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Lisa M Roberts,1,2 Byron C Jaeger,3 Liliana C Baptista,1,2 Sara A Harper,1,2 Anna K Gardner,4 Elizabeth A Jackson,5 Dorothy Pekmezi,6 Bhanuprasad Sandesara,4 Todd M Manini,4 Stephen D Anton,4 Thomas W Buford1,2 1Department of Medicine, Division of Gerontology/Geriatrics/Palliative Care, University of Alabama at Birmingham, Birmingham, AL, USA; 2Center for Exercise Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; 3Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA; 4Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, USA; 5Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL, USA; 6Department of Health Behavior, School of Public Health, the University of Alabama at Birmingham, Birmingham, AL, USACorrespondence: Thomas W BufordDepartment of Medicine, Division of Gerontology/Geriatrics/Palliative Care, University of Alabama at Birmingham, 1313 13th Street S., Birmingham, AL 35205, USATel +1 205 996 3008Fax +1 205 996 3110Email twbuford@uabmc.eduBackground: Physical exercise is associated with decreased cardiovascular disease (CVD) risk, but recent large-scale trials suggest that exercise alone is insufficient to reduce CVD events in high-risk older adults.Purpose: This pilot randomized clinical trial aimed to collect critical data on feasibility, safety, and protocol integrity necessary to design a fully powered randomized controlled trial (RCT) and evaluate the impact of combining structured exercise with an intervention designed to enhance non-exercise physical activity (EX+NEPA) compared to EX alone.Methods: Forty participants aged ≥60 years with moderate-to-high risk of coronary heart disease events were randomly assigned to either the EX+NEPA or EX groups and followed for 20 weeks. Both groups underwent a twice-weekly, 8-week center-based exercise intervention with aerobic and resistance exercises. EX+NEPA group also received a wearable activity tracking device along with behavioral monitoring and feedback throughout the study. Study outcomes were evaluated at 8 and 20 weeks.Results: Data are presented as adjusted mean change of the differences over time with 95% confidence intervals at 20 weeks. Relative to EX, the change in steps/day at 20 weeks was 1994 (−40.27, 4028) higher for EX+NEPA. For sedentary time at close-out, the EX+NEPA group was −6.8 (−45.2, 31.6) min/day relative to EX. The between-group differences for systolic and diastolic blood pressure were −9.9 (−19.6, −0.3) and −1.8 (−6.9, 3.3) mmHg, respectively.Conclusion: The addition of wearable technology intervention appeared to positively influence daily activity patterns and changes in blood pressure – potentially improving risk factors for CVD. A fully powered randomized trial is needed to ultimately test this hypothesis.Keywords: aging, cardiovascular, exercise, physical activity, activity monitor

