SenNet recommendations for detecting senescent cells in different tissues.

Once considered a tissue culture-specific phenomenon, cellular senescence has now been linked to various biological processes with both beneficial and detrimental roles in humans, rodents and other species. Much of our understanding of senescent cell biology still originates from tissue culture studies, where each cell in the culture is driven to an irreversible cell cycle arrest. By contrast, in tissues, these cells are relatively rare and difficult to characterize, and it is now established that fully differentiated, postmitotic cells can also acquire a senescence phenotype. The SenNet Biomarkers Working Group was formed to provide recommendations for the use of cellular senescence markers to identify and characterize senescent cells in tissues. Here, we provide recommendations for detecting senescent cells in different tissues based on a comprehensive analysis of existing literature reporting senescence markers in 14 tissues in mice and humans. We discuss some of the recent advances in detecting and characterizing cellular senescence, including molecular senescence signatures and morphological features, and the use of circulating markers. We aim for this work to be a valuable resource for both seasoned investigators in senescence-related studies and newcomers to the field.

Targeting NAD+ regeneration enhances antibiotic susceptibility of Streptococcus pneumoniae during invasive disease.

Anaerobic bacteria are responsible for half of all pulmonary infections. One such pathogen is Streptococcus pneumoniae (Spn), a leading cause of community-acquired pneumonia, bacteremia/sepsis, and meningitis. Using a panel of isogenic mutants deficient in lactate, acetyl-CoA, and ethanol fermentation, as well as pharmacological inhibition, we observed that NAD(H) redox balance during fermentation was vital for Spn energy generation, capsule production, and in vivo fitness. Redox balance disruption in fermentation pathway-specific fashion substantially enhanced susceptibility to killing in antimicrobial class-specific manner. Blocking of alcohol dehydrogenase activity with 4-methylpyrazole (fomepizole), an FDA-approved drug used as an antidote for toxic alcohol ingestion, enhanced susceptibility of multidrug-resistant Spn to erythromycin and reduced bacterial burden in the lungs of mice with pneumonia and prevented the development of invasive disease. Our results indicate fermentation enzymes are de novo targets for antibiotic development and a novel strategy to combat multidrug-resistant pathogens.

The effects of resistance training on denervated myofibers, senescent cells, and associated protein markers in middle-aged adults.

Denervated myofibers and senescent cells are hallmarks of skeletal muscle aging. However, sparse research has examined how resistance training affects these outcomes. We investigated the effects of unilateral leg extensor resistance training (2 days/week for 8 weeks) on denervated myofibers, senescent cells, and associated protein markers in apparently healthy middle-aged participants (MA, 55 ± 8 years old, 17 females, 9 males). We obtained dual-leg vastus lateralis (VL) muscle cross-sectional area (mCSA), VL biopsies, and strength assessments before and after training. Fiber cross-sectional area (fCSA), satellite cells (Pax7+), denervated myofibers (NCAM+), senescent cells (p16+ or p21+), proteins associated with denervation and senescence, and senescence-associated secretory phenotype (SASP) proteins were analyzed from biopsy specimens. Leg extensor peak torque increased after training (p < .001), while VL mCSA trended upward (interaction p = .082). No significant changes were observed for Type I/II fCSAs, NCAM+ myofibers, or senescent (p16+ or p21+) cells, albeit satellite cells increased after training (p = .037). While >90% satellite cells were not p16+ or p21+, most p16+ and p21+ cells were Pax7+ (>90% on average). Training altered 13 out of 46 proteins related to muscle-nerve communication (all upregulated, p < .05) and 10 out of 19 proteins related to cellular senescence (9 upregulated, p < .05). Only 1 out of 17 SASP protein increased with training (IGFBP-3, p = .031). In conclusion, resistance training upregulates proteins associated with muscle-nerve communication in MA participants but does not alter NCAM+ myofibers. Moreover, while training increased senescence-related proteins, this coincided with an increase in satellite cells but not alterations in senescent cell content or SASP proteins. These latter findings suggest shorter term resistance training is an unlikely inducer of cellular senescence in apparently healthy middle-aged participants. However, similar study designs are needed in older and diseased populations before definitive conclusions can be drawn.

