICU nurses lacked exposure to FPDR but were confident in their ability to perform, be observed, and support families during a resuscitation event. Therefore, confidence is likely not a factor in a decision to reject the practice. Further education is indicated as there remained a reluctance to adopt FPDR practice, despite many of the barriers reported having already been largely disproven by the available literature. Institutions have a role in policy development, ensuring adequate resources, and education.

Hyperactive Rac stimulates cannibalism of living target cells and enhances CAR-M-mediated cancer cell killing.

The 21kD GTPase Rac is an evolutionarily ancient regulator of cell shape and behavior. Rac2 is predominantly expressed in hematopoietic cells where it is essential for survival and motility. The hyperactivating mutation Rac2E62K also causes human immunodeficiency, although the mechanism remains unexplained. Here, we report that in Drosophila, hyperactivating Rac stimulates ovarian cells to cannibalize neighboring cells, destroying the tissue. We then show that hyperactive Rac2E62K stimulates human HL60-derived macrophage-like cells to engulf and kill living T cell leukemia cells. Primary mouse Rac2+/E62K bone-marrow-derived macrophages also cannibalize primary Rac2+/E62K T cells due to a combination of macrophage hyperactivity and T cell hypersensitivity to engulfment. Additionally, Rac2+/E62K macrophages non-autonomously stimulate wild-type macrophages to engulf T cells. Rac2E62K also enhances engulfment of target cancer cells by chimeric antigen receptor-expressing macrophages (CAR-M) in a CAR-dependent manner. We propose that Rac-mediated cell cannibalism may contribute to Rac2+/E62K human immunodeficiency and enhance CAR-M cancer immunotherapy.

Neonatal Hyperbilirubinemia Admissions Following Clinical Practice Guideline Implementation.

INTRODUCTION: Treatment of neonatal hyperbilirubinemia remains one of the most common reasons for readmission following delivery. Revised clinical practice guidelines (CPGs) for the treatment of neonatal hyperbilirubinemia were published on August 5, 2022. This report describes the preliminary outcomes following implementation of the new CPGs at Tripler Army Medical Center. MATERIALS AND METHODS: A retrospective chart review was performed for the 12 months prior to implementation and the 5 months post implementation. RESULTS: Bilirubin admissions decreased from 15.6% of total admissions during the 12 months prior to the new guidelines (69/441) to 4.1% of admissions (8/194) during the 5 months after implementation of the new guidelines (P < 0.001). This corresponds to a 74% reduction (risk ratio = 0.26, 95% confidence interval [CI] 0.13 to 0.54). The decrease in admissions was found to correlate to greater than $140,000 in annual savings. CONCLUSION: Adhering to the revised CPGs has the potential to increase resource availability at a time when nursing shortages and financial instability are impacting health care systems nationwide. No short-term adverse events were noted; however, long-term follow up will be needed.

Resistance training in humans and mechanical overload in rodents do not elevate muscle protein lactylation.

Although several reports have hypothesized that exercise may increase skeletal muscle protein lactylation, empirical evidence in humans is lacking. Thus, we adopted a multi-faceted approach to examine if acute and subchronic resistance training (RT) altered skeletal muscle protein lactylation levels. In mice, we also sought to examine if surgical ablation-induced plantaris hypertrophy coincided with increases in muscle protein lactylation. To examine acute responses, participants' blood lactate concentrations were assessed before, during, and after eight sets of an exhaustive lower body RT bout (n = 10 trained college-aged men). Vastus lateralis biopsies were also taken before, 3-h post, and 6-h post-exercise to assess muscle protein lactylation. To identify training responses, another cohort of trained college-aged men (n = 14) partook in 6 weeks of lower-body RT (3x/week) and biopsies were obtained before and following the intervention. Five-month-old C57BL/6 mice were subjected to 10 days of plantaris overload (OV, n = 8) or served as age-matched sham surgery controls (Sham, n = 8). Although acute resistance training significantly increased blood lactate responses ∼7.2-fold (p < 0.001), cytoplasmic and nuclear protein lactylation levels were not significantly altered at the post-exercise time points, and no putative lactylation-dependent mRNA was altered following exercise. Six weeks of RT did not alter cytoplasmic protein lactylation (p = 0.800) despite significantly increasing VL muscle size (+3.5%, p = 0.037), and again, no putative lactylation-dependent mRNA was significantly affected by training. Plantaris muscles were larger in OV versus Sham mice (+43.7%, p < 0.001). However, cytoplasmic protein lactylation was similar between groups (p = 0.369), and nuclear protein lactylation was significantly lower in OV versus Sham mice (p < 0.001). The current null findings, along with other recent null findings in the literature, challenge the thesis that lactate has an appreciable role in promoting skeletal muscle hypertrophy.