Purpose: Trimethylamine-N-oxide (TMAO) is a gut-derived metabolite associated with cardiovascular disease (CVD). In preclinical and observational studies, resveratrol and exercise training have been suggested as potential strategies to reduce the systemic levels of TMAO. However, evidence from experimental studies in humans remains unknown. This project examined the dose-dependent effects of a combined resveratrol intervention with exercise training on circulating TMAO and other related metabolite signatures in older adults with high CVD risk., Methods: Forty-one older adults [mean (±SD) age of 72.1 (6.8) years] participated in a 12-week supervised center-based, multi-component exercise training intervention [2×/week; 80 min/session] and were randomized to one of two resveratrol dosages [Low: 500 vs. High:1000 mg/day] or a cellulose-based placebo. Serum/plasma were collected at baseline and post-intervention and evaluated for TMAO and associated analytes., Results: After the 12-week intervention, TMAO concentration increased over time, regardless of treatment [mean (±SD) Placebo: 11262 (±3970); Low:13252 (±1193); High: 12661(±3359) AUC; p = 0.04]. Each resveratrol dose produced different changes in metabolite signatures. Low dose resveratrol upregulated metabolites associated with bile acids biosynthesis (i.e., glycochenodeoxycholic acid, glycoursodeoxycholic acid, and glycocholic acid). High dose resveratrol modulated metabolites enriched for glycolysis, and pyruvate, propanoate, β-alanine, and tryptophan metabolism. Different communities tightly correlated to TMAO and resveratrol metabolites were associated with the lipid and vascular inflammatory clinical markers [|r| > 0.4, p < 0.05]., Conclusion: These findings suggest a distinct dose-dependent adaptation response to resveratrol supplementation on circulating metabolite signatures but not on TMAO among high-risk CVD older adults when combined with an exercise training intervention., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Angiotensin (1-7) [Ang (1-7)] is an active heptapeptide of the noncanonical arm of the renin-angiotensin system that modulates molecular signaling pathways associated with vascular and cellular inflammation, vasoconstriction, and fibrosis. Preclinical evidence suggests that Ang (1-7) is a promising therapeutic target that may ameliorate physical and cognitive function in late life. However, treatment pharmacodynamics limits its clinical applicability. Therefore, this study explored the underlying mechanisms altered by a genetically modified probiotic (GMP) that expresses Ang (1-7) combined with and without exercise training in an aging male rat model as a potential adjunct strategy to exercise training to counteract the decline of physical and cognitive function. We evaluated cross-tissue (prefrontal cortex, hippocampus, colon, liver, and skeletal muscle) multi-omics responses. After 12 wk of intervention, the 16S mRNA microbiome analysis revealed a main effect of probiotic treatment within- and between groups. The probiotic treatment enhanced α diversity (Inverse Simpson ( F [2,56] = 4.44; P = 0.02); Shannon-Wiener ( F [2,56] = 4.27; P = 0.02)) and β-diversity ( F [2,56] = 2.66; P = 0.01) among rats receiving our GMP. The analysis of microbes' composition revealed three genera altered by our GMP ( Enterorhabdus , Muribaculaceae unclassified , and Faecalitalea ). The mRNA multi-tissue data analysis showed that our combined intervention upregulated neuroremodeling pathways on prefrontal cortex (i.e., 140 genes), inflammation gene expression in the liver (i.e., 63 genes), and circadian rhythm signaling on skeletal muscle. Finally, the integrative network analysis detected different communities of tightly (| r | > 0.8 and P < 0.05) correlated metabolites, genera , and genes in these tissues. NEW & NOTEWORTHY This manuscript uses a multiomics approach (i.e., microbiome, metabolomics, and transcriptomics) to explore the underlying mechanisms driven by a genetically modified probiotic (GMP) designed to express angiotensin (1-7) combined with moderate exercise training in an aged male rat model. After 12 wk of intervention, our findings suggest that our GMP enhanced gut microbial diversity while exercise training altered the transcriptional response in relevant neuroremodeling genes, inflammation, and circadian rhythm signaling pathways in an aging animal model.

Acromegaly is an uncommon metabolic disorder, often diagnosed after a long delay. One symptom seen in many patients with acromegaly is arthralgia, a finding that calls for the use of conventional radiography, which can reveal subtle changes that can go unnoticed. The objective of this pictorial essay is to portray the radiographic aspects of acromegaly, seeking to demonstrate the importance of conventional radiography, which, despite its simplicity, can suggest the diagnosis, even in the early stages, thus altering the clinical course of the disease.

Pregnancy in Sickle Cell Disease (SCD) women is associated to increased risk of clinical and obstetrical complications. Placentas from SCD pregnancies can present increased abnormal findings, which may lead to placental insufficiency, favoring adverse perinatal outcome. These placental abnormalities are well known and reported, however little is known about the molecular mechanisms, such as epigenetics. Thus, our aim was to evaluate the DNA methylation profile in placentas from women with SCD (HbSS and HbSC genotypes), compared to uncomplicated controls (HbAA). We included in this study 11 pregnant women with HbSS, 11 with HbSC and 21 with HbAA genotypes. Illumina Methylation EPIC BeadChip was used to assess the whole placental DNA methylation. Pyrosequencing was used for array data validation and qRT-PCR was applied for gene expression analysis. Our results showed high frequency of hypermethylated CpGs sites in HbSS and HbSC groups with 73.5% and 76.2% respectively, when compared with the control group. Differentially methylated regions (DMRs) also showed an increased hypermethylation status for the HbSS (89%) and HbSC (86%) groups, when compared with the control group methylation data. DMRs were selected for methylation validation (4 DMRs-HbSS and 3 DMRs the HbSC groups) and after analyses three were validated in the HbSS group, and none in the HbSC group. The gene expression analysis showed differential expression for the PTGFR (-2.97-fold) and GPR56 (3.0-fold) genes in the HbSS group, and for the SPOCK1 (-2.40-fold) and ADCY4 (1.80-fold) genes in the HbSC group. Taken together, these data strongly suggest that SCD (HbSS and HbSC genotypes) can alter placental DNA methylation and lead to gene expression changes. These changes possibly contribute to abnormal placental development and could impact in the clinical course, especially for the fetus, possibly leading to increased risk of abortion, fetal growth restriction (FGR), stillbirth, small for gestational age newborns and prematurity., Competing Interests: The authors have declared that no competing interests exist.

