Cycle Training Modulates Satellite Cell and Transcriptional Responses to a Bout of Resistance Exercise

This investigation evaluated whether moderate‐intensity cycle ergometer training affects satellite cell and molecular responses to acute maximal concentric/eccentric resistance exercise in middle‐aged women. Baseline and 72 h postresistance exercise vastus lateralis biopsies were obtained from seven healthy middle‐aged women (56 ± 5 years, BMI 26 ± 1, VO2max 27 ± 4) before and after 12 weeks of cycle training. Myosin heavy chain (MyHC) I‐ and II‐associated satellite cell density and cross‐sectional area was determined via immunohistochemistry. Expression of 93 genes representative of the muscle‐remodeling environment was also measured via NanoString. Overall fiber size increased ~20% with cycle training (P = 0.052). MyHC I satellite cell density increased 29% in response to acute resistance exercise before endurance training and 50% with endurance training (P \u3c 0.05). Following endurance training, MyHC I satellite cell density decreased by 13% in response to acute resistance exercise (acute resistance × training interaction, P \u3c 0.05). Genes with an interaction effect tracked with satellite cell behavior, increasing in the untrained state and decreasing in the endurance trained state in response to resistance exercise. Similar satellite cell and gene expression response patterns indicate coordinated regulation of the muscle environment to promote adaptation. Moderate‐intensity endurance cycle training modulates the response to acute resistance exercise, potentially conditioning the muscle for more intense concentric/eccentric activity. These results suggest that cycle training is an effective endurance exercise modality for promoting growth in middle‐aged women, who are susceptible to muscle mass loss with progressing age

Area balance and strain in an extensional fault system: Strategies for improved oil recovery in fractured chalk, Gilbertown Field, southwestern Alabama. Annual report, March 1996--March 1997

Gilbertown Field is the oldest oil field in Alabama and produces oil from chalk of the Upper Cretaceous Selma Group and from sandstone of the Eutaw Formation along the southern margin of the Gilbertown fault system. Most of the field has been in primary recovery since establishment, but production has declined to marginally economic levels. This investigation applies advanced geologic concepts designed to aid implementation of improved recovery programs. The Gilbertown fault system is detached at the base of Jurassic salt. The fault system began forming as a half graben and evolved in to a full graben by the Late Cretaceous. Conventional trapping mechanisms are effective in Eutaw sandstone, whereas oil in Selma chalk is trapped in faults and fault-related fractures. Burial modeling establishes that the subsidence history of the Gilbertown area is typical of extensional basins and includes a major component of sediment loading and compaction. Surface mapping and fracture analysis indicate that faults offset strata as young as Miocene and that joints may be related to regional uplift postdating fault movement. Preliminary balanced structural models of the Gilbertown fault system indicate that synsedimentary growth factors need to be incorporated into the basic equations of area balance to model strain and predict fractures in Selma and Eutaw reservoirs

Area balance and strain in an extensional fault system: Strategies for improved oil recovery in fractured chalk, Gilbertown Field, southwestern Alabama. Final report, March 1996--September 1998

This project was designed to analyze the structure of Mesozoic and Tertiary strata in Gilbertown Field and adjacent areas to suggest ways in which oil recovery can be improved. The Eutaw Formation comprises 7 major flow units and is dominated by low-resistivity, low-contrast play that is difficult to characterize quantitatively. Selma chalk produces strictly from fault-related fractures that were mineralized as warm fluid migrated from deep sources. Resistivity, dipmeter, and fracture identification logs corroborate that deformation is concentrated in the hanging-wall drag zones. New area balancing techniques were developed to characterize growth strata and confirm that strain is concentrated in hanging-wall drag zones. Curvature analysis indicates that the faults contain numerous fault bends that influence fracture distribution. Eutaw oil is produced strictly from footwall uplifts, whereas Selma oil is produced from fault-related fractures. Clay smear and mineralization may be significant trapping mechanisms in the Eutaw Formation. The critical seal for Selma reservoirs, by contrast, is where Tertiary clay in the hanging wall is juxtaposed with poorly fractured Selma chalk in the footwall. Gilbertown Field can be revitalized by infill drilling and recompletion of existing wells. Directional drilling may be a viable technique for recovering untapped oil from Selma chalk. Revitalization is now underway, and the first new production wells since 1985 are being drilled in the western part of the field

Pharmacokinetics and pharmacodynamics of fenoldopam mesylate for blood pressure control in pediatric patients

<p>Abstract</p> <p>Background</p> <p>Fenoldopam mesylate, a selective dopamine1-receptor agonist, is used by intravenous infusion to treat hypertension in adults. Fenoldopam is not approved by the FDA for use in children; reports describing its use in pediatrics are limited. In a multi-institutional, placebo controlled, double-blind, multi-dose trial we determined the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics and side-effect profile of fenoldopam in children.</p> <p>Methods</p> <p>Seventy seven (77) children from 3 weeks to 12 years of age scheduled for surgery in which deliberate hypotension would be induced were enrolled. Patients were randomly assigned to one of five, blinded treatment groups (placebo or fenoldopam 0.05, 0.2, 0.8, or 3.2 mcg/kg/min iv) for a 30-minute interval after stabilization of anesthesia and placement of vascular catheters. Following the 30-minute blinded interval, investigators adjusted the fenoldopam dose to achieve a target mean arterial pressure in the open-label period until deliberate hypotension was no longer indicated (e.g., muscle-layer closure). Mean arterial pressure and heart rate were continuously monitored and were the primary endpoints.</p> <p>Results</p> <p>Seventy-six children completed the trial. Fenoldopam at doses of 0.8 and 3.2 mcg/kg/min significantly reduced blood pressure (p < 0.05) during the blinded interval, and doses of 1.0–1.2 mcg/kg/min resulted in continued control of blood pressure during the open-label interval. Doses greater than 1.2 mcg/kg/min during the open-label period resulted in increasing heart rate without additional reduction in blood pressure. Fenoldopam was well-tolerated; side effects occurred in a minority of patients. The PK/PD relationship of fenoldopam in children was determined.</p> <p>Conclusion</p> <p>Fenoldopam is a rapid-acting, effective agent for intravenous control of blood pressure in children. The effective dose range is significantly higher in children undergoing anesthesia and surgery (0.8–1.2 mcg/kg/min) than as labeled for adults (0.05–0.3 mcg/kg/min). The PK and side-effect profiles for children and adults are similar.</p

