A Multidisciplinary Evaluation of a Virtually Supervised Home-Based High-Intensity Interval Training Intervention in People With Type 1 Diabetes.

Objective: Adopt a multidisciplinary approach to evaluate a virtually supervised home-based high-intensity interval training (Home-HIT) intervention in people with type 1 diabetes.

Research Design And Methods: Eleven individuals with type 1 diabetes (seven women; age 30 ± 3 years; [Formula: see text] 2.5 ± 0.

High-Fat Overfeeding Impairs Peripheral Glucose Metabolism and Muscle Microvascular eNOS Ser1177 Phosphorylation.

Context: The mechanisms responsible for dietary fat-induced insulin resistance of skeletal muscle and its microvasculature are only partially understood.

Objective: To determine the impact of high-fat overfeeding on postprandial glucose fluxes, muscle insulin signaling, and muscle microvascular endothelial nitric oxide synthase (eNOS) content and activation.

Design: Fifteen non-obese volunteers consumed a high-fat (64%) high-energy (+47%) diet for 7 days.

Age estimation using canine pulp volumes in adults: a CBCT image analysis.

Secondary dentine deposition is responsible for the decrease in the volume of the pulp cavity with age. Therefore, the volume of the pulp cavity can be considered as a predictor for estimating age. The aims of this study were to investigate the relationship strength between canine pulp volumes and chronological age from homogenous (approximately equal numbers of individuals in each age range) age distribution and to assess the effect of sex as predictor in age estimation.

Exposure-response analysis to inform the optimal dose of veliparib in combination with carboplatin and paclitaxel in BRCA-mutated advanced breast cancer patients.

Purpose: Veliparib, a poly(ADP-ribose)-polymerase (PARP) 1 and 2 enzyme inhibitor, was administered at 120 mg twice daily (BID) for 7 days in a 21-day cycle with carboplatin/paclitaxel in the Phase 2 BROCADE study in patients with BRCA-deficient recurrent or metastatic breast cancer, a dose based on Phase 1 results. Population pharmacokinetic (PK) and exposure-response analyses were undertaken to retrospectively evaluate whether an optimal dose was used in BROCADE.

Methods: A population PK analysis was performed using data from 168 patients in BROCADE along with data from 288 subjects in another 5 studies.

Abemaciclib, a potent cyclin-dependent kinase 4 and 6 inhibitor, for treatment of ER-positive metastatic breast cancer.

CDK 4/6 inhibitors have given patients with estrogen receptor (ER)-positive/HER2-negative (ER+/HER2ࢤ) advanced metastatic breast cancer important new therapeutic options. Abemaciclib is different to the other two licensed and approved CDK 4/6 inhibitors, palbociclib and ribociclib, both in dosing schedule (continuous vs intermittent) and toxicity profile (less neutropenia, more diarrhea), yet the magnitude of clinical benefit seen in first- and second-line studies is very similar. One of the key issues for clinicians is when to use these therapies.

Cervical muscle volume in individuals with idiopathic neck pain compared to asymptomatic controls: A cross-sectional magnetic resonance imaging study.

Background: Neck muscle compositional changes may represent potential biomarkers contributing towards chronic neck-related pain and disability.

Objectives: To determine differences in muscle volume in the cervical muscles of individuals with chronic idiopathic neck pain compared with age- and sex-matched asymptomatic individuals, and to determine if these muscle variables relate to spinal level, side (left or right), age, sex, body mass index (BMI) or muscle strength.

Study Design: Cross-sectional magnetic resonance imaging (MRI) study.

Phosphomannomutase and Guanosine Diphosphate-Mannose Pyrophosphorylase Ligandability Assessment.

Chagas' disease, which is caused by the parasite, has become a global health problem that is currently treated with poorly tolerated drugs that require prolonged dosing. Therefore, there is a clinical need for new therapeutic agents that can mitigate these issues. The phosphomannomutase (PMM) and GDP-mannose pyrophosphorylase (GDP-MP) enzymes form part of the biosynthetic pathway to the nucleotide sugar GDP-mannose.

End of season influenza vaccine effectiveness in adults and children in the United Kingdom in 2017/18.

