Development of a Life Orientation health education programme for high school learners

This cross-sectional descritive study aimed to develop a health education programme that could serve as a teaching aid for high school Life Orientation educators. A sequential approach was used to collect data that would inform the health education programme. The study population comprised high school Life Orientation teachers, as well as subject advisors who were considered experts in the field of Life Orientation. A total of 31 educators participated in the initial quantitative survey and this was followed by semi-structured interviews with five (5) experts in the area of Life Orienation. The content of the health education programme was based on the information obtained from semi-structured interviews. This study identified barriers to the teaching of Life Orientation, which included large classroom numbers, a lack of interest in the subject, and educators who were inadequately trained to teach the subject. The value of Life Orientation as a subject and the importance of a continually evolving education system with the aim of improving education for all learners, was identified. The health education programme designed based on the results of the study can function as an adjunct for Life Orientation teachers, to enhance the implementation of the subject by guiding educators in terms of the knowledge that should be transferred to learners. Educators are also provided with methods of transmitting knowledge to learners.Department of HE and Training approved lis

Structural Relations among Negative Affect, Mate Value, and Mating Effort

We compared the ability of models based on evolutionary economic theory and Life History (LH) Theory to explain relations among self-reported negative affect, mate value, and mating effort. Method: Two hundred thirty-eight undergraduates provided multiple measures of these latent constructs, permitting us to test a priori predictions based on Kirsner, Figueredo, and Jacobs (2003). We compared the fit of the initial model to the fit of five alternative theory-driven models using nested model comparisons of Structural Equations Models. Rejecting less parsimonious and explanatory models eliminated the original model. Two equally parsimonious models explained the data pattern well. The first, based on evolutionary economic theory, specified that Negative Affect increases both Personal Mate Value and Mating Effort via the direct effects specified in the original model. The second, based on LH Theory, specified that Negative Affect, Personal Mate Value, and Mating Effort relate spuriously through a common latent construct, the LH Factor. The primary limitation of the present study is generalizability. We used self-reports taken from a young, university-based sample that included a spectrum of affective states. We cannot know how well these models generalize to an older population or to actual behavior. Both models predict the presence of a rich pattern of mate acquisition and retention behaviors, including an alarming set of behavioral tactics often not considered or targeted during treatment. Moreover, each model suggests a unique set of problems may arise after an effective intervention. We describe several ways to distinguish these models empirically

Sodium-glucose cotransporter inhibitors: beyond glycaemic control

SGLT2; Chronic kidney disease; Diabetic nephropathySGLT2; Malaltia renal crònica; Nefropatia diabèticaSGLT2; Enfermedad renal crónica; Nefropatía diabéticaDiabetes increases the risk of adverse cardiovascular and renal events. Recently, sodium-glucose co-transporter 2 (SGLT2) inhibitors have been demonstrated to reduce cardiovascular complications and slow diabetic kidney disease progression in patients with type 2 diabetes. The glycaemic control exerted by these drugs is not greater than the one achieved with other classical glucose-lowering medications such as sulphonylureas. For that reason, plausible renoprotective mechanisms independent from glycaemic control have been proposed such as blood pressure control, body weight loss, intraglomerular pressure reduction and a decrease in urinary proximal tubular injury biomarkers. Interestingly, the hypothesis that SGLT2 inhibitors have a direct renoprotective effect has been addressed in diabetic and non-diabetic models. In this editorial, we update the different postulated mechanisms involved in the cardiorenal protection afforded by SGLT2 inhibition in chronic kidney disease.The authors are current recipients of research grants from the FONDO DE INVESTIGACIÓN SANITARIA-FEDER, ISCIII, PI17/00257 and REDINREN, RD16/0009/0030

