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An abstract of the article∣Progressive Torsion Dystonia and Blepharospasm With Bradykinesia,∣by R.A. Page, W.R. Gibb and A.A. Pinto is presented.

Given the aging global population, identifying heart failure (HF) phenotypes has become crucial, as distinct disease characteristics can influence treatment and prognosis in older adults. This study aimed to analyze the association between clustering of cardiovascular risk factors and HF in older adults. A cross-sectional epidemiological study was conducted with 1322 older adults (55% women, mean age 70.4) seen in primary health care. Diagnosis of HF was performed by a cardiologist based on diagnostic tests and medical history. Cardiovascular risk factors included hypertension, diabetes, hypercholesterolemia, and smoking. Using logistic regression, potential associations were tested. Individual risk factor analysis showed that older adults with hypertension, diabetes, or hypercholesterolemia had up to 7.6 times higher odds to have HF. The cluster where older adults had only one risk factor instead of none increased the odds of HF by 53.0%. Additionally, the odds of older patients having HF ranged from 3.59 times for the two-risk factor cluster to 20.61 times for the simultaneous presence of all four factors. The analysis of clusters substantially increasing HF risk in older adults revealed the importance of individualizing subgroups with distinct HF pathophysiologies. The clinical significance of these clusters can be beneficial in guiding a more personalized therapeutic approach.

Objective: This study aimed to assess the mediation effects of lean mass and fat mass on the relationship between body mass index (BMI) and handgrip strength (HGS) in adolescents., Method: The sample included 118 adolescents (60 girls) aged 10-14 years. Body composition, determined from lean mass (LM) and fat mass (FM), was measured by dual-energy x-ray absorptiometry. HGS was measured using a digital dynamometer. Moderate-to-vigorous physical activity and sexual maturation, treated as covariates, were evaluated by accelerometry and pubic hair development, respectively. Spearman correlation and simple mediation analysis were used for statistical analysis., Results: A positive relationship was observed between BMI and HGS (rho = .364, p < .001), BMI and LM (rho = .466, p < .001), LM and HGS (rho = .784, p < .001), BMI and FM (rho = .907, p < .001), and FM and HGS (rho = .291, p = .001). LM was the only significant mediator of the relationship between BMI and HGS., Conclusion: Only LM mediated the association between BMI and HGS, almost entirely explaining the relationship. The findings reinforce the need to include LM measurements in routine strength testing. Furthermore, strategies focused on LM development may be promising in preventing low muscle strength in adolescents., (© 2023 Wiley Periodicals LLC.)

Introduction: We assessed whether midlife sensory and motor functions added to prediction models using the Cardiovascular Risk Factors, Aging, and Incidence of Dementia Score (CAIDE) and Framingham Risk Score (FRS) improve risk predictions of 10-year changes in biomarkers of neurodegeneration and Alzheimer's disease., Methods: Longitudinal data of N  = 1529 (mean age 49years) Beaver Dam Offspring Study participants from baseline, 5-year, and 10-year follow-up were included. We tested whether including baseline sensory (hearing, vision, olfactory) impairment and motor function measures improves CAIDE or FRS risk predictions of 10-year incidence of biomarker positivity of serum-based neurofilament light chain (NfL) and amyloid beta (Aβ) 42 /Aβ 40 using logistic regression., Results: Adding sensory and motor measures to CAIDE-only and FRS-only models significantly improved NfL and Aβ 42 /Aβ 40 positivity predictions in adults above the age of 55., Discussion: Including midlife sensory and motor function improved long-term biomarker positivity predictions. Non-invasive sensory and motor assessments could contribute to cost-effective screening tools that identify individuals at risk for neurodegeneration early to target interventions and preventions., Highlights: Sensory and motor measures improve risk prediction models of neurodegenerative biomarkersSensory and motor measures improve risk prediction models of AD biomarkersPrediction improvements were strongest in late midlife (adults >55 years of age)Sensory and motor assessments may help identify high-risk individuals early., Competing Interests: The authors have no conflicts of interest to report. Author disclosures are available in the supporting information [Link], [Link]., (© 2024 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction: We aimed to assess whether midlife sensory and motor functions improve risk prediction of 10-year cognitive decline and impairment when added to risk prediction models using the Cardiovascular Risk Factors, Aging, and Incidence of Dementia Score (CAIDE) and Framingham Risk Score (FRS)., Methods: Longitudinal data of N  = 1529 (mean age 49 years; 54% women) Beaver Dam Offspring Study (BOSS) participants from baseline, 5 and 10-year follow-up were included. We tested whether including baseline sensory (hearing, vision, olfactory) impairment and motor function improves CAIDE or FRS risk predictions of 10-year cognitive decline or cognitive impairment incidence using logistic regressions., Results: Adding sensory and motor measures to CAIDE-only and FRS-only models significantly improved areas under the curve for cognitive decline and impairment models., Discussion: Including midlife sensory and motor function improved risk predictions of long-term cognitive decline and impairment in middle-aged to older adults. Sensory and motor assessments could contribute to cost-effective and non-invasive screening tools that identify high-risk individuals earlier to target intervention and prevention strategies., Highlights: Sensory and motor measures improve risk prediction models of cognitive decline.Sensory and motor measures improve risk prediction models of cognitive impairment.Prediction improvements were strongest in midlife (adults < 55 years of age).Sensory and motor changes may help identify high-risk individuals early., Competing Interests: The authors have no conflict of interest to report. Author disclosures are available in the supporting information., (© 2024 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