BackgroundIn the United Kingdom (UK), in recent influenza seasons, children are offered a quadrivalent live attenuated influenza vaccine (LAIV4), and eligible adults mainly trivalent inactivated vaccine (TIV).AimTo estimate the UK end-of-season 2017/18 adjusted vaccine effectiveness (aVE) and the seroprevalence in England of antibodies against influenza viruses cultured in eggs or tissue.MethodsThis observational study employed the test-negative case-control approach to estimate aVE in primary care.

Post-exercise carbohydrate and energy availability induce independent effects on skeletal muscle cell signalling and bone turnover: implications for training adaptation.

Key Points: Reduced carbohydrate (CHO) availability before and after exercise may augment endurance training-induced adaptations of human skeletal muscle, as mediated via modulation of cell signalling pathways. However, it is not known whether such responses are mediated by CHO restriction, energy restriction or a combination of both. In recovery from a twice per day training protocol where muscle glycogen concentration is maintained within 200-350 mmol kg dry weight (dw), we demonstrate that acute post-exercise CHO and energy restriction (i.

Identification of Novel Trypanosoma cruzi Proteasome Inhibitors Using a Luminescence-Based High-Throughput Screening Assay.

Chagas' disease, caused by the protozoan parasite , is a potentially life-threatening condition that has become a global issue. Current treatment is limited to two medicines that require prolonged dosing and are associated with multiple side effects, which often lead to treatment discontinuation and failure. One way to address these shortcomings is through target-based drug discovery on validated protein targets.

Oscillations of the baseline of solar magnetic field and solar irradiance on a millennial timescale.

Recently discovered long-term oscillations of the solar background magnetic field associated with double dynamo waves generated in inner and outer layers of the Sun indicate that the solar activity is heading in the next three decades (2019-2055) to a Modern grand minimum similar to Maunder one. On the other hand, a reconstruction of solar total irradiance suggests that since the Maunder minimum there is an increase in the cycle-averaged total solar irradiance (TSI) by a value of about 1-1.5 Wm closely correlated with an increase of the baseline (average) terrestrial temperature.

Home-hit improves muscle capillarisation and eNOS/NAD(P)Hoxidase protein ratio in obese individuals with elevated cardiovascular disease risk.

Key Points: Obesity and sedentary behaviour are associated with capillary rarefaction and impaired muscle microvascular vasoreactivity, due to reduced nitric oxide bioavailability. Low-volume high-intensity interval training (HIT) is a time-efficient alternative to traditional moderate-intensity continuous training (MICT), but its effect on the muscle microvasculature has not been studied. The applicability of current laboratory- and gym-based HIT protocols for obese individuals with low fitness and mobility has been disputed by public health experts, who cite the strenuous nature and complex protocols as major barriers.

Clinical decision support system to assess the risk of sepsis using Tree Augmented Bayesian networks and electronic medical record data.

Early and accurate diagnoses of sepsis enable practitioners to take timely preventive actions. The existing diagnostic criteria suffer from deficiencies, such as triggering false alarms or leaving conditions undiagnosed. This study aims to develop a clinical decision support system to predict the risk of sepsis using tree augmented naive Bayesian network by identifying the optimal set of biomarkers.

Ultrasound Does Not Detect Acute Changes in Glycogen in Vastus Lateralis of Man.

Purpose: To examine the validity of ultrasound (via cloud-based software that measures pixilation intensity according to a scale of 0-100) to noninvasively assess muscle glycogen in human skeletal muscle.

Methods: In study 1, 14 professional male rugby league players competed in an 80-min competitive rugby league game. In study 2 (in a randomized repeated measures design), 16 recreationally active males completed an exhaustive cycling protocol to deplete muscle glycogen followed by 36 h of HIGH or LOW carbohydrate intake (8 g·kg vs 3 g·kg body mass).

Passive heat therapy in sedentary humans increases skeletal muscle capillarization and eNOS content but not mitochondrial density or GLUT4 content.

Passive heat therapy (PHT) has been proposed as an alternative intervention to moderate-intensity continuous training (MICT) in individuals who are unable or unwilling to exercise. This study aimed to make the first comparison of the effect of PHT and MICT on ) skeletal muscle capillarization and endothelial-specific endothelial nitric oxide synthase (eNOS) content and ) mitochondrial density, glucose transporter 4 (GLUT4), and intramuscular triglyceride (IMTG) content. Twenty young sedentary males (21 ± 1 yr, body mass index 25 ± 1 kg/m) were allocated to either 6 wk of PHT ( = 10; 40-50 min at 40°C in a heat chamber, 3×/wk) or MICT ( = 10; time-matched cycling at ~65% V̇o).

