Fasted Sprint Interval Training Results in Some Beneficial Skeletal Muscle Metabolic, but Similar Metabolomic and Performance Adaptations Compared With Carbohydrate-Fed Training in Recreationally Active Male.

Endurance training in fasted conditions (FAST) induces favorable skeletal muscle metabolic adaptations compared with carbohydrate feeding (CHO), manifesting in improved exercise performance over time. Sprint interval training (SIT) is a potent metabolic stimulus, however nutritional strategies to optimize adaptations to SIT are poorly characterized. Here we investigated the efficacy of FAST versus CHO SIT (4-6 × 30-s Wingate sprints interspersed with 4-min rest) on muscle metabolic, serum metabolome and exercise performance adaptations in a double-blind parallel group design in recreationally active males.

Divergent serum metabolomic, skeletal muscle signaling, transcriptomic, and performance adaptations to fasted versus whey protein-fed sprint interval training.

Sprint interval training (SIT) is a time-efficient alternative to endurance exercise, conferring beneficial skeletal muscle metabolic adaptations. Current literature has investigated the nutritional regulation of acute and chronic exercise-induced metabolic adaptations in muscle following endurance exercise, principally comparing the impact of training in fasted and carbohydrate-fed (CHO) conditions. Alternative strategies such as exercising in low CHO, protein-fed conditions remain poorly characterized, specifically pertaining to adaptations associated with SIT.

Development of a multiplex assay to determine the expression of mitochondrial genes in human skeletal muscle.

New Findings: What is the central question of this study? Can a custom-designed multiplex gene expression assay be used to quantify expression levels of a targeted group of mitochondrial genes in human skeletal muscle? What is the main finding and its importance? A custom-designed GeXP multiplex assay was developed, and the ability to accurately quantify expression of a targeted set of mitochondrial genes in human skeletal muscle was demonstrated. It holds distinct methodological and practical advantages over other commonly used quantification methods.

Abstract: Skeletal muscle is an important endocrine tissue demonstrating plasticity in response to external stimuli, including exercise and nutrition.

Inter-Individual Variation in Postprandial Glycemic Responses in Women Co-Ingesting Green Leafy Vegetables with a Carbohydrate Meal: Interactions with the Sirtuin System.

Scope: Green leafy vegetables (GLV) may improve postprandial glycemic responses (PGR) and metabolic health. However, inter-individual variations (IIV) preclude conclusive evidence. Sirtuin system is emerging as a key player in blood glucose control.

Limited Systemic Exposure with Topical Glycopyrronium Tosylate in Primary Axillary Hyperhidrosis.

Background: Glycopyrronium tosylate (GT; Qbrexza [glycopyrronium] cloth, 2.4%) is a topical anticholinergic approved (USA) for primary axillary hyperhidrosis in patients aged ≥ 9 years.

Objective: The objective of this study was to compare the pharmacokinetics and safety of GT to oral glycopyrrolate (phase I study) and assess the relationship between glycopyrronium pharmacokinetics and anticholinergic-related adverse events or efficacy with population pharmacokinetics using data from two phase II studies.

Long-term efficacy and safety of topical glycopyrronium tosylate for the treatment of primary axillary hyperhidrosis: Post hoc pediatric subgroup analysis from a 44-week open-label extension study.

Background/objectives: Glycopyrronium tosylate (GT) cloth, 2.4% is a topical anticholinergic approved in the United States for primary axillary hyperhidrosis in patients ≥9 years. This post hoc analysis evaluated long-term response (efficacy and safety) in pediatric patients (≥9 to ≤16 years) to GT in the 44-week, open-label extension (NCT02553798) of two, phase 3, double-blind, vehicle-controlled, 4-week trials (NCT02530281, NCT02530294).

Challenges of the heterogeneous nutrition response: interpreting the group mean.

Extensive research demonstrates unequivocally that nutrition plays a fundamental role in maintaining health and preventing disease. In parallel nutrition research provides evidence that the risks and benefits of diet and lifestyle choices do not affect people equally, as people are inherently variable in their responses to nutrition and associated interventions to maintain health and prevent disease. To simplify the inherent complexity of human subjects and their nutrition, with the aim of managing expectations for dietary guidance required to ensure healthy populations and individuals, nutrition researchers often seek to group individuals based on commonly used criteria.

