Prolyl Hydroxylase Domain-2 Inhibition Improves Skeletal Muscle Regeneration in a Male Murine Model of Obesity.

Obesity leads to a loss of muscle mass and impaired muscle regeneration. In obese individuals, pathologically elevated levels of prolyl hydroxylase domain enzyme 2 (PHD2) limit skeletal muscle hypoxia-inducible factor-1 alpha and vascular endothelial growth factor (VEGF) expression. Loss of local VEGF may further impair skeletal muscle regeneration.

An Anatomical study for localisation of Zygomatic branch of Facial nerve and Masseteric nerve - An aid to nerve coaptation for facial reanimation surgery: A cadaver based study in Eastern India.

Context: In cases of chronic facial palsy, where direct neurotisation is possible, ipsilateral masseteric nerve is a very suitable motor donor. We have tried to specifically locate the masseteric nerve for this purpose.

Aims: Describing an approach of localisation and exposure of both the zygomatic branch of Facial nerve and the nerve to masseter, with respect to a soft tissue reference point over face.

Overview of systematic reviews of therapeutic ranges: methodologies and recommendations for practice.

Background: Many medicines are dosed to achieve a particular therapeutic range, and monitored using therapeutic drug monitoring (TDM). The evidence base for a therapeutic range can be evaluated using systematic reviews, to ensure it continues to reflect current indications, doses, routes and formulations, as well as updated adverse effect data. There is no consensus on the optimal methodology for systematic reviews of therapeutic ranges.

Gene expression profiling of skeletal muscle after volumetric muscle loss.

Volumetric muscle loss (VML), usually occurring following traumatic injury, results in a composite loss of muscle mass. These injuries manifest as decreased strength and functional impairments. Clinically, these injuries often heal with fibrosis, as opposed to skeletal muscle regeneration.

The cyclin-like protein, SPY1, regulates the ERα and ERK1/2 pathways promoting tamoxifen resistance.

The Ras/Raf/MEK/ERK pathway conveys growth factor and mitogen signalling to control the phosphorylation of a plethora of substrates regulating proliferation, survival, and migration. The Ras signalling pathway is frequently associated with poor prognosis and drug resistance in various cancers including those of the blood, breast and prostate. Activation of the downstream effector ERK does not always occur via a linear cascade of events; complicating the targeting of this pathway therapeutically.

The effect of pH on cell viability, cell migration, cell proliferation, wound closure, and wound reepithelialization: In vitro and in vivo study.

Wound microenvironment plays a major role in the process of wound healing. It contains various external and internal factors that participate in wound pathophysiology. The pH is an important factor that influences wound healing by changing throughout the healing process.

Intraoperative Feeding Improves Calorie and Protein Delivery in Acute Burn Patients.

Enteral nutrition support is a critical component of modern burn care for severely burned patients. However, tube feeds are frequently withheld during the perioperative period because of aspiration concerns. As a result, patients requiring multiple operative procedures risk accumulating significant protein-calorie deficits.

Functional specialization of two paralogous TAF12 variants by their selective association with SAGA and TFIID transcriptional regulatory complexes.

TATA box-binding protein (TBP)-associated factors (TAFs), evolutionarily conserved from yeast to humans, play a central role during transcription initiation. A subset of TAF proteins is shared in transcription factor II D (TFIID) and SAGA transcription regulatory complexes. Although higher eukaryotes contain multiple TAF variants that specify tissue- and developmental stage-specific organization of TFIID or SAGA complexes, in unicellular genomes, however, each TAF is encoded by a single gene.

Systemic Regulators of Skeletal Muscle Regeneration in Obesity.

Skeletal muscle maintenance is a dynamic process and undergoes constant repair and regeneration. However, skeletal muscle regenerative capacity declines in obesity. In this review, we focus on obesity-associated changes in inflammation, metabolism, and impaired insulin signaling, which are pathologically dysregulated and ultimately result in a loss of muscle mass and function.

Using pharmacokinetic modelling to improve prescribing practices of intravenous aminophylline in childhood asthma exacerbations.

Objective: To evaluate physiologically based pharmacokinetic modelling (PBPK) software in paediatric asthma patients using intravenous aminophylline.

Methods: Prospective clinical audit of children receiving iv aminophylline (July 2014 to June 2016), and in-silico modelling using Simcyp software.

Results: Thirty-eight admissions (25 children) were included.

Ataluren and similar compounds (specific therapies for premature termination codon class I mutations) for cystic fibrosis.

Background: Cystic fibrosis is a common life-shortening genetic disorder in the Caucasian population (less common in other ethnic groups) caused by the mutation of a single gene that codes for the production of the cystic fibrosis transmembrane conductance regulator protein. This protein coordinates the transport of salt (and bicarbonate) across cell surfaces and the mutation most notably affects the airways. In the lungs of people with cystic fibrosis, defective protein results in a dehydrated surface liquid and compromised mucociliary clearance.

