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To assess the interactions between individual cofactors and multisensory inputs on the postural sway of adults with type 2 diabetes and healthy subjects, 69 adults accepted to participate in the study (48 with/21 without diabetes). Assessments included neuro-otology (sinusoidal-rotation and unilateral-centrifugation), ophthalmology and physiatry evaluations, body mass index (BMI), physical activity, quadriceps strength, the ankle/brachial index and polypharmacy. Postural sway was recorded on hard/soft surface, either with eyes open/closed, or without/with 30° neck extension. The proportional differences from the baseline of each condition were analyzed using Multivariate and Multivariable analyses. Patients with polyneuropathy and no retinopathy showed visual dependence, while those with polyneuropathy and retinopathy showed adaptation. Across sensory challenges, the vestibulo-ocular gain at 1.28 Hz and the BMI were mainly related to changes in sway area, while the dynamic visual vertical was mainly related to changes in sway length. The ankle/brachial index was related to the effect of neck extension, with contributions from quadriceps strength/physical activity, polyneuropathy and polypharmacy. Across conditions, men showed less sway than women did. In conclusion, in adults with diabetes, sensory inputs and individual cofactors differently contribute to postural stability according to context. Rehabilitation programs for adults with diabetes may require an individualized approach.

Endothelial mechanics control vascular reactivity and are regulated by the mineralocorticoid receptor (MR) and its downstream target, the epithelial Na+ channel (ENaC). Endothelial dysfunction is a hallmark of chronic kidney disease (CKD), but its mechanisms are poorly understood. We hypothesized that CKD disrupts endothelial mechanics in an MR/ENaC-dependent process. Methods: Primary human endothelial cells were cultured with uremic serum derived from children with stage 3–5 (predialysis) CKD or adult hemodialysis (HD) patients or healthy controls. The height and stiffness of the endothelial glycocalyx (eGC) and cortex were monitored by atomic force microscopy (AFM) using an ultrasensitive mechanical nanosensor. Results: In a stage-dependent manner, sera from children with CKD induced a significant increase in eGC and cortex stiffness and an incremental reduction of the eGC height. AFM measurements were significantly associated with individual pulse wave velocity and serum concentrations of gut-derived uremic toxins. Serum from HD patients increased MR expression and mechanical stiffness of the endothelial cortex, an effect reversed by MR and ENaC antagonists, decreased eNOS expression and NO bioavailability, and augmented monocyte adhesion. Conclusion: These data indicate progressive structural damage of the endothelial surface with diminishing kidney function and identify the MR as a mediator of CKD-induced endothelial dysfunction.

Epilepsy is a neurological condition associated to significant brain damage produced by status epilepticus (SE) including neurodegeneration, gliosis and ectopic neurogenesis. Reduction of these processes constitutes a useful strategy to improve recovery and ameliorate negative outcomes after an initial insult. SGK1.1, the neuronal isoform of the serum and glucocorticoids-regulated kinase 1 (SGK1), has been shown to increase M-current density in neurons, leading to reduced excitability and protection against seizures. For this study, we used 4–5 months old male transgenic C57BL/6 J and FVB/NJ mice expressing near physiological levels of a constitutively active form of the kinase controlled by its endogenous promoter. Here we show that SGK1.1 activation potently reduces levels of neuronal death (assessed using Fluoro-Jade C staining) and reactive glial activation (reported by GFAP and Iba-1 markers) in limbic regions and cortex, 72 h after SE induced by kainate, even in the context of high seizure activity. This neuroprotective effect is not exclusively through M-current activation but is also directly linked to decreased apoptosis levels assessed by TUNEL assays and quantification of Bim and Bcl-xL by western blot of hippocampal protein extracts. Our results demonstrate that this newly described antiapoptotic role of SGK1.1 activation acts synergistically with the regulation of cellular excitability, resulting in a significant reduction of SE-induced brain damage in areas relevant to epileptogenesis.