A 44-Week Open-Label Study Evaluating Safety and Efficacy of Topical Glycopyrronium Tosylate in Patients with Primary Axillary Hyperhidrosis.

Background: Glycopyrronium tosylate is a topical anticholinergic approved in the USA for primary axillary hyperhidrosis in patients aged ≥ 9 years (Qbrexza™ [glycopyrronium] cloth, 2.4%).

Objective: This 44-week open-label extension study assessed glycopyrronium tosylate safety and descriptive efficacy in patients completing one of two, phase III, double-blind, vehicle-controlled, 4-week trials (NCT02530281; NCT02530294).

is a novel hypothalamic gene upregulated by a high-fat diet and leptin in mice.

Background: Energy homeostasis is regulated by the hypothalamus but fails when animals are fed a high-fat diet (HFD), and leptin insensitivity and obesity develops. To elucidate the possible mechanisms underlying these effects, a microarray-based transcriptomics approach was used to identify novel genes regulated by HFD and leptin in the mouse hypothalamus.

Results: Mouse global array data identified as a novel gene highly upregulated by both a HFD and leptin challenge.

Glycopyrronium tosylate in pediatric primary axillary hyperhidrosis: Post hoc analysis of efficacy and safety findings by age from two phase three randomized controlled trials.

Objectives: Hyperhidrosis in pediatric patients has been understudied. Post hoc analyses of two phase 3 randomized, vehicle-controlled, 4-week trials (ATMOS-1 [NCT02530281] and ATMOS-2 [NCT02530294]) were performed to assess efficacy and safety of topical anticholinergic glycopyrronium tosylate (GT) in pediatric patients.

Methods: Patients had primary axillary hyperhidrosis ≥ 6 months, average Axillary Sweating Daily Diary (ASDD/ASDD-Children [ASDD-C]) Item 2 (sweating severity) score ≥ 4, sweat production ≥ 50 mg/5 min (each axilla), and Hyperhidrosis Disease Severity Scale (HDSS) ≥ 3.

Topical Glycopyrronium Tosylate for the Treatment of Primary Axillary Hyperhidrosis: Patient-Reported Outcomes from the ATMOS-1 and ATMOS-2 Phase III Randomized Controlled Trials.

Background: Glycopyrronium tosylate (GT) is a topical anticholinergic approved in the USA for primary axillary hyperhidrosis in patients aged ≥ 9 years. GT was evaluated for primary axillary hyperhidrosis in replicate, randomized, double-blind, vehicle-controlled, phase III trials. GT reduced sweating severity and production versus vehicle and was generally well tolerated.

Dietary fibers inhibit obesity in mice, but host responses in the cecum and liver appear unrelated to fiber-specific changes in cecal bacterial taxonomic composition.

Dietary fibers (DF) can prevent obesity in rodents fed a high-fat diet (HFD). Their mode of action is not fully elucidated, but the gut microbiota have been implicated. This study aimed to identify the effects of seven dietary fibers (barley beta-glucan, apple pectin, inulin, inulin acetate ester, inulin propionate ester, inulin butyrate ester or a combination of inulin propionate ester and inulin butyrate ester) effective in preventing diet-induced obesity and links to differences in cecal bacteria and host gene expression.

Palmitic acid triggers inflammatory responses in N42 cultured hypothalamic cells partially via ceramide synthesis but not via TLR4.

A high-fat diet induces hypothalamic inflammation in rodents which, in turn, contributes to the development of obesity by eliciting both insulin and leptin resistance. However, the mechanism by which long-chain saturated fatty acids trigger inflammation is still contentious. To elucidate this mechanism, the effect of fatty acids on the expression of the pro-inflammatory cytokines and was investigated in the mHypoE-N42 hypothalamic cell line (N42).

Topical glycopyrronium tosylate for the treatment of primary axillary hyperhidrosis: Results from the ATMOS-1 and ATMOS-2 phase 3 randomized controlled trials.

Background: Glycopyrronium tosylate (GT) is a topical anticholinergic developed for once-daily treatment of primary axillary hyperhidrosis.

Objective: Assess the efficacy and safety of GT for primary axillary hyperhidrosis.