The Relation Between Attention and Memory.

The relation between attention and memory has long been deemed important for understanding cognition, and it was heavily researched even in the first experimental psychology laboratory by Wilhelm Wundt and his colleagues. Since then, the importance of the relation between attention and memory has been explored in myriad subdisciplines of psychology, and we incorporate a wide range of these diverse fields. Here, we examine some of the practical consequences of this relation and summarize work with various methodologies relating attention to memory in the fields of working memory, long-term memory, individual differences, life-span development, typical brain function, and neuropsychological conditions. We point out strengths and unanswered questions for our own embedded processes view of information processing, which is used to organize a large body of evidence. Last, we briefly consider the relation of the evidence to a range of other theoretical views before drawing conclusions about the state of the field.

Patients taking benralizumab, dupilumab, or mepolizumab have lower postvaccination SARS-CoV-2 immunity.

BACKGROUND: Biologic therapies inhibiting the IL-4 or IL-5 pathways are very effective in the treatment of asthma and other related conditions. However, the cytokines IL-4 and IL-5 also play a role in the generation of adaptive immune responses. Although these biologics do not cause overt immunosuppression, their effect in primary severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization has not been studied completely. OBJECTIVE: Our aim was to evaluate the antibody and cellular immunity after SARS-CoV-2 mRNA vaccination in patients on biologics (PoBs). METHODS: Patients with severe asthma or atopic dermatitis who were taking benralizumab, dupilumab, or mepolizumab and had received the initial dose of the 2-dose adult SARS-CoV-2 mRNA vaccine were enrolled in a prospective, observational study. As our control group, we used a cohort of immunologically healthy subjects (with no significant immunosuppression) who were not taking biologics (NBs). We used a multiplexed immunoassay to measure antibody levels, neutralization assays to assess antibody function, and flow cytometry to quantitate Spike-specific lymphocytes. RESULTS: We analyzed blood from 57 patients in the PoB group and 46 control subjects from the NB group. The patients in the PoB group had lower levels of SARS-CoV-2 antibodies, pseudovirus neutralization, live virus neutralization, and frequencies of Spike-specific B and CD8 T cells at 6 months after vaccination. In subgroup analyses, patients with asthma who were taking biologics had significantly lower pseudovirus neutralization than did subjects with asthma who were not taking biologics. CONCLUSION: The patients in the PoB group had reduced SARS-CoV-2-specific antibody titers, neutralizing activity, and virus-specific B- and CD8 T-cell counts. These results have implications when considering development of a more individualized immunization strategy in patients who receive biologic medications blocking IL-4 or IL-5 pathways.

A novel family of sugar-specific phosphodiesterases that remove zwitterionic modifications of GlcNAc.

The zwitterions phosphorylcholine (PC) and phosphoethanolamine (PE) are often found esterified to certain sugars in polysaccharides and glycoconjugates in a wide range of biological species. One such modification involves PC attachment to the 6-carbon of N-acetylglucosamine (GlcNAc-6-PC) in N-glycans and glycosphingolipids (GSLs) of parasitic nematodes, a modification that helps the parasite evade host immunity. Knowledge of enzymes involved in the synthesis and degradation of PC and PE modifications is limited. More detailed studies on such enzymes would contribute to a better understanding of the function of PC modifications and have potential application in the structural analysis of zwitterion-modified glycans. In this study, we used functional metagenomic screening to identify phosphodiesterases encoded in a human fecal DNA fosmid library that remove PC from GlcNAc-6-PC. A novel bacterial phosphodiesterase was identified and biochemically characterized. This enzyme (termed GlcNAc-PDase) shows remarkable substrate preference for GlcNAc-6-PC and GlcNAc-6-PE, with little or no activity on other zwitterion-modified hexoses. The identified GlcNAc-PDase protein sequence is a member of the large endonuclease/exonuclease/phosphatase superfamily where it defines a distinct subfamily of related sequences of previously unknown function, mostly from Clostridium bacteria species. Finally, we demonstrate use of GlcNAc-PDase to confirm the presence of GlcNAc-6-PC in N-glycans and GSLs of the parasitic nematode Brugia malayi in a glycoanalytical workflow.