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Meibomian Glands (MG) are sebaceous glands responsible for the production of meibum, the main component of the Tear Film Lipid Layer (TFLL). The TFLL facilitates the spread of the tear film over the ocular surface, provides stability and reduces tear evaporation. Alterations in meibum composition lead to different ocular alterations like Meibomian Gland Dysfunction (MGD) and subsequent Evaporative Dry Eye (EDE). The aim of the present study was to investigate the composition and abundance of meibum lipids and their relationship with eyelid margin abnormalities, lipid layer patterns and MG status. The study utilizes a lipidomic approach to identify and quantify lipids in meibum samples using an Elute UHPLC system. This system considered all four dimensions (mass/charge, retention time, ion mobility and intensity) to provide the accurate identification of lipid species. Samples were categorized as healthy or low/no signs of alteration (group 1) or severe signs of alteration or EDE/MGD (group 2). The current investigation found differences in Variable Importance in Projection lipid abundance between both groups for the MGD signs studied. Changes in meibum composition occur and are related to higher scores in eyelid margin hyperaemia, eyelid margin irregularity, MG orifice plugging, MG loss and lipid layer pattern. [ABSTRACT FROM AUTHOR]

The increasing prevalence of problems related to mental health and emotional well-being among children and young people underlines the importance of educational institutions, particularly Physical Education, to foster emotional well-being. Therefore, Physical Education is a suitable educational space for working on emotions. This research aims to investigate whether the introduction of competition in Physical Education games influences the emotional intensity of students. Method: The sample consisted of 46 people aged between 10 and 12 years (M = 10.87; SD = 0.75), of whom 26 were girls (57%) and 20 boys (43%). To carry out the study, the sample was divided into two groups, a control group and an experimental group, with which non-competitive and competitive games were played, respectively, in the area of Physical Education. The instruments used in the research were the GES-C questionnaire and an ad hoc sociodemographic questionnaire created specifically for this study. Results: The research showed that non-competitive games generated greater intensity in any of the 4 positive emotions evaluated, as well as with competitive games in the 5 negative emotions evaluated. In the same line, it was also evidenced that positive emotions are significantly more intense when winning and negative emotions are significantly more intense when losing during the practice of competitive games. Conclusions: Competitive games favor emotional development differently from non-competitive games. Therefore, neither type of game should be eliminated from educational practice. That is why Physical Education teachers must make a selection of the games to be used during their classes, competitive or non-competitive, based on the previously established educational objectives. [ABSTRACT FROM AUTHOR]

Sports coaching has used video feedback for decades to improve athlete and coach performance. More recently, artificial intelligence (AI) and machine-learning technologies have enabled analytics alongside visual review to accelerate development further. So too in coaching conversations, software allows the implementation of behavioural analytics, tracking speech patterns, body language and facial expressions to deliver performance data measured against core coaching competencies. In this study, we interviewed 15 coaches who used AI-enhanced video review software in coaching sessions with clients over several weeks and reflected on those sessions using the recordings and AI-generated data. Our aim was to discover the benefits and drawbacks of using such an approach in reflective practice. Clear benefits emerged: insights gained from video and data analysis drove deeper reflection and heightened self-awareness; coaches focused on skills development, made specific changes to their practice, developed over time and gained in confidence. Challenges included coaches' nervousness around using new technology, viewing and analysing their own performance, and a sense that the software does not understand the subtle nuances and context of conversations. Limitations are discussed as well as the implications for coach training, reflective practice and supervision. We suggest possibilities for further study in this area. [ABSTRACT FROM AUTHOR]

There are serious warnings of sedentary lifestyles among children. Therefore, it is necessary to take measures from school, especially in Physical Education (PE) classes. One way to do this, it is paying attention to the motivational climate and enjoyment in PE classes because these two factors are related to the intention to be physically active by students. This research’s aim was to evaluate multidimensional motivation and enjoyment in PE classes and relations between these dimensions. The sample included 315 Primary Education Galician students (Spain), 145 boys (46%) and 170 girls (54%), with an age range between 10 and 12 years (M=10.92, SD=0.792). Data were collected by means of two questionnaires. One of them was the ‘Physical Education Questionnaire in Primary Education´ (CMEF-EP), and the other one was ‘Physical Activity Enjoyment Scale´ (PACES). The following results were obtained: Intrinsic Motivation (IM) (M=5.12; SD=1.14), External Regulation (ER) (M=3.61; SD=1.63), Amotivation (AM) (M=1.93; SD=1.46), Enjoyment (ENJ) (M=4.51; SD=0.55). Regression analysis shows that the IM can predict 42.1% of ENJ in PE classes. Therefore, students’ intrinsic motivation is a solid framework for enjoyment in PE lessons. Consequently, it should be taken into account by Primary Education teachers in their classrooms. They should take appropriate measures to encourage intrinsic motivation: methodologies of inquiry, positive feedback, variety of tasks and materials, flexible grouping and meaningful assessment.