This study's aim was to identify risk factors associated with sensorineural and neurocognitive function (brain aging) in older adults. In N  = 1,478 Epidemiology of Hearing Loss Study participants (aged 64-100 years, 59% women), we conducted sensorineural and cognitive tests, which were combined into a summary measure using Principal Component Analysis (PCA). Participants with a PCA score <-1 standard deviation (SD) were considered to have brain aging. Incident brain aging was defined as PCA score <-1 SD at 5-year follow-up among participants who had a PCA score ≥-1 SD at baseline. Logistic regression and Poisson models were used to estimate associations between baseline risk factors of lifestyle, vascular and metabolic health, and inflammation and prevalent or incident brain aging, respectively. In an age-sex adjusted multivariable model, not consuming alcohol (odds ratio(OR) = 1.77, 95% confidence Interval (CI) = 1.18,2.66), higher interleukin-6 levels (OR = 1.30, 95% CI = 1.03,1.64), and depressive symptoms (OR = 2.44, 95% CI = 1.63,3.67) were associated with a higher odds of having brain aging, while higher education had protective effects (OR = 0.55, 95% CI = 0.33,0.94). A history of stroke, arterial stiffness, and obesity were associated with an increased risk of developing brain aging during the five years of follow-up. Lifestyle, vascular, metabolic and inflammatory factors were associated with brain aging in older adults, which adds to the evidence of shared pathways for sensorineural and neurocognitive declines in aging. Targeting these shared central processing etiological factors with interventions may lead to retention of better neurological function, benefiting multiple systems, i.e., hearing, smell, and cognition, ultimately helping older adults retain independence and higher quality of life longer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Merten, Fischer, Pinto, Chappell and Schubert.)

In this study, we explore the potential of functionalized two-dimensional (2D) diamond for spin-dependent electronic devices using first-principles calculations. Specifically, we investigate functionalizations with either hydroxyl (-OH) or fluorine (-F) groups. In the case of an isolated layer, we observe that the quantity and distribution of (-OH) or (-F) on the 2D diamond surface significantly influence the sp 2 / sp 3 ratio of the carbon atoms in the layer. As the coverage is reduced, both the band gap and magnetic moment decrease. When the 2D diamond is placed between gold contacts and functionalized with (-OH), it results in a device with lower resistance compared to the (-F) functionalization. We predict that the maximum current achieved in the device increases with decreasing (-OH) surface coverage, while the opposite behavior occurs for (-F). Additionally, the surface coverage alone can alter the direction of current rectification in (-F) functionalized 2D diamonds. For all studied systems, a single spin component contributes to the total current for certain values of applied bias, indicating a spin filter behavior., (© 2023 IOP Publishing Ltd.)

Aim: To determine whether exposure to neurotoxins in midlife is associated with changes in blood-based biomarkers of neurodegeneration and Alzheimer disease pathology., Methods: Blood cadmium, lead, neurofilament light (NfL) chain, total tau (TTau), and amyloid beta (Aβ) 40 and Aβ42 concentrations were measured in 1516 participants in the Beaver Dam Offspring Study. Linear mixed-effect models were used to determine associations between baseline cadmium and lead levels and baseline NfL, TTau, and Aβ42/Aβ40, and 10-year change in concentrations using repeated measures of these biomarkers as the outcome., Results: In women, higher cadmium and lead levels were associated with higher baseline TTau concentrations. A higher baseline cadmium level was associated with lower baseline Aβ42/Aβ40 in both men and women. In age-sex-adjusted models, a doubling in baseline cadmium level was associated with a 0.2% (95% CI: 0.0, 0.3) higher increase per year in NfL concentrations. In men, a doubling of baseline lead level was associated with a 0.9% (95% CI: 0.1, 1.7) higher increase per year in TTau concentration., Conclusions: Participants with relatively higher levels of cadmium and lead had blood biomarker concentrations consistent with more neuronal damage and Alzheimer disease pathology. Environmental exposure to neurotoxins may contribute to neurodegeneration., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Scolymus hispanicus L., also known as golden thistle, Spanish oyster thistle or, more commonly, as tagarnina is a plant that belongs to the Asteraceae family. It is collected from the wild for human consumption in Mediterranean countries. It is a relevant ingredient in Andalusian culinary culture, where the midribs of young plants are harvested for consumption. Scolymus hispanicus L. contains a wide variety of phenolic compounds such as caffeoylquinic acids (CQAs), among others. In the present work, the major phenolic compounds present in tagarnina have been identified, with 5-caffeoylquinic acid (5-CQA) and 3,5-dicaffeoylquinic acid (3,5-diCQA) being the main ones. A method based on ultrasound-assisted extraction (UAE) has been developed for the extraction of these compounds, with the percentage of methanol, sample-to-solvent ratio and the pH being the most influential factors. The developed method has been validated and employed to determine the concentration of 5-CQA and 3,5-diCQA in the midribs of Scolymus hispanicus , collected in six different places in the south of Spain. The antioxidant activity of the samples has also been determined, and a direct correlation with their caffeoylquinic compounds content has been established, showing an antioxidant effect.

Purpose : This study aimed to verify the agreement between body mass index (BMI) and body fat in adolescents with different physical activity (PA) levels. Method : This cross-sectional study collected body fat data in 118 adolescents (aged 10 to 14 years) estimated using air-displacement plethysmography (ADP). Body mass 10 and height were used to calculate BMI. Physical activity levels were measured objectively by accelerometers. Results : For boys with low PA, BMI overestimated body fat values measured by ADP (mean error = -0.42; p = .018) which also occurred in group high PA (mean error = -0.76; p = .001). For girls, BMI underestimated body fat values measured by ADP values in group high PA (mean error = 0.43; p = .001) and low PA (mean error = 0.72; p < .001). Conclusion : It is recommended that researchers and practitioners 15 cautiously interpret BMI results, especially considering that most adolescents do not practice enough PA.