Enteric glial cell network function is required for epithelial barrier restitution following intestinal ischemic injury in the early postnatal period.

Ischemic damage to the intestinal epithelial barrier, such as in necrotizing enterocolitis or small intestinal volvulus, is associated with higher mortality rates in younger patients. We have recently reported a powerful pig model to investigate these age-dependent outcomes in which mucosal barrier restitution is strikingly absent in neonates but can be rescued by direct application of homogenized mucosa from older, juvenile pigs by a yet-undefined mechanism. Within the mucosa, a postnatally developing network of enteric glial cells (EGCs) is gaining recognition as a key regulator of the mucosal barrier. Therefore, we hypothesized that the developing EGC network may play an important role in coordinating intestinal barrier repair in neonates. Neonatal and juvenile jejunal mucosa recovering from surgically induced intestinal ischemia was visualized by scanning electron microscopy and the transcriptomic phenotypes were assessed by bulk RNA sequencing. EGC network density and glial activity were examined by Gene Set Enrichment Analysis, three-dimensional (3-D) volume imaging, and Western blot and its function in regulating epithelial restitution was assessed ex vivo in Ussing chamber using the glia-specific inhibitor fluoroacetate (FA), and in vitro by coculture assay. Here we refine and elaborate our translational model, confirming a neonatal phenotype characterized by a complete lack of coordinated reparative signaling in the mucosal microenvironment. Furthermore, we report important evidence that the subepithelial EGC network changes significantly over the early postnatal period and demonstrate that the proximity of a specific functional population of EGC to wounded intestinal epithelium contributes to intestinal barrier restitution following ischemic injury.NEW & NOTEWORTHY This study refines a powerful translational pig model, defining an age-dependent relationship between enteric glia and the intestinal epithelium during intestinal ischemic injury and confirming an important role for enteric glial cell (EGC) activity in driving mucosal barrier restitution. This study suggests that targeting the enteric glial network could lead to novel interventions to improve recovery from intestinal injury in neonatal patients.

Non-enveloped virus membrane penetration: New advances leading to new insights.

Host cell membranes pose a particular challenge for non-enveloped viruses. Whereas enveloped viruses enter cells by fusing their lipid envelopes with the cellular membrane, non-enveloped viruses generally must (1) enter cells via endocytosis, then (2) penetrate the cellular endomembrane to reach the cytosol. Only then can the viruses begin to replicate (or transit to the nucleus to replicate). Although membrane penetration of non-enveloped viruses is a crucial entry step, many of the precise molecular details of this process remain unclear. Recent findings have begun to untangle the various mechanisms by which non-enveloped viral proteins disrupt and penetrate cellular endomembranes. Specifically, high-resolution microscopy studies have revealed precise conformational changes in viral proteins that enable penetration, while biochemical studies have identified key host proteins that promote viral penetration and transport. This brief article summarizes new discoveries in the membrane penetration process for three of the most intensely studied families of non-enveloped viruses: reoviruses, papillomaviruses, and polyomaviruses.

Integrated organismal responses induced by projected levels of CO2 and temperature exposures in the early life stages of lake sturgeon.

