Global DNA methylation patterns in Alcohol Use Disorder.

Alcohol Use Disorder (AUD) is a highly prevalent condition worldwide that produces a wide range of pathophysiological consequences, with a critical impact on health and social issues. Alcohol influences gene expression through epigenetic changes mainly through DNA methylation. In this sense, levels of 5-methylcytosine (5-mC), namely Global DNA methylation (GMe), which can be influenced by environmental and hormonal effects, represent a putative biological mechanism underlying alcohol effects. Our aim was to investigate the influence of AUD diagnosis and alcohol patterns (i.e., years of addiction, use in the last 30 days, and alcohol severity) on GMe levels. The sample consisted of 256 men diagnosed with AUD and 361 men without AUD. DNA samples from peripheral blood were used to assess GMe levels, measured through the levels of 5-mC using high-performance liquid chromatography. Results from multiple linear regression analysis indicated that the presence of AUD was associated with lower GMe levels (beta=-0.155, p=0.011). Other alcohol-related outcomes were not associated with DNA methylation. Our findings are consistent with the hypothesis that the impact of chronic and heavy alcohol use in GMe could be a potential mechanism mediating the multiple organ damages related to AUD.

Theophrastus's Anaisthetos Transdiagnostic Presentation: comment on Pehlivanidis and Papanikolaou (2022).

We were pleased to read Pehlivanidis and Papanikolaou's article1 and see that more colleagues are recognizing Theophrastus' text as the first description of Attention Deficit Hyperactivity Disorder (ADHD).2 We agree with the authors' perspective that Theophrastus' description may suggest the presence of more than one neurodevelopmental disorder. In fact, Theophrastus' description aligns with the shared clinical symptoms and underlying neurodevelopmental mechanisms of ADHD and Social Pragmatic Communication Disorder (SPCD). It is fascinating that a description from over 2000 years ago already presented prototypical individual transdiagnostic aspects that are compatible with a modern biological view of psychiatry. Indeed, it is not unexpected that heritable traits with clear biological underpinnings should have been perceived since the dawn of medicine. A significant leap forward in the development of this field came a few decades ago when Clements (1966)3 published a NIH-sponsored project entitled 'Minimal Brain Dysfunction in Children.' This seminal work prepared the terrain for the ongoing understanding of the grouping of signs, symptoms, and biological factors observed across various neurodevelopmental disorders. This grouping can be present in different spectrums, proportions, and nuances, including children and adults with some impairments that are not solely explained by their cognitive abilities. Thus, the characterization of 'The Obtuse Man' by Theophrastus could be considered a prototypical case of this more integrated and less fragmented view of what we call neurodevelopmental disorders.

Effect of physical training on cytokine expression in CD4+ T lymphocytes in subjects with stable COPD.

INTRODUCTION: Although evidence suggests that physical exercise reduces systemic inflammation, at the plasma level, there are still contradictions in chronic obstructive pulmonary disease (COPD). In this sense, analysis of intracellular cytokines could clear off the effect of physical exercise on the inflammatory profile of these subjects. AIM: The aim was to evaluate the effect of physical training on cytokine expression in CD4+ T lymphocytes from subjects with COPD. METHODS: This is a randomized controlled trial. Subjects with stable COPD were grouped into two groups, exercise and control. In total, 23 subjects with stable COPD were evaluated, of which 15 underwent aerobic strength training [physical exercise group (PEG)] and 8 underwent breathing exercises [respiratory physiotherapy group (RPG)]. Intracellular cytokines [interleukin (IL)-8, IL-13, IL-17, IL-6, IL-2, IL-10, and tumor necrosis factor alpha (TNF-α)] from CD4+ T lymphocytes were analyzed from peripheral blood through flow cytometry, before and after 8 weeks of intervention. RESULTS: The PEG and RPG groups had a mean age of 68 ± 5.96 and 72.25 ± 6.86 years and predicted forced expiratory volume in the first second (FEV1) of 58.6 ± 15.99% and 39.75 ± 10.39%, respectively. It was possible to detect a significant reduction in IL-8 (p = 0.0125) and an increase in IL-13 (p = 0.0014) and an increase in TNF-α (p < 0.001) in both groups. CONCLUSION: Eight weeks of physical training, both peripheral and respiratory, were able to reduce concentrations of IL-8 and to increase IL-13, and TNF-α in CD4+ T lymphocytes in subjects with stable COPD. The findings reinforce the benefits of interventions in subjects with COPD, revealing data not previously investigated.