Objective: The aim of this study was to analyze isolated and combined associations of physical inactivity excessive screen time with negative self-rated health, according to sex, among school adolescents., Methods: In this cross-sectional study conducted with 2,517 adolescents in Amazonas State, participants were asked about their self-rated health with the following question: How do you rate your health? Responses were dichotomized into positive (excellent and good) and negative (regular, bad, and terrible). Information on sex, age group, family income, physical activity, and screen time (watching TV, using a computer, or playing video games) was collected through a self-administered questionnaire. Adolescents simultaneously classified as physically inactive (<60 min/day) and having excessive screen time (>2 h/day) were considered to have two risk factors. Data was analyzed using binary logistic regression., Results: Out of every 10 adolescents, 2 had a negative self-rated health. After adjusting for age and family income, there were no isolated or combined associations between physical inactivity or excessive screen time and negative self-rated health in girls. In boys, negative self-rated health was associated with insufficient levels of physical activity (odds ratio [OR]: 2.39; 95% confidence interval [CI]: 1.03-5.59) and with the accumulation of two risk factors (OR: 1.61; 95%CI 1.10-2.34)., Conclusions: Being insufficiently active and the combination of physical inactivity and excessive screen time become exposure factors to the negative self-rated health of adolescent boys.

Background: Intravenous immunoglobulin (IVIg) and therapeutic plasma exchange (TPE) are among the main immunotherapies for neurological disorders. Their benefit is greatest in immune-mediated conditions, but their distinct efficacy cannot be simply explained., Objectives: This review aimed to systematically identify studies comparing the efficacy of TPE and IVIg treatments for selected autoimmune neurological disorders and identify optimal therapies for each condition., Data Sources and Methods: PubMed, MEDLINE and Embase databases were searched for original publications from 1990 to 2021. Additional publications were identified via expert recommendations. Conference abstracts older than 2017, review articles and articles without information on TPE and IVIg comparison in title and abstract were excluded. Risks of bias were descriptively addressed, without a meta-analysis., Results: Forty-four studies were included on Guillain-Barré syndrome (20 studies - 12 adult, 5 paediatric, 3 all ages), myasthenia gravis (11 studies -8 adult, 3 paediatric), chronic immune-mediated polyradiculoneuropathy (3 studies -1 adult, 2 paediatric), encephalitis (1 study in adults), neuromyelitis optica spectrum disorders (5 studies -2 adult, 3 all ages) and other conditions (4 studies - all ages). TPE and IVIg were mostly similarly efficacious, measured by clinical outcomes and disease severity scores. Some studies recommended IVIg as easy to administer. TPE procedures, however, have been simplified and the safety has been improved. TPE is currently recommended for management of neuromyelitis optica spectrum disorder relapses and some myasthenia gravis subtypes, in which rapid removal of autoantibodies is crucial., Conclusion: Despite some limitations (e.g. the low evidence levels), this review provides an extensive 30-year-long overview of treatments for various conditions. Both IVIg and TPE are usually comparably efficacious options for autoimmune neurological disorders, with few exceptions. Treatment choices should be patient-tailored and based on available clinical resources. Better designed studies are needed to provide higher-level quality of evidence regarding clinical efficacy of TPE and IVIg treatments., (© The Author(s), 2023.)

Introduction: Physical fitness concerns a set of attributes related to the ability to perform physical activity that may justify the symptoms reported by the elderly in the context of sarcopenia., Objective: This study aimed to investigate the relationship between the perception (symptomatology) of physical functioning (what the person thinks they are capable of) and the capacity itself for physical functioning in elderly people in northern Brazil., Methods: Cross-sectional study that analyzed 312 elderly people (72.6 ± 7.8 years) from the city of Novo Aripuanã, Amazonas, Brazil. Sarcopenia symptomatology was assessed using the SARC-F, a 5-item questionnaire designed for screening sarcopenia in older individuals in five domains: strength, walking aids, difficulty getting up from a chair, difficulty climbing stairs, and falls. Physical fitness was assessed by the Senior Fitness Test (SFT) battery including balance evaluated with the short version of the Fullerton Advanced Balance scale (FAB)., Results: ROC curve analysis revealed that the tests with the greatest ability to discriminate participants with significant symptoms for sarcopenia (≥4 points on SARC-F) were arm curl and 6 min walk: the probability of suspected sarcopenia increased exponentially with an arm curl < 11.5 reps for men (se = 71%; sp = 69%; AUC = 0.706, 95% CI: 0.612-0.788; p = 0.013) and women (se = 81%; sp = 51%; AUC = 0.671, 95% CI: 0.601-0.735; p ≤ 0.001) or with a 6-min walk <408.5 m for men (se = 71%; sp = 63%; AUC = 0.720, 95% CI: 0.628-0.690; p = 0.001) and <366.0 m for women (se = 69%; sp = 58%; AUC = 0.692, 95% CI: 0.623-0.755; p = 0.0001)., Conclusions: Physical fitness assessed through the senior fitness test, particularly the 30-s-arm curl test and the 6-min walk test, can discriminate for suspected symptoms of sarcopenia.