Atmospheric CO2 and temperature are rising concurrently, and may have profound impacts on the transcriptional, physiological and behavioural responses of aquatic organisms. Further, spring snowmelt may cause transient increases of pCO2 in many freshwater systems. We examined the behavioural, physiological and transcriptomic responses of an ancient fish, the lake sturgeon (Acipenser fulvescens) to projected levels of warming and pCO2 during its most vulnerable period of life, the first year. Specifically, larval fish were raised in either low (16°C) or high (22°C) temperature, and/or low (1000 µatm) or high (2500 µatm) pCO2 in a crossed experimental design over approximately 8 months. Following overwintering, lake sturgeon were exposed to a transient increase in pCO2 of 10,000 µatm, simulating a spring melt based on data in freshwater systems. Transcriptional analyses revealed potential connections to otolith formation and reduced growth in fish exposed to high pCO2 and temperature in combination. Network analyses of differential gene expression revealed different biological processes among the different treatments on the edges of transcriptional networks. Na+/K+-ATPase activity increased in fish not exposed to elevated pCO2 during development, and mRNA abundance of the ß subunit was most strongly predictive of enzyme activity. Behavioural assays revealed a decrease in total activity following an acute CO2 exposure. These results demonstrate compensatory and compounding mechanisms of pCO2 and warming dependent on developmental conditions in lake sturgeon. Conserved elements of the cellular stress response across all organisms provide key information for how other freshwater organisms may respond to future climate change.

Skeletal muscle myosin heavy chain fragmentation as a potential marker of protein degradation in response to resistance training and disuse atrophy.

We examined how resistance exercise (RE), cycling exercise and disuse atrophy affect myosin heavy chain (MyHC) protein fragmentation. The 1boutRE study involved younger men (n = 8; 5 ± 2 years of RE experience) performing a lower body RE bout with vastus lateralis (VL) biopsies being obtained prior to and acutely following exercise. With the 10weekRT study, VL biopsies were obtained in 36 younger adults before and 24 h after their first/naïve RE bout. Participants also engaged in 10 weeks of resistance training and donated VL biopsies before and 24 h after their last RE bout. VL biopsies were also examined in an acute cycling study (n = 7) and a study involving 2 weeks of leg immobilization (n = 20). In the 1boutRE study, fragmentation of all MyHC isoforms (MyHCTotal) increased 3 h post-RE (∼200%, P = 0.018) and returned to pre-exercise levels by 6 h post-RE. Interestingly, a greater magnitude increase in MyHC type IIa versus I isoform fragmentation occurred 3 h post-RE (8.6 ± 6.3-fold vs. 2.1 ± 0.7-fold, P = 0.018). In 10weekRT participants, the first/naïve and last RE bouts increased MyHCTotal fragmentation 24 h post-RE (+65% and +36%, P < 0.001); however, the last RE bout response was attenuated compared to the first bout (P = 0.045). Although cycling exercise did not alter MyHCTotal fragmentation, ∼8% VL atrophy with 2 weeks of leg immobilization increased MyHCTotal fragmentation (∼108%, P < 0.001). Mechanistic C2C12 myotube experiments indicated that MyHCTotal fragmentation is likely due to calpain proteases. In summary, RE and disuse atrophy increase MyHC protein fragmentation. Research into how ageing and disease-associated muscle atrophy affect these outcomes is needed. HIGHLIGHTS: What is the central question of this study? How different exercise stressors and disuse affect skeletal muscle myosin heavy chain fragmentation. What is the main finding and its importance? This investigation is the first to demonstrate that resistance exercise and disuse atrophy lead to skeletal muscle myosin heavy chain protein fragmentation in humans. Mechanistic in vitro experiments provide additional evidence that MyHC fragmentation occurs through calpain proteases.

Response of stream habitat and microbiomes to spruce budworm defoliation: New considerations for outbreak management.

