Genotypic Variations Associated with Changes in Body Mass in Response to Endurance Training.

This study investigates the extent to which different genotypes can explain changes in body mass following an 8-week running program, in a UK population. Participants were randomly assigned to either a training (n = 17) or control group (n = 21). Participants' diets were not altered, only the exercise regime was manipulated to isolate effects. The exercise group completed a periodized running program consisting of 20-30 min, over an agreed route, three times per-week, whilst the control groups refrained from daily exercise. Participants were screened at the end of the study for 1,000 gene variants using a DNA test kit. Results demonstrated a significant reduction in body mass, within the exercise, compared to the control group (p = .002). This reduction in body mass varied significantly (p = .024) between individuals within the exercise group. Moreover, genetic analysis identified 17 single nucleotide polymorphisms (SNPs) associated with this variation (r2 = .74; p < .001). These findings indicate that individuals with specific alleles are better predisposed to weight-management, compared to their counterparts, following an exercise program. This study helps to bridge the gap between population health and exercise science and can inform research in the application of genetics to help develop individually tailored health interventions.

Sex Differences in the Ergogenic Response of Acute Caffeine Intake on Muscular Strength, Power and Endurance Performance in Resistance-Trained Individuals: A Randomized Controlled Trial.

BACKGROUND: This study assessed the impact of acute caffeine intake on muscular strength, power, and endurance performance between resistance-trained male and female individuals according to load in upper- and lower-body exercises. METHODS: Here, 76 resistance-trained individuals (38 females, 38 males) participated in a study comparing caffeine and a placebo. Each received either 3 mg/kg of caffeine or a placebo 60 min before tests measuring muscular strength and power through bench press and back squat exercises at different intensities (25%, 50%, 75%, 90% 1RM). Muscular endurance at 65% 1RM was also assessed by performing reps until reaching task failure. RESULTS: Compared to placebo, caffeine increased mean, peak and time to reach peak velocity and power output (p < 0.01, ηp2 = 0.242-0.293) in the muscular strength/power test in males and females. This effect was particularly observed in the back squat exercise at 50%, 75% and 90% 1RM (2.5-8.5%, p < 0.05, g = 1.0-2.4). For muscular endurance, caffeine increased the number of repetitions, mean velocity and power output (p < 0.001, ηp2 = 0.177-0.255) in both sexes and exercises (3.0-8.9%, p < 0.05, g = 0.15-0.33). CONCLUSIONS: Acute caffeine intake resulted in a similar ergogenic effect on muscular strength, power, and endurance performance in upper- and lower-body exercises for male and female resistance-trained participants.

Cost analysis of one-time intravenous antibiotic doses in the emergency department.

BACKGROUND: Research shows that one-time doses of intravenous (IV) antibiotics do not improve resolution of infection. However, providers continue to use them-especially in the emergency department (ED). Very few studies have aimed to quantify the cost of this practice. OBJECTIVES: The primary objective was to evaluate the difference in average total cost of ED stay between patients who received a one-time dose of IV antibiotics in the ED before discharging on oral antibiotics and patients who were just discharged on oral antibiotics. Secondary objectives were to evaluate the differences in durations of stay between the 2 groups, as well as the differences in adverse drug effects and need for health care contact after discharge. METHODS: Chart review was conducted to identify patients who received and did not receive a one-time dose of IV antibiotics in the ED between April 30, 2020, and April 30, 2022. A microcosting approach was used to determine ED-associated costs per patient. Comparisons in primary and secondary outcomes were performed using statistical inferential tests. RESULTS: A total of 102 patients were analyzed in each group. Patients who received a one-time dose of IV antibiotics in the ED before being discharged on oral antibiotics had an average length of stay of 4.55 hours, as opposed to patients who did not receive a one-time dose of IV antibiotics before being discharged on oral antibiotics who had an average length of stay of 2.82 hours (absolute difference 1.73 hours, P < 0.001). One-time dosing of IV antibiotics in the ED incurred an additional cost of approximately $556 per patient, totaling to more than $56,000 in our study cohort. CONCLUSION: The use of one-time IV antibiotics in the ED did not confer any additional benefits to patients. The use of one-time doses resulted in statistically significant reduced throughput in the ED and statistically significant increased health care costs.

Cross-adaptation from heat stress to hypoxia: A systematic review and exploratory meta-analysis.