Reflections on a Decade of Face Transplantation.

On November 27, 2005, Isabelle Dinoire underwent the world's first partial face transplant in Amiens (France) after a dog attack had left her face severely disfigured. The abrupt surgical leap found the medical community and society unprepared to deal with the scientific, ethical, and societal implications of a surgical procedure that was striving to transition from sci-fi novels to science. Today, 10 years and over 35 transplants later, public opinion has become accustomed to the concept of "face restoration" through transplantation.

Late Surgical-Site Infection in Immediate Implant-Based Breast Reconstruction.

Background: Surgical-site infection causes devastating reconstructive failure in implant-based breast reconstructions. Large national database studies offer insights into complication rates, but only capture outcomes within 30 days postoperatively. This study evaluates both early and late surgical-site infection in immediate implant-based reconstruction and identifies predictors.

Age-associated NF-κB signaling in myofibers alters the satellite cell niche and re-strains muscle stem cell function.

Skeletal muscle is a highly regenerative tissue, but muscle repair potential is increasingly compromised with advancing age. In this study, we demonstrate that increased NF-κB activity in aged muscle fibers contributes to diminished myogenic potential of their associated satellite cells. We further examine the impact of genetic modulation of NF-κB signaling in muscle satellite cells or myofibers on recovery after damage.

Sucrose Nonfermenting-Related Kinase Enzyme-Mediated Rho-Associated Kinase Signaling is Responsible for Cardiac Function.

Background: Cardiac metabolism is critical for the functioning of the heart, and disturbance in this homeostasis is likely to influence cardiac disorders or cardiomyopathy. Our laboratory has previously shown that SNRK (sucrose nonfermenting related kinase) enzyme, which belongs to the AMPK (adenosine monophosphate-activated kinase) family, was essential for cardiac metabolism in mammals. Snrk global homozygous knockout (KO) mice die at postnatal day 0, and conditional deletion of Snrk in cardiomyocytes (Snrk cmcKO) leads to cardiac failure and death by 8 to 10 months.

Inhaled short-acting bronchodilators for managing emergency childhood asthma: an overview of reviews.

International guidelines provide conflicting recommendations on how to use bronchodilators to manage childhood acute wheezing conditions in the emergency department (ED), and there is variation within and among countries in how these conditions are managed. This may be reflective of uncertainty about the evidence. This overview of systematic reviews (SRs) aimed to synthesize, appraise, and present all SR evidence on the efficacy and safety of inhaled short-acting bronchodilators to treat asthma and wheeze exacerbations in children 0-18 years presenting to the ED.

Extended V-Y Advancement Flap Reconstruction of a Large Posterior Upper Midline Trunk Defect.

Large posterior upper trunk defects can be challenging to reconstruct. Trapezius or latissimus dorsi myocutaneous flaps are principally utilized for reconstruction; however, some defects may not be amenable to this standard approach. Here, we describe a patient with a full-thickness skin and subcutaneous tissue loss of the upper back and inferior cervical region after dermatofibrosarcoma protuberans resection.

The epigenetic signature of systemic insulin resistance in obese women.

Aims/hypothesis: Insulin resistance (IR) links obesity to type 2 diabetes. The aim of this study was to explore whether white adipose tissue (WAT) epigenetic dysregulation is associated with systemic IR by genome-wide CG dinucleotide (CpG) methylation and gene expression profiling in WAT from insulin-resistant and insulin-sensitive women. A secondary aim was to determine whether the DNA methylation signature in peripheral blood mononuclear cells (PBMCs) reflects WAT methylation and, if so, can be used as a marker for systemic IR.

Aminophylline Dosage In Asthma Exacerbations in Children: A Systematic Review.

Background: Adequate asthma treatment of childhood exacerbations with IV aminophylline depends on appropriate dosage. Recommendations to aim for a target therapeutic range may be inappropriate as serum concentrations correlate poorly with clinical improvement. This review aims to evaluate the evidence for the optimum dosage strategy of intravenous aminophylline in children suffering an exacerbation of asthma.

Estrogen Receptor α Promotes Breast Cancer by Reprogramming Choline Metabolism.

Estrogen receptor α (ERα) is a key regulator of breast growth and breast cancer development. Here, we report how ERα impacts these processes by reprogramming metabolism in malignant breast cells. We employed an integrated approach, combining genome-wide mapping of chromatin-bound ERα with estrogen-induced transcript and metabolic profiling, to demonstrate that ERα reprograms metabolism upon estrogen stimulation, including changes in aerobic glycolysis, nucleotide and amino acid synthesis, and choline (Cho) metabolism.