Measurement Of Activity Research Articles

Reliability of 24-h measurement of physical activity, sleep, and sedentary time in adult patients with asthma using a triaxial accelerometer

Objective Physical activity (PA), sleep, and sedentary time (SST) are important outcomes to monitor and to improve as part of patients’ asthma management. This study aimed to assess the number of measurement days needed to reliably measure PA and SST. Secondly, the influence of external factors on the reliability of measuring PA and SST was studied. Methods Adult patients with stable asthma were asked to wear a triaxial accelerometer for at least four days, with at least 22.5 h of wear time per day. The Intraclass Correlation Coefficients (ICCs) between different number of measurement days were used to determine reliability. Values ≥0.75 indicated good reliability. Results: Data from 452 patients were analyzed (63% women; age: 49 ± 16 years; FEV1: 87 ± 17% predicted). PA could reliably be measured with four valid measurement days (ICC 0.761). For SST, three days were needed (ICC 0.778). In summer and autumn, three days were needed to reliably measure PA, in winter four, in spring six. For SST, five days were needed in spring for good reliability, and two in all other seasons. Conclusion: Based on data from four valid days, PA and SST can reliably be measured with an accelerometer in patients with asthma. Seasonal influences are present, especially during spring. When measuring for four days, using only weekdays or three weekdays and one weekend day is recommended. The degree of asthma control, dyspnea or spirometric values did not influence the reliability.

Measurements of radioxenon activities during periods of gaseous release from an advanced gas-cooled reactor

Measurements of radioxenon activities during periods of gaseous release from an advanced gas-cooled reactor

The sympathetic nervous system in heart failure with preserved ejection fraction.

The sympathetic nervous system (SNS) is a major mediator of cardiovascular physiology during exercise in healthy people. However, its role in heart failure with preserved ejection fraction (HFpEF), where exercise intolerance is a cardinal symptom, has remained relatively unexplored. The present review summarizes and critically explores the currently limited data on SNS changes in HFpEF patients with a particular emphasis on caveats of the data and the implications for its subsequent interpretation. While direct measurements of SNS activity in HFpEF patients is scarce, modest increases in resting levels of muscle sympathetic nerve activity are apparent, although this may be due to the co-morbidities associated with the syndrome rather than HFpEF per se. In addition, despite some evidence for dysfunctional sympathetic signaling in the heart, there is no clear evidence for elevated cardiac sympathetic nerve activity. The lack of a compelling prognostic benefit with use of β-blockers in HFpEF patients also suggests a lack of sympathetic hyperactivity to the heart. Similarly, while renal and splanchnic denervation studies have been performed in HFpEF patients, there is no concrete evidence that the sympathetic nerves innervating these organs exhibit heightened activity. Taken together, the totality of data suggests limited evidence for elevated sympathetic nerve activity in HFpEF and that any SNS perturbations that do occur are not universal to all HFpEF patients. Finally, how the SNS responds during exertion in HFpEF patients remains unknown and requires urgent investigation.

A New Fluorescent Method for Measuring Peroxiredoxin Enzyme Activity Using Monobromobimane.

A novel fluorometric method is presented for accurately quantifying peroxiredoxin (Prx) enzyme activity in vitro. The rate-limiting step in the Prx-catalyzed reaction is the dissociation of peroxide. To avoid interference from catalase, we developed an assay using tert-butyl hydroperoxide (t-BOOH) as a substrate for specific Prx activity measurement. The assay involves incubating the enzyme substrates 1,4-dithio-DL-threitol (DTT) and t-BOOH in a suitable buffer at 37°C for 10min in a known volume of Prx enzyme. Following incubation, the reagent monobromobimane (mBB) is added to terminate the enzymatic reaction and produce a fluorescent product. Prx activity is subsequently determined by measuring thiol fluorescence, with reaction conditions optimized using a Bland-Altman plot. The efficacy of this novel protocol was rigorously validated by comparing Prx activity measurements from paired samples with those generated by a reference assay. A correlation coefficient of 0.995 was observed between the two methods, demonstrating superior precision and reliability compared to existing methods. The mBB-Prx protocol offers a significant safety advantage by using t-BOOH as a substrate for Prx activity measurement. As catalase does not catalyze t-BOOH dissociation, including sodium azide is unnecessary. Moreover, the method obviates the need for concentrated acids to terminate the Prx enzymatic reaction, as the mBB reagent efficiently inhibits Prx activity. This streamlined approach simplifies the assay and significantly improves its safety and usability, providing users with a reliable and convenient tool. The convenience of this method allows users to focus on their research without worrying about safety or complex procedures.