Rate of Intraoperative Crystalloid Administration During Thoracic Surgery Is Causal in Reducing Postoperative Hospital Length of Stay.

Background: Studies in thoracic surgery have long raised concerns that intraoperative administration of intravenous fluids exacerbates or causes postoperative complications and hence advocate fluid restriction. Methods: This retrospective 3-year study investigated the role of intraoperative crystalloid administration rates on the duration of postoperative hospital length of stay (phLOS) and on the incidences of previously reported adverse events (AEs) in 222 consecutive patients following thoracic surgery. Results: Higher rates of intraoperative crystalloid administration were significantly associated with shorter phLOS (P=0.0006) and with less variance in phLOS. Dose-response curves showed progressive decreases in the postoperative incidences of surgical, cardiovascular, pulmonary, renal, other, and long-term AEs with higher intraoperative crystalloid administration rates. Conclusion: The rate of intravenous crystalloid administration during thoracic surgery was significantly associated with duration of and variance in phLOS, and dose-response curves showed progressive decreases in the incidences of AEs associated with this surgery. We cannot confirm that restrictive intraoperative crystalloid administration benefits patients undergoing thoracic surgery.

Phenotypic screening identifies a trisubstituted imidazo[1,2-a]pyridine series that induces differentiation in multiple AML cell lines.

Acute myeloid leukaemia (AML) is an aggressive type of leukaemia with low rates of long-term survival. While the current standard of care is based on cytotoxic chemotherapy, a promising emerging approach is differentiation therapy. However, most current differentiating agents target specific mutations and are effective only in certain patient subtypes. To identify agents which may be effective in wider population cohorts, we performed a phenotypic screen with the myeloid marker CD11b and identified a compound series that was able to differentiate AML cell lines in vitro regardless of their mutation status. Structure-activity relationship studies revealed that replacing the formamide and catechol methyl ether groups with sulfonamide and indazole respectively improved the in vitro metabolic profile of the series while maintaining the differentiation profile in multiple cell lines. This optimisation exercise enabled progression of a lead compound to in vivo efficacy testing. Our work supports the promise of phenotypic screening to identify novel small molecules that induce differentiation in a wide range of AML subtypes.

Women's perspectives on disrespect and abuse during facility-based childbirth in Ethiopia: a qualitative study.

BACKGROUND: Disrespect and abuse violates women's basic human rights and autonomy and can traumatize women who are already in a vulnerable position during childbirth and deter them from utilizing skilled care for future childbirth. This study explored women's perspectives on the acceptability of disrespect and abuse during facility-based childbirth in Ethiopia. METHODS: A qualitative descriptive design using five focus group discussions and fifteen in-depth, semi-structured, interviews was conducted with women between October 2019 to January 2020 in north Showa zone of Oromia region, central Ethiopia. Using purposive sampling, women who had given birth at public health facilities of North Showa zone during the twelve months preceding data collection were recruited, regardless of birth outcome. Inductive thematic analysis using Open Code software was used to explore the perspectives of participants. RESULTS: While women reject disrespectful and abusive acts during childbirth generally, they may consider some disrespectful acts as acceptable and or necessary under certain circumstances. Four emerging themes were identified. (1) Disrespect and abuse is not acceptable, (2) Disrespectful and abusive actions are acceptable only if intended to save lives, (3) Disrespectful and abusive actions are an accepted part of everyday practice to prevent complications and adverse outcomes, (4) Disrespectful and abusive actions are necessary to discipline disobedient women. CONCLUSION: Women's perceptions of disrespectful and abusive acts of care providers is deeply rooted within the context of violence in Ethiopia and the societal hierarchies that have systematically disempowered women. Given the pervasiveness of disrespect and abusive actions during childbirth, policymakers, clinical managers and care providers must take these essential contextual and societal norms into account and devise comprehensive clinical interventions that addresses the root causes.

Cx3cr1 controls kidney resident macrophage heterogeneity.

