Cell-type-specific effects of autism-associated chromosome 15q11.2-13.1 duplications in human brain.

Recurrent copy number variation represents one of the most well-established genetic drivers in neurodevelopmental disorders, including autism spectrum disorder (ASD). Duplication of 15q11.2-13.1 (dup15q) is a well-described neurodevelopmental syndrome that increases the risk of ASD by over 40-fold. However, the effects of this duplication on gene expression and chromatin accessibility in specific cell types in the human brain remain unknown. To identify the cell-type-specific transcriptional and epigenetic effects of dup15q in the human frontal cortex we conducted single-nucleus RNA-sequencing and multi-omic sequencing on dup15q cases (n=6) as well as non-dup15q ASD (n=7) and neurotypical controls (n=7). Cell-type-specific differential expression analysis identified significantly regulated genes, critical biological pathways, and differentially accessible genomic regions. Although there was overall increased gene expression across the duplicated genomic region, cellular identity represented an important factor mediating gene expression changes. Neuronal subtypes, showed greater upregulation of gene expression across a critical region within the duplication as compared to other cell types. Genes within the duplicated region that had high baseline expression in control individuals showed only modest changes in dup15q, regardless of cell type. Of note, dup15q and ASD had largely distinct signatures of chromatin accessibility, but shared the majority of transcriptional regulatory motifs, suggesting convergent biological pathways. However, the transcriptional binding factor motifs implicated in each condition implicated distinct biological mechanisms; neuronal JUN/FOS networks in ASD vs. an inflammatory transcriptional network in dup15q microglia. This work provides a cell-type-specific analysis of how dup15q changes gene expression and chromatin accessibility in the human brain and finds evidence of marked cell-type-specific effects of this genetic driver. These findings have implications for guiding therapeutic development in dup15q syndrome, as well as understanding the functional effects CNVs more broadly in neurodevelopmental disorders.

Effects of traditional concurrent training and multicomponent training composed by strength training and dance classes on functional and cognitive capacity of older adults: a study protocol / Efeitos do treinamento combinado tradicional e do treinamento multicomponente composto por treinamento de força e aulas de dança na capacidade funcional e cognitiva de idosos: protocolo de estudo

The combination of strength and aerobic training (concurrent training - TG) has been a widely used intervention for improving health outcomes. Also, dance has been well described as a great aerobic activity and can be an interesting option to compose an alternative multicomponent training pro-gram. Therefore, the aim of the present protocol study is to describe the methods that will be used in a randomized controlled trial (RCT) design to identify and compare the impacts of traditional TG composed by strength and aerobic training and a multicomponent training consisting of strength training combined with dance classes (DG) on functional and cognitive capacity and quality of life of older people. The sample of RCT will consist of men and women aged between 60 and 75 years. Both interventions will occur twice a week for 12 weeks with progressive intensity and volume. Functional capacity will be assessed by gait, balance, sitting and standing and climbing tests. Strength will be assessed through one repetition maximum test (1RM) in knee extension exercise, and handgrip using a hand dynamometer. Muscle thickness will be assessed using quadriceps ultrasound. Muscle power will be assessed in the knee extension exercise at 30 and 70% of 1RM using an encoder. Aerobic capacity will be assessed using the 6-minute walk test. Quality of life and cognitive performance will be assessed by questionnaires. Comparisons between groups over time will be carried out using Generalized Estimating Equations with a significance level of p<0.01. This protocol follows the rec-ommendations of SPIRIT-2013.

A combinação de treinamento de força e aeróbico (treinamento combinado - TC) tem sido uma interven-ção amplamente utilizada para melhorar desfechos de saúde. Além disso, a dança tem sido bem descrita na literatura como uma ótima atividade aeróbica e pode ser uma opção interessante para compor um programa alternativo de treinamento multicomponente. Portanto, o objetivo do presente protocolo de estudo é descrever os métodos que serão utilizados em um ensaio clínico randomizado (ECR) que visa identificar e comparar os impactos do TC tradicional composto por treinamento de força e aeróbico e de um treinamento multi-componente composto por treinamento de força combinado com aulas de dança sobre capacidade funcional, cognitiva e qualidade de vida de idosos. A amostra do ECR será composta por homens e mulheres com idade entre 60 e 75 anos. Ambas as intervenções ocorrerão duas vezes por semana durante 12 semanas com intensidade e volume progressivos. A capacidade funcional será avaliada por meio de testes de marcha, equilíbrio, sentar e levantar e subir escadas. A força será avaliada por meio do teste de uma repetição máxima (1RM) no exercício de extensão de joelhos e por meio do teste de preensão palmar com o dinamômetro manual. A espessura muscular será avaliada por meio de ultrassonografia do quadríceps. A potência muscular será ava-liada no exercício de extensão de joelhos a 30 e 70% de 1RM por meio de um transdutor linear de posição. A capacidade aeróbica será avaliada por meio do teste de caminhada de 6 minutos. A qualidade de vida e o desempenho cognitivo serão avaliados por meio de questionários. As comparações entre os grupos ao longo do tempo serão realizadas por meio de Equações de Estimativas Generalizadas com nível de significância p<0,01. Este protocolo segue as recomendações do SPIRIT-2013.