Consumption, nicotine dependence and motivation for smoke cessation during early stages of COVID-19 pandemic in Brazil: A cross-sectional study.

INTRODUCTION: The COVID-19 pandemic may have changed smoking habits. For the smoking population, information regarding smoking habits and the pandemic could potentially aid COVID-19 prevention and control measures. Our study aimed to analyze the effects of the COVID-19 pandemic on tobacco consumption, nicotine dependence levels, and motivation for smoking cessation. We also collected information from smokers regarding their awareness of the consequences of tobacco use and the increased risks smokers have for severe complications from COVID-19. METHODS: In the survey for this observational cross-sectional study, 122 smokers responded to an online form. The participants provided general data about their smoking history, their smoking habits in the months of April and May 2020, and the effect of the pandemic on their smoking habits. They also completed a Fagerström test and were measured by the Wisconsin Smoking Withdrawal Scale. RESULTS: When compared to pre-pandemic levels, the majority of smokers reported increased tobacco consumption of between 1 and 10 cigarettes per day (37.7%). Their motivation to quit smoking (59.8%) and desire to smoke (53.2%) were unchanged by the pandemic. Most participants demonstrated an awareness of the increased risks smokers have for severe COVID-19-related complications (p<0.001). We identified the following correlations: cigarettes/day before pandemic and motivation for smoking cessation (r=0.19; p=0.030), cigarettes/day and nicotine dependence level (r=0.61; p<0.001), and load consumption and nicotine dependence level (r=0.69; p<0.001). No significant correlations were observed between load consumption and motivation to quit (r=0.13; p=0.120). CONCLUSIONS: Most smokers are well aware of their increased risks for severe COVID-19-related complications. In the early stages of the COVID-19 pandemic in Brazil, most smokers reported increased cigarette consumption. In addition, motivation to quit and desire to smoke were unchanged for the majority of smokers.

Global DNA methylation changes in adults with attention deficit-hyperactivity disorder and its comorbidity with bipolar disorder: links with polygenic scores.

Genetic and environmental factors contribute to the etiology of Attention Deficit-Hyperactivity Disorder (ADHD). In this sense, the study of epigenetic mechanisms could contribute to the understanding of the disorder's neurobiology. Global DNA methylation (GMe) evaluated through 5-methylcytosine levels could be a promising epigenetic biomarker to capture long-lasting biological effects in response to environmental and hormonal changes. We conducted the first assessment of GMe levels in subjects with ADHD (n = 394) and its main comorbidities in comparison to populational controls (n = 390). Furthermore, given the high genetic contribution to ADHD (heritability of 80%), polygenic risk scores (PRS) were calculated to verify the genetic contribution to GMe levels in ADHD and the comorbidities associated with GMe levels. The GMe levels observed in patients were lower than controls (P = 1.1e-8), with women being significantly less globally methylated than men (P = 0.002). Regarding comorbidities, the presence of bipolar disorder (BD) among patients with ADHD was associated with higher methylation levels compared to patients with ADHD without BD (P = 0.031). The results did not change when pharmacological treatment was accounted for in the analyses. The ADHD and BD most predictive PRSs were negatively (P = 0.0064) and positively (P = 0.0042) correlated with GMe, respectively. This study is the first to report an association between GMe, ADHD, and its comorbidity with BD and associations between PRSs for specific psychiatric disorders and GMe. Our findings add to previous evidence that GMe may be a relevant piece in the psychiatric disorders' etiological landscape.

The role of glucocorticoid receptor gene in the association between attention deficit-hyperactivity disorder and smaller brain structures.