Caffeine enhances upper body strength in resistance-trained women

BACKGROUND: Research has indicated that low-to-moderate dosages of caffeine supplementation are ergogenic for sustained endurance efforts as well as high-intensity exercise. The effects of caffeine supplementation on strength-power performance are equivocal, with some studies indicating a benefit and others demonstrating no change in performance. The majority of research that has examined the effects of caffeine supplementation on strength-power performance has been carried out in both trained and untrained men. Therefore, the purpose of this study was to determine the acute effects of caffeine supplementation on strength and muscular endurance in resistance-trained women. METHODS: In a randomized manner, 15 women consumed caffeine (6 mg/kg) or placebo (PL) seven days apart. Sixty min following supplementation, participants performed a one-repetition maximum (1RM) barbell bench press test and repetitions to failure at 60% of 1RM. Heart rate (HR) and blood pressure (BP) were assessed at rest, 60 minutes post-consumption, and immediately following completion of repetitions to failure. RESULTS: Repeated measures ANOVA indicated a significantly greater bench press maximum with caffeine (p CONCLUSIONS: These findings indicate a moderate dose of caffeine may be sufficient for enhancing strength performance in resistance-trained women

Intracellular vesicle trafficking plays an essential role in mitochondrial quality control

The Drosophila gene products Bet1, Slh, and CG10144, predicted to function in intracellular vesicle trafficking, were previously found to be essential for mitochondrial nucleoid maintenance. Here we show that Slh and Bet1 cooperate to maintain mitochondrial functions. In their absence, mitochondrial content, membrane potential, and respiration became abnormal, accompanied by mitochondrial proteotoxic stress, but without direct effects on mtDNA. Immunocytochemistry showed that both Slh and Bet1 are localized at the Golgi, together with a proportion of Rab5-positive vesicles. Some Bet1, as well as a tiny amount of Slh, cofractionated with highly purified mitochondria, while live-cell imaging showed coincidence of fluorescently tagged Bet1 with most Lysotracker-positive and a small proportion of Mitotracker-positive structures. This three-way association was disrupted in cells knocked down for Slh, although colocalized lysosomal and mitochondrial signals were still seen. Neither Slh nor Bet1 was required for global mitophagy or endocytosis, but prolonged Slh knockdown resulted in G2 growth arrest, with increased cell diameter. These effects were shared with knockdown of betaCOP but not of CG1044, Snap24, or Syntaxin6. Our findings implicate vesicle sorting at the cis-Golgi in mitochondrial quality control.Peer reviewe

Redistribution of Flexibility in Stabilizing Antibody Fragment Mutants Follows Le Chatelier's Principle

Le Châtelier's principle is the cornerstone of our understanding of chemical equilibria. When a system at equilibrium undergoes a change in concentration or thermodynamic state (i.e., temperature, pressure, etc.), La Châtelier's principle states that an equilibrium shift will occur to offset the perturbation and a new equilibrium is established. We demonstrate that the effects of stabilizing mutations on the rigidity ⇔ flexibility equilibrium within the native state ensemble manifest themselves through enthalpy-entropy compensation as the protein structure adjusts to restore the global balance between the two. Specifically, we characterize the effects of mutation to single chain fragments of the anti-lymphotoxin-β receptor antibody using a computational Distance Constraint Model. Statistically significant changes in the distribution of both rigidity and flexibility within the molecular structure is typically observed, where the local perturbations often lead to distal shifts in flexibility and rigidity profiles. Nevertheless, the net gain or loss in flexibility of individual mutants can be skewed. Despite all mutants being exclusively stabilizing in this dataset, increased flexibility is slightly more common than increased rigidity. Mechanistically the redistribution of flexibility is largely controlled by changes in the H-bond network. For example, a stabilizing mutation can induce an increase in rigidity locally due to the formation of new H-bonds, and simultaneously break H-bonds elsewhere leading to increased flexibility distant from the mutation site via Le Châtelier. Increased flexibility within the VH β4/β5 loop is a noteworthy illustration of this long-range effect

Measuring the activity of mental health services in England : variation in categorising activity for payment purposes

In the context of international interest in reforming mental health payment systems, national policy in England has sought to move towards an episodic funding approach. Patients are categorised into care clusters, and providers will be paid for episodes of care for patients within each cluster. For the payment system to work, clusters need to be appropriately homogenous in terms of financial resource use. We examine variation in costs and activity within clusters and across health care providers. We find that the large variation between providers with respect to costs within clusters mean that a cluster-based episodic payment system would have substantially different financial impacts across providers