Discovering dynamics and parameters of nonlinear oscillatory and chaotic systems from partial observations

Despite rapid progress in data acquisition techniques, many complex physical, chemical, and biological systems remain only partially observable, thus posing the challenge to identify valid theoretical models and estimate their parameters from an incomplete set of experimentally accessible time series. Here, we combine sensitivity methods and ranked-choice model selection to construct an automated hidden dynamics inference framework that can discover predictive nonlinear dynamical models for both observable and latent variables from noise-corrupted incomplete data in oscillatory and chaotic systems. After validating the framework for prototypical FitzHugh-Nagumo oscillations, we demonstrate its applicability to experimental data from squid neuron activity measurements and Belousov-Zhabotinsky reactions, as well as to the Lorenz system in the chaotic regime. Published by the American Physical Society 2024

Sustainable production of radionuclidically pure antimony-119

BackgroundRadiopharmaceutical therapy (RPT) uses radionuclides that decay via one of three therapeutically relevant decay modes (alpha, beta, and internal conversion (IC) / Auger electron (AE) emission) to deliver short range, highly damaging radiation inside of diseased cells, maintaining localized dose distribution and sparing healthy cells. Antimony-119 (119Sb, t1/2 = 38.19 h, EC = 100%) is one such IC/AE emitting radionuclide, previously limited to in silico computational investigation due to barriers in production, chemical separation, and chelation. A theranostic (therapeutic/diagnostic) pair can be formed with 119Sb’s radioisotopic imaging analogue 117Sb (t1/2 = 2.80 h, Eγ = 158.6 keV, Iγ = 85.9%, β+ = 262.4 keV, Iβ+ = 1.81%).ResultsWithin, we report techniques for sustainable and cost-effective production of pre-clinical quality and quantity, radionuclidically pure 119Sb and 117Sb, novel low energy photon measurement techniques for 119Sb activity determination, and physical yields for various tin target isotopic enrichments and thicknesses using (p, n) and (d, n) nuclear reactions. Additionally, we present a two-column separation providing a radioantimony yield of 73.1% ± 6.9% (N = 3) and tin separation factor of (6.8 ± 5.5) x 105 (N = 3). Apparent molar activity measurements for deuteron produced 117Sb using the chelator TREN-CAM were measured at 42.4 ± 25 MBq 117Sb/µmol (1.14 ± 0.68 mCi/µmol), and we recovered enriched 119Sn target material at a recycling efficiency of 80.2% ± 5.5% (N = 6) with losses of 11.6 mg ± 0.8 mg (N = 6) per production.ConclusionWe report significant steps in overcoming barriers in 119Sb production, chemical isolation and purification, enriched target material recycling, and chelation, helping promote accessibility and application of this promising therapeutic radionuclide. We describe a method for 119Sb activity measurement using its low energy gamma (23.87 keV), negating the need for attenuation correction. Finally, we report the largest yet-measured 119Sb production yields using proton and deuteron irradiation of natural and enriched targets and radioisotopic purity > 99.8% at end of purification.

The role of presence of wormlike micelles of ionic surfactants on the sterilization efficiency of sodium hypochlorite

Abstract This paper describes an attempt to increase the sterilising efficacy of sodium hypochlorite (SH) by prolonging its shelf life in gel mode through the presence of wormlike micelles. No effect was observed on the presence of SH on the ratio of highest viscosity peak of 20:80 of 3 % (w/w) sodium dodecylsulfate (SDS) and cetyltrimethylammonium bromide (CTAB). On the other side, the presence of SH has a relatively negative effect on transformation process from spherical (three-dimensional, 3D) micelles to wormlike (one-dimensional, 1D) micelles. The gel state of the aqueous SH solution is maintained even at a ratio of 20:80 SDS:CTAB 3 % (w/w). Measurements of the biological activity of the gel using Staphylococcus aureus bacteria show that the sterilizing efficiency of SH is enhanced by the presence of 1D micelles. In contrast, the stability of SH using the kinetic method shows a sudden decrease in its stability due to the presence of 1D micelles, and the same is the case when both SDS and CTAB micelles are present. It was concluded that the increase in the biological activity of SH due to presence of micelles in gel or liquid mode resulted from their chemical interference, which acts as an antibacterial formulation.