Vitiligo is an autoimmune disease characterized by progressive skin depigmentation and the appearance of white patches throughout the body caused by significant apoptosis of epidermal melanocytes. Despite not causing any physical pain, vitiligo can originate several psychosocial disorders, drastically reducing patients' quality of life. Emerging evidence has shown that vitiligo is associated with several genetic polymorphisms related to auto-reactivity from the immune system to melanocytes. Melanocytes from vitiligo patients suffer from excess reactive oxygen species (ROS) produced by defective mitochondria besides a poor endogenous antioxidant system (EAS). This redox imbalance results in dramatic melanocyte oxidative stress (OS), causing significant damage in proteins, lipid membranes, and DNA. The damaged melanocytes secret damage-associated molecular pattern (DAMPs), inducing and increasing inflammatory gene expression response that ultimately leads to melanocytes apoptosis. Vitiligo severity has been also associated with increasing the prevalence and incidence of metabolic syndrome (MetS) or associated disorders such as insulin resistance and hypercholesterolemia. Thus, suggesting that in genetically predisposed individuals, the environmental context that triggers MetS (i.e., sedentary lifestyle) may also be an important trigger for the development and severity of vitiligo disease. This paper will discuss the relationship between the immune system and epidermal melanocytes and their interplay with the redox system. Based on state-of-the-art evidence from the vitiligo research, physical exercise (PE) immunology, and redox system literature, we will also propose chronic PE as a potential therapeutic strategy to treat and prevent vitiligo disease progression. We will present evidence that chronic PE can change the balance of inflammatory to an anti-inflammatory state, improve both EAS and the mitochondrial structure and function (resulting in the decrease of OS). Finally, we will highlight clinically relevant markers that can be analyzed in a new research avenue to test the potential applicability of chronic PE in vitiligo disease., 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., (Copyright © 2022 de França, dos Santos, Baptista, Da Silva, Fukushima, Hirota, Martins and Caperuto.)

For centuries, regular exercise has been acknowledged as a potent stimulus to promote, maintain, and restore healthy functioning of nearly every physiological system of the human body. With advancing understanding of the complexity of human physiology, continually evolving methodological possibilities, and an increasingly dire public health situation, the study of exercise as a preventative or therapeutic treatment has never been more interdisciplinary, or more impactful. During the early stages of the NIH Common Fund Molecular Transducers of Physical Activity Consortium (MoTrPAC) Initiative, the field is well-positioned to build substantially upon the existing understanding of the mechanisms underlying benefits associated with exercise. Thus, we present a comprehensive body of the knowledge detailing the current literature basis surrounding the molecular adaptations to exercise in humans to provide a view of the state of the field at this critical juncture, as well as a resource for scientists bringing external expertise to the field of exercise physiology. In reviewing current literature related to molecular and cellular processes underlying exercise-induced benefits and adaptations, we also draw attention to existing knowledge gaps warranting continued research effort. © 2021 American Physiological Society. Compr Physiol 12:3193-3279, 2022., (Copyright © 2022 American Physiological Society. All rights reserved.)

Sickle cell disease (SCD) is a group of disorders whose common characteristic is the presence of hemoglobin (Hb) S in erythrocytes. The main consequence of this abnormality is vaso-occlusion, which can affect almost all organs including the placenta. This study aimed to evaluate the gene expression profile in placentas of women with SCD by means of total RNA sequencing. For this, we proposed a case-control study, with three groups of pregnant women: HbSS (n = 10), HbSC (n = 14) and HbAA (n = 21). The results showed differences in expression in a number of genes such as NOS2 (fold change, FC = 4.52), HLAG (FC = 5.56), ASCL2 (FC = 3.61), CXCL10 (FC = -3.66) and IL1R2 (FC = 3.92) for the HbSC group and S100A8 (FC = -3.82), CPXM2 (FC = 4.57), CXCL10 (FC = -4.59), CXCL11 (FC = -3.72) and CAMP (FC = -4.55) for the HbSS group. Differentially expressed genes are mainly associated with migration, trophoblast differentiation and inflammation. The causes leading to altered gene expression in placentas of sickle cell patients are not fully understood, but the presence of intravascular hemolysis and vaso-occlusion, with cycles of ischemia and reperfusion, may contribute to the emergence of an environment which can be very harmful for placental physiology, altering the nutrient supply and metabolic exchange for fetal growth., Competing Interests: Declaration of competing interest The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Declining cognitive functions in older individuals have enormous emotional, clinical, and public health consequences. Thus, therapeutics for preserving function and keeping older adults living independently are imperative. Aging is associated dysbiosis, defined as a loss of number and diversity in gut microbiota, which has been linked with various aspects of cognitive functions. Therefore, the gut microbiome has the potential to be an important therapeutic target for symptoms of cognitive impairment. In this review, we summarize the current literature regarding the potential for gut-targeted therapeutic strategies for prevention/treatment of the symptoms of cognitive impairment. Specifically, we discuss four primary therapeutic strategies: wild-type and genetically modified probiotics, fecal microbiota transplantation, physical exercise, and high-fiber diets and specifically link these therapies to reducing inflammation. These strategies may hold promise as treatment paradigm symptoms related to cognitive impairment., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