Effects of social distancing provoked by COVID-19 pandemic in the functional capacity and cognitive function in nonagenarians and centenarians.

INTRODUCTION: Due to the rapid advance of coronavírus SARS-CoV-2 (COVID-19) pandemic in 2020, social distancing was the main way to reduce the transmission of the virus. Although this measure was efficient and necessary, the social distancing had severe consequences for physical function, mainly in older individuals. Thus, the aim of this study was to investigate the effects of social distancing in the functional and cognitive capacity of community-dwelling oldest-old adults. METHODS: The present study is part of a larger prospective cohort study. Fifteen participants aged 90 years old or older were assessed in the 8-foot-timed-up-and-go test (8-footTUG), sit-to-stand-up test (STS), handgrip strength test (HGS), Mini Mental State Examination (MMSE), Katz Index and Lawton Scale before and after one year of social distancing. RESULTS: A significant worsening in the 8-footTUG and MMSE score was observed, while there were no significant changes in the other variables. When analyzing the decreases in relation to previous functional capacity, it was observed that individuals categorized as dependent by STS cut-off points had the worst decreases in functional capacity. CONCLUSION: The social distancing provoked by COVID-19 pandemic negatively affected the 8-footTUG and cognition. Moreover, individuals dependents showed greater decline in their functional capacity.

Acute effects of different proprioceptive neuromuscular facilitation stabilization techniques on the balance of elderly women.

AIM: To compare the acute effects of rhythmic stabilization (RS) and stabilizer reversal (SR) techniques of PNF on the balance of sedentary elderly women. METHODS: Women aged (≥70) were allocated into three groups: RS, SR and control (CR). The experimental groups (RS and SR) performed balance exercises with the addition of rhythmic stabilization techniques (RS group) or with stabilizers reversal (SR group) for 15 min. The CR group performed the exercises without adding the PNF stabilization techniques. Participants performed the Time Up and Go (TUG) test, the Functional Reach Test (FRT) and static and dynamic stabilometry pre and post intervention. Kruskal-Wallis and Mann-Whitney tests were used for comparison between groups and post hoc analysis, respectively, with p ≤ 0.05. For the effect size measurements, the r for Wilcoxon and Mann-Whitney signal were used. RESULTS: For functional tests intra-group analysis, a reduction in TUG time and an increase in FRT range (p ≤ 0.05) were observed in RS e SR groups. Stabilometry analysis showed a significant difference only for the RS group, with reduced average velocity of the centre of pressure (COP), and an increased in the left foot pressure. CONCLUSIONS: A single RS or SR session reduced the TUG time and the range distance in the FRT in elderly women. A single session of the RS technique was also able to reduce the mean velocity of the COP and the maximum pressure on the left foot. IMPACT: This study shows an easy-to-apply methods without additional materials that can help prevent falls in the elderly.

Glial dysregulation in the human brain in fragile X-associated tremor/ataxia syndrome.

