Molecular Mechanisms of Insulin Resistance in Polycystic Ovary Syndrome: Unraveling the Conundrum in Skeletal Muscle?

Context: Polycystic ovary syndrome (PCOS) is a common endocrine condition affecting 8% to 13% of women across the lifespan. PCOS affects reproductive, metabolic, and mental health, generating a considerable health burden. Advances in treatment of women with PCOS has been hampered by evolving diagnostic criteria and poor recognition by clinicians.

Multidisciplinary team clinic for vocal cord dysfunction directs therapy and significantly reduces healthcare utilization.

Background And Objective: Multidisciplinary team (MDT) clinics use an integrated approach to individualize care of complex medical conditions. Vocal cord dysfunction (VCD) is a challenging condition that is likely to benefit from MDT clinics but this has not been researched.

Methods: A prospective observational cohort study of a novel VCD MDT clinic was conducted in patients with suspected VCD.

Effectiveness on fertility outcome of tubal flushing with different contrast media: systematic review and network meta-analysis.

Objectives: To compare, in women with infertility, the effectiveness and safety of tubal flushing using oil-based contrast medium, water-based contrast medium or their combination, and no tubal flushing, and to evaluate the effectiveness of tubal flushing on fertility outcome over time.

Methods: We performed a systematic review and network meta-analysis, searching the electronic databases MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials, and trial registries, up to 25 September 2018. We included randomized controlled trials (RCTs) comparing the following interventions with each other or with no intervention in women with infertility: tubal flushing using water-based contrast medium, tubal flushing using oil-based contrast medium or additional tubal flushing with oil-based medium following diagnostic tubal flushing with water-based medium.

Impact of Preexisting Hepatitis C Virus Genotype 6 NS3, NS5A, and NS5B Polymorphisms on the Potency of Direct-Acting Antiviral Agents.

HCV genotype 6 (GT-6) is found predominantly in East and Southeast Asia. Clinical studies have focused on patients infected with hepatitis C virus (HCV) GT-6a, where high sustained virologic response (SVR) rates to direct-acting antivirals (DAAs) have been achieved. However, GT-6 is highly diverse, with 29 reported subtypes.

Aging and the relationships between long-axis systolic and early diastolic excursion, isovolumic relaxation time and left ventricular length-Implications for the interpretation of aging effects on e`.

Background: Both the left ventricular (LV) long-axis peak early diastolic lengthening velocity (e`) and long-axis early diastolic excursion (EDExc) decrease with age, but the mechanisms underlying these decreases are not fully understood. The aim of this study was to investigate the relative contributions to aging-related decreases in e`and EDExc from LV long-axis systolic excursion (SExc), isovolumic relaxation time (IVRT, as a measure of the speed of relaxation) and LV end-diastolic length (LVEDL).

Methods: The study group was 50 healthy adult subjects of ages 17-75 years with a normal LV ejection fraction.

Differences in the determinants of right ventricular and regional left ventricular long-axis dysfunction in Friedreich ataxia.

Background: Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative condition which also has effects on the heart. In 96% of affected individuals FRDA is due to homozygosity of a GAA repeat expansion in intron 1 of the frataxin (FXN) gene. The number of GAA repeats have been shown to relate to disease severity in FRDA, this thought to be via an inverse relationship of GAA repeat number and cellular frataxin levels.

SCOT: a comparison of cost-effectiveness from a large randomised phase III trial of two durations of adjuvant Oxaliplatin combination chemotherapy for colorectal cancer.

Background: The Short Course Oncology Therapy (SCOT) study is an international, multicentre, non-inferiority randomised controlled trial assessing the efficacy, toxicity, and cost-effectiveness of 3 months (3 M) versus the usually given 6 months (6 M) of adjuvant chemotherapy in colorectal cancer.

