Predictors of major adverse cardiac events among patients with chest pain and low HEART score in the emergency department.

AIM: For patients who present to the emergency departments (ED) with undifferentiated chest pain, the risk of major adverse cardiac events (MACE) may be underestimated in low-HEART score patients. We aimed to identify characteristics of patients who were classified as low risk by HEART score but subsequently developed MACE at 6 weeks. METHODS: We studied a multiethnic cohort of patients who presented with chest pain arousing suspicion of acute coronary syndrome to EDs in the Netherlands and Singapore. Patients were risk-stratified using HEART score and followed up for MACE at 6 weeks. Risk factors of developing MACE despite low HEART scores (scores 0-3) were identified using logistic and Cox regression models. RESULTS: Among 1376 (39.8%) patients with low HEART scores, 63 (4.6%) developed MACE at 6 weeks. More males (53/806, 6.6%) than females (10/570, 2.8%) with low HEART score developed MACE. There was no difference in outcomes between ethnic groups. Among low-HEART score patients with 2 points for history, 21% developed MACE. Among low-HEART score patients with 1 point for troponin, 50% developed MACE, while 100% of those with 2 points for troponin developed MACE. After adjusting for HEART score and potential confounders, male sex was independently associated with increased odds (OR 4.12, 95%CI 2.14-8.78) and hazards (HR 3.93, 95%CI 1.98-7.79) of developing MACE despite low HEART score. CONCLUSION: Male sex, highly suspicious history and elevated troponin were disproportionately associated with MACE. These characteristics should prompt clinicians to consider further investigation before discharge.

A method to automate the discharge summary hospital course for neurology patients.

OBJECTIVE: Generation of automated clinical notes has been posited as a strategy to mitigate physician burnout. In particular, an automated narrative summary of a patient's hospital stay could supplement the hospital course section of the discharge summary that inpatient physicians document in electronic health record (EHR) systems. In the current study, we developed and evaluated an automated method for summarizing the hospital course section using encoder-decoder sequence-to-sequence transformer models. MATERIALS AND METHODS: We fine-tuned BERT and BART models and optimized for factuality through constraining beam search, which we trained and tested using EHR data from patients admitted to the neurology unit of an academic medical center. RESULTS: The approach demonstrated good ROUGE scores with an R-2 of 13.76. In a blind evaluation, 2 board-certified physicians rated 62% of the automated summaries as meeting the standard of care, which suggests the method may be useful clinically. DISCUSSION AND CONCLUSION: To our knowledge, this study is among the first to demonstrate an automated method for generating a discharge summary hospital course that approaches a quality level of what a physician would write.

CPAP-induced airway hyper-reactivity in mice is modulated by hyaluronan synthase-3.

BACKGROUND: Continuous positive airway pressure (CPAP) is a primary mode of respiratory support for preterm infants. Animal studies have shown long-term detrimental effects on lung/airway development, particularly airway (AW) hyper-reactivity, as an unfortunate consequence of neonatal CPAP. Since the hyaluronan (HA) synthesizing enzyme hyaluronan synthase-3 (HAS3) is involved in various adult pulmonary disorders, the present study used a neonatal mouse model to investigate the role of HAS3 in CPAP-induced AW hyper-reactivity. METHODS: Male and female neonatal mice were fitted with a custom-made mask for delivery of daily CPAP 3 h/day for 7 days. At postnatal day 21 (2 weeks after CPAP ended), airway (AW) hyper-reactivity and HAS3 expression were assessed with and without in vitro HAS3 siRNA treatment. RESULTS: MRIs of 3-day-old mice confirmed that CPAP increased lung volume with incrementing inflation pressures. CPAP increased AW reactivity in both male and female mice, which was associated with increased airway smooth muscle and epithelial HAS3 immunoreactivity. CPAP did not affect HA accumulation, but HAS3 siRNA reversed CPAP-induced AW hyper-reactivity and reduced HAS3 expression. CONCLUSIONS: These data in mice implicate a role for HAS3 in long-term effects of CPAP in the developing airway in the context of preterm birth and CPAP therapy. IMPACT: Neonatal CPAP increases airway smooth muscle and epithelial HAS3 expression in mice. CPAP-induced airway hyper-reactivity is modulated by HAS3. These data enhance our understanding of the role mechanical forces play on lung development. These data are a significance step toward understanding CPAP effects on developing airway. These data may impact clinical recognition of the ways that CPAP may contribute to wheezing disorders of former preterm infants.