Methods: ATMOS-1 and ATMOS-2 were replicate randomized, double-blind, vehicle-controlled, 4-week phase 3 trials.

Certolizumab pegol for the treatment of chronic plaque psoriasis: Results through 48 weeks of a phase 3, multicenter, randomized, double-blind, etanercept- and placebo-controlled study (CIMPACT).

Background: Phase 2 psoriasis studies with the Fc-free, PEGylated, anti-tumor necrosis factor biologic certolizumab pegol demonstrated meaningful clinical activity.

Objective: Assess safety and efficacy of certolizumab in adults with moderate-to-severe chronic plaque psoriasis.

Methods: Patients were randomized 3:3:1:3 to certolizumab 400 mg, certolizumab 200 mg, or placebo every 2 weeks for 16 weeks or etanercept 50 mg twice weekly for 12 weeks.

Certolizumab pegol for the treatment of chronic plaque psoriasis: Results through 48 weeks from 2 phase 3, multicenter, randomized, double-blinded, placebo-controlled studies (CIMPASI-1 and CIMPASI-2).

Background: Certolizumab pegol, the only Fc-free, PEGylated anti-tumor necrosis factor biologic, demonstrated clinically meaningful improvements suggestive of a positive risk-benefit balance in phase 2 studies in adults with moderate-to-severe chronic plaque psoriasis.

Objective: Assess certolizumab efficacy and safety versus placebo in phase 3 studies.

Methods: Patients with moderate-to-severe chronic plaque psoriasis were randomized 2:2:1 to certolizumab 400 mg, certolizumab 200 mg, or placebo every 2 weeks.

Inter-individual responses to sprint interval training, a pilot study investigating interactions with the sirtuin system.

Sprint interval training (SIT) is reported to improve blood glucose control and may be a useful public health tool. The sirtuins and associated genes are emerging as key players in blood glucose control. This study investigated the interplay between the sirtuin/NAD system and individual variation in insulin sensitivity responses after SIT in young healthy individuals.

Olumacostat glasaretil, a novel topical sebum inhibitor, in the treatment of acne vulgaris: A phase IIa, multicenter, randomized, vehicle-controlled study.

Background: Olumacostat glasaretil (OG) inhibits acetyl-coenzyme A carboxylase, the enzyme responsible for the first, rate-limiting step in de novo fatty acid synthesis. OG inhibited in vitro human sebocyte lipid production and reduced in vivo sebaceous gland size in hamster ears.

Objectives: Safety and efficacy of OG 7.

Tissue-specific regulation of sirtuin and nicotinamide adenine dinucleotide biosynthetic pathways identified in C57Bl/6 mice in response to high-fat feeding.

The sirtuin (SIRT)/nicotinamide adenine dinucleotide (NAD) system is implicated in development of type 2 diabetes (T2D) and diet-induced obesity, a major risk factor for T2D. Mechanistic links have not yet been defined. SIRT/NAD system gene expression and NAD/NADH levels were measured in liver, white adipose tissue (WAT) and skeletal muscle from mice fed either a low-fat diet or high-fat diet (HFD) for 3 days up to 16 weeks.

Molecular Profiling of Multiplexed Gene Markers to Assess Viability of Ex Vivo Human Colon Explant Cultures.

Human colon tissue explant culture provides a physiologically relevant model system to study human gut biology. However, the small (20-30 mg) and complex tissue samples used present challenges for monitoring tissue stability, viability, and provision of sufficient tissue for analyses. Combining molecular profiling with explant culture has potential to overcome such limitations, permitting interrogation of complex gene regulation required to maintain gut mucosa in culture, monitor responses to culture environments and interventions.

Designing a broad-spectrum integrative approach for cancer prevention and treatment.

Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.

Dysregulated metabolism contributes to oncogenesis.

Cancer is a disease characterized by unrestrained cellular proliferation. In order to sustain growth, cancer cells undergo a complex metabolic rearrangement characterized by changes in metabolic pathways involved in energy production and biosynthetic processes. The relevance of the metabolic transformation of cancer cells has been recently included in the updated version of the review "Hallmarks of Cancer", where dysregulation of cellular metabolism was included as an emerging hallmark.