ADHD is associated with smaller subcortical brain volumes and cortical surface area, with greater effects observed in children than adults. It is also associated with dysregulation of the HPA axis. Considering the effects of the glucocorticoid receptor (NR3C1) in neurophysiology, we hypothesize that the blurred relationships between brain structures and ADHD in adults could be partly explained by NR3C1 gene variation. Structural T1-weighted images were acquired on a 3 T scanner (N = 166). Large-scale genotyping was performed, and it was followed by quality control and pruning procedures, which resulted in 48 independent NR3C1 gene variants analyzed. After a stringent Bonferroni correction, two SNPs (rs2398631 and rs72801070) moderated the association between ADHD and accumbens and amygdala volumes in adults. The significant SNPs that interacted with ADHD appear to have a role in gene expression regulation, and they are in linkage disequilibrium with NR3C1 variants that present well-characterized physiological functions. The literature-reported associations of ADHD with accumbens and amygdala were only observed for specific NR3C1 genotypes. Our findings reinforce the influence of the NR3C1 gene on subcortical volumes and ADHD. They suggest a genetic modulation of the effects of a pivotal HPA axis component in the neuroanatomical features of ADHD.

Appetite Is Suppressed After Full-Body Resistance Exercise Compared With Split-Body Resistance Exercise: The Potential Influence of Lactate and Autonomic Modulation.

ABSTRACT: Conrado de Freitas, M, Ricci-Vitor, AL, de Oliveira, JVNS, Quizzini, GH, Vanderlei, LCM, Silva, BSA, Zanchi, NE, Cholewa, JM, Lira, FS, and Rossi, FE. Appetite is suppressed after full-body resistance exercise compared with split-body resistance exercise: the potential influence of lactate and autonomic modulation. J Strength Cond Res 35(9): 2532-2540, 2021-The purposes of this study were to investigate the effects of full- vs. split-body resistance training on appetite and leptin response and to verify the potential involvement of lactate and autonomic modulation during this response in trained men. Twelve recreationally resistance-trained men (age = 26.1 ± 5.5 years) performed 3 randomized trials in 3 conditions: upper body (UB), lower body (LB), and full body (FB). The subjective rating of hunger was obtained through a visual analog scale. Leptin and lactate concentration were evaluated at rest, immediately after exercise, and during recovery. Heart rate variability in the time and frequency domains was recorded at baseline and during recovery (until 60 minutes after exercise) to assess autonomic modulation. The FB condition induced lower subjective hunger ratings than the UB at Post-1 hour (p < 0.05) and a significant difference in the area under the curve between conditions (p = 0.028) with lower hunger sensation for FB in relation to UB (p = 0.041). The FB presented greater lactate concentration and induced slower heart rate variability recovery in relation to UB and LB conditions (p < 0.05), and heart rate variability remained lower until 60 minutes after exercise compared with rest only in the FB condition. There was a significant negative correlation between subjective hunger ratings and lactate concentration only for the FB condition (r = -0.72, p = 0.028). Full-body resistance exercise induced lower subjective hunger ratings after exercise in relation to UB resistance exercise. The FB also induced higher lactate production and slower recovery of autonomic modulation compared with the UB and LB conditions. Future research is necessary to investigate a mechanistic relationship between lactate concentrations and hunger suppression after resistance exercise.

Elastic Resistance Training Produces Benefits Similar to Conventional Resistance Training in People With Chronic Obstructive Pulmonary Disease: Systematic Review and Meta-Analysis.