Effects of Concurrent Training and a Multi-Ingredient Performance Supplement Containing Rhodiola rosea and Cordyceps sinensis on Body Composition, Performance, and Health in Active Men.

INTRODUCTION: Supplementation with Rhodiola Rosea (RR) and Cordyceps Sinensis (CS) has been shown to improve aerobic performance, but their influence on concurrent training (resistance training plus high intensity interval training) outcomes has not been established. The purpose of this study was to determine the effects of supplementation with a multi-ingredient performance supplement (MIPS) containing RR and CS during a 14-week training and testing program on body composition, weekly exercise training outcomes, overall training and performance outcomes, and hormone profiles. METHODS: Active college-aged men (N = 21) were stratified into either a MIPS or a placebo (PLA) group. Both groups completed 14 weeks of training and testing. Body composition, overall training outcomes, and blood sample collection occurred at weeks 0, 7, and 14, while training performance was evaluated weekly. RESULTS: Both groups improved (p < 0.05) percent body fat (-1.3%), bench press (+4%) and squat strength (+8%), with no difference between groups. Serum cortisol concentrations significantly decreased (-11%) but there were no differences between groups. No other changes in blood hormone profiles occurred. Weekly exercise performance data suggests that MIPS improved sprint performance, bench press lifting volume, and total workload, but this did not lead to improved overall training performance compared to PLA over the14-week study. CONCLUSION: Despite MIPS improving certain aspects of weekly training performance, supplementation with MIPS for 14 weeks did not improve body composition, overall training and performance outcomes, or blood biomarkers of health in response to concurrent training in young men compared to PLA. This study was registered with clinicaltrials. gov (NCT02383017).

Cross-sectional IgM and IgG profiles in SARS-CoV-2 infection

BackgroundAccurate serological assays can improve the early diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but few studies have compared performance characteristics between assays in symptomatic and recovered patients. MethodsWe recruited 32 patients who had 2019 coronavirus disease (COVID-19; 18 hospitalized and actively symptomatic, 14 recovered mild cases), and measured levels of IgM (against the full-length S1 or the highly homologous SARS-CoV E protein) and IgG (against S1 receptor binding domain [RBD]). We performed the same analysis in 103 pre-2020 healthy adult control (HC) participants and 13 participants who had negative molecular testing for SARS-CoV-2. ResultsAnti-S1-RBD IgG levels were very elevated within days of symptom onset for hospitalized patients (median 2.04 optical density [OD], vs. 0.12 in HC). People who recovered from milder COVID-19 only reached similar IgG levels 28 days after symptom onset. IgM levels were elevated early in both groups (median 1.91 and 2.12 vs. 1.14 OD in HC for anti-S1 IgM, 2.23 and 2.26 vs 1.52 in HC for anti-E IgM), with downward trends in hospitalized cases having longer disease duration. The combination of the two IgM levels showed similar sensitivity for COVID-19 as IgG but greater specificity, and identified 4/10 people (vs. 3/10 by IgG) with prior symptoms and negative molecular testing to have had COVID-19. ConclusionsDisease severity and timing both influence levels of IgM and IgG against SARS-CoV-2, with IgG better for early detection of severe cases but IgM more suited for early detection of milder cases.

Acellular Biologic Nipple-Areolar Complex Graft: In Vivo Murine and Nonhuman Primate Host Response Evaluation.