Summary: Cyclin E, a key cell cycle regulatory protein, has been linked to oncogenesis when dysregulated. We have previously shown that overexpression of cyclin E causes replication stress, leading to failure to complete replication at specific chromosomal loci during S phase of the cell cycle. This in turn promotes chromosomal damage during anaphase. Here we show that non-transformed human mammary epithelial cell clones that survive such aberrant mitoses have a specific and reproducible pattern of chromosomal Copy Number Alterations (CNAs) that we have characterized and termed the cyclin E CNA signature. Using a number of computational approaches, we show that this signature resembles one specific CNA pattern enriched in differentiated epithelial-like tumors of the breast and ovary. Analysis of the CNA profile of these clones provides a potential mechanism for cyclin E-mediated oncogenesis. : Biological Sciences; Molecular Biology; Cell Biology; Cancer; Transcriptomics Subject Areas: Biological Sciences, Molecular Biology, Cell Biology, Cancer, Transcriptomics

En los últimos 15 años se han producido en las inmediaciones de la Frontera Sur de España una serie de acontecimientos y ensamblajes arquitectónicos aparentemente inconexos para mejorar la funcionalidad y capacidad de respuesta de la frontera construida. Este artículo aborda el giro dinámico que está sufriendo la frontera contemporánea según la detección de tres estrategias: impermeabilizar, retardar y contener. La cartografía crítica y la reconstrucción forense de una serie de acontecimientos permiten evidenciar la deriva de una transformación tipológica que desplaza el peso de construcciones estables a ensamblajes dinámicos e instantáneos. Estos ya no pueden enunciarse como soluciones estáticas, sino como un dispositivo o ensamblaje territorial que configura y define la frontera. Si la arquitectura de la frontera materializa de manera clara la soberanía, es necesario cuestionarse el modelo territorial, que ya no es representado por la norma sino por la condición de operatividad.

This paper addresses a major utility and regulator concern of characterizing customer net electricity consumption profiles to realize integrated distribution system planning. This is pivotal in assessing the capability of the power system to accommodate net load variability and its impacts on the grid such as voltage rise, narrowing peak demand duration, and reducing the cost of energy storage. Although the extant literature has focused on load clustering, this paper uses a symbolic aggregate approximation-based (SAX-based) dimensionality- reduction and k-means techniques to cluster net consumption of smart meter data for more than 3500 residential customers in a month at different temporal resolutions. This study proposes the use of cumulative explained variance in the principal component analysis to determine the optimal number of segments and dimensionality of the transformed space during discretization while retaining the data integrity instead of using intuition, as proposed by the extant literature. Also, this paper describes a screening methodology to determine the distribution of high-voltage customers among the resulting clusters of customers with and without on-site solar photovoltaic generation at different time resolutions.

Asthenozoospermia accounts for over 80% of primary male infertility cases. Reduced sperm motility in asthenozoospermic patients are often accompanied by teratozoospermia, or defective sperm morphology, with varying severity. Multiple morphological abnormalities of the flagella (MMAF) is one of the most severe forms of asthenoteratozoospermia, characterized by heterogeneous flagellar abnormalities. Among various genetic factors known to cause MMAF, multiple variants in the DNAH2 gene are reported to underlie MMAF in humans. However, the pathogenicity by DNAH2 mutations remains largely unknown. In this study, we identified a novel recessive variant (NM_020877:c.12720G > T;p.W4240C) in DNAH2 by whole-exome sequencing, which fully co-segregated with the infertile male members in a consanguineous Pakistani family diagnosed with asthenozoospermia. 80–90% of the sperm from the patients are morphologically abnormal, and in silico analysis models reveal that the non-synonymous variant substitutes a residue in dynein heavy chain domain and destabilizes DNAH2. To better understand the pathogenicity of various DNAH2 variants underlying MMAF in general, we functionally characterized Dnah2-mutant mice generated by CRISPR/Cas9 genome editing. Dnah2-null males, but not females, are infertile. Dnah2-null sperm cells display absent, short, bent, coiled, and/or irregular flagella consistent with the MMAF phenotype. We found misexpression of centriolar proteins and delocalization of annulus proteins in Dnah2-null spermatids and sperm, suggesting dysregulated flagella development in spermiogenesis. Scanning and transmission electron microscopy analyses revealed that flagella ultrastructure is severely disorganized in Dnah2-null sperm. Absence of DNAH2 compromises the expression of other axonemal components such as DNAH1 and RSPH3. Our results demonstrate that DNAH2 is essential for multiple steps in sperm flagella formation and provide insights into molecular and cellular mechanisms of MMAF pathogenesis.