Introduction: Neurodegeneration and cognitive decline in aging are growing public health concerns. This study investigates associations between central retinal arteriolar and venular equivalents (CRAE, CRVE) and brain-aging, a sensory and cognitive test composite measure, and macular ganglion cell-inner plexiform layer (mGCIPL) thickness, a biomarker of neurodegeneration., Methods: Beaver Dam Offspring Study (BOSS) participants are adult children (baseline (2005-2008) age 21-84 years) of the population-based Epidemiology of Hearing Loss Study participants. Follow-up occurred every 5 years. In 2010-2013, fundus photographs were used to measure retinal vessels. A brain-aging score was constructed by principal component analysis using sensorineural and cognitive data. Associations between incident brain-aging and vessel measures were investigated using logistic regression. Associations between CRAE and CRVE and mGCIPL thickness, measured in 2015-2017, were also investigated., Results: Participants (N = 2381; mean age: 53.9 years (SD = 9.8); 54% women) had a mean CRAE and CRVE of 148.8 µm (SD = 14.5) and 221.7 µm (SD = 20.7), respectively. Among those without ocular conditions, wider CRAE was associated with decreased 5-year brain-aging risk (33% per SD CRAE increase). Both vessel measures were independently associated with mGCIPL thickness. The mGCIPL thickness increased by approximately 1.7 µm and 2.0 µm per SD increase in CRAE and CRVE, respectively., Discussion: The association of CRAE with incident brain-aging indicates its potential use as a screening tool among those without eye disease. The associations between CRAE and CRVE and mGCIPL thickness indicate narrower vasculature could affect neuronal health. These associations point to potential usefulness of retinal vessel measurements to identify people at higher risk of sensorineural declines and neurodegeneration.

Background: Age-related declines in cognitive function may begin in midlife., Purpose: To determine whether blood-based biomarkers of inflammation, metabolic dysregulation and neurotoxins are associated with risk of cognitive decline and impairment., Methods: Baseline blood samples from the longitudinal Beaver Dam Offspring Study (2005-2008) were assayed for markers of inflammation, metabolic dysregulation, and environmental neurotoxins. Cognitive function was measured at baseline, 5-year (2010-2013) and 10-year (2015-2017) examinations. Participants without cognitive impairment at baseline and with cognitive data from at least one follow-up were included. Cox proportional hazards models were used to evaluate associations between baseline blood biomarkers and the 10-year cumulative incidence of cognitive impairment. Poisson models were used to estimate the relative risk (RR) of 5-year decline in cognitive function by baseline blood biomarkers. Models were adjusted for age, sex, education, and cardiovascular related risk factors., Results: Participants (N = 2421) were a mean age of 49 years and 55% were women. Soluble vascular cell adhesion molecule-1 (sVCAM-1 Tertile(T)3 vs T1-2 hazard ratio (HR) = 1.72, 95% confidence interval (CI) = 1.05,2.82) and hemoglobin A1C (HR = 1.75, 95% CI = 1.18,2.59, per 1% in women) were associated with the 10-year cumulative incidence of cognitive impairment. sVCAM-1 (RR T3 vs T1-2  = 1.45, 95% CI = 1.06,1.99) and white blood cell count (RR = 1.10, 95% CI = 1.02,1.19, per 10 3 /μL) were associated with 5-year cognitive decline., Conclusions: Biomarkers related to inflammation and metabolic dysregulation were associated with an increased risk of developing cognitive decline and impairment. These results extend previous research in cognitive aging to early markers of cognitive decline in midlife, a time when intervention methods may be more efficacious., (© 2022. Fondazione Società Italiana di Neurologia.)

Background: Pathological biomarkers of Alzheimer's disease (AD) and other dementias can change decades before clinical symptoms. Lifestyle and health factors might be relevant modifiable risk factors for dementia. Many previous studies have been focusing on associations of lifestyle and health-related factors with clinical outcomes later in life., Objective: We aimed to determine to what extent midlife factors of lifestyle, inflammation, vascular, and metabolic health were associated with long-term changes in blood-based biomarkers of AD (amyloid beta (Aβ)) and neurodegeneration (neurofilament light chain (NfL); total tau(TTau))., Methods: In 1,529 Beaver Dam Offspring Study (BOSS) participants (mean age 49 years, standard deviation (SD) = 9; 54% were women), we applied mixed-effects models with baseline risk factors as determinants and 10-year serum biomarker change as outcomes., Results: We found that education and inflammatory markers were associated with levels and/or change over time across all three markers of AD and neurodegeneration in the blood. There were baseline associations of measures of cardiovascular health with lower Aβ42/Aβ40. TTau changed little over time and was higher in individuals with diabetes. Individuals with lower risk in a number of cardiovascular and metabolic risk factors, including diabetes, hypertension, and atherosclerosis had slower accumulation of neurodegeneration over time, as determined by NfL levels., Conclusion: Various lifestyle and health factors, including education and inflammation, were associated with longitudinal changes of neurodegenerative and AD biomarker levels in midlife. If confirmed, these findings could have important implications for developing early lifestyle and health interventions that could potentially slow processes of neurodegeneration and AD.

