High energy flux mediates the tonically augmented beta-adrenergic support of resting metabolic rate in habitually exercising older adults

The sympathetic nervous system contributes to resting metabolic rate (RMR) via beta-adrenergic receptor (beta-AR) stimulation of energy metabolism. RMR and beta-AR support of RMR are greater in habitually exercising compared with sedentary older adults possibly due to greater energy flux (magnitude of energy intake and energy expenditure during energy balance). In 10 older adults regularly performing aerobic endurance exercise (mean +/- se, 66 +/- 1 yr) compared with baseline, a reduction in energy flux (via abstention of exercise and proportional reduction in dietary intake) decreased (P < 0.05) energy expenditure (7746 +/- 440 vs. 9630 +/- 662 kJ.d(-1)), caloric intake (7808 +/- 431 vs. 9433 +/- 528 kJ.d(-1)), RMR (5192 +/- 167 vs. 5401 +/- 209 kJ.d(-1)), and skeletal muscle sympathetic nervous system activity (36 +/- 2 vs. 42 +/- 2 bursts.min(-1)). Significant beta-AR support of RMR was observed at baseline (167 +/- 42 kJ.d(-1)) but not during reduced energy flux. The change in RMR from baseline to reduced energy flux was related to the corresponding change in beta-AR support of RMR (r = 0.77, P = 0.009). No changes were observed in seven time controls (69 +/- 3 yr) who maintained energy flux. High energy flux is a key mechanism contributing to the elevated RMR and beta-AR support of RMR in habitually exercising older adults. Maintenance of high energy flux via regular exercise may be an effective strategy for maintaining energy expenditure and preventing age-associated obesity.     

COVID‐19 in solid organ transplant recipients: Initial report from the US epicenter

Solid organ transplant recipients may be at a high risk for SARS‐CoV‐2 infection and poor associated outcomes. We herein report our initial experience with solid organ transplant recipients with SARS‐CoV‐2 infection at two centers during the first 3 weeks of the outbreak in New York City. Baseline characteristics, clinical presentation, antiviral and immunosuppressive management were compared between patients with mild/moderate and severe disease (defined as ICU admission, intubation or death). Ninety patients were analyzed with a median age of 57 years. Forty‐six were kidney recipients, 17 lung, 13 liver, 9 heart, and 5 dual‐organ transplants. The most common presenting symptoms were fever (70%), cough (59%), and dyspnea (43%). Twenty‐two (24%) had mild, 41 (46%) moderate, and 27 (30%) severe disease. Among the 68 hospitalized patients, 12% required non‐rebreather and 35% required intubation. 91% received hydroxychloroquine, 66% azithromycin, 3% remdesivir, 21% tocilizumab, and 24% bolus steroids. Sixteen patients died (18% overall, 24% of hospitalized, 52% of ICU) and 37 (54%) were discharged. In this initial cohort, transplant recipients with COVID‐19 appear to have more severe outcomes, although testing limitations likely led to undercounting of mild/asymptomatic cases. As this outbreak unfolds, COVID‐19 has the potential to severely impact solid organ transplant recipients.     

Molecular variants of human papilloma virus 16 E2, E4, E5, E6 and E7 genes associated with cervical neoplasia in Romanian patients

The aim of this study was to identify and associate the sequence variations of human Papillomavirus 16 (HPV16) genes from women who live in two different areas of Romania and associate them with malignant progression. One hundred twenty-four HPV16-positive cervical isolates were collected, and the E2, E4, E5, E6 and E7 viral genes were sequenced. Two new missense mutations in the E6 gene (C279G and A305C) were found (together or alone, in association with other mutations) in 44 of 124 cases. The most frequently simultaneously mutated genes were E4/E2 hinge, E5 and E6 (p = 0.0004) in squamous cell carcinoma (SCC) samples. Also, for SCC patients, the best-correlated mutation patterns were obtained for E4/E2 hinge-E5 (r = 0.7984; p < 0.0001). No sample was found to have all of the investigated viral genes concurrently mutated. Phylogenetic analysis was performed to characterize the viral variants. Similar results were found for SCC and cervical intraepithelial neoplasia III (CINIII) cases. After all of the target gene sequences were assembled, all patients were found to be infected with viruses of the HPV16- European-German (EG) lineage, and two clusters were identified, the first (55/96 variants) from Moldavia and the second (41/96 variants) from Bucharest. The distinct cluster derived from EG in Moldavia could partially explain the increased frequency of SCC in this area. This study has generated a comprehensive set of sequence variation data on HPV16 circulating in Romania to join the existing data and highlight the important role of HPV16 variants during cervical carcinogenesis.     