There are more than 3 million breast cancer survivors living in the United States of which a significant number have undergone mastectomy followed by breast and nipple-areolar complex (NAC) reconstruction. Current strategies for NAC reconstruction are dependent on nonliving or nonpermanent techniques, including tattooing, nipple prosthetics, or surgical nipple-like structures. Described herein is a tissue engineering approach demonstrating the feasibility of an allogeneic acellular graft for nipple reconstruction. Nonhuman primate (NHP)-derived NAC tissues were decellularized and their extracellular matrix components analyzed by both proteomic and histological analyses. Decellularized NHP nipple tissue showed the removal of intact cells and greatly diminished profiles for intracellular proteins, as compared with intact NHP nipple tissue. We further evaluated the biocompatibility of decellularized grafts and their potential to support host-mediated neovascularization against commercially available acellular dermal grafts by performing in vivo studies in a murine model. A follow-up NHP pilot study evaluated the host-mediated neovascularization and re-epithelialization of onlay engrafted decellularized NAC grafts. The murine model revealed greater neovascularization in the decellularized NAC than in the commercially available control grafts, with no observed biocompatibility issues. The in vivo NHP model confirmed that the decellularized NAC grafts encourage neovascularization as well as re-epithelialization. These results support the concept that a biologically derived acellular nipple graft is a feasible approach for nipple reconstruction, supporting neovascularization in the absence of adverse systemic responses. Impact statement Currently, women in the United States most often undergo a mastectomy, followed by reconstruction, after being diagnosed with breast cancer. These breast cancer survivors are often left with nipple-areolar complex (NAC) reconstructions that are subsatisfactory, nonliving, and/or nonpermanent. Utilizing an acellular biologically derived whole NAC graft would allow these patients a living and permanent tissue engineering solution to nipple reconstruction.

Validation of Acute Gastroenteritis-related International Classification of Diseases, Clinical Modification Codes in Pediatric and Adult US Populations.

International Classification of Diseases diagnostic codes are used to estimate acute gastroenteritis (AGE) disease burden. We validated AGE-related codes in pediatric and adult populations using 2 multiregional active surveillance platforms. The sensitivity of AGE codes was similar (54% and 58%) in both populations and increased with addition of vomiting-specific codes.

The Effects of Leucine-Enriched Branched-Chain Amino Acid Supplementation on Recovery After High-Intensity Resistance Exercise.

CONTEXT: Of the 3 branched-chain amino acids (BCAA), leucine has arguably received the most attribution for the role of BCAA supplementation in alleviating symptoms of exercise-induced muscle damage and facilitation of acute performance recovery. PURPOSE: To examine whether enrichment of a standard BCAA supplement with additional leucine or a standalone leucine (LEU) supplement differentially affects exercise-induced muscle damage and performance recovery compared with a standard BCAA supplement. METHODS: A total of 22 recreationally active male and female subjects were recruited and assigned to consume a BCAA, leucine-enriched BCAA (LBCAA), or LEU supplement for 11 d. On the eighth day, subjects performed eccentric-based resistance exercise (ECRE). Lower-body mean average and peak power, plasma creatine kinase, soreness, and pain threshold were measured before and 24, 48, and 72 h after ECRE. RESULTS: LEU showed decreased mean average power (P = .02) and mean peak power (P = .01) from baseline to 48 h post-ECRE, whereas LBCAA and BCAA only trended toward a reduction at 24 hours post-ECRE. At 48 h post-ECRE, BCAA showed greater recovery of mean peak power than LEU (P = .04). At 24 h post-ECRE, LEU demonstrated a greater increase in plasma creatine kinase from baseline than BCAA (P = .04). Area under the curve for creatine kinase was greater in LEU than BCAA (P = .02), whereas BCAA and LBCAA did not differ. Only LEU demonstrated increased soreness during rest and under muscular tension at 24 and 48 h post-ECRE (P < .05). CONCLUSIONS: LBCAA failed to afford any advantages over a standard BCAA supplement for postexercise muscle recovery, whereas a LEU supplement was comparatively ineffective.

Internalized HIV stigma, bullying, major depressive disorder, and high-risk suicidality among HIV-positive adolescents in rural Uganda.