OBJECTIVE: The purpose of this study was to investigate the effectiveness of elastic resistance training on improving muscle strength, functional exercise capacity, health-related quality of life (HRQoL), and dyspnea in people with stable chronic obstructive pulmonary disease (COPD). METHODS: For this systematic review, PubMed, The Cochrane Library, Embase (OVID), PEDro, SciELO, and CINAHL were searched from inception to November 2019. Included studies were randomized clinical trials in which people with stable COPD were allocated to (1) an experimental group that received lower-limb resistance training, upper-limb resistance training, or both using elastic resistance; or (2) a control group that received no or sham resistance training or conventional resistance training using weight machines. Data extraction was performed by 3 review authors. The methodological quality of the studies was assessed using the PEDro scale. Eight studies on 332 participants were included. RESULTS: Knee extensor strength was higher in the experimental group (standardized mean difference = 0.52, 95% CI = 0.09-0.95) compared with the non-exercise control group. Compared with the conventional exercise control, the experimental group presented similar effects for muscle strength, functional exercise capacity, HRQoL, and dyspnea (95% CI overlapped the line of no effect for all). CONCLUSIONS: Elastic resistance training improves muscle strength in people with COPD. The current review suggests elastic resistance as a potential alternative to conventional resistance training using weight machines, as they show similar effects on muscle strength, functional exercise capacity, HRQoL, and dyspnea. IMPACT: Due to its beneficial effects, including reduced risk of exacerbation-related hospitalizations, exercise training is viewed as the cornerstone of pulmonary rehabilitation in people with COPD. This study shows that elastic resistance training can be an effective, portable, practical, and low-cost alternative to conventional weight resistance training. LAY SUMMARY: Training with elastic resistance tubes or bands-which are easy to carry, easy to use, and relatively low cost-can be an effective way to improve strength for people with COPD and promote similar benefits to those achieved with weight machines.

Integrative proteomics and pharmacogenomics analysis of methylphenidate treatment response.

Transcriptomics and candidate gene/protein expression studies have indicated several biological processes modulated by methylphenidate (MPH), widely used in attention-deficit/hyperactivity disorder (ADHD) treatment. However, the lack of a differential proteomic profiling of MPH treatment limits the understanding of the most relevant mechanisms by which MPH exerts its pharmacological effects at the molecular level. Therefore, our aim is to investigate the MPH-induced proteomic alterations using an experimental design integrated with a pharmacogenomic analysis in a translational perspective. Proteomic analysis was performed using the cortices of Wistar-Kyoto rats, which were treated by gavage with MPH (2 mg/kg) or saline for two weeks (n = 6/group). After functional enrichment analysis of the differentially expressed proteins (DEP) in rats, the significant biological pathways were tested for association with MPH response in adults with ADHD (n = 189) using genome-wide data. Following MPH treatment in rats, 98 DEPs were found (P < 0.05 and FC < -1.0 or > 1.0). The functional enrichment analysis of the DEPs revealed 18 significant biological pathways (gene-sets) modulated by MPH, including some with recognized biological plausibility, such as those related to synaptic transmission. The pharmacogenomic analysis in the clinical sample evaluating these pathways revealed nominal associations for gene-sets related to neurotransmitter release and GABA transmission. Our results, which integrate proteomics and pharmacogenomics, revealed putative molecular effects of MPH on several biological processes, including oxidative stress, cellular respiration, and metabolism, and extended the results involving synaptic transmission pathways to a clinical sample. These findings shed light on the molecular signatures of MPH effects and possible biological sources of treatment response variability.

The association between SYT1-rs2251214 and cocaine use disorder further supports its role in psychiatry.

Synaptotagmin-1 is an essential regulator of synaptic vesicle exocytosis, and its encoding gene (SYT1) is a genome and transcriptome-wide association hit in cognitive performance, personality and cocaine use disorder (CUD) studies. Additionally, in candidate gene studies the specific variant rs2251214 has been associated with attention-deficit/hyperactivity disorder (ADHD), antisocial personality disorder and other externalizing phenotypes in adults with ADHD, as well as with response to methylphenidate (MPH) treatment. In this context, we sought to evaluate, in an independent sample, the association of this variant with CUD, a phenotype that shares common biological underpinnings with the previously associated traits. We tested the association between SYT1-rs2251214 and CUD susceptibility and severity (addiction severity index) in a sample composed by 315 patients addicted to smoked cocaine and 769 non-addicted volunteers. SYT1-rs2251214 was significantly associated with susceptibility to CUD, where the G allele presented increased risk for the disorder in the genetic models tested (P = 0.0021, OR = 1.44, allelic; P = 0.0012, OR = 1.48, additive; P = 0.0127, OR = 1.41, dominant). This is the same allele that was associated with increased risk for ADHD and other externalizing behaviors, as well as poor response to MPH treatment in previous studies. These findings suggest that the neurotransmitter exocytosis pathway might play a critical role in the liability for psychiatric disorders, especially externalizing behaviors and CUD.