Cross-adaptation (CA) refers to the successful induction of physiological adaptation under one environmental stressor (e.g., heat), to enable subsequent benefit in another (e.g., hypoxia). This systematic review and exploratory meta-analysis investigated the effect of heat acclimation (HA) on physiological, perceptual and physical performance outcome measures during rest, and submaximal and maximal intensity exercise in hypoxia. Database searches in Scopus and MEDLINE were performed. Studies were included when they met the Population, Intervention, Comparison, and Outcome criteria, were of English-language, peer-reviewed, full-text original articles, using human participants. Risk of bias and study quality were assessed using the COnsensus based Standards for the selection of health status Measurement INstruments checklist. Nine studies were included, totalling 79 participants (100 % recreationally trained males). The most common method of HA included fixed-intensity exercise comprising 9 ± 3 sessions, 89 ± 24-min in duration and occurred within 39 ± 2 °C and 32 ± 13 % relative humidity. CA induced a moderate, beneficial effect on physiological measures at rest (oxygen saturation: g = 0.60) and during submaximal exercise (heart rate: g = -0.65, core temperature: g = -0.68 and skin temperature: g = -0.72). A small effect was found for ventilation (g = 0.24) and performance measures (peak power: g = 0.32 and time trial time: g = -0.43) during maximal intensity exercise. No effect was observed for perceptual outcome measures. CA may be appropriate for individuals, such as occupational or military workers, whose access to altitude exposure prior to undertaking submaximal activity in hypoxic conditions is restricted. Methodological variances exist within the current literature, and females and well-trained individuals have yet to be investigated. Future research should focus on these cohorts and explore the mechanistic underpinnings of CA.

Construction of an arrayed CRISPRi library as a resource for essential gene function studies in Streptococcus mutans.

IMPORTANCE: The construction of arrayed mutant libraries has advanced the field of bacterial genetics by allowing researchers to more efficiently study the exact function and importance of encoded genes. In this study, we constructed an arrayed clustered regularly interspaced short palindromic repeats interference (CRISPRi) library, known as S treptococcus mutans arrayed CRISPRi (SNAP), as a resource to study >250 essential and growth-supporting genes in Streptococcus mutans. SNAP will be made available to the research community, and we anticipate that its distribution will lead to high-quality, high-throughput, and reproducible studies of essential genes.

Prevented harm and cost avoidance with pharmacist intervention while utilizing a discharge medication reconciliation tool.

PURPOSE: The aim of this study was to determine prevented harm and cost avoidance following pharmacist intervention utilizing a discharge medication reconciliation tool. METHODS: A retrospective chart review was conducted to identify patients with pharmacist-initiated, provider-accepted discharge medication reconciliation interventions completed at a community teaching hospital in January 2021. Investigators assigned the discrepancies targeted for intervention a National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) category, probability of harm, and calculated cost avoidance. The primary endpoint was the total cost avoidance associated with discharge medication reconciliation. RESULTS: Pharmacists intervened 190 times in January 2021, avoiding an estimated $46,958 to $231,032 in cost. High-risk medications were associated with $33,920 to $147,203 in cost avoidance. The 3 high-risk therapeutic classes associated with the highest cost avoidance were insulin ($16,738-$70,793), antithrombotics ($13,884-$60,016), and opioids ($2,638-$11,834). CONCLUSION: Targeted pharmacist discharge medication reconciliation and related interventions avoid significant cost and patient harm.

Pre-sleep protein supplementation does not improve performance, body composition, and recovery in British Army recruits (part 1).