Baccharis genus Asteraceae is widely used in traditional treatment against fever, headache, hepatobiliary disorders, skin ulcers, diabetes, and rheumatism, as well as an antispasmodic and diuretic. Its phytochemistry mainly shows the presence of flavonoids and terpenoids such as monoterpenes, sesquiterpenes, diterpenes, and triterpenes. Some of them have been evaluated for biological activities presenting allelopathic, antimicrobial, cytotoxic, and anti-inflammatory properties. In this paper, our research group reported the isolation, characterization, and antifungal evaluation of several molecules isolated from the dichloromethane extract from Baccharis prunifolia , Baccharis trinervis , and Baccharis zumbadorensis against the phytopathogen fungus Botrytis cinerea . The isolated compounds have not previously been tested against Botrytis , revealing an important source of antifungals in the genus Baccharis . Six known flavones were isolated from B. prunifolia . The dichloromethane extracts of B. trinervis and B. zumbadorensis were subjected to a bio-guided isolation, obtaining three known flavones, an α-hydroxidihydrochalcone mixture, one labdane, one triterpene, and two norbisabolenes from the most active fractions. The compounds 4'-methoxy-α-hydroxydihydrochalcone ( 7A ), 3β,15-dihydroxylabdan-7-en-17-al ( 8 ), and 13-nor-11,12-dihydroxybisabol-2-enone ( 11 ) are novel. The most active compounds were the Salvigenin ( 5 ) and 1,2-dihydrosenedigital-2-one ( 10 ) with an IC50 of 13.5 and 3.1 μg/mL, respectively.

Only a small proportion of Brazilian adolescents practice sufficient physical activity (PA). However, it is not clear whether this proportion has been decreasing over time. This study aimed to examine the 10-year trends of sufficient PA in adolescents and to investigate differences by sex and age. Using a standard protocol, we compared two cross-sectional cohorts of adolescents aged 15 to 18 years, recruited in 2007 (n = 1040) and in 2017/18 (n = 978). Using the International Physical Activity Questionnaire-Short Form (IPAQ-SF), the adolescents reported moderate-to-vigorous PA (MVPA) performed in the last seven days. Sufficient PA was defined as engaging in at least 60 min/day of MVPA. In the subgroups, investigated by sex or age, there was an increase in the prevalence of sufficient PA. Overall, sufficient PA declined by 28.1% from 2007 to 2017/18. Boys in 2007 were more active than their 2017/18 peers, and this was equally observed in girls in 2007 compared to those in 2017/18. The findings show decreasing secular trends in sufficient PA in the investigated adolescents. Not only are public health authorities in Brazil witnessing an escalation of insufficient PA, but they are also losing ground with the most active adolescents.

Pathological biomarkers of dementia and Alzheimer's disease (AD) change decades before clinical symptoms. Common sensory and motor changes in aging adults may be early markers of neurodegeneration. We investigated if midlife sensory and motor functions in Beaver Dam Offspring Study (BOSS) participants (N = 1529) were associated with longitudinal changes in blood-based biomarkers of neurodegeneration (neurofilament light chain (NfL); total tau (TTau)) and AD (amyloid beta (Aβ)). Mixed-effects models with baseline sensory and motor function as determinants and 10-year biomarker change as outcome were used. Participants with hearing impairment and worse motor function (among women) showed faster increases in NfL level over time (0.8% per year; 0.3% per year, respectively). There were no significant associations with TTau or Aβ. We found consistent relationships between worse baseline hearing and motor function with a faster increase in neurodegeneration, specifically serum NfL level. Future studies with longer follow-up should determine if sensory and motor changes are more reflective of general neurodegeneration than AD-specific pathology and whether sensory and motor tests may be useful screening tools for neurodegeneration risk., (Copyright © 2022. Published by Elsevier Inc.)

Adolescence is a period characterized by large accumulation of bone mass. Body composition is an important determinant of bone mass. This study aimed to assess the relationship of bone mass with lean mass (LM) and fat mass (FM) in normal-weight and overweight adolescents with consideration of sex, sexual maturation and physical activity covariates. A total of 118 adolescents (60 girls and 58 boys) aged between 10 and 14 years participated in the study. Individuals were classified as normal weight or overweight according to body mass index. Bone mineral density (BMD), bone mineral content (BMC), LM, and FM were measured by dual-energy X-ray absorptiometry. In normal-weight adolescents, LM ( β  = 0.725, p < 0.001) and FM ( β  = 0.185, p = 0.019) were associated with lumbar spine BMC, whereas in overweight adolescents only LM ( β  = 0.736, p < 0.001) was associated with lumbar spine BMC. Furthermore, in the normal-weight group, FM and LM were associated with total body less head BMD (LM, β  = 0.792, p < 0.001; FM, β  = 0.257, p = 0.007) and lumbar spine BMD (LM, β  = 0.553, p < 0.001; FM, β  = 0.199, p < 0.035). In the overweight group, only LM was associated with total body less head BMD ( β  = 0.682, p < 0.001) and lumbar spine BMD ( β  = 0.528, p < 0.001). LM was the main predictor of bone mass in normal-weight and overweight adolescents. FM was associated with bone mass in normal-weight adolescents only. LM may be considered an important and useful marker in adolescents, when investigating bone health in this population. Activities that promote LM gain to reduce the risk of bone fractures and diseases in adulthood are recommended., Competing Interests: The authors declare there are no competing interests., (©2022 Bim et al.)

Objective: One in five adolescents has been estimated to perform sufficient physical activity (PA), thus potentially indicating that PA among adolescents has declined. This systematic review was aimed at reporting and summarizing the available knowledge regarding PA secular trends in adolescents over time., Methods: Seven databases were consulted (Web of Science, Scopus/Elsevier, Medline/PubMed, ScienceDirect, Lilacs, Physical Education Index, and SPORTDiscus), and 1809 studies were examined. According to the PRISMA guidelines, relevant research on secular PA trends in adolescents was screened for inclusion in a narrative synthesis. The risk of bias in the articles included was also assessed., Results: Forty-three studies with data collected between 1969 and 2018 met the inclusion criteria, and data from high-income countries predominated. PA was estimated predominantly by self-reporting, except in seven studies, and diverse contexts and domains were analyzed. Increased PA was reported in 16 studies (from 2.9% to 43.5%), decreased PA was reported in 15 studies (-2.5% to -69.5%), and no change was reported in 22 studies (-12.0% to 14.4%)., Conclusions: Although PA has increased in some countries, very little information is available in low- and middle-income countries. Efforts should support studies on PA trends in adolescents from economically disadvantaged countries., (© 2022 [The Author/The Authors].)