Defoliation by eastern spruce budworm is one of the most important natural disturbances in Canadian boreal and hemi-boreal forests with annual area affected surpassing that of fire and harvest combined, and its impacts are projected to increase in frequency, severity, and range under future climate scenarios. Deciding on an active management strategy to control outbreaks and minimize broader economic, ecological, and social impacts is becoming increasingly important. These strategies differ in the degree to which defoliation is suppressed, but little is known about the downstream consequences of defoliation and, thus, the implications of management. Given the disproportionate role of headwater streams and their microbiomes on net riverine productivity across forested landscapes, we investigated the effects of defoliation by spruce budworm on headwater stream habitat and microbiome structure and function to inform management decisions. We experimentally manipulated a gradient of defoliation among 12 watersheds during a spruce budworm outbreak in the Gaspésie Peninsula, Québec, Canada. From May through October of 2019-2021, stream habitat (flow rates, dissolved organic matter [DOM], water chemistry, and nutrients), algal biomass, and water temperatures were assessed. Bacterial and fungal biofilm communities were examined by incubating six leaf packs for five weeks (mid-August to late September) in one stream reach per watershed. Microbiome community structure was determined using metabarcoding of 16S and ITS rRNA genes, and community functions were examined using extracellular enzyme assays, leaf litter decomposition rates, and taxonomic functional assignments. We found that cumulative defoliation was correlated with increased streamflow rates and temperatures, and more aromatic DOM (measured as specific ultraviolet absorbance at 254 nm), but was not correlated to nutrient concentrations. Cumulative defoliation was also associated with altered microbial community composition, an increase in carbohydrate biosynthesis, and a reduction in aromatic compound degradation, suggesting that microbes are shifting to the preferential use of simple carbohydrates rather than more complex aromatic compounds. These results demonstrate that high levels of defoliation can affect headwater stream microbiomes to the point of altering stream ecosystem productivity and carbon cycling potential, highlighting the importance of incorporating broader ecological processes into spruce budworm management decisions.

Low Parts Per Trillion Detection of Iodinated Disinfection Byproducts in Drinking Water and Urine using Vacuum-Assisted Sorbent Extraction and GC-MS/MS.

Disinfection byproducts (DBPs) are ubiquitous environmental contaminants, which are present in virtually all drinking water and linked to detrimental health effects. Iodinated-DBPs are more cytotoxic and genotoxic than chloro- and bromo-DBPs and are formed during disinfection of iodide-containing source water. Liquid-liquid extraction (LLE) paired with gas chromatography (GC)-mass spectrometry (MS) has been the method of choice in the study of low molecular weight iodinated-DBPs; however, this method is laborious and time-consuming and struggles with complex matrices. We developed an environmentally friendly method utilizing headspace solid phase extraction with the application of vacuum to measure six iodinated-trihalomethanes (I-THMs) in drinking water and urine. Vacuum-assisted sorbent extraction (VASE) has the ability to exhaustively and rapidly extract volatile and semivolatile compounds from liquid matrices without the use of solvent. Using VASE with GC-MS/MS provides improved analyte recovery and reduced matrix interference compared to LLE. Additionally, VASE enables extraction of 30 samples simultaneously with minimal sample handling and improved method reproducibility. Using VASE with GC-MS/MS, we achieved quantification limits of 3-4 ng/L. This technique was demonstrated on drinking water from four cities, where five I-THMs were quantified at levels 10-33 times below comparable LLE methods with 10 times lower volumes of sample (10 mL vs 100 mL).

Intimate partner violence exposure during infancy and social functioning in middle childhood: An Australian mother and child cohort study.

Social functioning of children with experiences of intimate partner violence (IPV) between caregivers in early childhood has received less attention than emotional-behavioral outcomes. Drawing on data from 1507 ten-year-old Australian-born children and their mothers participating in a community-based longitudinal study, this study examined the associations between IPV exposure during infancy and social development during middle childhood. IPV during the first 12 months of life was associated with lower social skills, higher peer problems, and peer victimization at age 10 years, while accounting for concurrent IPV. This study provides evidence for the long-term impacts of early-life IPV exposure on children's social functioning, and the importance of prevention and early intervention programs focused on social development following experiences of IPV.

Persistent interactive effects of developmental salinity and temperature in Atlantic killifish (Fundulus heteroclitus).

