6-Year Follow-Up of a World Record Breaking Master Marathon Runner.

Endurance performance declines with advancing age. Of the three main physiological factors that determine endurance running performance (maximal oxygen consumption [V̇O2max], lactate threshold, and running economy [RE]), V̇O2max appears to be most affected by age. While endurance performance declines with age, recently, endurance performance has rapidly improved in master athletes as the number of master athletes competing in endurance events has increased. Master athletes represent an intriguing model to study healthy aging. In this case study, we reassessed the physiological profile of a 76-year-old distance runner who broke the marathon world record for men over 70 years of age in 2018. This runner was tested a few months before breaking the world record and retested in 2024. Between 2018 and 2024, his marathon running velocity decreased significantly. Therefore, the purpose of this case study was to determine the physiological changes that explain his performance decline. RE remained similar to 2018, and while there was not a clear breakpoint in blood lactate, he still likely runs marathons at a high percentage (~90%) of his V̇O2max. However, V̇O2max declined by 15.1%. HRmax declined by 3.2% and maximal O2 pulse declined by 12.4%, suggesting that maximal stroke volume and/or arteriovenous O2 difference decreased. Altogether, although this marathoner continues to compete at an elite level, his performance has declined since his record-breaking marathon due to a reduction in V̇O2max. This is likely caused by reductions in maximal stroke volume and/or arteriovenous O2 difference. We speculate that these changes reflect primarily age-related processes.

Cardiology Consult for the General Pediatrician after Cardiac Manifestations from a SARS-CoV-2 Infection.

The novel Coronavirus Disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, created a need for evidence-based guidelines for the evaluation, management, and follow-up after infection. Data have become rapidly available, creating a challenge for medical providers to stay abreast of the ever-evolving recommendations. This document, written collaboratively by pediatric cardiovascular experts, pediatricians, and sports medicine specialists, is focused on SARS-- CoV-2-related pediatric cardiac manifestations. It aims to provide a systemic review of high-yield literature related to all cardiovascular entities as a tool for primary pediatric clinicians to utilize as they consider the cardiac consequences of acute SARS-CoV-2 infection, MIS-C, vaccine-related myocarditis, return-to-play, and long COVID-19 syndrome.

ProtekDuo Cannula for Pre-, Intra-, and Postoperative Lung Transplantation Management.

ABSTRACT: We present a 61-year-old patient with pulmonary hypertension, acute respiratory failure, and acute severe right ventricular (RV) dysfunction. Preoperatively, a ProtekDuo® was inserted for extracorporeal membrane oxygenation (ECMO) and RV protection with venopulmonary (VP) ECMO in (dl) V-P ECMO configuration. Intraoperatively, it provided venous drainage for venoarterial (VA) ECMO in (dl) VP-/AO configuration for bilateral orthotopic lung transplantation (BOLT). Postoperatively, the patient remained on (dl) V-P ECMO for RV support and was decannulated with mild RV dysfunction after 5 days. This is the first description of the ProtekDuo® used in (dl) V-P to (dl) VP-/AO to (dl) V-P configuration for the entire perioperative period of BOLT.

Examination of plasma biomarkers of amyloid, tau, neurodegeneration, and neuroinflammation in former elite American football players.

INTRODUCTION: Blood-based biomarkers offer a promising approach for the detection of neuropathologies from repetitive head impacts (RHI). We evaluated plasma biomarkers of amyloid, tau, neurodegeneration, and inflammation in former football players. METHODS: The sample included 180 former football players and 60 asymptomatic, unexposed male participants (aged 45-74). Plasma assays were conducted for beta-amyloid (Aß) 40, Aß42, hyper-phosphorylated tau (p-tau) 181+231, total tau (t-tau), neurofilament light (NfL), glial fibrillary acidic protein (GFAP), interleukin-6 (IL-6), Aß42/p-tau181 and Aß42/Aß40 ratios. We evaluated their ability to differentiate the groups and associations with RHI proxies and traumatic encephalopathy syndrome (TES). RESULTS: P-tau181 and p-tau231(padj = 0.016) were higher and Aß42/p-tau181 was lower(padj = 0.004) in football players compared to controls. Discrimination accuracy for p-tau was modest (area under the curve [AUC] = 0.742). Effects were not attributable to AD-related pathology. Younger age of first exposure (AFE) correlated with higher NfL (padj = 0.03) and GFAP (padj = 0.033). Plasma GFAP was higher in TES-chronic traumatic encephalopathy (TES-CTE) Possible/Probable (padj = 0.008). DISCUSSION: Plasma p-tau181 and p-tau231, GFAP, and NfL may offer some usefulness for the characterization of RHI-related neuropathologies. HIGHLIGHTS: Former football players had higher plasma p-tau181 and p-tau231 and lower Aß42/ptau-181 compared to asymptomatic, unexposed men. Younger age of first exposure was associated with increased plasma NfL and GFAP in older but not younger participants. Plasma GFAP was higher in participants with TES-CTE possible/probable compared to TES-CTE no/suggestive.