Genome-wide imputation study identifies novel HLA locus for pulmonary fibrosis and potential role for auto-immunity in fibrotic idiopathic interstitial pneumonia.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Fibrotic idiopathic interstitial pneumonias (fIIP) are a group of fatal lung diseases with largely unknown etiology and without definitive treatment other than lung transplant to prolong life. There is strong evidence for the importance of both rare and common genetic risk alleles in familial and sporadic disease. We have previously used genome-wide single nucleotide polymorphism data to identify 10 risk loci for fIIP. Here we extend that work to imputed genome-wide genotypes and conduct new RNA sequencing studies of lung tissue to identify and characterize new fIIP risk loci.We performed genome-wide genotype imputation association analyses in 1616 non-Hispanic white (NHW) cases and 4683 NHW controls followed by validation and replication (878 cases, 2017 controls) genotyping and targeted gene expression in lung tissue. Following meta-analysis of the discovery and replication populations, we identified a novel fIIP locus in the HLA region of chromosome 6 (rs7887 P meta  = 3.7 × 10(-09)). Imputation of classic HLA alleles identified two in high linkage disequilibrium that are associated with fIIP (DRB1*15:01 P = 1.3 × 10(-7) and DQB1*06:02 P = 6.1 × 10(-8)). Targeted RNA-sequencing of the HLA locus identified 21 genes differentially expressed between fibrotic and control lung tissue (Q < 0.001), many of which are involved in immune and inflammatory response regulation. In addition, the putative risk alleles, DRB1*15:01 and DQB1*06:02, are associated with expression of the DQB1 gene among fIIP cases (Q < 1 × 10(-16)).We have identified a genome-wide significant association between the HLA region and fIIP. Two HLA alleles are associated with fIIP and affect expression of HLA genes in lung tissue, indicating that the potential genetic risk due to HLA alleles may involve gene regulation in addition to altered protein structure. These studies reveal the importance of the HLA region for risk of fIIP and a basis for the potential etiologic role of auto-immunity in fIIP.National Heart, Lung and Blood Institute R01-HL095393 R01-HL097163 P01-HL092870 RC2-HL101715 U01-HL089897 U01-HL089856 U01-HL108642 P50-HL089493

SARS-CoV-2 infection produces chronic pulmonary epithelial and immune cell dysfunction with fibrosis in mice

A subset of individuals who recover from coronavirus disease 2019 (COVID-19) develop post-acute sequelae of SARS-CoV-2 (PASC), but the mechanistic basis of PASC-associated lung abnormalities suffers from a lack of longitudinal tissue samples. The mouse-adapted severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain MA10 produces an acute respiratory distress syndrome (ARDS) in mice similar to humans. To investigate PASC pathogenesis, studies of MA10-infected mice were extended from acute to clinical recovery phases. At 15 to 120 days post-virus clearance, pulmonary histologic findings included subpleural lesions composed of collagen, proliferative fibroblasts, and chronic inflammation, including tertiary lymphoid structures. Longitudinal spatial transcriptional profiling identified global reparative and fibrotic pathways dysregulated in diseased regions, similar to human COVID-19. Populations of alveolar intermediate cells, coupled with focal up-regulation of pro-fibrotic markers, were identified in persistently diseased regions. Early intervention with antiviral EIDD-2801 reduced chronic disease, and early anti-fibrotic agent (nintedanib) intervention modified early disease severity. This murine model provides opportunities to identify pathways associated with persistent SARS-CoV-2 pulmonary disease and test countermeasures to ameliorate PASC., After recovery from acute SARS-CoV-2 infection, mice exhibit chronic lung disease similar to some humans, allowing for testing of therapeutics

Detecting circumscribed lesions with the Hough transform

We have designed and implemented a circumscribed lesion detection algorithm, based on the Hough Transform, which will detect zero or more approximately circular structures in a mammogram over a range of radii from a few pixels to nearly the size of the breast. We address the geometrical behavior of peaks in Hough parameter space (x,y,r) for both the true radius of a circular structure in the image (r = r{sub o}), and for the parameter r as it passes through this radius. In addition, we evaluate peaks in Hough parameter space by re-analyzing the underlying mammogram in the vicinity of the circular disk indicated by the peak. Discs suggested by the resulting peaks are accumulated in a feature image, scaled by a measure of their quality. These results are then rectified with respect to image contrast extremes and average value. The result is a feature with a continuously scaled pixel level output which suggests the likelihood that a pixel is located inside a circular structure, irrespective of the radius of the structure and overall mammogram contrast. These features are evaluated fast qualitative and quantitative performance metrics which permit circumscribed lesion detection features to be initially evaluated without a full end-to-end classification experiment