Graded reductions in preexercise muscle glycogen impair exercise capacity but do not augment skeletal muscle cell signaling: implications for CHO periodization.

We examined the effects of graded muscle glycogen on exercise capacity and modulation of skeletal muscle signaling pathways associated with the regulation of mitochondrial biogenesis. In a repeated-measures design, eight men completed a sleep-low, train-low model comprising an evening glycogen-depleting cycling protocol followed by an exhaustive exercise capacity test [8 × 3 min at 80% peak power output (PPO), followed by 1-min efforts at 80% PPO until exhaustion] the subsequent morning. After glycogen-depleting exercise, subjects ingested a total of 0 g/kg (L-CHO), 3.

Understanding contemporary forms of exploitation: Attributions of passion serve to legitimize the poor treatment of workers.

The pursuit of passion in one's work is touted in contemporary discourse. Although passion may indeed be beneficial in many ways, we suggest that the modern cultural emphasis may also serve to facilitate the legitimization of unfair and demeaning management practices-a phenomenon we term the legitimization of passion exploitation. Across 7 studies and a meta-analysis, we show that people do in fact deem poor worker treatment (e.

Re-emergence of HIV related to injecting drug use despite a comprehensive harm reduction environment: a cross-sectional analysis.

Background: In 2015, an outbreak of HIV was identified among people who inject drugs (PWID) in the Greater Glasgow and Clyde (GGC) area of Scotland, an area which distributes more than 1 million needles and syringes per year. This is the largest such incident in the UK for 30 years. Here, we provide an epidemiological analysis of the impact of the outbreak on HIV prevalence trends in the population and the individual and environmental risk factors associated with infection.

Do pain management websites foster self-management support for people with persistent pain? A scoping review.

Objectives: To evaluate if the contents of pain management websites include the current best practice self-management support strategies for people with persistent pain, are cultural tailored and to determine the website quality.

Methods: Websites were searched from three major search engines (Google, Bing, and Yahoo). Websites providing information on self-management strategies and websites that were freely available to the public were included.

Metabolism of the dual FLT-3/Aurora kinase inhibitor CCT241736 in preclinical and human in vitro models: Implication for the choice of toxicology species.

CCT241736 is a dual fms-like tyrosine kinase 3 (FLT3)/Aurora kinase inhibitor in development for the treatment of acute myeloid leukaemia. The successful development of any new drug relies on adequate safety testing including preclinical toxicology studies. Selection of an appropriate preclinical species requires a thorough understanding of the compound's metabolic clearance and pathways, as well as other pharmacokinetic and pharmacodynamic considerations.

Identification of UDP-Sugar Pyrophosphorylase Inhibitors Using Biosensor-Based Small Molecule Fragment Library Screening.

Leishmaniasis is a neglected disease that is caused by different species of the protozoan parasite , and it currently affects 12 million people worldwide. The antileishmanial therapeutic arsenal remains very limited in number and efficacy, and there is no vaccine for this parasitic disease. One pathway that has been genetically validated as an antileishmanial drug target is the biosynthesis of uridine diphosphate-glucose (UDP-Glc), and its direct derivative UDP-galactose (UDP-Gal).

A multi-component intervention to sit less and move more in a contact centre setting: a feasibility study.

Background: Call agents spend ~ 90% of their working day seated, which may negatively impact health, productivity, and wellbeing. This study aimed to explore the acceptability and feasibility of a multi-component workplace intervention targeting increased activity and decreased prolonged sitting in the contact centre setting prior to a full-scale effectiveness trial.

Methods: An 8-week non-randomised pre-post feasibility study was conducted.

Skeletal Fragility and Its Clinical Determinants in Children With Type 1 Diabetes.

Context: Type 1 diabetes (T1D) is associated with an increased fracture risk at all ages.

Objective: To understand the determinants of bone health and fractures in children with T1D.

Design: Case-control study of children with T1D on bone-turnover markers, dual-energy X-ray absorptiometry, and 3 Tesla-MRI of the proximal tibia to assess bone microarchitecture and vertebral marrow adiposity compared with age- and sex-matched healthy children.