Low and high frequency isometric handgrip exercise training similarly reduce resting blood pressure in young normotensive adults: A randomised controlled trial.

We investigated the effects of low and high frequency isometric handgrip exercise training (IHGT) on resting blood pressure, and the affective/perceptual responses during training. Sixty young normotensive adults were randomised to either a no-intervention control group (CON:  = 20; 12 female) or a group performing either two (LOW:  = 20; 18 female) or four (HIGH:  = 20; 13 female) sessions/week of IHGT for 4 weeks. IHGT involved 4 × 2-min holds at 30% maximal voluntary contraction using the dominant hand.

14-3-3 binding maintains the Parkinson's associated kinase LRRK2 in an inactive state.

Leucine-rich repeat kinase 2 (LRRK2) is a central player in cellular signaling and a significant contributor to Parkinson's disease (PD) pathogenesis. 14-3-3 proteins are essential regulators of LRRK2, modulating its activity. Here, we present the cryo- electron microscopy structure of the LRRK2:14-3-3 autoinhibitory complex, showing that a 14-3-3 dimer stabilizes an autoinhibited LRRK2 monomer by binding to key phosphorylation sites and the COR-A and COR-B subdomains within the Roc-COR GTPase domain of LRRK2.

Evolution of radionuclide transport and retardation processes in uplifting granitic rocks: Part 2 - Modelling coupled processes in uplift scenarios.

Uplifting fractured granitic rocks occur in substantial areas of countries such as Japan. Some of these areas might be considered when siting a deep geological repository for radioactive wastes. A repository site would be selected in such an area only if it is possible to make a safety case, accounting for the changing conditions during uplift.

Rising mortality among people who inject drugs living with HIV in Scotland, UK: A 20-year retrospective cohort study.

Objectives: Our aim was to examine mortality trends in the era of antiretroviral therapy, among people who inject drugs (PWID) who are living with HIV. The study objectives were to assess and quantify mortality among PWID diagnosed with HIV over time in Scotland, in the context of a recent outbreak of HIV and rise in drug-related mortality.

Methods: This was a retrospective cohort study of those diagnosed with HIV in Scotland between January 2000 and February 2020, with acquisition related to injecting drug use, linked to mortality data.

Evolution of radionuclide transport and retardation processes in uplifting granitic rocks: Part 1 - Key processes, conceptual models and scenario.

A safety case for an underground radioactive waste repository must show that groundwater will not in future transport radionuclides from the repository to the near-surface environment (the biosphere) in harmful quantities. Safety cases are developed step-wise throughout a programme to site and develop a repository. At early stages, before a site is selected, safety cases are generic and based on simplified safety assessment models of the disposal system that have conservative parameter values.

The structure of the IL-11 signalling complex provides insight into receptor variants associated with craniosynostosis.

Interleukin 11 (IL-11), a member of the IL-6 family of cytokines, has roles in haematopoiesis, inflammation, bone metabolism, and craniofacial development. IL-11 also has pathological roles in chronic inflammatory diseases, fibrosis, and cancer. In this structural snapshot, we explore our recently published cryo-EM structure of the human IL-11 signalling complex to understand the molecular mechanisms of complex formation and disease-associated mutations.

Acute caffeine supplementation offsets the impairment in 10-km running performance following one night of partial sleep deprivation: a randomized controlled crossover trial.

Introduction: Whether acute caffeine supplementation can offset the negative effects of one-night of partial sleep deprivation (PSD) on endurance exercise performance is currently unknown.

Methods: Ten healthy recreational male runners (age: 27 ± 6 years; : 61 ± 9 mL/kg/min) completed 4 trials in a balanced Latin square design, which were PSD + caffeine (PSD-Caf), PSD + placebo (PSD-Pla), normal sleep (NS) + caffeine (NS-Caf) and NS + placebo (NS-Pla). 3 and 8 h sleep windows were scheduled in PSD and NS, respectively.

Examining trends in the incidence of HIV infection among people with a history of drug use to inform an outbreak investigation and response: A retrospective cohort study.

Background: In the context of an outbreak of HIV among people who inject drugs in Glasgow, Scotland, identified in 2015, our objectives were to: (1) develop epidemiological methods to estimate HIV incidence using data linkage, and (2) examine temporal changes in HIV incidence to inform public health responses.

Methods: This was a retrospective cohort study involving data linkage of laboratory HIV testing data to identify individuals with a history of drug use. Person-years (PY) and Poisson regression were used to estimate incidence by time period (pre-outbreak: 2000-2010 and 2011-2013; early outbreak: 2014-2016; ongoing outbreak: 2017-2019).

Physiological and perceptual responses to sprint interval exercise using arm versus leg cycling ergometry.

Increases in power output and maximal oxygen consumption ( max) occur in response to sprint interval exercise (SIE), but common use of "all-out" intensities presents a barrier for many adults. Furthermore, lower-body SIE is not feasible for all adults. We compared physiological and perceptual responses to supramaximal, but "non-all-out" SIE between leg and arm cycling exercise.

Client preferences for the design and delivery of injectable opioid agonist treatment services: Results from a best-worst scaling task.