Climate change alters multiple abiotic environmental factors in aquatic environments but relatively little is known about their interacting impacts, particularly in developing organisms where these exposures have the potential to cause long-lasting effects. To explore these issues, we exposed developing killifish embryos (Fundulus heteroclitus) to 26 °C or 20 °C and 20 ppt or 3 ppt salinity in a fully-factorial design. After hatching, fish were transferred to common conditions of 20 °C and 20 ppt to assess the potential for persistent developmental plasticity. Warm temperature increased hatching success and decreased hatch time, whereas low salinity negatively affected hatching success, but this was only significant in fish developed at 20 °C. Temperature, salinity, or their interaction affected mRNA levels of genes typically associated with thermal and hypoxia tolerance (hif1a, hsp90b, hsp90a, hsc70, and hsp70.2) across multiple developmental timepoints. These differences were persistent into the juvenile stage, where the fish that developed at 26 °C had higher expression of hif1a, hsp90b, hsp90a, and hsp70.2 than fish developed at 20 °C, and this was particularly evident for the group developed at both high temperature and salinity. There were also long-lasting effects of developmental treatments on body size after four months of rearing under common conditions. Fish developed at low salinity or temperature were larger than fish developed at high temperature or salinity, but there was no interaction between the two factors. These data highlight the complex nature of the developmental effects of interacting stressors which has important implications for predicting the resilience of fishes in the context of climate change.

Total Knee Arthroplasty Periprosthetic Joint Infection With Concomitant Extensor Mechanism Disruption and Soft-Tissue Defect: The Knee Arthroplasty Terrible Triad.

BACKGROUND: Periprosthetic infection (PJI) with concomitant extensor mechanism disruption (EMD) and soft-tissue defect-hereinafter termed the "Terrible Triad"-is a devastating complication following total knee arthroplasty. The purpose of this study was to define the surgical and clinical outcomes following management of a cohort of patients who have the Terrible Triad. METHODS: From 2000 to 2022, 127 patients underwent operative management for PJI alone, 25 for PJI with soft-tissue defects (defined as defects requiring flap reconstruction or being a factor contributing to the decision of performing above-knee amputation or arthrodesis), 14 for PJI with EMD, and 22 for the Terrible Triad. A composite outcome of infection status, range of motion, extensor lag, and ambulatory status at final follow-up was used to compare the proportion of patients in each group with a favorable overall knee outcome. Differences between groups were determined using one-way analyses of variance with post hoc Tukey's tests and Pearson's Chi-square tests or Fisher's exact tests with post hoc Bonferroni adjustments, where applicable. Odds ratios (OR) were calculated for comparison of the overall knee outcome between groups. A Kaplan-Meier survival analysis for patient mortality was performed. RESULTS: The mean follow-up was 8.4 years and similar between groups (P = .064). Patients who had the Terrible Triad had a 45.5% incidence of above-knee amputation, or arthrodesis, and an 86.4% incidence of an unfavorable outcome. Compared to patients in the PJI group, patients in the PJI who had a soft-tissue defect (OR = 5.8, 95% CI [confidence interval] 2.2 to 15.7), PJI with EMD (OR = 3.7, 95%CI 1.0 to 12.9), and Terrible Triad groups (OR = 11.6, 95% CI 3.3 to 41.5) showed higher odds of an unfavorable knee outcome. CONCLUSIONS: This study demonstrates that the total knee arthroplasty Terrible Triad is a dreaded diagnosis with poor outcomes. Clinicians and patients might consider early treatment with amputation or arthrodesis. LEVEL OF EVIDENCE: III.

The VirTra V-100 Is a Test-Retest Reliable Shooting Simulator for Measuring Accuracy/Precision, Decision-Making, and Reaction Time in Civilians, Police/SWAT, and Military Personnel.