Optimal Instruments for Measurement of Dietary Intake, Physical Activity, and Sleep Among Adults in Population-Based Studies: Report of a National Heart, Lung, and Blood Institute Workshop.

The National Heart, Lung, and Blood Institute convened a virtual workshop in September 2022 to discuss "Optimal Instruments for Measurement of Diet, Physical Activity, and Sleep." This report summarizes the proceedings, identifying current research gaps and future directions for measuring different lifestyle behaviors in adult population-based studies. Key discussions centered on integrating report-based methods, like questionnaires, with device-based assessments, including wearables and physiological measures such as biomarkers and omics to enhance self-reported metrics and better understand the underlying biologic mechanisms of chronic diseases. Emphasis was placed on the need for data harmonization, including the adoption of standard terminology, reproducible metrics, and accessible raw data, to enhance the analysis through artificial intelligence and machine learning techniques. The workshop highlighted the importance of standardizing procedures for integrated behavioral phenotypes using time-series data. These efforts aim to refine data accuracy and comparability across studies and populations, thereby advancing our understanding of lifestyle behaviors and their impact on chronic disease outcomes over the life course.

Quantitative characterization of immune cells by measuring cellular signal transduction pathway activity

For many diseases, including cancer, infections, and auto-immune diseases, the immune response is a major determinant of disease progression, response to therapy, and clinical outcome. Innate and adaptive immune responses are controlled by coordinated activity of different immune cell types. The functional activity state of immune cells is determined by Signal Transduction Pathways (STPs). A recently developed technology (Simultaneous Transcriptome-based Activity Profiling of Signal Transduction Pathways, STAP-STP) enables simultaneous and quantitative activity measurement of relevant STPs in immune cells based on mRNA-analysis. STAP-STP technology was used to analyze public transcriptome data of a variety of immune cell types in resting and activated functional state. In addition, a clinical study on rheumatoid arthritis (RA) was analyzed to illustrate utility of the technology. Per sample, activity of androgen and estrogen receptor, PI3K, MAPK, TGFβ, Notch, NFκB, JAK-STAT1/2, and JAK-STAT3 STPs was calculated, generating an STP activity profile (SAP) consisting of 9 activity scores. Each analyzed immune cell type, i.e. naive/resting and immune-activated CD4 + and CD8 + T cells, T helper cells, B cells, NK cells, monocytes, macrophages, and dendritic cells, had a reproducible and characteristic SAP, reflecting both cell type and its activity state. Analysis of clinical RA samples revealed increased TGFβ STP activity in whole blood samples. In conclusion, STAP-STP technology enables quantitative measurement of the functional activity state of immune cells of the innate and adaptive immune system. Aside from diagnostic applications, utility lies in unravelling abnormal immune function in disease and immunomodulatory drug development.

Neurophysiological Correlates of Expert Knowledge: An Event-Related Potential (ERP) Study about Law-Relevant Versus Law-Irrelevant Terms.

The evaluation of evidence, which frequently takes the form of scientific evidence, necessitates the input of experts in relevant fields. The results are presented as expert opinions or expert evaluations, which are generally accepted as a reliable representation of the facts. A further issue that remains unresolved though is the process of evaluating the expertise and knowledge of an expert in the first instance. In general, earned certificates, grades and other objective criteria are typically regarded as representative documentation to substantiate an expert status. However, there is a possibility that these may not always be sufficiently representative. The goal of the present study was to provide evidence that the neural processing of law-relevant and law-irrelevant terms varies significantly between participants who have received training in the field of law (experts) and those who have not (novices). To this end, changes in brain activity were recorded via electroencephalography (EEG) during visual presentations of terms belonging to five different categories (fake right, democracy, filler word, basic right and rule of law). Event-related potentials (ERPs) were subsequently averaged for each category and subjected to statistical analysis. The results clearly demonstrate that participants trained in law processed fake rights and filler words in a similar manner. Furthermore, both of these conditions elicited different levels of brain activity compared to all law-relevant terms. This was not the case in participants who had not received legal training. The brains of untrained participants processed all five term categories in a strikingly similar manner. In light of prior knowledge regarding language processing, the primary focus was on two distinct electrode locations: one in the left posterior region, and the other in the left frontal region. In both locations, the most prominent differences in brain activity elicited by the aforementioned term categories in law-trained participants occurred approximately 450 milliseconds after stimulus onset. The results were further corroborated by a repeated-measures ANOVA and subsequent t-tests, which also demonstrated the absence of this effect in law-untrained participants. The findings of this study provide empirical evidence that brain activity measurements, in particular ERPs, can be used to distinguish between experts trained in a specific field of expertise and novices in that field. Such findings have the potential to facilitate objective assessments of expertise, enabling comparisons between experts and novices that extend beyond traditional criteria such as qualifications and experience. Instead, individuals can be evaluated based on their cognitive processes, as observed through brain activity.