Background And Aims: Clinical trials support injectable opioid agonist treatment (iOAT) for individuals with opioid use disorder (OUD) for whom other pharmacological management approaches are not well-suited. However, despite substantial research indicating that person-centered care improves engagement, retention and health outcomes for individuals with OUD, structural requirements (e.g.

Testing and Treatment Interventions in Community Settings Key to Controlling a Recent Human Immunodeficiency Virus Outbreak Among People Who Inject Drugs in Glasgow: A Modeling Study.

Background: A human immunodeficiency virus (HIV) outbreak was identified among people who inject drugs (PWID) in Glasgow in 2015, with >150 diagnoses by the end of 2019. The outbreak response involved scaling up HIV testing and improving HIV treatment initiation and retention.

Methods: We parameterized and calibrated a dynamic, deterministic model of HIV transmission among PWID in Glasgow to epidemiological data.

Effects of acute and chronic stair-climbing exercise on metabolic health: A systematic review.

Stair climbing exercise (SE) provides a feasible approach to elevate physical activity, but the effects on metabolic health are unclear. We systematically reviewed the currently available evidence on the effects of SE on fasting and postprandial glycaemia and lipidaemia. Studies were included if they investigated the effects of acute or chronic (at least 2 weeks) SE on fasting and/or postprandial glycaemic (insulin and glucose) and lipidaemic (triacylglycerols and non-esterified fatty acids) responses in healthy, prediabetic or type 2 diabetic adult populations.

Reduced-exertion high-intensity interval training (REHIT): a feasible approach for improving health and fitness?

In recent years, research investigating the dose-response to sprint interval training (SIT) has provided evidence that the number and duration of repetitions in a SIT session can be reduced whilst preserving the beneficial health-related adaptations. Together this research has led to the development of protocols involving minimal doses of SIT: regularly performing just two or three 20-30 s all-out sprints in a 10 min training session has been shown to elicit beneficial metabolic and cardiovascular adaptations. These SIT protocols, which we originally termed "reduced-exertion high-intensity interval training" (or REHIT), have the potential to remove many of the common barriers associated with other SIT protocols, as well as with HIT and aerobic exercise.

Impact of the COVID-19 Pandemic on HIV Test Uptake Among People Who Inject Drugs in the Context of an HIV Outbreak.

Glasgow, Scotland's largest city, has been experiencing an HIV outbreak among people who inject drugs (PWID) since 2015. A key focus of the public health response has been to increase HIV testing among those at risk of infection. Our aim was to assess the impact of COVID-19 on HIV testing among PWID in Glasgow.

Reaction hijacking inhibition of Plasmodium falciparum asparagine tRNA synthetase.

Malaria poses an enormous threat to human health. With ever increasing resistance to currently deployed drugs, breakthrough compounds with novel mechanisms of action are urgently needed. Here, we explore pyrimidine-based sulfonamides as a new low molecular weight inhibitor class with drug-like physical parameters and a synthetically accessible scaffold.

Structures of the interleukin 11 signalling complex reveal gp130 dynamics and the inhibitory mechanism of a cytokine variant.

Interleukin (IL-)11, an IL-6 family cytokine, has pivotal roles in autoimmune diseases, fibrotic complications, and solid cancers. Despite intense therapeutic targeting efforts, structural understanding of IL-11 signalling and mechanistic insights into current inhibitors are lacking. Here we present cryo-EM and crystal structures of the human IL-11 signalling complex, including the complex containing the complete extracellular domains of the shared IL-6 family β-receptor, gp130.

How Do Survivor and Mandatory Reporter Status Correlate with Program Outcomes for an Adult-Focused Child Sexual Abuse Prevention Program?

This exploratory study investigated group differences and pre-post changes in knowledge, beliefs, and behavior by mandatory reporters and Child Sexual Abuse (CSA) survivor status for a CSA prevention training designed for the general public. Of the 8,114 study participants, 32% identified as having experienced CSA, and 77% indicated they were mandatory reporters for child abuse and neglect. Mandatory reporters had higher baseline knowledge about CSA than those who were not mandatory reporters and reported more CSA preventative behaviors.

Structure and regulation of full-length human leucine-rich repeat kinase 1.

The human leucine-rich repeat kinases (LRRKs), LRRK1 and LRRK2 are large and unusually complex multi-domain kinases, which regulate fundamental cellular processes and have been implicated in human disease. Structures of LRRK2 have recently been determined, but the structure and molecular mechanisms regulating the activity of the LRRK1 as well as differences in the regulation of LRRK1 and LRRK2 remain unclear. Here, we report a cryo-EM structure of the LRRK1 monomer and a lower-resolution cryo-EM map of the LRRK1 dimer.

Reaction hijacking inhibition of asparagine tRNA synthetase.

Malaria poses an enormous threat to human health. With ever increasing resistance to currently deployed drugs, breakthrough compounds with novel mechanisms of action are urgently needed. Here, we explore pyrimidine-based sulfonamides as a new low molecular weight inhibitor class with drug-like physical parameters and a synthetically accessible scaffold.