Dietary protein is crucial for optimising physical training adaptations such as muscular strength and mass, which are key aims for athletic populations, including British Army recruits. New recruits fail to meet the recommended protein intake during basic training (BT), with negligible amounts consumed in the evening. This study assessed the influence of a daily bolus of protein prior to sleep on performance adaptations, body composition and recovery in British Army recruits. 99 men and 23 women [mean ± standard deviation (SD): age: 21.3 ± 3.5 years, height: 174.8 ± 8.4 cm, body mass 75.4 ± 12.2 kg] were randomised into a dietary control (CON), carbohydrate placebo (PLA), moderate (20 g) protein (MOD) or high (60 g) protein (HIGH) supplementation group. Supplements were isocaloric and were consumed on weekday evenings between 2000 and 2100 for 12 weeks during BT. Performance tests (mid-thigh pull, medicine ball throw, 2 km run time, maximal push-up, and maximal vertical jump) and body composition were assessed at the start and end of BT. Dietary intake, energy expenditure, salivary hormones, urinary nitrogen balance, perceived muscle soreness, rating of perceived exertion, mood, and fatigue were assessed at the start, middle and end of BT. Protein supplementation increased protein intake in HIGH (2.16 ± 0.50 g⸱kg-1⸱day-1) and MOD (1.71 ± 0.48 g⸱kg-1⸱day-1) compared to CON (1.17 ± 0.24 g⸱kg-1⸱day-1) and PLA (1.31 ± 0.29 g⸱kg-1⸱day-1; p < 0.001). Despite this, there was no impact of supplementation on mid-thigh pull performance (CON = 7 ± 19%, PLA = 7 ± 19%, MOD = 0 ± 16%, and HIGH = 4 ± 14%; p = 0.554) or any other performance measures (p > 0.05). Fat-free mass changes were also similar between groups (CON = 4 ± 3%, PLA = 4 ± 4%, MOD = 3 ± 3%, HIGH = 5 ± 4%, p = 0.959). There was no impact of protein supplementation on any other body composition or recovery measure. We conclude no benefits of pre-bed protein supplementation to improve performance, body composition and recovery during BT. It is possible the training stimulus was great enough, limiting the impact of protein supplementation. However, the high degree of inter-participant variability suggests an individualised use of protein supplementation should be explored, particularly in those who consume sub-optimal (<1.6 g⸱kg-1⸱day-1) habitual amounts of protein. Clinical trial registration: The study was registered with ClinicalTrials.gov, U.S. national institutes (identifier: NCT05998590).

Pre-sleep protein supplementation does not improve recovery from load carriage in British Army recruits (part 2).

British Army basic training (BT) is physically demanding with new recruits completing multiple bouts of physical activity each day with limited recovery. Load carriage is one of the most physically demanding BT activities and has been shown to induce acute exercise-induced muscle damage (EIMD) and impair muscle function. Protein supplementation can accelerate muscle recovery by attenuating EIMD and muscle function loss. This study investigated the impact of an additional daily bolus of protein prior to sleep throughout training on acute muscle recovery following a load carriage test in British Army recruits. Ninety nine men and 23 women (mean ± SD: age: 21.3 ± 3.5 yrs., height: 174.8 ± 8.4 cm, body mass 75.4 ± 12.2 kg) were randomized to dietary control (CON), carbohydrate placebo (PLA), moderate (20 g; MOD) or high (60 g; HIGH) protein supplementation. Muscle function (maximal jump height), perceived muscle soreness and urinary markers of muscle damage were assessed before (PRE), immediately post (POST), 24-h post (24 h-POST) and 40-h post (40 h-POST) a load carriage test. There was no impact of supplementation on muscle function at POST (p = 0.752) or 40 h-POST (p = 0.989) load carriage but jump height was greater in PLA compared to HIGH at 24 h-POST (p = 0.037). There was no impact of protein supplementation on muscle soreness POST (p = 0.605), 24 h-POST (p = 0.182) or 40 h-POST (p = 0.333). All groups had increased concentrations of urinary myoglobin and 3-methylhistidine, but there was no statistical difference between groups at any timepoint (p > 0.05). We conclude that pre-sleep protein supplementation does not accelerate acute muscle recovery following load carriage in British Army recruits during basic training. The data suggests that consuming additional energy in the form of CHO or protein was beneficial at attenuating EIMD, although it is acknowledged there were no statistical differences between groups. Although EIMD did occur as indicated by elevated urinary muscle damage markers, it is likely that the load carriage test was not arduous enough to reduce muscle function, limiting the impact of protein supplementation. Practically, protein supplementation above protein intakes of 1.2 g⸱kg-1⸱day-1 following load carriage over similar distances (4 km) and carrying similar loads (15-20 kg) does not appear to be warranted.

Implementation of a Protocol for Management of Febrile Neutropenia in the Emergency Department at Veteran Health Indiana.