Interleukin-1 receptor-dependent and -independent caspase-1 activity in retinal cells mediated by receptor interacting protein 2.

Inflammation and cell death play an important role in the pathogenesis of diabetic retinopathy. Previously we observed sustained activation of pro-inflammatory caspase-1 in retinas of diabetic animals and patients. In this study, we aimed to look at mechanisms underlying chronic caspase-1 activation in vitro and in vivo. Non-diabetic and diabetic wild type and IL-1 receptor (IL-1R1) knockout mice were used for in vivo experiments. Diabetes was induced using STZ (streptozotocin). Human Müller cells were used for in vitro studies. Cells were treated with either 5mM or 25mM glucose or interleukin-1beta (IL-1β) in the presence or absence of IL-1 receptor antagonist (IL-1ra) or siRNA against RIP2 (receptor interacting protein-2) for up to 96h. Outcome measurements to assess Müller cell functions included measurements of caspase-1 activity using a fluorescence peptide substrate, production of IL-1β by Elisa, and cell death using trypan blue exclusion assays. Our in vivo results demonstrate that caspase-1 activation progresses from an IL-1R1 independent mechanism at 10weeks of diabetes to an IL-1R1 dependent mechanism at 20weeks indicating that feedback through IL-1R1 is crucial for sustained caspase-1 activity in retinas of mice. A similar hyperglycemia-mediated caspase-1/IL-1β/IL-1R1 feedback signaling was detected in vitro in human Müller cells which was prevented by treatment with IL-1ra. Our data also indicate that hyperglycemia induces caspase-1 activation initially but IL-1β sustains caspase-1 activation via caspase-1/IL-1β/IL-1R1 feedback and we identified RIP2 as mediator for both hyperglycemia- and IL-1β-induced caspase-1 activation. Activation of caspase-1/IL-1β/IL-1R1 feedback signaling caused Müller cell death which was prevented by RIP2 knockdown. We conclude that any intervention in caspase-1/IL-1β/IL-1R1 feedback signaling presents novel therapeutic options for the treatment of diabetic retinopathy.

DNA methylation profiles of transgenerational rat hyperactivity primed by silver nanoparticles: Comparison with valproate model rats of autism

There is an increasing body of evidence suggesting that a single exposure to certain chemicals can have transgenerational effects, with the underlying mechanism believed to be epigenetic. However, it remains largely unknown whether psychiatric conditions like ADHD or autism, induced by environmental chemicals, can be inherited across generations. Pregnant rats were purchased from a commercial breeder. On the 7th day of gestation (E7), they were divided into two groups: one group was orally exposed to silver nanoparticles (AgNP; 4 mg/kg), while the control group received vehicle alone. The subsequent generation (F1) underwent spontaneous motor activity (SMA) measurements at 8–11 weeks of age. For breeding at 26 weeks of age, rats with higher SMA were selected from hyperactive litters, while untreated rats were randomly selected. This process was continued for four generations in both groups. The AgNP-primed rats at 4th generation displayed significantly higher SMA, 1.8 times greater than that of untreated rats. Intraperitoneal injection of valproic acid (150 mg/kg), an epigenetic modifier to 5-day-old rats causes adult hyperactivity (1.4-fold), suggesting that epigenetic modification contributes to rat hyperactivity. Global DNA methylation profiles in the mesencephalon were positively correlated in both groups of hyperactive rats. Furthermore, there were 7–8 common genes showing both hypermethylation and hypomethylation, which are involved in neuronal development, neuronal function, transcriptional activity, DNA binding activity, cell differentiation, ubiquitination processes, or histone modification, including Pax 6 and Mecp 2. Thus, it is most likely that rats retain hyperactivity through mesencephalic DNA methylation status across transgeneration.