BACKGROUND: Studies conducted in sub-Saharan Africa suggest a high prevalence of depression and suicidality among adolescents living with HIV (ALWH). This is an important public health issue because depression is known to compromise HIV treatment adherence. However, the drivers of depression and suicidality in this population are unclear. We conducted a cross-sectional study to estimate the associations between internalized stigma, bullying, major depressive disorder, and suicidality. METHODS: We conducted a cross-sectional survey between November 2016 and March 2017, enrolling a consecutive sample of 224 ALWH aged 13-17 years. We collected information on demographic characteristics, internalized HIV-related stigma (using the six-item Internalized AIDS-Related Stigma Scale), bullying victimization (using the nine-item Social and Health Assessment Peer Victimization Scale), major depressive disorder [using the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID)], and suicidality (also using the MINI-KID). We fitted multivariable logistic regression models to estimate the associations between stigma, bullying, major depressive disorder, and suicidality. RESULTS: Thirty-seven participants (16%) had major depressive disorder, 30 (13%) had suicidality, and nine (4%) had high-risk suicidality. Ninety-one participants (41%) had high levels of internalized stigma, while 97 (43%) reported two or more bullying events in the past year. In multivariable logistic regression models, major depressive disorder had a statistically significant association with bullying (AOR = 1.09; 95% CI 1.00-1.20; p = 0.04); while suicidality (low, moderate, high risk) had statistically significant associations with both bullying (AOR = 1.09; 95% CI 1.01-1.17; p = 0.02) and stigma (AOR = 1.30; 95% CI 1.03-1.30; p = 0.02). CONCLUSIONS: Among ALWH in rural Uganda, stigma and bullying are strongly associated with major depressive disorder and suicidality. There is a need to incorporate psychological interventions in the mainstream HIV care to address these challenges for optimal management of HIV among ALWH.

A pathophysiological role of PDE3 in allergic airway inflammation.

Phosphodiesterase 3 (PDE3) and PDE4 regulate levels of cyclic AMP, which are critical in various cell types involved in allergic airway inflammation. Although PDE4 inhibition attenuates allergic airway inflammation, reported side effects preclude its application as an antiasthma drug in humans. Case reports showed that enoximone, which is a smooth muscle relaxant that inhibits PDE3, is beneficial and lifesaving in status asthmaticus and is well tolerated. However, clinical observations also showed antiinflammatory effects of PDE3 inhibition. In this study, we investigated the role of PDE3 in a house dust mite-driven (HDM-driven) allergic airway inflammation (AAI) model that is characterized by T helper 2 cell activation, eosinophilia, and reduced mucosal barrier function. Compared with wild-type (WT) littermates, mice with a targeted deletion of the PDE3A or PDE3B gene showed significantly reduced HDM-driven AAI. Therapeutic intervention in WT mice showed that all hallmarks of HDM-driven AAI were abrogated by the PDE3 inhibitors enoximone and milrinone. Importantly, we found that enoximone also reduced the upregulation of the CD11b integrin on mouse and human eosinophils in vitro, which is crucial for their recruitment during allergic inflammation. This study provides evidence for a hitherto unknown antiinflammatory role of PDE3 inhibition in allergic airway inflammation and offers a potentially novel treatment approach.

HEART score performance in Asian and Caucasian patients presenting to the emergency department with suspected acute coronary syndrome.