Background: Febrile neutropenia (FN) is a life-threatening oncologic emergency requiring timely evaluation and treatment. Unrecognized fever and infection can progress quickly and have been shown to increase morbidity and mortality in patients with malignancy. It is critical to identify patients with neutropenic fever on presentation to the emergency department (ED) and to initiate treatment immediately. Observations: This quality improvement initiative sought to optimize ED care of patients presenting with FN. Delays in antibiotic prescribing for patients with FN presenting to the ED were identified. A protocol was implemented to streamline clinical decision making and decrease the time from triage to the first dose of antibiotics in the ED. Key interventions included obtaining ED staff support, developing a standard empiric therapy protocol, increasing prescriber awareness of the neutropenic fever protocol and integrating it into the electronic health record. Before the protocol, the mean time from triage to the first dose of antibiotics was 3.3 hours with only 6% of patients receiving appropriate empiric therapy within 1 hour. Postimplementation, the average time to antibiotics decreased to 2.3 hours. In the postimplementation group, 17% of patients within 1 hour. Conclusions: Early identification and timely empiric antibiotic therapy are critical to improving outcomes for patients presenting to the ED with FN. Additional optimization of the order sets along with increased protocol comfort and staff education will help to further reduce the time to antibiotic administration in alignment with guideline recommendations.

Research Trends in the Effect of Caffeine Intake on Fat Oxidation: A Bibliometric and Visual Analysis.

In the last few decades, numerous studies pertaining to research groups worldwide have investigated the effects of oral caffeine intake on fat oxidation at rest, during exercise, and after exercise. However, there is no bibliometric analysis to assess the large volume of scientific output associated with this topic. A bibliometric analysis of this topic may be used by researchers to assess the current scientific interest in the application of caffeine as a nutritional strategy to augment fat oxidation, the journals with more interest in this type of publication, and to draw international collaborations between groups working in the same area. For these reasons, the purpose of this study was to assess the research activity regarding oral caffeine intake and fat oxidation rate in the last few decades by conducting a bibliometric and visual analysis. Relevant publications from 1992 to 2022 were retrieved from the Web of Science (WoS) Core Collection database. Quantitative and qualitative variables were collected, including the number of publications and citations, H-indexes, journals of citation reports, co-authorship, co-citation, and the co-occurrence of keywords. There were 182 total publications, while the number of annual publications is saw-shaped with a modest increase of 11.3% from 2000 to 2009 to 2010 to 2019. The United States was the country with the highest number of publications (24.17% of the total number of articles), followed by the Netherlands (17.03%). According to citation analyses, the average number of citations per document is 130, although there are 21 documents that have received more than 100 citations; the most cited document reached 644 citations. These citation data support the overall relevance of this topic in the fields of nutrition and dietetics and sport sciences that when combined harbored 85.71% of all articles published in the WoS. The most productive author was Westerterp-Plantenga with 16 articles (8.79% of the total number of articles). Nutrients was the journal that published the largest number of articles on this topic (6.59% of the total number of articles). Last, there is a tendency to include keywords such as "performance", "carbohydrate", and "ergogenic aid" in the newer articles, while "obesity", "thermogenic", and "tea" are the keywords more commonly included in older documents. Although research into the role of caffeine on fat oxidation has existed since the 1970s, our analysis suggests that the scientific output associated with this topic has progressively increased since 1992, demonstrating that this is a nutritional research area with a strong foundational base of scientific evidence. Based on the findings of this bibliometric analysis, future investigation may consider focusing on the effects of sex and tolerance to caffeine to widen the assessment of the effectiveness of oral caffeine intake as a nutritional strategy to augment the use of fat as a fuel, as these terms rarely appear in the studies included in this analysis. Additionally, more translational research is necessary as the studies that investigate the effect of oral caffeine intake in ecologically valid contexts (i.e., exercise training programs for individuals with excessive adiposity) are only a minor part of the studies on this topic.

Development and Antibacterial Properties of 4-[4-(Anilinomethyl)-3-phenylpyrazol-1-yl]benzoic Acid Derivatives as Fatty Acid Biosynthesis Inhibitors.

A number of novel pyrazole derivatives have been synthesized, and several of these compounds are potent antibacterial agents with minimum inhibitory concentrations as low as 0.5 µg/mL. Human cell lines were tolerant to these lead compounds, and they showed negligible hemolytic effects at high concentrations. These bactericidal compounds are very effective against bacterial growth in both planktonic and biofilm contexts. Various techniques were applied to show the inhibition of biofilm growth and eradication of preformed biofilms by lead compounds. Potent compounds are more effective against persisters than positive controls. In vivo studies revealed that lead compounds are effective in rescuing C. elegans from bacterial infections. Several methods were applied to determine the mode of action including membrane permeability assay and SEM micrograph studies. Furthermore, CRISPRi studies led to the determination of these compounds as fatty acid biosynthesis (FAB) inhibitors.