To date, there are several knowledge gaps on how to properly prescribe concurrent training to achieve the best dose-response, especially regarding the optimal intensity or volume of the aerobic component. Thus, the objective of this study is to analyze the effects of different aerobic exercise modes and intensities [i.e. aerobic high-intensity interval training (HIIT) versus moderate-intensity continuous aerobic training (MICT) combined with a resistance training (RT) program] on metabolic outcomes in participants with metabolic syndrome (MetS). Thirty-nine men and women (67.0 ± 6.7 years) volunteered to a 12-weeks exercise intervention (3 week -1 , 50 min/session) and were randomly assigned to one of three groups: (a) RT plus MICT (RT+MICT) (2 males; 11 females); (b) RT plus HIIT (RT+HIIT) (4 males; 9 females); and (c) control group (CON) - without formal exercise (4 males; 9 females). Intensity was established between 60 and 70% of maximum heart rate (HRmax) in RT+MICT and ranged from 55-65% to 80-90% HRmax in the RT+HIIT group. Dependent outcomes included morphological, metabolic and hemodynamic variables. Both training groups improved waist circumference (RT+MICT: P = 0.019; RT+HIIT: P = 0.003), but not body weight, fat mass or fat-free mass ( P ≥ 0.114). RT+HIIT group improved fasting glucose ( P = 0.014), low density lipoprotein [LDL ( P = 0.022)], insulin ( P = 0.034) and homeostatic model assessment ( P = 0.028). RT+MICT group reduced triglycerides ( P = 0.053). Both exercise interventions did not change high sensitivity C-reactive protein, glycated hemoglobin, high density lipoprotein and total cholesterol, systolic, diastolic or mean arterial blood pressure ( P ≥ 0.05). The CON group reduced the LDL ( P = 0.031). This trial suggests that short-term exercise mode and intensity may differently impact the metabolic profile of individuals with MetS. Further, our data suggests that both concurrent trainings promote important cardiometabolic gains, particularly in the RT+HIIT. Nonetheless, due to the small-to-moderate effect size and the short-term intervention length, our data suggests that the intervention length also has an important modulating role in these benefits in older adults with MetS. Therefore, more research is needed to confirm our results using longer exercise interventions and larger groups., (Copyright © 2020 Da Silva, Baptista, Neves, De França, Loureiro, Lira, Caperuto, Veríssimo and Martins.)

Cognitive frailty is a geriatric condition defined by the coexistence of cognitive impairment and physical frailty. This "composite" aging phenotype is associated with a higher risk of several adverse health-related outcomes, including dementia. In the last decade, cognitive frailty has gained increased attention from the scientific community that has focused on understanding the clinical impact and the physiological and pathological mechanisms of development and on identifying preventive and/or rehabilitative therapeutic interventions. The emergence of gut microbiome in neural signaling increased the interest in targeting the gut-brain axis as a modulation strategy. Multiple studies on gastroenteric, metabolic, and neurodegenerative diseases support the existence of a wide bidirectional communication network of signaling mediators, e.g., bioactive lipids, that can modulate inflammation, gut permeability, microbiota composition, and the gut-brain axis. This crosstalk between the gut-brain axis, microbiome, and bioactive lipids may emerge as the basis of a promising therapeutic strategy to counteract cognitive frailty. In this review, we summarize the evidence in the literature regarding the link between the gut microbiome, brain, and several families of bioactive lipids. In addition, we also explore the applicability of several bioactive lipid members as a potential routes for therapeutic interventions to combat cognitive frailty., (Copyright © 2020 Baptista, Sun, Carter and Buford.)