A potent pan-sarbecovirus neutralizing antibody resilient to epitope diversification.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution has resulted in viral escape from clinically authorized monoclonal antibodies (mAbs), creating a need for mAbs that are resilient to epitope diversification. Broadly neutralizing coronavirus mAbs that are sufficiently potent for clinical development and retain activity despite viral evolution remain elusive. We identified a human mAb, designated VIR-7229, which targets the viral receptor-binding motif (RBM) with unprecedented cross-reactivity to all sarbecovirus clades, including non-ACE2-utilizing bat sarbecoviruses, while potently neutralizing SARS-CoV-2 variants since 2019, including the recent EG.5, BA.2.86, and JN.1. VIR-7229 tolerates extraordinary epitope variability, partly attributed to its high binding affinity, receptor molecular mimicry, and interactions with RBM backbone atoms. Consequently, VIR-7229 features a high barrier for selection of escape mutants, which are rare and associated with reduced viral fitness, underscoring its potential to be resilient to future viral evolution. VIR-7229 is a strong candidate to become a next-generation medicine.

Neuroprotective effects of magnesium: implications for neuroinflammation and cognitive decline.

Neurodegenerative diseases, which are characterized by progressive neuronal loss and cognitive decline, are a significant concern for the aging population. Neuroinflammation, a shared characteristic of these diseases, is implicated in their pathogenesis. This article briefly summarizes the role of magnesium, an essential mineral involved in numerous enzymatic reactions and critical for neuronal bioactivity, in the context of neuroinflammation and cognitive decline. The potential neuroprotective effects of magnesium, including the mechanisms of neuroprotection by magnesium through maintaining neuronal ion homeostasis, reducing inflammation, and preventing excitotoxicity, are also described. Additionally, we discuss the impact of inadequate magnesium on neuroinflammation and its potential as a therapeutic agent for attenuating cognitive decline to improve neurodegenerative conditions.

Imaging the translocator protein 18 kDa within cognitive control and declarative memory circuits in virally-suppressed people with HIV.

OBJECTIVES: Virally-suppressed people with HIV (VS-PWH) show heterogeneity in patterns of cognitive dysfunction. To better understand the relationship between the neuroimmune response and cognition, we used positron emission tomography (PET) to image the translocator protein 18 kDa (TSPO). The study examined HIV-serostatus differences in TSPO as well as associations between regional TSPO and select cognitive processes defined using the Research Domain Criteria (RDoC) framework. DESIGN: Cross-sectional investigation in VS-PWH (n = 25) versus HIV-uninfected individuals (n = 18) of cognitive control and declarative memory, as well as [11C]DPA-713 PET measures of TSPO within cognitive control and declarative memory regions of interest. METHODS: Group differences in [11C]DPA-713 binding (VT) in cognitive control or declarative memory regions were examined using linear mixed models. Tests of associations between factor-derived cognitive system measures and PET measures were performed, controlling for TSPO genotype. RESULTS: There were no group differences in any of the four factor-derived cognitive system measures. VS-PWH had higher log [11C]DPA-713 VT across cognitive control regions(unstandardized beta coefficient reflecting mean difference [B] = 0.23, SE = 0.11, 95% confidence interval [CI] 0.01, 0.45, P = 0.04) and declarative memory regions (B = 0.24, SE = 0.11, 95%CI 0.02, 0.45, P = 0.03). Higher log [11C]DPA-713 VT in cognitive control regions related to poorer cognitive control in each group, and to worse self-reported cognitive performance in VS-PWH. Log [11C]DPA-713 VT in each declarative memory region did not associate with measured declarative memory. CONCLUSIONS: A localized neuroimmune response marked by high TSPO in brain regions that subserve cognitive control may contribute to poorer cognitive control in VS-PWH.

Effectiveness of the original monovalent mRNA COVID-19 vaccination series against hospitalization for COVID-19-associated venous thromboembolism.