Human YRNA 4 (HY4) plasma levels are a prognostic indicator of SARS-CoV-2 infection clinical severity.

SARS-CoV-2 infection can result in a range of outcomes from asymptomatic/mild disease to severe COVID-19/fatality. In this study, we investigated the differential expression of small noncoding RNAs (sncRNAs) between patient cohorts defined by disease severity. We collected plasma samples, stratified these based on clinical outcomes, and sequenced their circulating sncRNAs. Excitingly, we found YRNA HY4 displays significant differential expression (p=0.025) between patients experiencing mild and severe disease. In agreement with recent reports identifying plasma YRNAs as indicators of influenza infection severity, our results strongly suggest that circulating HY4 levels represent a powerful prognostic indicator of likely SARS-CoV-2 patient infection outcome.

Responsiveness to endurance training can be partly explained by the number of favorable single nucleotide polymorphisms an individual possesses.

Cardiorespiratory fitness is a key component of health-related fitness. It is a necessary focus of improvement, especially for those that have poor fitness and are classed as untrained. However, much research has shown individuals respond differentially to identical training programs, suggesting the involvement of a genetic component in individual exercise responses. Previous research has focused predominantly on a relatively low number of candidate genes and their overall influence on exercise responsiveness. However, examination of gene-specific alleles may provide a greater level of understanding. Accordingly, this study aimed to investigate the associations between cardiorespiratory fitness and an individual's genotype following a field-based endurance program within a previously untrained population. Participants (age: 29 ± 7 years, height: 175 ± 9 cm, mass: 79 ± 21 kg, body mass index: 26 ± 7 kg/m2) were randomly assigned to either a training (n = 21) or control group (n = 24). The training group completed a periodized running program for 8-weeks (duration: 20-30-minutes per session, intensity: 6-7 Borg Category-Ratio-10 scale rating, frequency: 3 sessions per week). Both groups completed a Cooper 12-minute run test to estimate cardiorespiratory fitness at baseline, mid-study, and post-study. One thousand single nucleotide polymorphisms (SNPs) were assessed via saliva sample collections. Cooper run distance showed a significant improvement (0.23 ± 0.17 km [11.51 ± 9.09%], p < 0.001, ES = 0.48 [95%CI: 0.16-0.32]), following the 8-week program, whilst controls displayed no significant changes (0.03 ± 0.15 km [1.55 ± 6.98%], p = 0.346, ES = 0.08, [95%CI: -0.35-0.95]). A significant portion of the inter-individual variation in Cooper scores could be explained by the number of positive alleles a participant possessed (r = 0.92, R2 = 0.85, p < 0.001). These findings demonstrate the relative influence of key allele variants on an individual's responsiveness to endurance training.

Muscle Protein Synthesis with a Hybrid Dairy and Plant-Based Protein Blend (P4) Is Equal to Whey Protein in a Murine Ageing Model after Fasting.

P4, a specific combination of dairy proteins (whey and casein) and plant-based protein isolates (pea and soy), has been shown to provide a more balanced amino acid (AA) profile than its single constituent proteins; however, less is known about how this translates to muscle protein synthesis (MPS). The aim of this study was to investigate the effect of P4 compared to whey or casein against fasted control on MPS. C57BL/6J mice, aged 25 months, were fasted overnight, followed by oral gavage of either whey, P4, casein, or water as a fasted control. Thirty minutes after ingestion, puromycin (0.04 µmol∙g-1 bodyweight) was subcutaneously injected; 30-min thereafter, mice were sacrificed. MPS was measured by the SUnSET method, and signalling proteins were determined in the left-tibialis anterior (TA) muscle by the WES technique. AA composition was determined in plasma and right-TA muscle. Dried blood spots (DBS) were analysed for postprandial AA dynamics at 10, 20, 45, 60 min. MPS was 1.6-fold increased with whey (p = 0.006) and 1.5-fold with P4 compared to fasted (p = 0.008), while no change was seen with casein. This was confirmed by a significant increase of phosphorylated/total ratio of 4E-BP1 for both whey (p = 0.012) and P4 (p = 0.001). No changes were observed in p70S6K and mTOR phosphorylation/total ratio with whey or P4. Intramuscular leucine levels were lower for P4 (0.71 µmol∙g dry weight-1) compared to whey (0.97 µmol∙g dry weight-1) (p = 0.0007). Ten minutes postprandial, DBS showed significantly increased blood AA levels of BCAAs, histidine, lysine, threonine, arginine, and tyrosine for P4 versus fasted. In conclusion, a hybrid mix of dairy and plant-based proteins (P4) resulted in a MPS response that was similar to whey protein in aged mice after fasting. This suggests that other anabolic triggers beyond leucine or the well-balanced amino acid profile and bioavailability of the blend benefit stimulation of MPS.