Background The clinical aspects of sickle cell anemia (SCA) are heterogeneous, and different patients may present significantly different clinical evolutions. Almost all organs can be affected, particularly the central nervous system. Transient ischemic events, infarcts, and cerebral hemorrhage can be observed and affect ≈25% of the patients with SCA. Differences in the expression of molecules produced by endothelial cells may be associated with the clinical heterogeneity of patients affected by vascular diseases. In this study, we investigated the differential expression of genes involved in endothelial cell biology in SCA patients with and without stroke. Methods and Results Endothelial progenitor cells from 4 SCA patients with stroke and 6 SCA patients without stroke were evaluated through the polymerase chain reaction array technique. The analysis of gene expression profiling identified 29 differentially expressed genes. Eleven of these genes were upregulated, and most were associated with angiogenesis (55%), inflammatory response (18%), and coagulation (18%) pathways. Downregulated expression was observed in 18 genes, with the majority associated with angiogenesis (28%), apoptosis (28%), and cell adhesion (22%) pathways. Remarkable overexpression of the MMP1 (matrix metalloproteinase 1) gene in the endothelial progenitor cells of all SCA patients with stroke (fold change: 204.64; P =0.0004) was observed. Conclusions Our results strongly suggest that angiogenesis is an important process in sickle cell stroke, and differences in the gene expression profile of endothelial cell biology, especially MMP1 , may be related to stroke in SCA patients.

Prior evidence suggests that the choice of antihypertensive medication may influence functional status among older adults with hypertension, particularly in conjunction with exercise. In particular, angiotensin converting enzyme (ACE) inhibitors have shown potential to positively influence function. However, randomized, controlled trials are needed to confirm this hypothesis. This paper outlines an RCT designed to determine if choice of first-line antihypertensive medication influences functional and cardiovascular risk factor responses to exercise among older adults with hypertension. Two hundred and thirteen inactive, community-dwelling adults ≥60 years of age with hypertension and functional limitations will be recruited to engage in a 32-week intervention study. Participants will be randomized to one of three first-line antihypertensive agents: (1) the ACE inhibitor perindopril, (2) the AT1 receptor antagonist losartan, or (3) the thiazide diuretic hydrochlorothiazide (HCTZ). Six weeks after randomization, participants will begin a 20-week structured aerobic exercise intervention. Participants will perform two 45-min center-based sessions coupled with 60 min of home-based walking per week. The primary aim is to determine if perindopril improves self-paced gait speed when compared with losartan and HCTZ. The secondary aim is to determine the relative effect of perindopril on secondary outcomes such as: (a) exercise capacity, (b) body mass and composition, and (c) circulating indices of cardiovascular risk. This RCT is expected to identify differential effects of first-line antihypertensive medications when combined with physical exercise thus have potential implications for antihypertensive prescription guidelines for older adults. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03295734., (Copyright © 2020 Harper, Baptista, Roberts, Wherry, Boxer, Hildreth, Seay, Allman, Carter, Aban, Kohrt and Buford.)

Impact Statement: Environmentally induced changes in placental morphological and molecular phenotypes may provide relevant insight towards pathophysiology of diseases. The rare opportunity to evaluate the same patient, with sickle cell anemia (SCA), in two different pregnancies, of opposite outcomes (one early onset severe preeclampsia (PE) and the other mostly non-complicated) can prove such concept. In addition, the comparison to other conditions of known placental and vascular/inflammatory involvement strengthens such findings. Our results suggest that the clinical association between SCA and PE can be supported by common pathophysiological mechanisms, but that pathways involving response to copper and triglyceride metabolism may be important drivers of the pathophysiology of PE. Future studies using in a larger number of samples should confirm these findings and explore pathways involved in the pathophysiology of PE and its relationship with SCA.

This pilot randomized controlled trial (RCT) was designed to provide the preliminary data necessary to conduct a full-scale trial to compare the efficacy of differing first-line antihypertensive medications in improving functional status in older adults, when combined with exercise. The primary objectives were to assess study feasibility, safety, and protocol integrity. Dependent outcomes included gait speed, exercise capacity, body composition, and systemic cardiometabolic biomarkers. Thirty-one physically inactive older adults (70.6 ± 6.1 years) with hypertension and functional limitations were randomly assigned to 1) Perindopril (8 mg/day n = 10), 2) Losartan (100 mg/day; n = 13), or 3) Hydrochlorothiazide (HCTZ: 25 mg/day; n = 8). Participants were also assigned to a 24-week multimodal exercise intervention, separated into an aerobic and concurrent (aerobic + resistance) phase to evaluate potential mode effects. Retention was 84% (26/31), and compliance was >90% and >79% with medication and exercise, respectively. A total of 29 adverse events (Perindopril = 5; Losartan = 12; HCTZ = 11) and one unrelated serious adverse event were observed throughout the trial. Overall, this pilot RCT provided critical data and identified several challenges to ultimately designing and implementing a fully powered trial., Competing Interests: The authors declare no conflicts of interest