ABSTRACT: Buga, A, Decker, DD, Robinson, BT, Crabtree, CD, Stoner, JT, Arce, LF, El-Shazly, X, Kackley, ML, Sapper, TN, Anders, JPV, Kraemer, WJ, and Volek, JS. The VirTra V-100 is a test-retest reliable shooting simulator for measuring accuracy/precision, decision-making, and reaction time in civilians, police/SWAT, and military personnel. J Strength Cond Res XX(X): 000-000, 2024-Law-enforcement agencies and the military have increasingly used virtual reality (VR) to augment job readiness. However, whether VR technology captures consistent data for shooting performance evaluation has never been explored. We enrolled 30 adults (24 M/6 F) to examine test-retest reliability of the VirTra shooting simulator. Approximately 30% of the sample had a tactical background (PD/SWAT and military). Trained research staff familiarized subjects with how to shoot the infrared-guided M4 rifle at digitally projected targets. Subjects then performed 3 identical experimental shooting sessions (consecutive or separated by 1-2 days) that assessed accuracy/precision, decision-making, and reaction time. Key metrics comprised projectile Cartesian position ( x , y ), score, time, and throughput (score or accuracy divided by time). Test-retest reliability was measured with intraclass correlation coefficients (ICC). After each visit, subjects completed a perceptual survey to self-evaluate their shooting performance and perceived VR realism. The simulator captured 21 ballistic variables with good to excellent test-retest agreement, producing a global ICC of 0.78. Notable metrics were the individual projectile distances to the center of the target (0.81), shot group radius (0.91), time-to-first decision (0.97), decision-making throughput (0.95), and target transition reaction time (0.91). Subjects had positive self-evaluations about their shooting performance, with "confidence" increasing from baseline to the end of the study ( p = 0.014). The VirTra V-100 virtual ballistic shooting simulator captures data with a high degree of test-retest reliability and is easy to familiarize regardless of starting expertise levels, making it appropriate for use as a method to objectively track progress or a tactical research testing tool.

The Rural Youth Public Health Summit: A Pilot Pathway Program for Rural Adolescents.

There is a pressing need to increase the health care and public health workforce in rural communities across the United States. In Colorado, many of the rural communities are medically underserved, lacking resources and employment prospects to appropriately address the health needs of its communities. A potential strategy to address these medically underserved areas and the public health workforce shortage is to develop pathway programs for rural adolescents into health-related careers. The Rural Youth Public Health Summit (Summit) was a pilot pathway program for rural secondary school students hosted at a 4-year public university. The planning and formation of the Summit were done through the collaboration of school administration and teachers, university faculty and staff, educational non-profits, and health care and public health professionals. The Summit's goals were to increase awareness and interest in public health careers and to further partnerships between a university and rural secondary schools. Participants included 22 secondary school students and 10 chaperones from rural schools. Throughout the 2-day Summit, participants engaged in campus tours, a keynote speaker, workshops facilitated by faculty and public health professionals, and an overnight stay in the dorms. Despite some limitations, the Summit showed promising results as a pilot program in its ability to conduct planning, outreach, recruitment, and facilitation of a pathway program to connect rural adolescents to college education and career opportunities in public health.

Chronic social defeat alters brain vascular-associated cell gene expression patterns leading to vascular dysfunction and immune system activation.

Brain vascular integrity is critical for brain health, and its disruption is implicated in many brain pathologies, including psychiatric disorders. Brain-vascular barriers are a complex cellular landscape composed of endothelial, glial, mural, and immune cells. Yet currently, little is known about these brain vascular-associated cells (BVACs) in health and disease. Previously, we demonstrated that 14 days of chronic social defeat (CSD), a mouse paradigm that produces anxiety and depressive-like behaviors, causes cerebrovascular damage in the form of scattered microbleeds. Here, we developed a technique to isolate barrier-related cells from the mouse brain and subjected the isolated cells to single-cell RNA sequencing. Using this isolation technique, we found an enrichment in BVAC populations, including distinct subsets of endothelial and microglial cells. In CSD compared to non-stress, home-cage control, differential gene expression patterns disclosed biological pathways involving vascular dysfunction, vascular healing, and immune system activation. Overall, our work demonstrates a unique technique to study BVAC populations from fresh brain tissue and suggests that neurovascular dysfunction is a key driver of psychosocial stress-induced brain pathology.

Metabolic and ruck performance effects of a novel, light-weight, energy-dense ketogenic bar.