Chemical epigenetic manipulation of Botrytis cinerea strain B05.10 with the histone deacetylase inhibitor SAHA led to the isolation of a new cryptic metabolite, botrycinereic acid (22a). This compound was also overproduced by inactivating the stc2 gene, which encodes an unknown sesquiterpene cyclase. Its structure and absolute configuration were determined by extensive spectroscopic NMR and HRESIMS studies, and electronic circular dichroism calculations. Its biosynthesis was studied by feeding 2 H and 13 C isotopically labeled precursors to B. cinerea Δstc2 mutant. A detailed analysis of the labeling and coupling patterns into botrycinereic acid (22a) revealed that this compound derives from l-phenylalanine and l-leucine., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Understanding generational trends in dementia and cognitive decline is essential to quantify future healthcare needs and may help identify interventions and preventions. We aimed to determine whether individuals from more recent generations showed better neurocognitive function., Methods: This cross-sectional study combined data from 4439 participants (mean age 64 years (SD = 13); 57% were women) from the Epidemiology of Hearing Loss Study and Beaver Dam Offspring Study. We assessed participants' birth cohort (1901-1924, Greatest Generation; 1925-1945, Silent Generation; 1946-1964, Baby Boom Generation; 1965-1984, Generation X) and neurocognition (Trail-Making Tests A and B, Digit Symbol Substitution Test, Auditory Verbal Learning Test, Verbal Fluency Test). Multivariable linear regression models were utilized., Results: Adjusted for age, sex, education, and known risk factors for cognitive decline, more recent generations showed better processing speed, executive function, attention, and verbal fluency than the Greatest Generation. Largest benefits were found in the Baby Boom Generation. Compared with the Greatest Generation, individuals from the Baby Boom Generation performed better on Trail-Making Tests A (-0.21 ln(time in s); 95% confidence interval (CI) -0.29, -0.13) and B (-0.31 ln(time in s); 95% CI -0.40, -0.22), Digit Symbol Substitution Test (6.07 numbers correct; 95% CI 3.61, 8.52) and Verbal Fluency Test (8.75 numbers correct; 95% CI 5.07, 12.42 in women; 5.28 numbers correct; 95% CI 0.79, 9.78 in men), with effect sizes similar to effects of 11-15 years of less aging., Conclusions: This indicates that some benefits of younger generations might be related to yet unknown and potentially modifiable environmental, health-related or lifestyle factors and motivates research of such underlying factors to promote healthy cognitive aging., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: Psychological well-being (PWB) may be a potential modifiable risk factor of age-related diseases. We aimed to determine associations of PWB with sensorineural and cognitive function and neuronal health in middle-aged adults., Methods: This study included 2039 Beaver Dam Offspring Study participants. We assessed PWB, hearing, visual acuity, contrast sensitivity impairment, olfactory impairment, cognition, and retinal (macular ganglion cell inner-plexiform layer, mGCIPL) thickness. Age-sex-education-adjusted multivariable linear, logistic regression, and generalized estimating equation models were used and then further adjusted for health-related confounders., Results: Individuals with higher PWB had better hearing functions, visual acuity, and thicker mGCIPL and reduced odds for hearing, contrast sensitivity and olfactory impairment in age-sex-education-adjusted models. Effects on mGCIPL and visual and olfactory measures decreased with adjustment. Higher PWB was associated with better cognition, better combined sensorineural-cognitive function, and decreased cognitive impairment., Discussion: Psychological well-being was associated with sensorineural-cognitive health indicating a potential of PWB interventions for healthy aging.