Background: Exercise training (EX) and statins are first-line therapies to manage dyslipidemia., Purpose: This study aims to analyze the effect of EX and statins on functional status and cardiovascular risk (CVR) in dyslipidemic older adults with comorbidities., Methods: Participants (n = 981) underwent one of 3 conditions: (a) multicomponent exercise training (EX; n = 298; 74% females); (b) statins (ST; n = 178; 65% females); (c) combined therapy-exercise plus ST therapy (ST+EX; n = 505; 79% females). Functional fitness, anthropometry, hemodynamic and lipid profiles, and were assessed at baseline and after 2-years., Results: EX and ST+EX participants improved all the functional status variables, whereas ST participants aggravated all the outcomes. Triglycerides and HDL-cholesterol maintained unchanged and total cholesterol decreased in the three groups, whereas LDL-cholesterol (LDL-C) decreased in EX and ST+EX groups but not in ST group. EX and ST+EX groups decreased body mass index (BMI), systolic and diastolic blood pressure; contrarily, ST group increased these variables., Conclusion: Statins combined with exercise training or exercise alone are more effective to improve functional status, to manage cholesterol levels and overall cardiovascular risk factors in dyslipidemic older adults with comorbidities than ST alone. Furthermore, current results suggest that isolated statin therapy decreases functional status and other cardiovascular risk factors., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The increasing prevalence of functionally-limited hypertensive individuals highlights the need for interventions to reduce the burden of hypertension-aging-disability and to maximize the chances of healthy aging., Aim: This study aims to compare the effects of multicomponent exercise and different pharmacological treatments on functional status and cardiovascular risk outcomes in hypertensive older adults with comorbidities., Methods: Participants (n = 96) engage in a 3 days/week multicomponent (aerobic + resistance) exercise program and for one of the following three conditions: (1) thiazide-related diuretics (TDs; n = 33, 69.9 ± 9.5 years); (2) calcium channel blockers (CCBs; n = 23, 67.0 ± 9.0 years); (3) and β-blockers (βBs; n = 40, 65.6 ± 7.2 years) medication. Baseline and 2-year follow-up evaluations included the Senior Fitness Test battery, anthropometrics and hemodynamic profile, health-related quality of life (HRQoL; Short-Form Health Survey 36) and health history questionnaires., Results: All groups have significantly improved the physical functional status; particularly upper and lower body strength and aerobic endurance and systolic blood pressure. The TDs and βBs groups have diminished the waist circumference and body mass. The CCBs decreased total cholesterol (P = 0.028), perceived better physical functioning, physical component score but also augmented bodily pain (P < 0.05). The βB group decreased triglycerides (P = 0.013). No group differences were found., Conclusion: Multicomponent exercise training has improved functional status regardless of the antihypertensive medication options. Hypertensive older adults should add exercise training to pharmacological antihypertensive therapy to reduce the rate of physical disability.

To establish the effect of three types of treatment - multicomponent exercise (MEX); the oral hypoglycaemic drug metformin (MET); combined therapy comprising exercise plus metformin (MEXMET) - on cardiovascular risk in older adults with type 2 diabetes (T2D) and with comorbidities in an early stage of the disease (HbA1c < 7.5%). A sample of 284 participants was evaluated for multifactorial cardiovascular risk at baseline and at 24-month intervention according to anthropometric and hemodynamic components, lipid profile, glycaemia and cardiorespiratory fitness (CRF). Participants underwent one of three conditions: MEX (n = 59), training in three sessions per week; MET (n = 30), using metformin 850 mg twice daily; MEXMET (n = 195), combining exercise and metformin. After the 24-month intervention MEX and MEXMET showed more positive results than MET therapy. MEX decreased body mass (BM; 4%), waist circumference (WC; 4%), body mass index (BMI; 3%), systolic blood pressure (SBP; 11%), diastolic blood pressure (DBP; 11%), triglycerides (21%), and glycaemia (12%), and increased cardiorespiratory fitness (CRF; 18%). Conversely, the MET group showed increased WC (2%), waist-to-hip ratio (WHR) (3%), and SBP (5%). Differences between MEX and MET groups presented large effect sizes for BM, WC, WHR, SBP, DBP and CRF, and moderate effect sizes for BMI and glycaemia. MEX was the most effective therapy in decreasing cardiovascular risk in the early stage of T2D in older adults with multimorbidity and attenuated the adverse effects of pharmacological therapy in MEXMET treatment.