BACKGROUND: The HEART score is a simple and effective tool to predict short-term major adverse cardiovascular events in patients suspected of acute coronary syndrome. Patients are assigned to three risk categories using History, ECG, Age, Risk factors and Troponin (HEART). The purpose is early rule out and discharge is considered safe for patients in the low risk category. Its performance in patients of Asian ethnicity is unknown. We evaluated the performance of the HEART score in patients of Caucasian, Chinese, Indian and Malay ethnicity. METHODS: The HEART score was assessed retrospectively in 3456 patients presenting to the emergency department with suspected acute coronary syndrome (1791 Caucasians, 1059 Chinese, 344 Indians, 262 Malays), assigning them into three risk categories. RESULTS: The incidence of major adverse cardiovascular events within six weeks after presentation was similar between the ethnic groups. A smaller proportion of Caucasians was in the low risk category compared with Asians (Caucasians 35.8%, Chinese 43.5%, Indians 45.3%, Malays 44.7%, p<0.001). The negative predictive value of a low HEART score was comparable across the ethnic groups, but lower than previously reported (Caucasians 95.3%, Chinese 95.0%, Indians 96.2%, Malays 96.6%). Also the c-statistic for the HEART score was not significantly different between the groups. CONCLUSIONS: These results show that the overall performance of the HEART score is equal among Caucasian and Asian ethnic groups. The event rate in the low risk group, however, was higher than reported in previous studies, which queries the safety of early discharge of patients in the low risk category.

Household water insecurity, missed schooling, and the mediating role of caregiver depression in rural Uganda.

BACKGROUND: School attendance rates in sub-Saharan Africa are among the lowest worldwide, placing children at heightened risk for poor educational and economic outcomes. One understudied risk factor for missed schooling is household water insecurity, which is linked to depression among women and may increase children's water-fetching burden at the expense of educational activities, particularly among children of depressed caregivers. In this study conducted in rural Uganda, we assessed the association between household water insecurity and child school participation and the mediating pathways behind these associations. METHOD: We conducted a population-based, cross-sectional study of female household heads (N = 257) and their children ages 5-17 (N = 551) in the rural regions surrounding the town of Mbarara, in southwestern Uganda. We used multivariable linear regressions to estimate the association between water insecurity and missed schooling. We then assessed the extent to which the association was mediated by caregiver depression. RESULTS: Among children, water insecurity had a statistically significant association with the number of missed school days (a standard deviation increase in water insecurity resulted in 0.30 more missed school days in the last week). The estimated association was partially mediated by caregiver depression. When stratified by sex, this mediating pathway remained significant for boys, but not among girls. CONCLUSIONS: Water insecurity is a risk factor for missed schooling among children in rural Uganda. Caregiver depression partially mediated this relationship. Also addressing caregiver mental health in water insecure families may more fully address the needs of sub-Saharan African families and promote educational participation among youth.

Sex-Based Differences in the Performance of the HEART Score in Patients Presenting to the Emergency Department With Acute Chest Pain.

BACKGROUND: Sex-based differences in clinical presentation, pathophysiology, and outcomes of patients with acute chest pain are increasingly being recognized, but are not implemented in guidelines and clinical prediction tools. We evaluated the performance of the HEART score in women versus men, because sex-based differences may exist among the algorithm's components: history, electrocardiogram, age, risk factors, and admission troponin level. METHODS AND RESULTS: The HEART score was retrospectively assessed in 831 women and 1084 men presenting to the emergency department with acute chest pain, assigning patients to the low-, intermediate-, or high-risk category for the occurrence of major adverse cardiac events (MACE) within 6 weeks. MACE, consisting of myocardial infarction, coronary revascularization, and all-cause death, also included events during index visit. Six-week MACE rates were 2 times lower in women than men (10.0% versus 20.8%; P<0.01). Despite similar discriminatory accuracy of the HEART score among women and men (c-statistic, 0.80 [0.75-0.84] versus 0.77 [0.74-0.81]; P=0.43), 6-week MACE rates were significantly lower in women than men across all HEART risk categories: 2.1% versus 6.5% (P<0.01) in the low-risk category, 12.7% versus 21.3% (P<0.01) in intermediate-risk category, and 53.1% versus 77.0% (P=0.02) in the high-risk category. The HEART score-adjusted risk ratio for men was 1.6 (1.3-2.0; P<0.01). CONCLUSIONS: The markedly higher 6-week MACE risk in men across all HEART risk categories should be taken into account when using the HEART score to guide clinical decision making; early discharge with a low-risk HEART score appears less safe for men than women with acute chest pain.

BLM germline and somatic PKMYT1 and AHCY mutations: Genetic variations beyond MYCN and prognosis in neuroblastoma.