Glioblastoma (GBM) is the most common and malignant primary brain tumor in adults. The prognosis of patients is very poor, with a median overall survival of ~ 15 months after diagnosis. Cadherin-3 (also known as P-cadherin), a cell-cell adhesion molecule encoded by the CDH3 gene, is deregulated in several cancer types, but its relevance in GBM is unknown. In this study, we investigated the functional roles, the associated molecular signatures, and the prognostic value of CDH3/P-cadherin in this highly malignant brain tumor. CDH3/P-cadherin mRNA and protein levels were evaluated in human glioma samples. Knockdown and overexpression models of P-cadherin in GBM were used to evaluate its functional role in vitro and in vivo. CDH3-associated gene signatures were identified by enrichment analyses and correlations. The impact of CDH3 in the survival of GBM patients was assessed in independent cohorts using both univariable and multivariable models. We found that P-cadherin protein is expressed in a subset of gliomas, with an increased percentage of positive samples in grade IV tumors. Concordantly, CDH3 mRNA levels in glioma samples from The Cancer Genome Atlas (TCGA) database are increased in high-grade gliomas. P-cadherin displays oncogenic functions in multiple knockdown and overexpression GBM cell models by affecting cell viability, cell cycle, cell invasion, migration, and neurosphere formation capacity. Genes that were positively correlated with CDH3 are enriched for oncogenic pathways commonly activated in GBM. In vivo, GBM cells expressing high levels of P-cadherin generate larger subcutaneous tumors and cause shorter survival of mice in an orthotopic intracranial model. Concomitantly, high CDH3 expression is predictive of shorter overall survival of GBM patients in independent cohorts. Together, our results show that CDH3/P-cadherin expression is associated with aggressiveness features of GBM and poor patient prognosis, suggesting that it may be a novel therapeutic target for this deadly brain tumor., (© 2021 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Aims: The evidence relating the pupil light reflex (PLR) and cognition have been inconsistent. In this cross-sectional study, we evaluated the association between the PLR and cognition in community-dwelling middle-aged and older individuals., Methods: Pupil reactivity was recorded in a subgroup of 403 participants (mean age 60.7 years, 57.3% females) in an epidemiologic study of aging. Ten pupil parameters were calculated to describe pupil constriction to light stimuli. A principal component analysis (PCA) score was used to calculate an overall performance over four cognitive testings. Linear regression was used to assess the association between pupil parameters and PCA scores, adjusting for age, sex, education, medications, health-related quality of life questionnaire, and systemic and ocular comorbidities., Results: The PCA scores decreased by 0.039 [95% CI (- 0.050, - 0.028)] per year increase in age and were lower in males than females by 0.76 [95% CI (- 0.96, - 0.55)] (p < 0.001). Pupil constriction amplitude in millimeters and the duration from stimulus onset to maximal constriction velocity were significantly associated with cognition after adjusting for (1) age and sex and (2) age, sex, and multiple covariates (p < 0.05)., Conclusions: In this study, we provided moderate evidence suggesting the association between PLR and neuropsychological cognitive measures. The findings suggest the potential of pupil reactivity to serve as a biomarker of brain aging and warrant further longitudinal study to assess if changes in the PLR can predict cognitive decline over time., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Systemic inflammatory response, as observed in sepsis and severe COVID-19, may lead to endothelial damage. Therefore, we aim to compare the extent of endothelial injury and its relationship to inflammation in both diseases. We included patients diagnosed with sepsis (SEPSIS group, n = 21), mild COVID-19 (MILD group, n = 31), and severe COVID-19 (SEVERE group, n = 24). Clinical and routine laboratory data were obtained, circulating cytokines (INF-γ, TNF-α, and IL-10) and endothelial injury markers (E-Selectin, Tissue Factor (TF) and von Willebrand factor (vWF)) were measured. Compared to the SEPSIS group, patients with severe COVID-19 present similar clinical and laboratory data, except for lower circulating IL-10 and E-Selectin levels. Compared to the MILD group, patients in the SEVERE group showed higher levels of TNF-α, IL-10, and TF. There was no clear relationship between cytokines and endothelial injury markers among the three studied groups; however, in SEVERE COVID-19 patients, there is a positive relationship between INF-γ with TF and a negative relationship between IL-10 and vWF. In conclusion, COVID-19 and septic patients have a similar pattern of cytokines and endothelial dysfunction markers. These findings highlight the importance of endothelium dysfunction in COVID-19 and suggest that endothelium should be better evaluated as a therapeutic target for the disease., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Stored blood samples from longitudinal cohort studies may be useful for studying biomarkers of preclinical Alzheimer's disease., Objective: This study aimed to determine the reliability of amyloid-β40 and amyloid-β42 (Aβ40, Aβ42), total tau (TTau), and neurofilament light (NfL) concentrations measured in blood samples stored long-term at -80°C., Methods: Aβ40, Aβ42, TTau, and NfL were measured in serum and plasma samples from two longitudinal cohort studies. Serum samples had been stored at -80°C for 5 (n = 24), 14 (n = 24), and 20 years (N = 78) and plasma samples had been stored for 16 years (N = 78). Biomarker concentrations were measured in duplicate using a single molecule array assay (Simoa; Quanterix, Billerica, MA). Replicate samples for each sample type and storage length were included., Results: The concentrations of Aβ40, Aβ42, TTau, and NfL were within expected ranges. Some serum TTau concentrations were below the limit of detection. The average intra-assay coefficients of variation (CV) for duplicate measures were 2-7% for all assays except for serum TTau, which were higher (CVs 13% and 17%). Mean differences in original replicate pair Aβ40, Aβ42, and NfL concentrations were slightly greater in samples stored for longer versus shorter time periods., Conclusion: Aβ40, Aβ42, TTau, and NfL can be measured in serum and plasma samples that have been stored up to 20 years at -80°C. Long-term storage may be associated with small increases in the variability of concentrations in samples stored 14 or more years.

Adolescence is an important period for the acquisition of bone mass, which can be enhanced by several factors. This study aimed examine the relationships of handgrip strength, free-fat mass, and fat mass with bone mineral density in adolescents. 118 adolescents (60 girls), aged 10 to 14 years, participated in the study. Information on sex, age, handgrip strength, free-fat mass, fat mass and bone mineral density were collected. Multiple linear regression analyses were conducted to examine possible relationships between bone mineral density and handgrip strength, free-fat mass and fat mass. There was a relation between handgrip strength and free-fat mass with bone mineral density in both sexes. Fat mass was correlated with bone mineral density only in girls (r= 0.314, p< 0.014). The final models, adjusted for sexual maturation, included free-fat mass (girls - β= 0.419, p< 0.001; boys - β= 0.455; p< 0.001) and handgrip strength (girls - β= 0.358, p< 0.05; boys - β= 0.325; p< 0.05) and these variables together explained 51.8% and 62.9% of the variation of bone mineral density, in girls and boys, respectively. Handgrip strength and free-fat mass were positively associated with bone mineral density. A sex-specific difference indicated that higher levels of free-fat mass are of paramount importance for both sexes., (Copyright © 2021 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