Structure-based virtual screening of novel chitin synthase inhibitors for the control of Phytophthora sojae.

Chitin synthase (CHS) is an important target for pesticide development as chitin biosynthesis is essential for the survival and reproduction of various organisms, such as oomycetes, fungi and insects. Small-molecule inhibitors of CHS have potential applications for the control of agricultural pests and diseases. In this study, exploiting the cryo-EM structures of PsChs1, the CHS indispensable to the sporangial production and virulence of soybean root rot pathogenic oomycete Phytophthora sojae, a virtual screening method combining by molecular docking, inhibitory activity measurement and biological activity determination was conducted, to identify novel small-molecule inhibitors of CHS. A chemical library containing ≈1.8 million compounds was screened, and four potent inhibitors (HS-20, HS-24, HS-36 and HS-40) were identified. Amongst these compounds, HS-20 showed the most potent inhibitory activity with a Ki value of 4.2 ± 0.2 μM. Besides inhibitory activities towards PsChs1, these compounds were effective in decreasing sporangial production and preventing zoospore infection. When inoculated with zoospores, HS-20 and HS-24 completely inhibited the growth of P. sojae, suggesting their potential in its prevention and control. This study identified four new compounds with potent chitin synthase (CHS) inhibitory activity, all of which significantly reduce sporangia production and zoospore infection. It also presents promising in silico techniques and small molecule candidates for the design and development of novel CHS inhibitors. © 2024 Society of Chemical Industry. Published by John Wiley & Sons Ltd.

The Orexin OX2 Receptor-Dependent Pathway Is Implicated in the Development of Overactive Bladder and Depression in Rats Exposed to Corticosterone.

In the present study, we wanted to check whether TCS OX2 29 (TCS), a potent selective antagonist of OX2 receptors, would have positive effects in an animal model of detrusor overactivity co-existed with the depression-like state in Wistar male rats. The forced swim test with the measurement of spontaneous locomotor activity, conscious cystometry, determination of c-Fos expression in central micturition areas, and a set of biochemical analyses (with the use of urine, hippocampus, bladder urothelium, and detrusor muscle of tested animals) were carried out. The outcomes showed that a 7-day administration of TCS (3 mg/kg/day, subcutaneously) normalizes the cystometric parameters corresponding to overactivity of the detrusor and reverses the pro-depressive response. Furthermore, the antagonism of OX2 receptors restored the abnormal levels of overactive bladder markers (i.e., ATP, CGRP, OCT3, TRPV1, ROCK1, and VAChT), diminished neuronal overactivity in central micturition areas (i.e., pontine micturition center, ventrolateral periaqueductal gray, and medial preoptic area) as well as restored the altered hippocampal levels of CRF, cytokines (IL-1β, IL-6, IL-10, and TNF-α), and growth factors (BDNF and NGF) that reflected biochemical disturbances detected in depressed people. It seems that our findings open new perspectives regarding the implication of the orexin system in the functioning of the urinary bladder and in the pathophysiology of depression.

Improving Hydrolytic Activity and Enantioselectivity of Epoxide Hydrolase from Phanerochaete chrysosporium by Directed Evolution.

Epoxide hydrolases (EHs) catalyze the conversion of epoxides into vicinal diols. The epoxide hydrolase gene from P. chrysosporium was previously cloned and subjected to site-directed mutation to study its enzyme activity, but the results were unsatisfactory. This study used error prone PCR and DNA shuffling to construct a PchEHA mutation library. We performed mutation-site combinations on PchEHA based on enzyme activity measurement results combined with directed evolution technology. More than 15,000 mutants were randomly selected for the preliminary screening of PchEHA enzyme activity alongside 38 mutant strains with increased enzyme activity or enantioselectivity. Protein expression and purification were conducted to determine the hydrolytic activity of PchEHA, and three mutants increased their activity by more than 95% compared with that of the wt. After multiple rounds of screening and site-specific mutagenesis, we found that F3 offers the best enzyme activity and enantioselectivity; furthermore, the molecular docking results confirmed this result. Overall, this study uncovered novel mutants with potential value as industrial biocatalysts.