Dietary Nitrate Ingestion Does Not Improve Neuromuscular Performance in Male Sport Climbers.

Beetroot juice (BJ) is commonly used as an ergogenic aid in endurance and team sports, however, the effect of this supplement on climbing performance is barely studied. The purpose of the current study was to investigate the effect of acute BJ ingestion on neuromuscular and biochemical variables in amateur male sport climbers. Ten physically active sport climbers (28.8 ± 3.7 years) underwent a battery of neuromuscular tests consisting of the half crimp test, the pull-up to failure test, the isometric handgrip strength test, the countermovement jump (CMJ) and the squat jump (SJ). Participants performed the neuromuscular test battery twice in a cross-over design separated by 10 days, 150 min after having consumed either 70-mL of BJ (6.4 mmol NO3-) or a 70-mL placebo (0.0034 mmol NO3-). In addition, nitrate (NO3-) and nitrite (NO2-) saliva concentrations were analysed, and a side effect questionnaire related to ingestion was administrated. No differences were reported in particular neuromuscular variables measured such as the CMJ (p = 0.960; ES = 0.03), the SJ (p = 0.581; ES = -0.25), isometric handgrip strength (dominant/non dominant) (p = 0.459-0.447; ES = 0.34-0.35), the pull-up failure test (p = 0.272; ES = 0.51) or the maximal isometric half crimp test (p = 0.521-0.824; ES = 0.10-0.28). Salivary NO3- and NO2- increased significantly post BJ supplementation compared to the placebo (p < 0.001), while no side effects associated to ingestion were reported (p = 0.330-1.000) between conditions (BJ/placebo ingestion). Acute dietary nitrate supplementation (70-mL) did not produce any statistically significant improvement in neuromuscular performance or side effects in amateur sport climbers.

PFKFB3 Inhibits Fructose Metabolism in Pulmonary Microvascular Endothelial Cells.

Pulmonary microvascular endothelial cells contribute to the integrity of the lung gas exchange interface, and they are highly glycolytic. Although glucose and fructose represent discrete substrates available for glycolysis, pulmonary microvascular endothelial cells prefer glucose over fructose, and the mechanisms involved in this selection are unknown. 6-Phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 3 (PFKFB3) is an important glycolytic enzyme that drives glycolytic flux against negative feedback and links glycolytic and fructolytic pathways. We hypothesized that PFKFB3 inhibits fructose metabolism in pulmonary microvascular endothelial cells. We found that PFKFB3 knockout cells survive better than wild-type cells in fructose-rich medium under hypoxia. Seahorse assays, lactate and glucose measurements, and stable isotope tracing showed that PFKFB3 inhibits fructose-hexokinase-mediated glycolysis and oxidative phosphorylation. Microarray analysis revealed that fructose upregulates PFKFB3, and PFKFB3 knockout cells increase fructose-specific GLUT5 (glucose transporter 5) expression. Using conditional endothelial-specific PFKFB3 knockout mice, we demonstrated that endothelial PFKFB3 knockout increases lung tissue lactate production after fructose gavage. Last, we showed that pneumonia increases fructose in BAL fluid in mechanically ventilated ICU patients. Thus, PFKFB3 knockout increases GLUT5 expression and the hexokinase-mediated fructose use in pulmonary microvascular endothelial cells that promotes their survival. Our findings indicate that PFKFB3 is a molecular switch that controls glucose versus fructose use in glycolysis and help better understand lung endothelial cell metabolism during respiratory failure.

The efficacy of a home-use metabolic device (Lumen) in response to a short-term low and high carbohydrate diet in healthy volunteers.