Short trinucleotide expansions at the FMR1 locus are associated with the late-onset condition fragile X-associated tremor/ataxia syndrome (FXTAS), which shows very different clinical and pathological features from fragile X syndrome (associated with longer expansions), with no clear molecular explanation for these marked differences. One prevailing theory posits that the shorter, premutation expansion uniquely causes extreme neurotoxic increases in FMR1 mRNA (i.e., four to eightfold increases), but evidence to support this hypothesis is largely derived from analysis of peripheral blood. We applied single-nucleus RNA sequencing to postmortem frontal cortex and cerebellum from 7 individuals with premutation and matched controls (n = 6) to assess cell type-specific molecular neuropathology. We found only modest upregulation (~1.3-fold) of FMR1 in some glial populations associated with premutation expansions. In premutation cases, we also identified decreased astrocyte proportions in the cortex. Differential expression and gene ontology analysis demonstrated altered neuroregulatory roles of glia. Using network analyses, we identified cell type-specific and region-specific patterns of FMR1 protein target gene dysregulation unique to premutation cases, with notable network dysregulation in the cortical oligodendrocyte lineage. We used pseudotime trajectory analysis to determine how oligodendrocyte development was altered and identified differences in early gene expression in oligodendrocyte trajectories in premutation cases specifically, implicating early cortical glial developmental perturbations. These findings challenge dogma regarding extremely elevated FMR1 increases in FXTAS and implicate glial dysregulation as a critical facet of premutation pathophysiology, representing potential unique therapeutic targets directly derived from the human condition.

COVID-19 in older adult residents in nursing homes: factors associated with mortality and impact on functional capacity.

Objective: To verify if the functional capacity prior to COVID-19 infection was different between Survivor and Non-survivor older adults. Also, to verify the effect of the isolation period after COVID-19 infection on the functional capacity of the Survivors residing in nursing homes. Materials and methods: Older adults residing in nursing homes were evaluated 30 days before the COVID-19 outbreak at the site for (i) general health characteristics (obtained from medical records); (ii) gait speed, handgrip strength and 30-s sit-to-stand; (iii) sarcopenia and (iv) estimated muscle mass. Comparisons were made between Survivors and Non-survivors of COVID-19. After the isolation, the Survivors performed the assessments again. Results: Twenty-one (81 ± 9.3 years) participants tested positive for COVID-19 and participated in the study, 12 survivors. No difference was observed between Survivors and Non-survivors in any of the outcomes evaluated. However, a moderate effect size was observed for handgrip strength, with lower values for the Non-survivors group (- 16%; d = 0.53). The isolation period reduced the number of sit-to-stand repetitions with moderate effect size in the Survivors (p = 0.046, gav = 0.66). Conclusion: Although the null hypothesis analysis did not find significant differences between the groups, the effect size suggests that older adults residing in nursing homes who died from COVID-19 had lower handgrip strength. In the survivors, the isolation period after COVID-19 infection only negatively impacted the sit-to-stand performance.

Cut-off score of the modified Ashworth scale corresponding to walking ability and functional mobility in individuals with chronic stroke.

PURPOSE: To determine the optimal cut-off score for the Modified Ashworth Scale (MAS) corresponding to unfavorable outcomes for mobility and walking ability. METHODS: The level of plantar flexor muscle spasticity and the 10-meter walking test (10mWT), timed up and go (TUG), and five time sit-to-stand (FTSTS) outcomes were evaluated in individuals after stroke. The correlation between MAS and the tests was investigated, and the optimal cut-off score, sensitivity, and specificity were evaluated through receiver operating characteristic (ROC) curve. RESULTS: Twenty-one participants with chronic stroke and plantar flexors spasticity (11 men; 10 women; mean age = 57.6 ± 12.5 years) participated in the study. Significant correlations between MAS and 10mWT (r= -0.45; p < 0.05), MAS and TUG (r = 0.48; p < 0.05) were found. The optimal cut-off scores were MAS > 2 for unfavorable 10mWT (sensitivity = 100%; specificity = 54.5%; ROC = 0.782) and MAS ≤ 2 for favorable TUG outcomes (sensitivity = 55.5%; specificity = 91.6%; ROC = 0.782). CONCLUSIONS: This study revealed that moderate level of plantar flexors spasticity results in the highest sensitivity to predict poor gait speed performance and the highest specificity to predict good mobility performance in individuals after stroke. These findings will help clinicians in their evidence-based decision making on the role of spasticity for mobility and walking ability.Implications for rehabilitationModerate level of spasticity (MAS <2) is the optimal cut-off score for 10mWT and TUG tests.Reducing the level of spasticity of plantar flexors below this cut-off point might be associated with an increased walking speed in this population.MAS <2 might not limit walking and mobility in individuals after stroke.Calf muscles spasticity might not compromise five time sit-to-stand (FTSTS) performances and might be related to a smaller influence on the sit to stand task.

Identification of D-Limonene Metabolites by LC-HRMS: An Exploratory Metabolic Switching Approach in a Mouse Model of Diet-Induced Obesity.