Social Media Addiction and Cognitive Behavioral Physical Activity Among Adolescent Girls: A Cross-Sectional Study.

To measure a multivariate analysis of social media addiction and cognitive-behavioral physical activity associated with several sociodemographic characteristics in adolescent girls. A cross-sectional study. The sample consisted of adolescent girls studying in a vocational high-school in the Middle-Black-Sea region in Türkiye (n = 333). A questionnaire, Social Media Addiction Scale-for-Adolescents (SMAS-A), and Cognitive-Behavioral Physical Activity Questionnaire (CBPAQ) were used to collect the data. The mean age was 15.35(SD=1.15), and 29.4% were the ninth-class students. Of the adolescent girls, 85.9% were social-media users, 59.8% used the internet 2-hours-or-more/daily, 67.9% declared themselves as moderately-active. The mean scores of the SMAS-A and the CBPAQ were 3.40 (SD=1.61) and 21.03(SD=7.64), respectively. There was a significantly-negative correlation between cognitive-behavioral physical activity and social-media addiction levels. The One-Way MANOVA results showed significant differences in the academic level, family income, mother education, and physical activity measurement application usage affected to cognitive-behavioral physical activity. Social media usage habit affected to the social media addiction level. Daily internet usage time and self-declared physical activity level were the mutually affected factors. School nurses should act to improve healthy social media usage habits to promote well-being and encourage the positive attitudes towards regular physical activity in this population.

How Can Near‐Infrared Spectroscopy (NIRS) Help Understanding of the Psychotherapy Process? A Scoping Review of Therapeutic Interactions

AbstractIn recent years, near‐infrared spectroscopy (NIRS) has garnered significant attention for its potential clinical applications as a non‐invasive and straightforward method for measuring brain functions. While NIRS has become useful in psychiatric contexts by aiding in the differential diagnosis of depression, its application in clinical psychology is still developing. Due to its ecological validity, which allows for measurements in natural settings, NIRS shows promise in revealing the dynamic elements of the psychotherapy process. In this study, we conducted a scoping literature review of the use of NIRS in psychotherapeutic interactions, exploring its potential to unveil the complexities of psychotherapy settings involving interpersonal interactions. Employing a scoping review approach, we systematically searched the PubMed, PsycINFO, and Web of Science databases for articles published through October 19, 2023 about studies using NIRS as a measurement instrument: This yielded various therapeutic interactions. Of the 155 retrieved results that remained after the initial screening, seven met the inclusion criteria. Of these, six studies examined the synchronization of brain functions through the simultaneous brain activity measurements (hyperscanning) of two participants. The review revealed that, despite the anticipated potential of NIRS, it has become evident there is a dearth of research focusing on interactions during psychotherapy. Furthermore, the few available studies have not explored changes in line with the progression of psychotherapeutic interactions. Consequently, future studies should address whether NIRS can effectively assess alterations in brain function resulting from micro‐level events, such as the therapeutic interaction between therapists and clients during psychotherapy.

Influence of physical activity measurement on the association between Life’s Essential 8 and incident cardiovascular disease in older women

ObjectiveThe American Heart Association’s Life’s Essential 8 (LE8) metric includes self-reported physical activity as one of the metrics for assessing cardiovascular health. Self-reported physical activity is prone to misclassification, whereas accelerometer measures are less biased. We examined associations of LE8 and incident cardiovascular disease (CVD) using self-reported and accelerometer-measured physical activity. MethodsParticipants in the Women’s Health Initiative (WHI) Objective Physical Activity and Cardiovascular Health Study (n = 4,243; mean age = 79 ± 7 years) with no CVD history completed the WHI physical activity questionnaire and the Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire prior to wearing a hip-worn accelerometer for up to seven days in 2012–2014. LE8 components (physical activity, diet, sleep, body mass index, smoking, blood pressure, non-HDL cholesterol, and glucose) were scored according to guidelines. Scores were created using five physical activity measures: WHI questionnaire (LE8WHI), CHAMPS (LE8CHAMPS), accelerometer-measured physical activity (LE8A), and sample quantiles of accelerometer-measured physical activity (LE8AQ) and daily steps (LE8STEPS). Hazard ratios (HR) for physician-adjudicated CVD were estimated using Cox regression. Results707 incident CVD events occurred over an average 7.5 years. Multivariable HRs (95 % CI) comparing women in the highest vs. lowest quartiles of LE8 scores were: LE8WHI = 0.53 (0.43–0.67), LE8CHAMPS = 0.47 (0.38–0.60), LE8A = 0.44 (0.36–0.56), LE8AQ = 0.44 (0.35–0.55), and LE8STEPS = 0.45 (0.35–0.57). ConclusionsThe LE8-incident CVD association varies by physical activity measurement, however all methods showed reduced risk. Device-measures of physical activity may be more accurate in the LE8, but when impractical to implement, also support use of self-reported measures.