Methods: In total, 6088 patients with fully resected high-risk stage II or stage III colorectal cancer were randomised and followed up for 3-8 years. The within-trial cost-effectiveness analysis from a UK health-care perspective is presented using the resource use data, quality of life (EQ-5D-3L), time on treatment (ToT), disease-free survival after treatment (DFS) and overall survival (OS) data.

The safety of inactivated influenza vaccines in pregnancy for birth outcomes: a systematic review.

Pregnant women are at increased risk of morbidity and mortality from influenza and are recognized as a priority group for influenza vaccination. Despite this, uptake is often poor and one reason cited for this is concerns about safety. The objective of this study was to perform a systematic review of the safety of inactivated influenza vaccination (IIV) in pregnancy.

Health professionals' perceptions of the allied health role in the acute setting following hip and knee joint replacement surgery: a qualitative study.

To describe health professionals' perceptions of the role of allied health during the acute phase following elective lower limb joint replacement surgery to inform the development of efficient allied health service models. This was a qualitative descriptive study conducted using semi-structured focus groups and thematic analysis. Participants were 25 medical, nursing, and allied health professionals working on two orthopaedic wards in a tertiary hospital in Victoria, Australia.

Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome.

Study Question: What is the recommended assessment and management of women with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise and consumer preference?

Summary Answer: International evidence-based guidelines, including 166 recommendations and practice points, addressed prioritized questions to promote consistent, evidence-based care and improve the experience and health outcomes of women with PCOS.

What Is Known Already: Previous guidelines either lacked rigorous evidence-based processes, did not engage consumer and international multidisciplinary perspectives, or were outdated. Diagnosis of PCOS remains controversial, and assessment and management are inconsistent.

Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome.

Study Question: What is the recommended assessment and management of women with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise, and consumer preference?

Summary Answer: International evidence-based guidelines including 166 recommendations and practice points, addressed prioritized questions to promote consistent, evidence-based care and improve the experience and health outcomes of women with PCOS.

What Is Known Already: Previous guidelines either lacked rigorous evidence-based processes, did not engage consumer and international multidisciplinary perspectives, or were outdated. Diagnosis of PCOS remains controversial and assessment and management are inconsistent.

Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome.

Study Question: What is the recommended assessment and management of women with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise, and consumer preference?

Summary Answer: International evidence-based guidelines including 166 recommendations and practice points, addressed prioritized questions to promote consistent, evidence-based care and improve the experience and health outcomes of women with PCOS.

What Is Known Already: Previous guidelines either lacked rigorous evidence-based processes, did not engage consumer and international multidisciplinary perspectives, or were outdated. Diagnosis of PCOS remains controversial and assessment and management are inconsistent.

Implementation of evidence-based weekend service recommendations for allied health managers: a cluster randomised controlled trial protocol.

Background: It is widely acknowledged that health policy and practice do not always reflect current research evidence. Whether knowledge transfer from research to practice is more successful when specific implementation approaches are used remains unclear. A model to assist engagement of allied health managers and clinicians with research implementation could involve disseminating evidence-based policy recommendations, along with the use of knowledge brokers.

Sedation Intensity in the First 48 Hours of Mechanical Ventilation and 180-Day Mortality: A Multinational Prospective Longitudinal Cohort Study.

Objectives: In the absence of a universal definition of light or deep sedation, the level of sedation that conveys favorable outcomes is unknown. We quantified the relationship between escalating intensity of sedation in the first 48 hours of mechanical ventilation and 180-day survival, time to extubation, and delirium.

Design: Harmonized data from prospective multicenter international longitudinal cohort studies SETTING:: Diverse mix of ICUs.

Elevated peripheral expression of neuregulin-1 (NRG1) mRNA isoforms in clozapine-treated schizophrenia patients.