Background: The study aims to analyze the effect of three types of treatment on functional status, and cardiovascular risk outcomes in hypertensive older adults with comorbidities., Methods: Participants (n=418) underwent one of the following 3 conditions: i) multicomponent exercise training 3 times/week (MEX; n=116); ii) angiotensin converting enzyme inhibitors used mono-dose daily (ACEi; n=70); iii) combined exercise and ACEi drugs (ACEiMEX; n=232). The trial was completed by 82% of the participants (n=342): MEX (n=90); ACEi (n=66); ACEiMEX (n=186). Baseline and 2-year follow-up evaluations included the Senior Fitness Test battery, Short Form Health Survey 36 (SF-36), the health history questionnaires, anthropometric and hemodynamic profile., Results: MEX and ACEiMEX groups improved all physical functional status outcomes, decreased systolic (SBP) and diastolic blood pressure (p<0.001) and augmented the physical functioning, role physical and physical component score (PCS) (p<0.05), but also bodily pain (p<0.05). The ACEi group reduced the upper body strength, upper and lower body flexibility and aerobic endurance (p<0.05); worsened the anthropometric profile, and SBP (p<0.001); and decreased general health and PCS (p<0.05)., Conclusions: The improvement of the physical functioning and HRQoL in older hypertensive adults using ACEi medications only occur if they adopt an exercise training regimen, increasing also the management of the blood pressure and other cardiovascular risk factors., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: This study aims to analyze the effects of anti-hypertensive monotherapy and combined therapy on functional status, and cardiovascular risk outcomes in older adults., Methods: This longitudinal non-randomized cohort study, involved hypertensive older adults (n = 440) aged 60 or more years with comorbidities. Participants underwent a community exercise training program and one of the following 2 conditions: i) use of daily mono-dose angiotensin-converting enzyme inhibitors (ACEi; n= 232); ii) combined therapy including ACEi plus other class agent (Combined; n= 208). Baseline and 2-year follow-up evaluations included the functional fitness, health-related quality of life (HRQoL), health history questionnaires, anthropometric and hemodynamic profile., Results: Both experimental groups have significantly improved physical functional status, and have significantly decreased blood pressure and waist circumference. ACEi group has significantly reduced body mass and body mass index, the Combined group significantly reduced the waist-to-hip ratio. Additionally, both groups perceived better physical HRQoL., Conclusions: Functional status has improved with ACEi medication and exercise training, regardless the ACEi medication therapy. Exercise training plus ACEi antihypertensive therapy should be recommended into the standard prescription practice to reduce the rate of physical disability among hypertensive older adults.

Purpose: To establish the effect of a long-term multicomponent exercise (LTMEX) intervention (24 months) on health-related quality of life (HRQoL), in older adults with type 2 diabetes (T2D)., Methods: This longitudinal retrospective cohort study analyzes the effects of a supervised LTMEX program on HRQoL in older adults with T2D (n = 279). Participants underwent one of two conditions: LTMEX (n = 241) trained three times per week; and unchanged lifestyle-the control group (CO; n = 38). Participants completed baseline, and 2-year follow-up evaluations including the Short Form Health Survey 36 (SF-36), anthropometric, hemodynamic components, and cardiorespiratory fitness (VO 2 peak)., Results: LTMEX improves HRQoL, specifically physical functioning (P < 0.001), general health (P < 0.05), vitality (P < 0.001), mental health (MH; P < 0.05), physical component score (P < 0.001), mental component score (P < 0.001), and total SF-36 (P < 0.001). LTMEX group also decreased body weight (BW; P < 0.005), waist circumference (WC; P < 0.001), waist-to-hip ratio (WHR; P < 0.001), and systolic blood pressure (SBP; P < 0.001), and increased VO 2 peak (P < 0.001). CO group increased WC (P = 0.012), BMI (P = 0.024), waist-to-hip ratio (WHR; P = 0.003) and SBP (P < 0.001), and decreased vitality (P < 0.001) and MH (P < 0.05)., Conclusions: A LTMEX intervention improves physical and mental HRQoL in older adults with T2D, and also anthropometric, hemodynamic profile, and cardiorespiratory fitness.

The aim of this cohort study is to analyse the effect of three types of treatment: (i) exercise training with multicomponent exercise (E); (ii) pharmacologic treatment with oral hypoglycaemic drug - metformin (M); and (iii) a combined therapy - exercise and metformin (E + M) on health-related quality of life (HRQoL) and mood states in older adults with type 2 diabetes (T2D) with comorbidity in an early stage of the disease. Participants (n = 284) underwent 1 of the following 3 conditions: (i) E (n = 59) trained three times/week; (ii) M (n = 30) used 850 mg of metformin twice daily; and (iii) E + M (n = 195) combined exercise and metformin. Furthermore, participants completed baseline and 2-year follow-up evaluations including a Shortform Health Survey 36, Profile of Mood States - Short-form, the health history questionnaires, anthropometric, and blood biochemistry. E and E + M revealed improved mood states, with large effect size on the vigour domain, and moderate effect size in the anger and total mood disturbance (TMD) domains (P < 0.05), in comparison with the M group. After 24 months' intervention, the E and E + M groups perceived better physical and mental HRQoL than the M group. The M group unchanged HRQoL domains (P > 0.05). Metformin had no significant effect on the self-referred HRQoL in T2D participants aged above 60 years, in an early stage of the disease. The E and E + M were the most effective long-term therapies to improve mood states and HRQoL in older adults with T2D.