NEW FINDINGS: What is the central question of the study? Can a novel, energy-dense and lightweight ketogenic bar (1000 kcal) consumed 3 h before exercise modulate steady-state incline rucksack march ('ruck') performance compared to isocaloric carbohydrate bars in recreationally active, college-aged men? What is the main finding and its importance? Acute ingestion of either nutritional bar sustained ∼1 h of exhaustive rucking with a 30% of body weight rucksack. This proof-of-concept study is the first to demonstrate that carbohydrate bars and lipid bars are equally feasible for preserving ruck performance. Novel ketogenic nutrition bars may have military-relevant applications to lessen carry load without compromising exercise capacity. ABSTRACT: Rucksack marches ('rucks') are strenuous, military-relevant exercises that may benefit from pre-event fuelling. The purpose of this investigation was to explore whether acute ingestion of carbohydrate- or lipid-based nutritional bars before rucking can elicit unique advantages that augment exercise performance. Recreationally active and healthy males (n = 29) were randomized and counterbalanced to consume 1000 kcal derived from a novel, energy-dense (percentage energy from carbohydrate/fat/protein: 5/83/12) ketogenic bar (KB), or isocaloric high-carbohydrate bars (CB; 61/23/16) 3 h before a time-to-exhaustion (TTE) ruck. Conditions were separated by a 1-week washout. The rucksack weight was standardized to 30% of bodyweight. Steady-state treadmill pace was set at 3.2 km/h (0.89 m/s) and 14% grade. TTE was the primary outcome; respiratory exchange ratio (RER), capillary ketones (R-ß-hydroxybutyrate), glucose and lactate, plus subjective thirst/hunger were the secondary outcomes. Mean TTE was similar between conditions (KB: 55 ± 25 vs. CB: 54 ± 22 min; P = 0.687). The RER and substrate oxidation rates revealed greater fat and carbohydrate oxidation after the KB and CB, respectively (all P < 0.0001). Capillary R-ßHB increased modestly after the KB ingestion (P < 0.0001). Neither bar influenced glycaemia. Lactate increased during the ruck independent of the condition (P < 0.0001). Thirst/fullness perceptions changed independent of the nutritional bar consumed. A novel KB nutritional bar produced equivalent TTE ruck results to the isocaloric CBs. The KB's energy density relative to CB (6.6 vs. 3.8 kcal/g) may provide a lightweight (-42% weight), pre-event fuelling alternative that does not compromise ruck physical performance.

"There's no playbook for when your kid has cancer": Desired elements of an electronic resource to support pediatric cancer communication.

INTRODUCTION: Acute lymphoblastic leukemia (ALL), the most common childhood malignancy, has a relatively favorable long-term prognosis. Yet the complexity of treatment and the emotionality of the diagnosis leave families feeling unprepared for many aspects of therapy. This qualitative study aimed to identify desired elements and format of a communication resource to support patients and families facing a diagnosis of ALL. METHODS: Semi-structured interviews of 12 parents of children receiving ALL treatment, 10 parents of survivors of ALL, and eight adolescent and young adult (AYA) survivors of ALL were conducted between February and June 2021. The interviews focused on communication experiences throughout treatment and identified domains to be addressed in a resource in development. RESULTS: All participants supported the development of an interactive, electronic health (eHealth) resource to help navigate ALL treatment. They felt a website would be helpful in addressing information gaps and mitigating pervasive feelings of overwhelm. Participants specifically sought: (a) information resources to address feelings of cognitive overload; (b) practical tips to help navigate logistical challenges; (c) clear depictions of treatment choices and trajectories to facilitate decision-making; and (d) additional psychosocial resources and support. Two overarching themes that families felt should be interwoven throughout the eHealth resource were connections with other patients/families and extra support at transitions between phases of treatment. CONCLUSIONS: A new diagnosis of ALL and its treatment are extremely overwhelming. Patients and families unanimously supported an eHealth resource to provide additional information and connect them with emotional support, starting at diagnosis and extending throughout treatment.