Kidney macrophages are comprised of both monocyte-derived and tissue resident populations; however, the heterogeneity of kidney macrophages and factors that regulate their heterogeneity are poorly understood. Herein, we performed single cell RNA sequencing (scRNAseq), fate mapping, and parabiosis to define the cellular heterogeneity of kidney macrophages in healthy mice. Our data indicate that healthy mouse kidneys contain four major subsets of monocytes and two major subsets of kidney resident macrophages (KRM) including a population with enriched Ccr2 expression, suggesting monocyte origin. Surprisingly, fate mapping data using the newly developed Ms4a3Cre Rosa Stopf/f TdT model indicate that less than 50% of Ccr2+ KRM are derived from Ly6chi monocytes. Instead, we find that Ccr2 expression in KRM reflects their spatial distribution as this cell population is almost exclusively found in the kidney cortex. We also identified Cx3cr1 as a gene that governs cortex specific accumulation of Ccr2+ KRM and show that loss of Ccr2+ KRM reduces the severity of cystic kidney disease in a mouse model where cysts are mainly localized to the kidney cortex. Collectively, our data indicate that Cx3cr1 regulates KRM heterogeneity and niche-specific disease progression.

The effects of resistance training to near failure on strength, hypertrophy, and motor unit adaptations in previously trained adults.

Limited research exists examining how resistance training to failure affects applied outcomes and single motor unit characteristics in previously trained individuals. Herein, resistance-trained adults (24 ± 3 years old, self-reported resistance training experience was 6 ± 4 years, 11 men and 8 women) were randomly assigned to either a low-repetitions-in-reserve (RIR; i.e., training near failure, n = 10) or high-RIR (i.e., not training near failure, n = 9) group. All participants implemented progressive overload during 5 weeks where low-RIR performed squat, bench press, and deadlift twice weekly and were instructed to end each training set with 0-1 RIR. high-RIR performed identical training except for being instructed to maintain 4-6 RIR after each set. During week 6, participants performed a reduced volume-load. The following were assessed prior to and following the intervention: (i) vastus lateralis (VL) muscle cross-sectional area (mCSA) at multiple sites; (ii) squat, bench press, and deadlift one-repetition maximums (1RMs); and (iii) maximal isometric knee extensor torque and VL motor unit firing rates during an 80% maximal voluntary contraction. Although RIR was lower in the low- versus high-RIR group during the intervention (p < 0.001), total training volume did not significantly differ between groups (p = 0.222). There were main effects of time for squat, bench press, and deadlift 1RMs (all p-values < 0.05), but no significant condition × time interactions existed for these or proximal/middle/distal VL mCSA data. There were significant interactions for the slope and y-intercept of the motor unit mean firing rate versus recruitment threshold relationship. Post hoc analyses indicated low-RIR group slope values decreased and y-intercept values increased after training suggesting low-RIR training increased lower-threshold motor unit firing rates. This study provides insight into how resistance training in proximity to failure affects strength, hypertrophy, and single motor unit characteristics, and may inform those who aim to program for resistance-trained individuals.

Contact Area and Deformation of Escherichia coli Cells Adhered on a Cationic Surface.

When bacteria adhere to surfaces, the chemical and mechanical character of the cell-substrate interface guides cell function and the development of microcolonies and biofilms. Alternately on bactericidal surfaces, intimate contact is critical to biofilm prevention. The direct study of the buried cell-substrate interfaces at the heart of these behaviors is hindered by the small bacterial cell size and inaccessibility of the contact region. Here, we present a total internal reflectance fluorescence depletion approach to measure the size of the cell-substrate contact region and quantify the gap separation and curvature near the contact zone, providing an assessment of the shapes of the near-surface undersides of adhered bacterial cells. Resolution of the gap height is about 10%, down to a few nanometers at contact. Using 1 and 2 µm silica spheres as calibration standards we report that, for flagella-free Escherichia coli (E. coli) adhering on a cationic poly-l-lysine layer, the cell-surface contact and apparent cell deformation vary with adsorbed cell configuration. Most cells adhere by their ends, achieving small contact areas of 0.15 µm2, corresponding to about 1-2% of the cell's surface. The altered Gaussian curvatures of end-adhered cells suggest the flattening of the envelope within the small contact region. When cells adhere by their sides, the contact area is larger, in the range 0.3-1.1 µm2 and comprising up to ∼12% of the cell's total surface. A region of sharper curvature, greater than that of the cells' original spherocylindrical shape, borders the flat contact region in cases of side-on or end-on cell adhesion, suggesting envelope stress. From the measured curvatures, precise stress distributions over the cell surface could be calculated in future studies that incorporate knowledge of envelope moduli. Overall the small contact areas of end-adhered cells may be a limiting factor for antimicrobial surfaces that kill on contact rather than releasing bactericide.

Evaluating elimination thresholds and stopping criteria for interventions against the vector-borne macroparasitic disease, lymphatic filariasis, using mathematical modelling.