BACKGROUND: Based on stoichiometric assumptions, and real-time assessment of expired carbon dioxide (%CO2) and flow rate, the Lumen device provides potential for consumers/athletes to monitor metabolic responses to dietary programs outside of laboratory conditions. However, there is a paucity of research exploring device efficacy. This study aimed to evaluate Lumen device response to: i) a high-carbohydrate meal under laboratory conditions, and ii) a short-term low- or high-carbohydrate diet in healthy volunteers. METHODS: Following institutional ethical approval, 12 healthy volunteers (age: 36 ± 4 yrs; body mass: 72.1 ± 3.6 kg; height: 1.71 ± 0.02 m) performed Lumen breath and Douglas bag expired air measures under fasted laboratory conditions and at 30 and 60 min after a high-carbohydrate (2 g·kg-1) meal, along with capilliarized blood glucose assessment. Data were analyzed using a one-way ANOVA, with ordinary least squares regression used to assess the model between Lumen expired carbon dioxide percentage (L%CO2) and respiratory exchange ratio (RER). In a separate phase, 27 recreationally active adults (age: 42 ± 2 yrs; body mass: 71.9 ± 1.9 kg; height: 1.72 ± 0.02 m) completed a 7-day low- (~20% of energy intake [EI]; LOW) or high-carbohydrate diet (~60% of EI; HIGH) in a randomized, cross-over design under free-living conditions. L%CO2 and derived Lumen Index (LI) were recorded daily across morning (fasted and post-breakfast) and evening (pre/post meal, pre-bed) periods. Repeated measures ANOVA were employed for main analyses, with Bonferroni post-hoc assessment applied (P ≤ 0.05). RESULTS: Following the carbohydrate test-meal, L%CO2 increased from 4.49 ± 0.05% to 4.80 ± 0.06% by 30 min, remaining elevated at 4.76 ± 0.06% by 60 min post-feeding (P < 0.001, ηp2 = 0.74). Similarly, RER increased by 18.1% from 0.77 ± 0.03 to 0.91 ± 0.02 by 30 min post-meal (P = 0.002). When considering peak data, regression analysis demonstrated a significant model effect between RER and L%CO2 (F = 5.62, P = 0.03, R2 = 0.20). Following main dietary interventions, no significant interactions (diet × day) were found. However, main diet effects were evident across all time-points assessed, highlighting significant differences for both L%CO2 and LI between LOW and HIGH conditions (P < 0.003). For L%CO2, this was particularly noted under fasted (4.35 ± 0.07 vs. 4.46 ± 0.06%, P = 0.001), pre-evening meal (4.35 ± 0.07 vs. 4.50 ± 0.06%, P < 0.001), and pre-bed time-points (4.51 ± 0.08 vs. 4.61 ± 0.06%, P = 0.005). CONCLUSION: Our findings demonstrated that a portable, home-use metabolic device (Lumen) detected significantly increased expired %CO2 in response to a high-carbohydrate meal, and may be useful in tracking mean weekly changes to acute dietary carbohydrate modifications. Additional research is warranted to further determine the practical and clinical efficacy of the Lumen device in applied compared to laboratory settings.

Effects of protein-carbohydrate vs. carbohydrate alone supplementation on immune inflammation markers in endurance athletes: a randomized controlled trial.

PURPOSE: The impact of ingesting carbohydrates alone or combined with proteins to support exercise immune adaptation in endurance athletes is scarcely investigated. The present study compares the effect of ingesting a combined protein-carbohydrate supplement vs. a carbohydrate-only supplement post-workout on immune inflammation markers following a 10 week periodized endurance training program in well-trained athletes. METHODS: Twenty-five men completed the study after being randomly assigned to one of the following intervention groups: combined protein-carbohydrate (PRO-CHO n = 12, 31 ± 9 years, [Formula: see text]O2peak 61.0 ± 5.6 ml.kg-1.min-1) or non-protein isoenergetic carbohydrate (CHO, n = 13, 33 ± 8 years, [Formula: see text]O2peak 60.6 ± 6.9 ml.kg-1.min-1). Treatment consisted of ingesting 24 g of assigned supplement, mixed with 250 ml of orange juice, once a day for 10 weeks immediately post-workout (or before breakfast on non-training days). Measurements were conducted pre- and post-intervention on total leukocytes, leukocyte subsets (i.e., neutrophils, eosinophils, basophils, monocytes, and lymphocytes), and platelets. The inflammatory status was assessed by the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), and the systemic-immune inflammation index (SII). RESULTS: Post-intervention, significant increases were observed for CHO group only for the three inflammatory markers: NLR (p = 0.050, d = 0.58), PLR (p = 0.041, d = 0.60), and SII (p = 0.004, d = 0.81) but not for PRO-CHO (p > 0.05). CONCLUSION: Ingesting a post-workout protein-carbohydrate combined beverage promoted a more favourable immune status than carbohydrate-only ingestion by attenuating cellular inflammation over a 10 week training period in endurance male athletes. TRIAL REGISTRATION: The study was registered in ClinicalTrials.gov with the following ID: NCT02954367. The study was registered by 3 November 2016.