ADGRL3 rs6551665 as a Common Vulnerability Factor Underlying Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder.

Neurodevelopmental disorders are prevalent, frequently occur in comorbidity and share substantial genetic correlation. Previous evidence has suggested a role for the ADGRL3 gene in Attention-Deficit/Hyperactivity Disorder (ADHD) susceptibility in several samples. Considering ADGRL3 functionality in central nervous system development and its previous association with neurodevelopmental disorders, we aimed to assess ADGRL3 influence in early-onset ADHD (before 7 years of age) and Autism Spectrum Disorder (ASD). The sample comprises 187 men diagnosed with early-onset ADHD, 135 boys diagnosed with ASD and 468 male blood donors. We tested the association of an ADGRL3 variant (rs6551665) with both early-onset ADHD and ASD susceptibility. We observed significant associations between ADGRL3-rs6551665 on ADHD and ASD susceptibilities; we found that G-carriers were at increased risk of ADHD and ASD, in accordance with previous studies. The overall evidence from the literature, corroborated by our results, suggests that ADGRL3 might be involved in brain development, and genetic modifications related to it might be part of a shared vulnerability factor associated with the underlying neurobiology of neurodevelopmental disorders such as ADHD and ASD.

Influence of skeletal muscle mass and fat mass on the metabolic and inflammatory profile in sarcopenic and non-sarcopenic overfat elderly.

BACKGROUND: Sarcopenic elderly present low muscle mass and strength, however, it is not clear if the inflammatory and metabolic profile is more related to low lean mass or high fat mass in sarcopenic and non-sarcopenic overfat elderly. AIM: To verify the difference in inflammatory and metabolic responses in sarcopenic and non-sarcopenic overfat elderly and the relationship between these markers, body composition, and strength in this population. METHODS: Fifty-seven elderly were divided into two groups: sarcopenic (n = 30) and non-sarcopenic (n = 27). Body composition was evaluated with octopolar bioimpedance. Total cholesterol, high-density lipoprotein cholesterol, triacylglycerol, glucose, cortisol, leptin, adiponectin, Plasminogen activator inhibitor-1 (PAI-1), TNF-α, IL-6, IL-8, and IL-10 were assessed. The handgrip test was used to evaluate strength. RESULTS: When comparing the inflammatory profile, sarcopenic individuals showed greater adiponectin concentration (p = 0.019), adiponectin/fat mass ratio (p < 0.001), adiponectin/visceral fat (p < 0.001), and higher PAI-1 (p = 0.019) than non-sarcopenic overfat elderly. After adjusting the inflammatory profile by skeletal muscle mass the significant differences between groups were maintained (p < 0.05) but no significant differences between groups were observed when adjusting by fat mass, despite a tendency to a significant difference for adiponectin concentration (p = 0.06). In addition, after adjusting leptin by fat mass there was a statistically significant lower concentration in the sarcopenic compared to non-sarcopenic overfat elderly. CONCLUSION: Non-sarcopenic overfat elderly presented lower anti-inflammatory and anti-atherogenic responses than sarcopenic elderly. Furthermore, fat mass but not skeletal muscle mass seem to change these responses.

Acute Effects of Different Types of Resistance Training on Cardiac Autonomic Modulation in COPD.