Differential expression of neuregulin-1 (NRG1) mRNA isoforms and proteins has been reported in schizophrenia, primarily in post-mortem brain tissue. In this study, we examined 12 NRG1 SNPs, eight NRG1 mRNA isoforms (type I, type I, type II, type III, type IV, EGFα, EGFβ, pan-NRG1) in whole blood, and NRG1-β1 protein in serum of clozapine-treated schizophrenia patients (N = 71) and healthy controls (N = 57). In addition, using cultured peripheral blood mononuclear cells (PBMC) from 15 healthy individuals, we examined the effect of clozapine on NRG1 mRNA isoform and protein expression.

Peripheral Transcription of Pathway Genes Are Upregulated in Treatment-Resistant Schizophrenia.

Investigation of peripheral gene expression patterns of transcripts within the signaling pathway, other than neuregulin-1 (), among patients with schizophrenia and more specifically treatment-resistant schizophrenia (TRS) is limited. The present study built on our previous work demonstrating elevated levels of EGFα, EGFβ, and type I containing transcripts in TRS by investigating 11 signaling pathway mRNA transcripts () in whole blood of TRS patients ( = 71) and healthy controls ( = 57). We also examined the effect of clozapine exposure on transcript levels using cultured peripheral blood mononuclear cells (PBMCs) from 15 healthy individuals.

Acute exercise alters skeletal muscle mitochondrial respiration and H2O2 emission in response to hyperinsulinemic-euglycemic clamp in middle-aged obese men.

Obesity, sedentary lifestyle and aging are associated with mitochondrial dysfunction and impaired insulin sensitivity. Acute exercise increases insulin sensitivity in skeletal muscle; however, whether mitochondria are involved in these processes remains unclear. The aim of this study was to investigate the effects of insulin stimulation at rest and after acute exercise on skeletal muscle mitochondrial respiratory function (JO2) and hydrogen peroxide emission (JH2O2), and the associations with insulin sensitivity in obese, sedentary men.

The effectiveness of research implementation strategies for promoting evidence-informed policy and management decisions in healthcare: a systematic review.

Background: It is widely acknowledged that health policy and management decisions rarely reflect research evidence. Therefore, it is important to determine how to improve evidence-informed decision-making. The primary aim of this systematic review was to evaluate the effectiveness of research implementation strategies for promoting evidence-informed policy and management decisions in healthcare.

Widespread white matter microstructural differences in schizophrenia across 4322 individuals: results from the ENIGMA Schizophrenia DTI Working Group.

The regional distribution of white matter (WM) abnormalities in schizophrenia remains poorly understood, and reported disease effects on the brain vary widely between studies. In an effort to identify commonalities across studies, we perform what we believe is the first ever large-scale coordinated study of WM microstructural differences in schizophrenia. Our analysis consisted of 2359 healthy controls and 1963 schizophrenia patients from 29 independent international studies; we harmonized the processing and statistical analyses of diffusion tensor imaging (DTI) data across sites and meta-analyzed effects across studies.

My Kite Will Fly: Improving Communication and Understanding in Young Children When a Mother Is Diagnosed with Life-Threatening Gynecological Cancer.

Study Aims: The My Kite Will Fly (MKWF) research program is built on the well-documented need for effective clinical communication tools and therapeutic interventions where a child's mother is diagnosed with life-threatening gynecological cancer.

Methods: The Dignity Model and Child-Centered approach were two key study foundations in this pilot cohort. Quantitative survey and qualitative semistructured methods were employed to gather data from patient families at three distinct phases: Diagnosis, Treatment, and Palliative care.

Exercise-intensity dependent alterations in plasma redox status do not reflect skeletal muscle redox-sensitive protein signaling.

Objectives: Redox homeostasis and redox-sensitive protein signaling play a role in exercise-induced adaptation. The effects of sprint-interval exercise (SIE), high-intensity interval exercise (HIIE) and continuous moderate-intensity exercise (CMIE), on post-exercise plasma redox status are unclear. Furthermore, whether post-exercise plasma redox status reflects skeletal muscle redox-sensitive protein signaling is unknown.