Application of the Summary of Diabetes Self-Care Activities Questionnaire in Evaluating the Self-Care of People with Diabetes

Objectives: This uncontrolled open study aimed to measure the levels of self-care of patients before and after education, their initial knowledge, and their knowledge two months after interacting with healthcare providers using the Summary of Diabetes Self-Care Activities (SDSCA) questionnaire. Methods: The data for this study were collected over 14 months from 396 patients with diabetes. This study was conducted in three phases: initial questionnaire testing, education, and retesting after two months. The education included specific diabetes-related topics: nutrition, exercise, self-monitoring of blood glucose, foot care, and smoking. Results: The results showed that all self-care activities between the first and second assessments were different. The initial assessment showed that the more successful the general diet, the specific diet, and physical activity were, the better the hemoglobin A1c value was. When considering the impact of gender on self-care effectiveness results, it was noted that women were more successful in foot care and specific diet in the initial testing, while men excelled in physical activity. The most successful age group in the scales of general diet, physical activity, and blood glucose testing was 31–45 years. Those with type 1 diabetes (36% of the study population) were more successful in self-care in the first and second measurements but without any differences in self-care in the retesting. Conclusions: our study observed a difference in self-care results between the two measurements of self-care activities in patients with diabetes, evaluated by the SDSCA questionnaire.

Dysregulation of protein SUMOylation networks in Huntington's disease R6/2 mouse striatum.

Huntington's disease (HD) is a neurodegenerative disorder caused by an expanded CAG repeat mutation in the Huntingtin (HTT) gene. The mutation impacts neuronal protein homeostasis and cortical/striatal circuitry. SUMOylation is a post-translational modification with broad cellular effects including via modification of synaptic proteins. Here, we used an optimised SUMO protein-enrichment and mass spectrometry method to identify the protein SUMOylation/SUMO interaction proteome in the context of HD using R6/2 transgenic and non-transgenic (NT) mice. Significant changes in enrichment of SUMOylated and SUMO-interacting proteins were observed, including those involved in presynaptic function, cytomatrix at the active zone scaffolding, cytoskeleton organization, and glutamatergic signaling. Mitochondrial and RNA-binding proteins also showed altered enrichment. Modified SUMO-associated pathways in HD tissue include clathrin-mediated endocytosis signaling, synaptogenesis signaling, synaptic long-term potentiation, and SNARE signaling. To evaluate how modulation of SUMOylation might influence functional measures of neuronal activity in HD cells in vitro, we utilised primary neuronal cultures from R6/2 and NT mice. A receptor internalization assay for the metabotropic glutamate receptor 7 (mGLUR7), a SUMO enriched protein in the mass spec, showed decreased internalization in R6/2 neurons compared to NT. siRNA-mediated knockdown of the E3 SUMO ligase Protein Inhibitor of Activated STAT1 (Pias1), which can SUMO modify mGLUR7, prevented this HD phenotype. In addition, microelectrode array analysis of primary neuronal cultures indicated early hyperactivity in HD cells, while later timepoints demonstrated deficits in several measurements of neuronal activity within cortical neurons. HD phenotypes were rescued at selected timepoints following knockdown of Pias1. Collectively, our results provide a mouse brain SUMOome resource and show that significant alterations occur within the post-translational landscape of SUMO-protein interactions of synaptic proteins in HD mice, suggesting that targeting of synaptic SUMO networks may provide a proteostatic systems-based therapeutic approach for HD and other neurological. Disorders.