BACKGROUND: An exercise modality that has been gaining significant importance in the rehabilitation of subjects with COPD is resistance training. When considering that patients with COPD present alterations in autonomic cardiac modulation caused by the disease itself, it is necessary to investigate the behavior of the autonomic nervous system in relation to this type of exercise. Thus, the objective of this study was to compare the acute effects of resistance training with elastic tubes, elastic bands, and conventional weightlifitng on the behavior of cardiac autonomic modulation in post-exercise recovery in subjects with COPD. METHODS: Thirty-four subjects with COPD performed an single session of resistance training divided according to the therapeutic resource used: elastic tubes (n = 10), elastic bands (n = 11), and conventional bodybuilding (n = 13). For analysis of cardiac autonomic modulation, the heart rate was obtained beat to beat at rest and immediately after the end of the session for 60 min in a seated position. Heart rate variability indices were obtained in the time and frequency domains. RESULTS: The 3 therapeutic resource types used in the single session of resistance training promoted changes in heart rate variability linear indices in the time and frequency domains; however, post-exercise recovery time was similar for all protocols performed. CONCLUSIONS: After single resistance training the elastic tubes group presented a minimum alteration in the post-exercise recovery of cardiac autonomic modulation in the subjects with COPD; however, at 5 min after exercising, the subjects with COPD had already recovered. Therefore, if the purpose of the training is to restore autonomic cardiac modulation, the use of elastic tubes is suggested, when considering their low cost and versatility.

Attention-deficit hyperactivity disorder in ancient Greece: The Obtuse Man of Theophrastus.

We present an ancient Greek description written by the philosopher Theophrastus in his classic book ' Characters' comparable with modern attention-deficit hyperactivity disorder. The arguments are based in one chapter of this book-The Obtuse Man-presenting features of a character closely resembling the modern description of attention-deficit hyperactivity disorder. In a free comparative exercise, we compared Theophrastus descriptions with modern Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) attention-deficit hyperactivity disorder symptoms. The sentences describing The Obtuse Man written by Theophrastus are similar to several symptoms of attention-deficit hyperactivity disorder and he would probably be currently diagnosed with this disorder as an adult. To our knowledge, this is the oldest description compatible with the current conception of attention-deficit hyperactivity disorder in adults in the Western literature. Differently than the moralistic view of ancient Greece regarding those symptoms, the medical attention-deficit hyperactivity disorder conception may be advantageous to patients since it might reduce prejudice and allow individuals to seek treatment.

Inflammatory and Metabolic Responses to Different Resistance Training on Chronic Obstructive Pulmonary Disease: A Randomized Control Trial.

Background: Low-grade inflammation can be present in chronic obstructive pulmonary disease (COPD), which may affect the regulation of muscle protein and body metabolism. Regular exercise show improvement in muscle strength and dyspnea in patients with COPD, however, the response to training on inflammatory and metabolic disorders is unclear. In this study, we compared the effects of resistance training using weight machines and elastic resistance (bands and tubes) on the inflammatory and metabolic responses in patients with COPD. Methods: Patients with COPD were randomized into three groups: elastic band group (EBG), elastic tube group (ETG), and weight machines equipment group (MG). EBG and ETG were analyzed together [elastic group (EG)]. The participants were evaluated for pulmonary function (spirometry), peripheral muscle strength (digital dynamometry), IL-6, TNF-α, IL-10, IL-15 (Immunoassay), glucose, triacylglycerol, total cholesterol, HDL-c, and albumin levels (Enzymatic colorimetric). Blood samples were collected to assess the acute and chronic exercise responses after 12 weeks of training protocol. Results: The patient's mean age was 71.53 ± 6.97 years old. FEV1 (percent predicted) was 50.69 ± 16.67 and 45.40 ± 15.15% for EG and MG, respectively (p = 0.28). All groups increased muscle strength (p < 0.05) with no differences between groups. The acute response to exercise after 12 weeks of training showed improvement of inflammation when compared to baseline. Regarding the chronic effects, it was observed a decrease of all cytokines, except IL-10 (p < 0.05). After 12 weeks of training, the analysis of the metabolic profile presented a reduction in glucose concentration (p < 0.01), with no differences between groups (p = 0.30) and a decrease in triacylglycerol for the EG (p > 0.01). Conclusions: Training with elastic resistances or conventional weight machines showed improvement of inflammation response after 12 weeks of training. Chronically, both training groups showed anti-inflammatory effects, with the EG showing a strong tendency to improve IL-10/TNF-α ratio and IL-10 levels. TRIAL REGISTRATION: RBR-6V9SJJ.