Neuroblastoma (NB) is the most common extra cranial solid tumor of childhood and often lethal in childhood. Clinical and biologic characteristics that are independently prognostic of outcome in NB are currently used for risk stratification to optimally the therapy. It includes age at diagnosis, International Neuroblastoma Staging System tumor histopathology and MYCN amplification. However, even in patients with theoretically good prognosis, such as localized tumor and non-amplified MYCN, either disease progress or recurrence may occur. Potential genetic determinants of this unfavorable behavior are not yet fully clarified. The presence of elevated expression of AHCY, PKMYT1, and BLM has accompanied poor prognosis MYCN-amplified neuroblastoma patients. Considering the potential implication of these genes on the clinical management of NB, we hypothesize that the identification of genetic variations may have significant impact during development of the recurrent or progressive disease. Using targeted DNA sequencing, we analyzed the mutation profiles of the genes PKMYT1, AHCY, and BLM in tumor samples of five patients with MYCN amplified and 15 MYCN non-amplified NB. In our study, BLM germline variants were detected in two patients with MYCN-non-amplified neuroblastoma. Our data allow us to hypothesize that, regardless of MYCN status, these mutations partially abolish BLM protein activity by impairing its ATPase and helicase activities. BLM mutations are also clinically relevant because BLM plays an important role in DNA damage repair and the maintenance of genomic integrity. We also found a novel variant in our cohort, PKMYT1 mutation localized in the C-terminal domain with effect unknown on NB. We hypothesize that this variant may affect the catalytic activity of PKMYT1 in NB, specifically when CDK1 is complexed to cyclins. The prognostic value of this mutation must be further investigated. Another mutation identified was a nonsynonymous variant in AHCY. This variant may be related to the slow progression of the disease, even in more aggressive cases. It affects the maintenance of the catalytic capacity of AHCY, leading to the consequent functional effects observed in the NB patients studied. In conclusion, our hypothesis may provide that mutations in BLM, AHCY and PKMYT1 genes found in children with MYCN-amplified or MYCN-non amplified neuroblastomas, may be associated with the prognosis of the disease.

Ethnic differences in clinical outcome of patients presenting to the emergency department with chest pain.

BACKGROUND: Ethnicity, although known to influence cardiovascular outcome in assorted clinical settings, has not been investigated previously as a risk factor in patients presenting to the emergency department with suspected acute myocardial infarction. METHODS: In this multi-ethnic cohort study conducted in Singapore and The Netherlands, 2784 patients presenting to the emergency department with chest pain were enrolled (788 Caucasians, 1281 Chinese, 404 Indians and 311 Malays) and were followed up for 1 year. RESULTS: Although Caucasian patients on average were older and had incurred more cardiovascular adverse events, the Asian ethnic groups carried a greater burden of cardiovascular risk factors. Caucasian and Malay patients were most frequently diagnosed with acute myocardial infarction (Caucasians 11.2%, Chinese and Indians 6.4%, Malays 10.6%, P<0.001), also after correction for baseline differences. Chinese and Indian patients, however, more often had unstable angina. Asian patients had strikingly more extensive coronary artery disease than Caucasian patients (triple-vessel disease: Caucasians 6.5%, Chinese 22.8%, Indians 32.4%, Malays 32.8%, P<0.001) and Chinese patients with myocardial infarction more frequently underwent coronary revascularisation compared with Caucasian patients (Caucasians 41.4%, Chinese 67.5%, Indians 62.5%, Malay 46.7%, P=0.005). Ethnicity was not an independent predictor of major adverse cardiovascular events during 1-year follow-up in all chest pain patients. CONCLUSIONS: The prevalence of myocardial infarction and unstable angina, revascularisation rate and extent of coronary artery disease differ significantly among chest pain patients of different ethnic groups. These findings have important clinical implications and support consideration of ethnicity in risk stratification and determination of the patient management strategy in patients with symptoms suggestive of myocardial infarction.