Metabolic switching has been raised as an important phenomenon to be studied in relation to xenobiotic metabolites, since the dose of the exposure determines the formation of metabolites and their bioactivity. Limonene is a monoterpene mostly found in citrus fruits with health activity, and its phase II metabolites and activity are still not clear. The aim of this work was to evaluate the effects of D-limonene in the development of diet-induced obesity in mice and to investigate metabolites that could be generated in a study assessing different doses of supplementation. Animals were induced to obesity and supplemented with 0.1% or 0.8% D-limonene added to the feed. Limonene phase I and II metabolites were identified in liver and urine by LC-ESI-qToF-MS/MS. To the best of our knowledge, in this study three new phase I metabolites and ten different phase II metabolites were first attributed to D-limonene. Supplementation with 0.1% D-limonene was associated with lower weight gain and a trend to lower accumulation of adipose tissue deposits. The metabolites limonene-8,9-diol, perillic acid and perillic acid-8,9-diol should be explored in future research as anti-obesogenic agents as they were the metabolites most abundant in the urine of mice that received 0.1% D-limonene in their feed.

Interindividual variability of adaptations following either traditional strength or power training combined to endurance training in older men: A secondary analysis of a randomized clinical trial.

This study aimed to investigate the interindividual responses following two different concurrent training (CT) regimens in neuromuscular, cardiorespiratory and functional outcomes of older men. Thirty-five older men (65.8 ± 3.9 years) were randomly allocated into one of two CT groups: power training (PT) + high-intensity interval training (HIIT) (n = 17); or traditional strength training (TST) + HIIT (n = 18). Maximal dynamic strength (one-repetition maximum, 1RM), rate of force development at 100 milliseconds (RDF100), countermovement jump power (CMJ), quadriceps femoris muscle thickness (QF MT), functional tests (sit-to-stand, timed-up-and-go, and stair climbing), and peak oxygen consumption (VO2peak) were assessed pre-, post-8 and post-16 weeks of training. The Chi-squared test was used for assessing differences in the prevalence of responders (Rs), non-responders (NRs), and adverse responders (ARs). Similar prevalence of individual responses (Rs, NRs and ARs) between groups were observed after intervention in almost all outcomes: 1RM; power at CMJ; QF MT, and functional tests (P > 0.05). However, a significant difference in the distribution of Rs, NRs and ARs between groups was observed in the RFD100 after 16 weeks (p = 0.003), with PT + HIIT group presenting high prevalence of Rs than TST + HIIT (100 % vs. 50 %). The inclusion of explosive-type of contractions in a concurrent training regime induces greater responsiveness in the RFD100 in older men, while no differences compared to traditional strength training are observed in maximal strength, muscle size, VO2peak, and functional performance.

Analysis of somatic mutations in 131 human brains reveals aging-associated hypermutability.

We analyzed 131 human brains (44 neurotypical, 19 with Tourette syndrome, 9 with schizophrenia, and 59 with autism) for somatic mutations after whole genome sequencing to a depth of more than 200×. Typically, brains had 20 to 60 detectable single-nucleotide mutations, but ~6% of brains harbored hundreds of somatic mutations. Hypermutability was associated with age and damaging mutations in genes implicated in cancers and, in some brains, reflected in vivo clonal expansions. Somatic duplications, likely arising during development, were found in ~5% of normal and diseased brains, reflecting background mutagenesis. Brains with autism were associated with mutations creating putative transcription factor binding motifs in enhancer-like regions in the developing brain. The top-ranked affected motifs corresponded to MEIS (myeloid ectopic viral integration site) transcription factors, suggesting a potential link between their involvement in gene regulation and autism.

Low handgrip strength is associated with higher cancer prevalence in frail nonagenarians and centenarians.

It is known that muscle strength is associated with adverse health outcomes associated with cancer-related symptoms. The purpose of this study was to investigate the association between handgrip strength and cancer in frail oldest old. In this prospective cohort study, 81 nonagenarians and centenarians were included [mean age (SD): 94.2 (3.8) years]. Data related to prevalent cancer were self-reported and global strength was assessed by handgrip strength. Logistic regressions were calculated for age- and sex-specific tertiles of relative grip strength, with participants in the highest tertile considered as the reference group. The χ2 test was used to assess differences in tertile categories of normalized handgrip strength between groups (i.e., cancer diagnoses or not). Significant differences were obtained for normalized handgrip strength tertile categories between groups: older adults without a diagnosis of cancer had higher handgrip strength values than peers with cancer (p = 0.039). Of those with cancer, 50% were classified in tertile 1, 36% in tertile 2 and 14% in tertile 3. Considering those without a diagnosis of cancer, 27% were in tertile 1, 32% in tertile 2 and 41% in tertile 3. Low handgrip strength is associated with higher cancer prevalence in frail nonagenarians and centenarians.