Histologic Comparison of Vibrating Guidewire with Conventional Guidewire Technique in an Experimental Coronary In Vivo Model

Purpose: To compare the damage caused by vibrating guidewire manipulation and conventional guidewire manipulation of soft coronary wires in normal sheep coronary arteries. Methods: Using an intact sheep model the two methods of passing a coronary guidewire down a normal coronary artery under fluoroscopic screening control were studied. The resulting arterial damage caused by the two techniques was studied histologically. The severity of damage was scored from 1 (no damage) to 4 (severe damage) and expressed as: (a) percentage of damaged sections, (b) mean damage score per section and (c) percentage of sections suffering the most severe degree of damage (scores 3 and 4). Results: One hundred and sixty-eight sections were studied. The percentage of damaged sections was lower in the vibrating guidewire group (p = 0.004). The mean damage score and the percentage of sections with a damage score of 3 or 4 were smaller in the vibrating guidewire group than in the conventional guidewire manipulation group (p = 0.001 and p = 0.009, respectively). Conclusions: Both methods of guidewire manipulation cause identifiable vascular damage. The extent and severity of damage appear greater when the guidewire is manipulated manually.     

Alginate‐encapsulated HepG2 Cells in a Fluidized Bed Bioreactor Maintain Function in Human Liver Failure Plasma

Alginate‐encapsulated HepG2 cells cultured in microgravity have the potential to serve as the cellular component of a bioartificial liver. This study investigates their performance in normal and liver failure (LF) human plasma over 6–8 h in a fluidized bed bioreactor. After 8 days of microgravity culture, beads containing 1.5 × 10⁹ cells were perfused for up to 8 h at 48 mL/min with 300 mL of plasma. After exposure to 90% LF plasma, vital dye staining showed maintained cell viability, while a 7% increase in lactate dehydrogenase activity indicated minimal cell damage. Glucose consumption, lactate production, and a 4.3‐fold linear increase in alpha‐fetoprotein levels were observed. Detoxificatory function was demonstrated by quantification of bilirubin conjugation, urea synthesis, and Cyp450 1A activity. These data show that in LF plasma, alginate‐encapsulated HepG2 cells can maintain viability, and metabolic, synthetic, and detoxificatory activities, indicating that the system can be scaled‐up to form the biological component of a bioartificial liver.     

Airway obstruction and acute respiratory failure due to Aspergillus tracheobronchitis

OBJECTIVE: To report a patient with lymphoma who developed Aspergillus tracheobronchitis resulting in airway obstruction and acute respiratory failure. DESIGN: Case report. SETTING: Intensive care unit of a tertiary care hospital. PATIENT: A 22-yr-old female with lymphoma who developed a respiratory infection 3 months after completing immunosuppressive therapy. She was treated empirically with broad spectrum antibiotics and subsequently received a supplementary chemotherapeutic course. Soon afterward she developed severe respiratory failure. Chest radiograph showed atelectasis of the right upper and lower lobes. INTERVENTIONS: Emergent mechanical ventilation; fiberoptic bronchoscopy. MEASUREMENTS AND MAIN RESULTS: Fiberoptic bronchoscopy revealed extensive obstruction of both main and subsegmental bronchi with a solid mass strongly adhered to the bronchial wall; both histologic examination and culture of that mass revealed Aspergillus. The patient died of refractory hypoxemia a few days later. CONCLUSIONS: Aspergillus tracheobronchitis should be considered in immunocompromised patients with suspected lung infection even when the main radiographic finding is atelectasis. Bronchoscopy and histologic examination of identified intraluminal material should be performed as soon as possible.     

Comparison of a healthy miRNome with melanoma patient miRNomes: are microRNAs suitable serum biomarkers for cancer?

MiRNAs are increasingly recognized as biomarkers for the diagnosis of cancers where they are profiled from tumor tissue (intracellular miRNAs) or serum/plasma samples (extracellular miRNAs). To improve detection of reliable biomarkers from blood samples, we first compiled a healthy reference miRNome and established a well-controlled analysis pipeline allowing for standardized quantification of circulating miRNAs. Using whole miRNome and custom qPCR arrays, miRNA expression profiles were analyzed in 126 serum, whole blood and tissue samples of healthy volunteers and melanoma patients and in primary melanocyte and keratinocyte cell lines. We found characteristic signatures with excellent prognostic scores only in late stage but not in early stage melanoma patients. Upon comparison of melanoma tissue miRNomes with matching serum samples, several miRNAs were identified to be exclusively tissue-derived (miR-30b-5p, miR-374a-5p and others) while others had higher expression levels in serum (miR-3201 and miR-122-5p). Here we have compiled a healthy and widely applicable miRNome from serum samples and we provide strong evidence that levels of cell-free miRNAs only change significantly at later stages of melanoma progression, which has serious implications for miRNA biomarker studies in cancer.