Implementation of a compulsory clinical pharmacist-led medication deprescribing intervention in high-risk seniors in the emergency department.

OBJECTIVES: The objective of this study was to assess the impact of an emergency department (ED) deprescribing intervention for geriatric adults. We hypothesized that pharmacist-led medication reconciliation for at-risk aging patients would increase the 60-day case rate of primary care provider (PCP) deprescribing of potentially inappropriate medications (PIMs). METHODS: This was a retrospective, before-and-after intervention pilot study conducted at an urban Veterans Affairs ED. In November 2020, a protocol utilizing pharmacists to perform medication reconciliations for patients 75 years or older who screened positive using an Identification of Seniors at Risk tool at triage was implemented. Reconciliations focused on identifying PIMs and providing deprescribing recommendations to patients' PCPs. A preintervention group was collected between October 2019 and October 2020, and a postintervention group was collected between February 2021 to February 2022. The primary outcome compared case rates of PIM deprescribing in the preintervention group to the postintervention group. Secondary outcomes include per-medication PIM deprescribing rate, 30-day PCP follow-up visits, 7- and 30-day ED visits, 7- and 30-day hospitalizations, and 60-day mortality. RESULTS: A total of 149 patients were analyzed in each group. Both groups were similar in age and sex, with an average age of 82 years and 98% male. The case rate of PIM deprescribing at 60 days was 11.1% preintervention compared to 57.1% postintervention (p < 0.001). Preintervention, 91% of PIMs remained unchanged at 60 days compared to 49% (p < 0.05) postintervention. Regardless of PIM identification, the 30-day primary care follow-up rate increased postintervention: 31.5% and 55.7% (p < 0.0001), respectively. There was no improvement in 7- or 30-day subsequent ED visits, hospitalization, or mortality. CONCLUSIONS: Pharmacist-led medication reconciliation in high-risk geriatric patients was associated with an increase both in the rate of PIM deprescribing and in post-ED primary care engagement.

RUNX1 Is Regulated by Androgen Receptor to Promote Cancer Stem Markers and Chemotherapy Resistance in Triple Negative Breast Cancer.

Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype for which no effective targeted therapies are available. Growing evidence suggests that chemotherapy-resistant cancer cells with stem-like properties (CSC) may repopulate the tumor. The androgen receptor (AR) is expressed in up to 50% of TNBCs, and AR inhibition decreases CSC and tumor initiation. Runt-related transcription factor 1 (RUNX1) correlates with poor prognosis in TNBC and is regulated by the AR in prostate cancer. Our group has shown that RUNX1 promotes TNBC cell migration and regulates tumor gene expression. We hypothesized that RUNX1 is regulated by the AR and that both may work together in TNBC CSC to promote disease recurrence following chemotherapy. Chromatin immunoprecipitation sequencing (ChIP-seq) experiments in MDA-MB-453 revealed AR binding to RUNX1 regulatory regions. RUNX1 expression is upregulated by dihydrotestosterone (DHT) in MDA-MB-453 and in an AR+-TNBC HCI-009 patient-derived xenograft (PDX) tumors (p < 0.05). RUNX1 is increased in a CSC-like experimental model in MDA-MB-453 and SUM-159PT cells (p < 0.05). Inhibition of RUNX1 transcriptional activity reduced the expression of CSC markers. Interestingly, RUNX1 inhibition reduced cell viability and enhanced paclitaxel and enzalutamide sensitivity. Targeting RUNX1 may be an attractive strategy to potentiate the anti-tumor effects of AR inhibition, specifically in the slow-growing CSC-like populations that resist chemotherapy which lead to metastatic disease.