BACKGROUND: COVID-19 is a strong risk factor for venous thromboembolism (VTE). Few studies have evaluated the effectiveness of COVID-19 vaccination in preventing hospitalization for COVID-19 with VTE. METHODS: Adults hospitalized at 21 sites between March 2021 and October 2022 with symptoms of acute respiratory illness were assessed for COVID-19, completion of the original monovalent mRNA COVID-19 vaccination series, and VTE. Prevalence of VTE was compared between unvaccinated and vaccinated patients with COVID-19. Vaccine effectiveness in preventing COVID-19 hospitalization with VTE was calculated using a test negative design. Vaccine effectiveness was also stratified by predominant circulating SARS-CoV-2 variant. RESULTS: Among 18,811 patients (median age 63 [IQR:50-73], 49% women, 59% non-Hispanic White, 20% non-Hispanic Black, 14% Hispanic, and median of 2 comorbid conditions [IQR:1-3]), 9,792 were admitted with COVID-19 (44% vaccinated) and 9,019 were test-negative controls (73% vaccinated). Among patients with COVID-19, 601 were diagnosed with VTE by hospital day 28, of whom 170 were vaccinated. VTE was more common among unvaccinated than vaccinated COVID-19 patients (7.8% versus 4.0%; p=0.001). Vaccine effectiveness against COVID-19 hospitalization with VTE was 84% (95% CI: 80-87%) overall. Vaccine effectiveness stratified by predominant circulating variant was 88% (73-95%) for alpha, 93% (90-95%) for delta, and 68% (58-76%) for omicron variants. CONCLUSIONS AND RELEVANCE: Vaccination with the original monovalent mRNA series was associated with a decrease in COVID-19 hospitalization with VTE, though data detailing prior history of VTE and use of anticoagulation were not available. These findings will inform risk-benefit considerations for those considering vaccination.

Endothelial ENaC-α Restrains Oxidative Stress in Lung Capillaries in Murine Pneumococcal Pneumonia-associated Acute Lung Injury.

Infection of lung endothelial cells with pneumococci activates the superoxide-generating enzyme NADPH oxidase 2 (NOX2), involving the pneumococcal virulence factor pneumolysin (PLY). Excessive NOX2 activity disturbs capillary barriers, but its global inhibition can impair bactericidal phagocyte activity during pneumococcal pneumonia. Depletion of the α subunit of the epithelial sodium channel (ENaC) in pulmonary endothelial cells increases expression and PMA-induced activity of NOX2. Direct ENaC activation by TIP peptide improves capillary barrier function -measured by electrical cell substrate impedance sensing in endothelial monolayers and by Evans Blue Dye incorporation in mouse lungs- following infection with pneumococci. PLY-induced hyperpermeability in HL-MVEC monolayers is abrogated by both NOX2 inhibitor gp91dstat and TIP peptide. Endothelial NOX2 expression is assessed by increased surface membrane presence of phosphorylated p47phox subunit (Western blotting) in vitro and by co-localization of CD31 and gp91phox in mouse lung slices using DuoLink, whereas NOX2-generated superoxide is measured by chemiluminescence. TIP peptide blunts PMA-induced NOX2 activity in cells expressing ENaC-α, but not in neutrophils, which lack ENaC. Conditional endothelial ENaC-α KO (enENaC-α KO) mice develop increased capillary leak upon i.t. instillation with PLY or pneumococci, compared to wild type (wt) animals. TIP peptide diminishes capillary leak in Sp-infected wt mice, without significantly increasing lung bacterial load. Lung slices from Sp-infected enENaC-α KO mice have a significantly increased endothelial NOX2 expression, as compared to infected CRE mice. In conclusion, endothelial ENaC may represent a novel therapeutic target to reduce NOX2-mediated oxidative stress and capillary leak in ARDS, without impairing host defense.

Comment on Vicente, F.; Pereira, P.C. Pork Meat Composition and Health: A Review of the Evidence. Foods 2024, 13, 1905.

In their recent review, Vicente and Pereira concluded that pork meat can be an option for a healthful and sustainable diet [...].

Analysis of polyclonal and monoclonal antibody to the influenza virus nucleoprotein in different oligomeric states.

Influenza virus nucleoprotein (NP) is one of the most conserved influenza proteins. Both NP antigen and anti-NP antibodies are used as reagents in influenza diagnostic kits, with applications in both clinical practice, and influenza zoonotic surveillance programs. Despite this, studies on the biochemical basis of NP diagnostic serology and NP epitopes are not as developed as for hemagglutinin (HA), the fast-evolving antigen which has been the critical component of current influenza vaccines. Here, we characterized the NP serology of mice, ferret, and human sera and the immunogenic effects of NP antigen presented as different structural complexes. Furthermore, we show that a classical anti-NP mouse mAb HB65 could detect NP in some commercial influenza vaccines. MAb HB65 bound a linear epitope with nanomolar affinity. Our analysis suggests that linear NP epitopes paired with their corresponding characterized detection antibodies could aid in designing and improving diagnostic technologies for influenza virus.