We leveraged the ability of EPIFIL transmission models fit to field data to evaluate the use of the WHO Transmission Assessment Survey (TAS) for supporting Lymphatic Filariasis (LF) intervention stopping decisions. Our results indicate that understanding the underlying parasite extinction dynamics, particularly the protracted transient dynamics involved in shifts to the extinct state, is crucial for understanding the impacts of using TAS for determining the achievement of LF elimination. These findings warn that employing stopping criteria set for operational purposes, as employed in the TAS strategy, without a full consideration of the dynamics of extinction could seriously undermine the goal of achieving global LF elimination.

Risk factors associated with higher mortality in patients with cardiac implantable electronic device infection.

INTRODUCTION: Cardiac Implantable Electronic Devices (CIEDs) are widely used for the management of advanced heart failure and ventricular arrhythmias. CIED-Infection (CIED-I) has very high mortality, especially in the subsets of patients with limited health-care access and delayed presentation. The purpose of this study is to identify the risk-predictors mortality in subjects with CIED-I. METHODS: We performed a retrospective cohort study of a regional database in patients presenting with CIED infections to tertiary care medical centers across Western New York, USA from 2012 to 2020. The clinical outcomes included recurrent device infection (any admission for CIED-I after the first hospitalization for device infection), septic complications (pulmonary embolism, respiratory failure, septic shock, decompensated HF, acute kidney injury) and mortality outcomes (death during hospitalization, within 30 days from CIED-I, and within 1 year from CIED-I). We studied associations between categorical variables and hard outcomes using χ2 tests and used one-way analysis of variance to measure between-groups differences. RESULTS: We identified 296 patients with CIED-I, among which 218 (74%) were male, 237 (80%) were white and the mean age at the time of infection was 69.2 ± 13.7 years. One-third of the patients were referred from the regional facilities. Staphylococcus aureus was responsible for most infections, followed by Enterococcus fecalis. On multivariate analysis, the covariates associated with significantly increased mortality risk included referral from regional facility (OR: 2.0;1.0-4.0), hypertension (Odds ratio, OR: 3.2;1.3-8.8), right ventricular dysfunction (OR: 2.6;1.2-5.1), end-stage renal disease (OR: 2.6;1.1-6.2), immunosuppression (OR: 11.4;2.5-53.3), and septic shock as a complication of CIED-I (OR: 3.9;1.3-10.8). CONCLUSION: Hypertension, right ventricular dysfunction, immunosuppression, and end-stage renal disease are associated with higher mortality after CIED-I. Disproportionately higher mortality was also noted in subjects referred from the regional facilities. This underscores the importance of early clinical risk-assessment, and the need for a robust referral infrastructure to improve patient outcomes.

Molecular predictors of resistance training outcomes in young untrained female adults.

We sought to determine if the myofibrillar protein synthetic (MyoPS) response to a naïve resistance exercise (RE) bout, or chronic changes in satellite cell number and muscle ribosome content, were associated with hypertrophic outcomes in females or differed in those who classified as higher (HR) or lower (LR) responders to resistance training (RT). Thirty-four untrained college-aged females (23.4 ± 3.4 kg/m2) completed a 10-wk RT protocol (twice weekly). Body composition and leg imaging assessments, a right leg vastus lateralis biopsy, and strength testing occurred before and following the intervention. A composite score, which included changes in whole body lean/soft tissue mass (LSTM), vastus lateralis (VL) muscle cross-sectional area (mCSA), midthigh mCSA, and deadlift strength, was used to delineate upper and lower HR (n = 8) and LR (n = 8) quartiles. In all participants, training significantly (P < 0.05) increased LSTM, VL mCSA, midthigh mCSA, deadlift strength, mean muscle fiber cross-sectional area, satellite cell abundance, and myonuclear number. Increases in LSTM (P < 0.001), VL mCSA (P < 0.001), midthigh mCSA (P < 0.001), and deadlift strength (P = 0.001) were greater in HR vs. LR. The first-bout 24-hour MyoPS response was similar between HR and LR (P = 0.367). While no significant responder × time interaction existed for muscle total RNA concentrations (i.e., ribosome content) (P = 0.888), satellite cell abundance increased in HR (P = 0.026) but not LR (P = 0.628). Pretraining LSTM (P = 0.010), VL mCSA (P = 0.028), and midthigh mCSA (P < 0.001) were also greater in HR vs. LR. Female participants with an enhanced satellite cell response to RT, and more muscle mass before RT, exhibited favorable resistance training adaptations.NEW & NOTEWORTHY This study continues to delineate muscle biology differences between lower and higher responders to resistance training and is unique in that a female population was interrogated. As has been reported in prior studies, increases in satellite cell numbers are related to positive responses to resistance training. Satellite cell responsivity, rather than changes in muscle ribosome content per milligrams of tissue, may be a more important factor in delineating resistance-training responses in women.