Dance as an Intervention to Reduce Fall Risk in Older Adults: A Systematic Review With a Meta-Analysis.

The purpose of this study was to summarize the evidence from randomized clinical trials on the effects of dance on fall risk in older adults through a systematic review with meta-analysis. Fall risk was assessed through timed up and go, Berg Balance Scale, or one-leg stand tests. Data are presented as mean differences for timed up and go test and standardized mean differences for Berg Balance Scale and one-leg stand tests between treatments with 95% confidence intervals, and calculations were performed using random effects models. Significance was accepted when p < .05. A significant difference was found between dance interventions and the control groups in the general analysis of fall risk assessed by timed up and go (mean differences: -1.446 s; 95% confidence interval [-1.586, -1.306]; p < .001) and Berg Balance Scale and one-leg stand tests (standardized mean differences: 0.737; 95% confidence interval [0.508, 0.966]; p < .001) in favor of the intervention group. Different dance interventions decreased the fall risk in older practitioners.

Caregiving of children with Down syndrome: impact on quality of life, stress, mental and oral health.

AIM: Parental caregivers of children with Down Syndrome (DS) have a greater burden of daily activities that may affect their health. The aim of this exploratory study was to evaluate the impact of caregiving of children with Down syndrome on parenting quality of life, stress, mental and oral health. METHODS: Fifty-four parental caregivers of children with DS and 51 parents of children without physical or mental disabilities participated of this study. All participants were clinically examined to evaluate the presence of dental caries, gingival conditions and answered a sociodemographic questionnaire. Depression, anxiety, quality of life and coping strategies were assessed using specific instruments. Hair cortisol level was assessed as biological marker of chronic stress. RESULTS: Psychological and quality of life parameters were similar between the groups of caregivers (p > .05). Caregivers of children with DS were older (48.6 vs. 41.5, p < .001), had longer caregiving period (> 10 vs < 10 years, p = .003), presented higher gingival bleeding index (6.1 vs. 4.7, p = .014) and higher cortisol levels (55.9 vs. 38.4, p = .07) as compared with parents of children without disabilities. Sociodemographic data has no influence on cortisol levels (p > .05). CONCLUSIONS: These findings suggest that the caregiving of children with DS has an impact on parenting oral health and stress.

The effects of acute exercise on memory of cognitively healthy seniors: A systematic review.

OBJECTIVE: To systematically review the acute effects of physical exercise on memory in healthy elderly people. METHODS: The present study consists of a systematic review based on the criteria of the Preferred Reporting Items for Systematic Reviews and Meta - Analyzes (PRISMA). Searches were carried out in the health databases: PubMed (Medline); ScienceDirect (Elsevier); SciELO, Cochrane and LILACS, including articles published until April 2021. The included studies should be randomized clinical trials in healthy elderly populations, have acute physical exercise as an intervention compared to another type of exercise or to a control session, and assess memory as an outcome. RESULTS: A total of 3711 records were found in the databases. After reading titles and abstracts, 27 full texts of studies were selected. A total of 10 records met the inclusion criteria and were considered eligible for qualitative analysis. The total sample consisted of 465 healthy individuals, of both sexes, aged between 60 and 95 years. The aerobic and resistance exercises performed at low (7-11 Borg scale, 54% FCM or 40-54% 1RM) and moderate intensities (12-15 Borg scale, 50-70% FCM and 55-75% 1RM) lead to memory improvement in cognitively healthy elderly people. CONCLUSIONS: The paucity of studies with this population, using higher exercise intensities, as well as a reduced variety of memory tests, were limiting factors. Maintaining a training routine is important, in order to preserve physical and mental health. More studies addressing the effects of exercise protocols in healthy individuals are warranted.

Whole-genome analysis reveals the contribution of non-coding de novo transposon insertions to autism spectrum disorder.