Clovane and isocaryolane derivatives have been proven to show several levels of activity against the phytopathogenic fungus Botrytis cinerea . Both classes of sesquiterpenes are reminiscent of biosynthetic intermediates of botrydial, a virulence factor of B. cinerea . Further development of both classes of antifungal agent requires exploration of the structure-activity relationships for the antifungal effects on B. cinerea and phytotoxic effects on a model crop. In this paper, we report on the preparation of a series of alkoxy-clovane and -isocaryolane derivatives, some of them described here for the first time ( 2b , 2d , 2f - 2h , and 4c - 4e ); the evaluation of their antifungal properties against B. cinerea , and their phytotoxic activites on the germination of seeds and the growth of radicles and shoots of Lactuca sativa (lettuce). Both classes of compound show a correlation of antifungal activity with the nature of side chains, with the best activity against B. cinerea for 2d , 2h , 4c and 4d . In general terms, while 2-alkoxyclovan-9-ols ( 2a - 2e ) exert a general phytotoxic effect, this is not the case for 2-arylalkoxyclovan-9-ols ( 2f - 2i ) and 8-alkoxyisocaryolan-9-ols ( 4a - 4d ), where stimulating effects would make them suitable candidates for application to plants.

Amyotrophic lateral sclerosis is a progressive and devastating neurodegenerative disease. Despite decades of clinical trials, effective disease-modifying drugs remain scarce. To understand the challenges of trial design and delivery, we performed a systematic review of Phase II, Phase II/III and Phase III amyotrophic lateral sclerosis clinical drug trials on trial registries and PubMed between 2008 and 2019. We identified 125 trials, investigating 76 drugs and recruiting more than 15 000 people with amyotrophic lateral sclerosis. About 90% of trials used traditional fixed designs. The limitations in understanding of disease biology, outcome measures, resources and barriers to trial participation in a rapidly progressive, disabling and heterogenous disease hindered timely and definitive evaluation of drugs in two-arm trials. Innovative trial designs, especially adaptive platform trials may offer significant efficiency gains to this end. We propose a flexible and scalable multi-arm, multi-stage trial platform where opportunities to participate in a clinical trial can become the default for people with amyotrophic lateral sclerosis., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Objective: To verify the prevalence of abdominal obesity with the waist-to-height ratio (WHtR) and associated factors in adolescents from a city in Southern Brazil., Methods: A total of 960 adolescents (494 boys) aged 15-18 years old participated in this study. The dependent variable was WHtR; independent variables were self-reported age, economic level, sexual maturation, physical activity level, screen time, and body fat. Data were analyzed using descriptive statistics and logistic regression., Results: It was observed that 36.7% of the adolescents presented high WHtR (50.2% in girls and 23.9% in boys). Regardless of sex, adolescents with high body fat were more likely of having high WHtR (boys: Odds Ratio [OR] 29.79; 95% confidence interval [95%CI] 16.87-52.62; girls: OR 19.43; 95%CI 10.51-35.94). In girls, high WHtR was associated with age (OR 1.83; 95%CI 1.17-2.87), and in boys, with economic level (OR 2.34; 95%CI 1.01-5.45)., Conclusions: One in each three adolescents has abdominal obesity. Among adolescents with high body fat, girls aged 15-16 and boys with high-income are the groups most exposed to abdominal obesity.

Background: The handgrip strength (HGS) is an indicator of muscle strength associated with several health outcomes in adolescents and adults. This cross-sectional study aimed to identify HGS levels and associated modifiable and non-modifiable risk factors in adolescents., Methods: The study included 971 adolescents (496 boys) aged 15-18 years. The HGS was measured by a dynamometer, and the maximum value of right and left hands were summed for a total score. Age, economic status, balanced diet, physical activity, and sedentary behavior were assessed by questionnaires, while body mass index was determined by measuring body weight and height. Multiple linear regression was carried out to examine the association., Results: 65.4% of the adolescents presented low levels of HGS (boys: 73.8%; girls: 56.6%). Low levels of HGS were associated with weight status and height in both sexes. In boys, low levels of HGS were associated with age, balanced diet, physical activity, and sedentary behavior., Conclusion: About six out of ten adolescentes presented low levels of HGS. The main predictors of low levels of HGS in boys were age, physical activity, sedentary behavior, and balanced diet, and weight status and height in both sexes., Competing Interests: Declaration of competing interest Author MAB declares that he has no conflict of interest. Author AAP declares that he has no conflict of interest. Author KSS declares that she has no conflict of interest. Author GSC declares that she has no conflict of interest. Author AP declares that she has no conflict of interest., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

In order to form functional filaments, human septins must assemble into hetero-oligomeric rod-like particles which polymerize end-to-end. The rules governing the assembly of these particles and the subsequent filaments are incompletely understood. Although crystallographic approaches have been successful in studying the separate components of the system, there has been difficulty in obtaining high resolution structures of the full particle. Here we report a first cryo-EM structure for a hexameric rod composed of human septins 2, 6 and 7 with a global resolution of ~3.6 Å and a local resolution of between ~3.0 Å and ~5.0 Å. By fitting the previously determined high-resolution crystal structures of the component subunits into the cryo-EM map, we are able to provide an essentially complete model for the particle. This exposes SEPT2 NC-interfaces at the termini of the hexamer and leaves internal cavities between the SEPT6-SEPT7 pairs. The floor of the cavity is formed by the two α 0 helices including their polybasic regions. These are locked into place between the two subunits by interactions made with the α 5 and α 6 helices of the neighbouring monomer together with its polyacidic region. The cavity may serve to provide space allowing the subunits to move with respect to one another. The elongated particle shows a tendency to bend at its centre where two copies of SEPT7 form a homodimeric G-interface. Such bending is almost certainly related to the ability of septin filaments to recognize and even induce membrane curvature., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)