Resistance Training using Low Cost Elastic Tubing is Equally Effective to Conventional Weight Machines in Middle-Aged to Older Healthy Adults: A Quasi-Randomized Controlled Clinical Trial.

The objectives of the study were to compare the effects of resistance training using either a low cost and portable elastic tubing or conventional weight machines on muscle force, functional exercise capacity, and health-related quality of life (HRQOL) in middle-aged to older healthy adults. In this clinical trial twenty-nine middle-aged to older healthy adults were randomly assigned to one of the three groups a priori defined: resistance training with elastic tubing (ETG; n = 10), conventional resistance training (weight machines) (CTG; n = 9) and control group (CG, n = 10). Both ETG and CTG followed a 12-week resistance training (3x/week - upper and lower limbs). Muscle force, functional exercise capacity and HRQOL were evaluated at baseline, 6 and 12 weeks. CG underwent the three evaluations with no formal intervention or activity counseling provided. ETG and CTG increased similarly and significantly muscle force (Δ16-44% in ETG and Δ25-46% in CTG, p < 0.05 for both), functional exercise capacity (ETG Δ4 ± 4% and CTG Δ6±8%; p < 0.05 for both). Improvement on "pain" domain of HRQOL could only be observed in the CTG (Δ21 ± 26% p = 0.037). CG showed no statistical improvement in any of the variables investigated. Resistance training using elastic tubing (a low cost and portable tool) and conventional resistance training using weight machines promoted similar positive effects on peripheral muscle force and functional exercise capacity in middle-aged to older healthy adults.

Genome-wide association study reveals candidate genes influencing lipids and diterpenes contents in Coffea arabica L.

Lipids, including the diterpenes cafestol and kahweol, are key compounds that contribute to the quality of coffee beverages. We determined total lipid content and cafestol and kahweol concentrations in green beans and genotyped 107 Coffea arabica accessions, including wild genotypes from the historical FAO collection from Ethiopia. A genome-wide association study was performed to identify genomic regions associated with lipid, cafestol and kahweol contents and cafestol/kahweol ratio. Using the diploid Coffea canephora genome as a reference, we identified 6,696 SNPs. Population structure analyses suggested the presence of two to three groups (K = 2 and K = 3) corresponding to the east and west sides of the Great Rift Valley and an additional group formed by wild accessions collected in western forests. We identified 5 SNPs associated with lipid content, 4 with cafestol, 3 with kahweol and 9 with cafestol/kahweol ratio. Most of these SNPs are located inside or near candidate genes related to metabolic pathways of these chemical compounds in coffee beans. In addition, three trait-associated SNPs showed evidence of directional selection among cultivated and wild coffee accessions. Our results also confirm a great allelic richness in wild accessions from Ethiopia, especially in accessions originating from forests in the west side of the Great Rift Valley.

Severity of COPD and its relationship with IL-10.

BACKGROUND: The present study was designed to compare inflammatory and metabolic responses according to severity of airflow among patients with COPD and to verify the relationship between pulmonary function, body composition, metabolic and inflammatory profile. METHODS: Fifty-one patients with mild to very severe COPD were recruited and divided according lung function in Mild-moderate (GOLD 1-2) n= 21; Severe (GOLD 3) n=25 and Very severe (GOLD 4) n=5. Patients were submitted to assessments of lung function (spirometry), functional exercise capacity (6-min walk test), body composition (Octopolar bioelectrical impedance), metabolic profile (glucose, triglycerides, total cholesterol, HDL-cholesterol and albumin (colorimetric assay)) and inflammatory profile (cytokines: IL-6, IL-10, TNF-α and IL-15 (ELISA)). RESULTS: We found that patients in GOLD 3 group had lower levels of IL-10, triglycerides, visceral fat area, and higher IL-6 and IL-6/IL-10 ratio when compared to GOLD 1-2 patients. Additionally, GOLD 1-2 group presented negative correlation between TNF-α and HDL cholesterol (p= .01) and positive correlation between IL-15 and FEV1/FVC (p=.01), while GOLD 3 group showed positive correlation between IL-6 and IL-10 (p< .01), IL-6 and total cholesterol (p<.01) and negative correlation between IL-10 and HDL-cholesterol (p=.01). CONCLUSION: Our findings suggest that patients with severe COPD can exhibit compromised "inflammatory status", characterized by higher IL6, IL-6/IL-10 ratio and lower IL-10 concentration. Furthermore, IL-10 seems to be an interesting cytokine to be investigated in this kind of patients.