Structure-guided assembly of an influenza spike nanobicelle vaccine provides pan H1 intranasal protection.

Development of intranasal vaccines for respiratory viruses has gained popularity. However, currently only a live-attenuated influenza vaccine is FDA-approved for intranasal administration. Here, we focused on influenza virus as it circulates seasonally, has pandemic potential, and has vaccine formulations that present hemagglutinin (HA) in different structural arrangements. These display differences have not been correlated with induction of pan-H1 antibodies or shown to provide intranasal protection. Using electron microscopy, biochemistry and animal studies, we identified HA complexes arranged as lipid discs with multiple trimeric HAs displayed along the perimeter, termed spike nanobicelles (SNB). We utilized a structure-guided approach to synthesize in vitro assembled spiked nanobicelles (IA-SNB) from a classical 1934 H1N1 influenza virus. IA-SNBs elicited pan-H1 antibodies and provided protection against antigenically divergent H1N1 viruses via intranasal immunizations. Viral glycoprotein spikes displayed as SNBs could aid in combating antigenic variation and provide innovative intranasal vaccines to aid universal influenza vaccine development.

Minimally invasive vs open vs hybrid esophagectomy for esophageal cancer: a systematic review and network meta-analysis.

Robot-assisted minimally invasive esophagectomy (RAMIE) for esophageal carcinoma has emerged as the contemporary alternative to conventional laparoscopic minimally invasive (LMIE), hybrid (HE) and open (OE) surgical approaches. No single study has compared all four approaches with a view to postoperative outcomes. A systematic search of electronic databases was undertaken. A network meta-analysis was performed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-network meta-analysis guidelines. Statistical analysis was performed using R and Shiny. Seven randomised controlled trials (RCTs) with 1063 patients were included. Overall, 32.9% of patients underwent OE (350/1063), 11.0% underwent HE (117/1063), 34.0% of patients underwent LMIE (361/1063), and 22.1% of patients underwent RAMIE (235/1063). OE had the lowest anastomotic leak rate 7.7% (27/350), while LMIE had the lowest pulmonary 10.8% (39/361), cardiac 0.56% (1/177) complications, re-intervention rates 5.08% (12/236), 90-day mortality 1.05% (2/191), and shortest length of hospital stay (mean 11.25 days). RAMIE displayed the lowest 30-day mortality rate at 0.80% (2/250). There was a significant increase in pulmonary complications for those undergoing OE (OR 3.63 [95% confidence interval: 1.4-9.77]) when compared to RAMIE. LMIE is a safe and feasible option for esophagectomy when compared to OE and HE. The upcoming RCTs will provide further data to make a more robust interrogation of the surgical outcomes following RAMIE compared to conventional open surgery to determine equipoise or superiority of each approach as the era of minimally invasive esophagectomy continues to evolve (International Prospective Register of Systematic Reviews Registration: CRD42023438790).

A Rare Presentation of a Transverse Mesocolic Internal Hernia: A Case Report.

Internal hernias (IHs) are a rare but potentially life-threatening cause of bowel obstruction, with a high morbidity and mortality rate if not promptly diagnosed and treated. This case report highlights the clinical course of a 75-year-old female who developed a transverse mesocolic internal hernia, a subtype of transmesenteric hernia (TH), following a Hartmann reversal procedure. The patient presented to the emergency department (ED) with a sudden onset of severe, diffuse abdominal pain. Her medical history was significant for systemic lupus erythematosus, pulmonary fibrosis, multiple pulmonary embolisms, and a recent Hartmann reversal procedure the month prior. Initial imaging suggested postoperative ileus, but the patient's symptoms persisted despite conservative management. Subsequent imaging raised suspicion of an internal hernia, and on hospital day 6, an urgent diagnostic laparoscopy revealed a herniated segment of the small bowel through a defect in the transverse mesocolon with herniation into the lesser sac. The herniated bowel was successfully reduced, and the defect was repaired. The patient had an uneventful recovery and was discharged in stable condition. Transmesenteric hernias, though more common in the pediatric population, can occur in adults, particularly following abdominal surgery. Diagnosis can be challenging due to variable symptoms and imaging findings. However, prompt recognition and surgical intervention are crucial to prevent complications such as bowel ischemia and strangulation. This case underscores the importance of considering internal hernias in the differential diagnosis of small bowel obstruction (SBO), especially in patients with a history of recent abdominal surgery. Early diagnosis and timely surgical management are essential for a favorable outcome.