BACKGROUND: Retrotransposons have been implicated as causes of Mendelian disease, but their role in autism spectrum disorder (ASD) has not been systematically defined, because they are only called with adequate sensitivity from whole genome sequencing (WGS) data and a large enough cohort for this analysis has only recently become available. RESULTS: We analyzed WGS data from a cohort of 2288 ASD families from the Simons Simplex Collection by establishing a scalable computational pipeline for retrotransposon insertion detection. We report 86,154 polymorphic retrotransposon insertions-including > 60% not previously reported-and 158 de novo retrotransposition events. The overall burden of de novo events was similar between ASD individuals and unaffected siblings, with 1 de novo insertion per 29, 117, and 206 births for Alu, L1, and SVA respectively, and 1 de novo insertion per 21 births total. However, ASD cases showed more de novo L1 insertions than expected in ASD genes. Additionally, we observed exonic insertions in loss-of-function intolerant genes, including a likely pathogenic exonic insertion in CSDE1, only in ASD individuals. CONCLUSIONS: These findings suggest a modest, but important, impact of intronic and exonic retrotransposon insertions in ASD, show the importance of WGS for their analysis, and highlight the utility of specific bioinformatic tools for high-throughput detection of retrotransposon insertions.

Depression Impairs Level of Functioning in Chronic Kidney Disease Inpatients: A Case-Control Study.

Objectives To evaluate the difference in demographics and clinical correlates during hospitalization for chronic kidney disease (CKD) between patients with depression and those without depression, and its impact on the severity of illness and in-hospital mortality. Methods We conducted a case-control study and included 2,296 adult inpatients (age ≥18 years) with a primary discharge diagnosis of CKD using the nationwide inpatient sample (NIS). We used propensity score matching to extract the cases i.e., CKD inpatients with depression (N = 1,264) and the controls i.e. CKD inpatients without depression (N = 1,032). The matching was done based on demographic characteristics of age at admission, sex, race, and median household income. Our outcomes of interest are the severity of illness and all-cause in-hospital mortality. All patient refined drg (APR-DRG) are allocated using health information systems software by the NIS and the severity of illness within each base APR-DRG was classified into minor, moderate, or major loss of body functions. Binomial logistic regression analysis was conducted to find the odds ratio (OR) of association for major loss of function in CKD inpatients with depression, and this model was adjusted for potential confounders of congestive heart failure (CHF), coronary artery disease (CAD), diabetes, hypertension, obesity, and tobacco abuse, and utilization of hemodialysis. Results A higher proportion of CKD inpatients with depression had a statistically significant higher prevalence of major loss of function (49.8% vs. 40.3% in non-depressed). There was a statistically significant difference with higher utilization of hemodialysis in CKD inpatients with depression (76.2% vs. 70.7% in non-depressed). The all-cause in-hospital mortality rate was lower in CKD inpatients with depression (2.1% vs. 3.5% in non-depressed). After controlling the logistic regression model for potential comorbidities and utilization of hemodialysis, depression was associated with increased odds (OR 1.46; 95% CI 1.227 - 1.734) for major loss of function versus in non-depressed CKD inpatients Conclusion Comorbid depression increases the likelihood of major loss of functioning in CKD inpatients by 46%. Treating depression can allow patients to better cope emotionally and physically with CKD and other comorbidities and significantly improve the patient's quality of life (QoL) and health outcome.

Rating of Perceived Exertion as a Method to Determine Training Loads in Strength Training in Elderly Women: A Randomized Controlled Study.

Objective: The aim of this study was to compare the effects of training using loads from a repetition maximum value (%1RM) and rating of perceived exertion (RPE) in elderly women. Methods: Twenty-five elderly women (60-75 years old) were randomly assigned to a group that trained using loads determined by 1RM test (G%; n = 12) or to a group that trained using loads determined by RPE (GPE; n = 13). Elderly women trained for 12 weeks using five exercises performed with 2-3 sets of 8-15 repetitions. Loads progressed from 45% to 75% of 1RM (G%) and from 13 to 18 from Rating Perceived Exertion of Borg Scale (GPE). The outcome measures, 1RM and maximum repetitions (RMs with 70% 1RM), were assessed before, between and after training programs. Results: Increased 1RM value and RMs were observed in both groups (20-42%, p < 0.001 and 56-76%, p < 0.001, respectively, for %G; and 17-56%, p < 0.001 and 47-106%, p < 0.001, respectively, for GPE), without differences between them. Conclusions: Prescribing loads using the RPE and 1RM might be similarly effective for training elderly women in order to promote strength gains. As a practical application, RPE could be an additional method to determine training loads. In spite of the promising results of the present study, it is not possible to state that the use of RPE is effective in monitoring loads during sub maximal strength training in elderly and more research must be carried out to confirm it.