Evidence of sexual dimorphism of HTR1B gene on major adult ADHD comorbidities.

Attention-deficit/hyperactivity disorder (ADHD) is a very common psychiatric disorder across the life cycle and frequently presents comorbidities. Since ADHD is highly heritable, several studies have focused in the underlying genetic factors involved in its etiology. One of the major challenges in this search is the phenotypic heterogeneity, which could be partly attributable to the sexual dimorphism frequently seen in psychiatric disorders. Taking into account the well-known sexual dimorphic effect observed in serotonergic system characteristics, we differentially tested the influence of HTR1B SNPs (rs11568817, rs130058, rs6296 and rs13212041) on ADHD susceptibility and on its major comorbidities according to sex. The sample comprised 564 adults with ADHD diagnosed according to DSM-IV criteria and 635 controls. There was no association of any HTR1B SNPs tested in relation to ADHD susceptibility. As for the comorbidities evaluated, after correction for multiple tests, significant associations were observed for both rs11568817 and rs130058 with substance use disorders (Pcorr = 0.009 and Pcorr = 0.018, respectively) and for rs11568817 with nicotine dependence (Pcorr = 0.025) in men with ADHD. In women with ADHD, the same rs11568817 was associated with generalized anxiety disorder (Pcorr = 0.031). The observed effects of rs11568817 G allele presence conferring risk to either substance use disorders or generalized anxiety disorder according to sex, suggest an overall scenario where a higher transcriptional activity of HTR1B, resulting from the presence of this allele, is related to externalizing behaviors in men and internalizing behaviors in women. These results are consistent with and expand previous evidence of sexual dimorphism of the serotoninergic system.

Further replication of the synergistic interaction between LPHN3 and the NTAD gene cluster on ADHD and its clinical course throughout adulthood.

Attention-Deficit/Hyperactivity Disorder (ADHD) is a common and highly heritable neuropsychiatric disorder. Despite the high heritability, the unraveling of specific genetic factors related to ADHD is hampered by its considerable genetic complexity. Recent evidence suggests that gene-gene interactions can explain part of this complexity. We examined the impact of strongly supported interaction effects between the LPHN3 gene and the NTAD gene cluster (NCAM1-TTC12-ANKK1-DRD2) in a 7-year follow-up of a clinical sample of adults with ADHD, addressing associations with susceptibility, symptomatology and stability of diagnosis. The sample comprises 548 adults with ADHD and 643 controls. Entropy-based analysis indicated a potential interaction between the LPHN3-rs6551665 and TTC12-rs2303380 SNPs influencing ADHD symptom counts. Further analyses revealed significant interaction effects on ADHD total symptoms (p=0.002), and with hyperactivity/impulsivity symptom counts (p=0.005). In the group composed by predominantly hyperactive/impulsive and combined presentation, the presence of LPHN3-rs6551665 G allele was related to increased ADHD risk only in individuals carrying the TTC12-rs2303380 AA genotype (p=0.026). Also, the same allelic constellation is involved in maintenance of ADHD in a predominantly hyperactive/impulsive or combined presentation after a 7-year follow-up (p=0.008). These observations reinforce and replicate previous evidence suggesting that an interaction effect between the LPHN3 gene and the NTAD cluster may have a role in the genetic substrate associated to ADHD also in adults. Moreover, it is possible that the interactions between LPHN3 and NTAD are specific factors contributing to the development of an ADHD phenotype with increased hyperactivity/impulsivity that is maintained throughout adulthood.