Antioxidant Roles of SGLT2 Inhibitors in the Kidney

Diabetic kidney disease; Mitochondrial dysfunction; Oxidative stressMalaltia renal diabètica; Disfunció mitocondrial; Estrès oxidatiuEnfermedad renal diabética; Disfunción mitocondrial; Estrés oxidativoThe reduction-oxidation (redox) system consists of the coupling and coordination of various electron gradients that are generated thanks to serial reduction-oxidation enzymatic reactions. These reactions happen in every cell and produce radical oxidants that can be mainly classified into reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS and RNS modulate cell-signaling pathways and cellular processes fundamental to normal cell function. However, overproduction of oxidative species can lead to oxidative stress (OS) that is pathological. Oxidative stress is a main contributor to diabetic kidney disease (DKD) onset. In the kidney, the proximal tubular cells require a high energy supply to reabsorb proteins, metabolites, ions, and water. In a diabetic milieu, glucose-induced toxicity promotes oxidative stress and mitochondrial dysfunction, impairing tubular function. Increased glucose level in urine and ROS enhance the activity of sodium/glucose co-transporter type 2 (SGLT2), which in turn exacerbates OS. SGLT2 inhibitors have demonstrated clear cardiovascular benefits in DKD which may be in part ascribed to the generation of a beneficial equilibrium between oxidant and antioxidant mechanisms.The authors are current recipients of grants from FONDO DE INVESTIGACIÓN SANITARIA-FEDER, ISCIII (PI17/00257 and RICORS RD21/0005/0016), and Fundació la Marató de TV3 (421/C/2020, 759/U/2020 and 215/C/2021)

RNase H1 promotes replication fork progression through oppositely transcribed regions of Drosophila mitochondrial DNA

Mitochondrial DNA (mtDNA) replication uses a simple core machinery similar to those of bacterial viruses and plasmids, but its components are challenging to unravel. Here, we found that, as in mammals, the single Drosophila gene for RNase H1 (rnh1) has alternative translational start sites, resulting in two polypeptides, targeted to either mitochondria or the nucleus. RNAi-mediated rnh1 knockdown did not influence growth or viability of S2 cells, but compromised mtDNA integrity and copy number. rnh1 knockdown in intact flies also produced a phenotype of impaired mitochondrial function, characterized by respiratory chain deficiency, locomotor dysfunction, and decreased lifespan. Its overexpression in S2 cells resulted in cell lethality after 5-9 days, attributable to the nuclearly localized isoform. rnh1 knockdown and overexpression produced opposite effects on mtDNA replication intermediates. The most pronounced effects were seen in genome regions beyond the major replication pauses where the replication fork needs to progress through a gene cluster that is transcribed in the opposite direction. RNase H1 deficiency led to an accumulation of replication intermediates in these zones, abundant mtDNA molecules joined by four-way junctions, and species consistent with fork regression from the origin. These findings indicate replication stalling due to the presence of unprocessed RNA/DNA heteroduplexes, potentially leading to the degradation of collapsed forks or to replication restart by a mechanism involving strand invasion. Both mitochondrial RNA and DNA syntheses were affected by rnh1 knockdown, suggesting that RNase H1 also plays a role in integrating or coregulating these processes in Drosophila mitochondria.Peer reviewe

CD277 is a Negative Co-stimulatory Molecule Universally Expressed by Ovarian Cancer Microenvironmental Cells

CD277, a member of the butyrophilin subfamily 3 (BTN3), shares significant sequence similarities and predicted common structural features with inhibitory B7-H4 and other members of the B7 superfamily. Here we report that CD277 is consistently expressed in stromal, as well as tumor cells in the microenvironment of human advanced ovarian carcinoma specimens, both of primary and metastatic origin. MHC-II+ myeloid antigenpresenting leukocytes (dendritic cells and macrophages) express significantly higher levels of surface CD277, compared to other tumor-infiltrating leukocyte subsets, and this expression is significantly up-regulated by multiple common tumor microenvironmental signals, including VEGF and CCL3. Most importantly, engagement of CD277 on the surface of TCR-stimulated T cells inhibits their otherwise robust expansion and production of Th1 cytokines by preventing the up-regulation of cFLIP. Our results point to a role for CD277 up-regulated by microenvironmental signals in the acquisition of a regulatory phenotype by tumor-associated myeloid cells. Consequently, CD277, and likely other butyrophilins and butyrophilin-like molecules, emerge as regular players in the orchestration of immunosuppressive networks in ovarian cancer, and therefore new targets for interventions to overcome immune evasion and boost anti-tumor immunity in cancer patients