Psychiatric Comorbidities in Pediatric Inpatients With Human Immunodeficiency Virus Infection and Impact on Hospital Course: Inputs From a Case-Control Inpatient Study.

Objectives In this study, we aimed to delineate psychiatric comorbidities in pediatric inpatients with versus without human immunodeficiency virus (HIV) infection and to measure its impact on the length of stay (LOS) and cost of treatment during hospitalization. Methodology We conducted a case-control study using the Nationwide Inpatient Sample and included 4,920 pediatric inpatients between the ages of six and 18 years who were sub-grouped by a comorbid diagnosis of HIV (N = 2,595) and non-HIV (N = 2,325) and matched for demographics (age, sex, and race) by propensity case-control matching. Logistic regression analyses were used to evaluate the adjusted odds ratio (aOR) of association for psychiatric comorbidities (depression, anxiety, post-traumatic stress disorder, psychosis, and drug abuse) in the HIV-positive compared with the HIV-negative (as reference category) pediatric inpatients. We measured the differences in the LOS and cost using the independent sample t-test. Results We found that the most prevalent psychiatric comorbidities in the HIV-positive group were anxiety (6.9%), drug abuse (6.6%), psychosis (6.4%), and depression (6.2%). The HIV-positive group had a significantly higher likelihood of comorbid psychosis (aOR: 1.82; 95% confidence interval [CI]: 1.38-2.40) and depression (aOR: 1.79; 95% CI: 1.36-2.36). The mean LOS per hospitalization episode was longer for the HIV-positive group (11.1 days vs. 6.0 days; P < 0.001) compared to the HIV-negative pediatric inpatients. Conclusions We found an increased risk of depression by 79% and psychosis by 82% in the HIV-positive pediatric population. These inpatients also had an extended hospitalization stay (by five days), adding to the healthcare economic burden.

De novo variants in TCF7L2 are associated with a syndromic neurodevelopmental disorder.

TCF7L2 encodes transcription factor 7-like 2 (OMIM 602228), a key mediator of the evolutionary conserved canonical Wnt signaling pathway. Although several large-scale sequencing studies have implicated TCF7L2 in intellectual disability and autism, both the genetic mechanism and clinical phenotype have remained incompletely characterized. We present here a comprehensive genetic and phenotypic description of 11 individuals who have been identified to carry de novo variants in TCF7L2, both truncating and missense. Missense variation is clustered in or near a high mobility group box domain, involving this region in these variants' pathogenicity. All affected individuals present with developmental delays in childhood, but most ultimately achieved normal intelligence or had only mild intellectual disability. Myopia was present in approximately half of the individuals, and some individuals also possessed dysmorphic craniofacial features, orthopedic abnormalities, or neuropsychiatric comorbidities including autism and attention-deficit/hyperactivity disorder (ADHD). We thus present an initial clinical and genotypic spectrum associated with variation in TCF7L2, which will be important in informing both medical management and future research.

Constraint Induced Movement Therapy Increases Functionality and Quality of Life after Stroke.

This blind randomized clinical trial evaluated the effect of CIMT on the functionality and quality of life (QOL) of chronic hemiparetics. Thirty volunteers were divided into two groups: Control (CG) and CIMT (CIMTG); evaluated before and after 12 and 24 intervention sessions. The scales used were: adapted Fugl-Meyer Motor Assessment (FMA), Modified Ashworth, Stroke Specific Quality Of Life (SS-QOL) and the Functional Reach Test (FRT). The scores for all FMA variables in the CIMTG increased until the 24th session, differing from the pre-treatment. In the CG, the scores increased for pain, coordination/ speed and sensitivity. In the FRT there was an increase in the scores in both groups; after the 12th and 24th sessions, the result of the CIMTG was superior to the CG. For the SS-QOL in the CIMTG, the general score and most of the variables increased, as well as in the CG. Muscle tone in CIMTG was lower compared to CG after 24 sessions. Both protocols used in the study were effective, the CIMT protocol showed benefits in recovering the functionality of the paretic upper limb, in the functional range and in reducing muscle tone, with a consequent improvement in quality of life.