Impact of Four Weeks of a Multi-Ingredient Performance Supplement on Muscular Strength, Body Composition, and Anabolic Hormones in Resistance-Trained Young Men.

Although multi-ingredient performance supplements (MIPS) have increased in popularity because of their array of ergogenic ingredients, their efficacy and safety remain in question. The objective of this study was to determine the impact of supplementation with T+ (SUP; Onnit Labs, Austin, TX, USA), an MIPS containing long jack root, beta-alanine, and branched-chain amino acids, and other proprietary blends, on strength, body composition, and hormones in young resistance-trained men. Subjects were randomized to consume either T+ (SUP; n = 14; age, 21 ± 3 years; body fat, 18.3 ± 4.7%) or an isocaloric placebo (PL; n = 13; age, 21 ± 3 years; body fat, 21.5 ± 6.2%) for 4 weeks. Both groups underwent a progressive, 4-week high-intensity resistance training protocol. Before and after the training protocol, mood state, body composition, blood hormones (also collected at midpoint), and maximal strength were measured. SUP had significantly greater increases in bench press (SUP, 102 ± 16 kg to 108 ± 16 kg vs. PL, 96 ± 22 kg to 101 ± 22 kg; p < 0.001) and total weight lifted (SUP, 379 ± 59 kg to 413 ± 60 kg vs. PL, 376 ± 70 kg to 400 ± 75 kg; p < 0.001) compared with PL. Additionally, deadlift strength relative to total body mass (calculated as weight lifted/body mass; kg:kg) (2.08 ± 0.18 to 2.23 ± 0.16; p = 0.036) and lean mass (2.55 ± 0.19 to 2.72 ± 0.16; p = 0.021) increased significantly in SUP but not PL (2.02 ± 0.30 to 2.15 ± 0.36 and 2.56 ± 0.31 to 2.70 ± 0.36, respectively). No other significant differences were detected between groups for the remaining variables. Supplementing with SUP enhanced resistance training adaptations independent of hormonal status, and thus SUP use may warrant inclusion into peri-workout nutrition regimens. This study was registered with clinicaltrials.gov (identifier: NCT01971723).

BLT1 antagonist LSN2792613 reduces infarct size in a mouse model of myocardial ischaemia-reperfusion injury.

AIMS: Restoration of coronary blood flow is crucial in the treatment of acute myocardial infarction. Reperfusion, however, induces ischaemia-reperfusion (IR) injury, which further deteriorates myocardial function. The innate immune system plays an important role in this process, mediating rapid influx of immune cells into the reperfused myocardium. Leukotriene B4 is an important leucocyte chemoattractant, performing its actions through binding to its specific receptor BLT1. We hypothesized that treatment with LSN2792613, a selective BLT1 antagonist, reduces infarct size (IS) in a mouse model of myocardial IR injury. METHODS AND RESULTS: Male C57Bl/6J mice were subjected to myocardial ischaemia for 30 min by surgical coronary artery ligation, followed by reperfusion. Mice received either LSN2792613 or vehicle, three times daily (orally) for up to 72 h after reperfusion. BLT1 inhibition with LSN2792613 reduced IS compared with vehicle treatment (26.9 ± 2.7 vs. 34.9 ± 2.2%, P = 0.030) at 24 h after reperfusion. The levels of IL-6 and keratinocyte chemoattractant were reduced in the infarcted tissue of LSN2792613-treated mice. Reduced apoptosis in LSN2792613-treated mice was suggested by increased levels of phosphorylated JNK and GSK3α/ß, and confirmed by flow cytometric analysis showing less apoptotic and necrotic cardiomyocytes in the infarcted myocardium. Echocardiography at 4 weeks after myocardial IR showed a slightly higher ejection fraction and stroke volume in mice treated with LSN2792613 compared with vehicle-treated mice, whereas left ventricular volumes were comparable. CONCLUSION: Selective BLT1 inhibition with LSN2792613 reduces inflammation and apoptosis following IR, resulting in reduced IS, and therefore might be a promising strategy to prevent myocardial IR injury.