Background: Data about the presence of fungi on the cutaneous surface of wild animals are scarce. The aim of this study was to survey dermatophytes and Malassezia sp in the external ear canal and haircoat of Leontopithecus chrysomelas., Methods: A total of 928 clinical samples were collected from 232 animals: For Malassezia screening 696 samples were studied, 464 of cerumen and 232 of haircoat; another 232 haircoat samples were studied for dermatophyte analysis., Results: A geophilic dermatophyte, Microsporum cookie, was isolated from one young female. Lipodependent Malassezia was isolated from 76 animals and 87 clinical samples, 26 from the cerumen and 61 from the haircoat (statistically significant); there were no differences related to gender and age., Conclusions: Results suggested that lipodependent Malassezia is part of the skin microbiome of these animals. The prevalence of dermatophytes was too low and probably not relevant for the health of the studied population., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Sickle cell disease (SCD) is a complex disease that is characterized by the polymerization of deoxyhemoglobin S, altered red blood cell membrane biology, endothelial activation, hemolysis, a procoagulant state, acute and chronic inflammation, and vaso-occlusion. Among the physiological changes that occur during pregnancy, oxygen is consumed by fetal growth, and pregnant women with SCD are more frequently exposed to low oxygen levels. This might lead to red blood cells sickling, and, consequently, to vaso-occlusion. The mechanisms by which SCD affects placental physiology are largely unknown, and chronic inflammation might be involved in this process. This study aimed to evaluate the gene expression profile of inflammatory response mediators in the placentas of pregnant women with sickle cell cell anemia (HbSS) and hemoglobinopathy SC (HbSC). Our results show differences in a number of these genes. For the HbSS group, when compared to the control group, the following genes showed differential expression: IL1RAP (2.76-fold), BCL6 (4.49-fold), CXCL10 (-2.12-fold), CXCR1 (-3.66-fold), and C3 (-2.0-fold). On the other hand, the HbSC group presented differential expressions of the following genes, when compared to the control group: IL1RAP (4.33-fold), CXCL1 (3.05-fold), BCL6 (4.13-fold), CXCL10 (-3.32-fold), C3 (-2.0-fold), and TLR3 (2.38-fold). Taken together, these data strongly suggest a differential expression of several inflammatory genes in both SCD (HbSS and HbSC), indicating that the placenta might become an environment with hypoxia, and increased inflammation, which could lead to improper placental development.

Background: Preeclampsia is one of the leading causes of maternal and neonatal morbidity and mortality in the world, but its appearance is still unpredictable and its pathophysiology has not been entirely elucidated. Genetic studies have associated single nucleotide polymorphisms in genes encoding nitric oxide synthase and matrix metalloproteases with preeclampsia, but the results are largely inconclusive across different populations., Objectives: To investigate the association of single nucleotide polymorphisms (SNPs) in NOS3 (G894T, T-786C, and a variable number of tandem repetitions VNTR in intron 4), MMP2 (C-1306T), and MMP9 (C-1562T) genes with preeclampsia in patients from Southeastern Brazil., Methods: This prospective case-control study enrolled 77 women with preeclampsia and 266 control pregnant women. Clinical data were collected to assess risk factors and the presence of severe complications, such as eclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome., Results: We found a significant association between the single nucleotide polymorphism NOS3 T-786C and preeclampsia, independently from age, height, weight, or the other SNPs studied, and no association was found with the other polymorphisms. Age and history of preeclampsia were also identified as risk factors. The presence of at least one polymorphic allele for NOS3 T-786C was also associated with the occurrence of eclampsia or HELLP syndrome among preeclamptic women., Conclusions: Our data support that the NOS3 T-786C SNP is associated with preeclampsia and the severity of its complications.

1. The effect of bacterial endotoxin injection was studied in growing pullets of different ages. Commercial chicks were divided into 5 groups according to age. Bacterial endotoxins (E. coli and S. typhimurium) were injected intravenously and rectal temperature was measured over a period of 300 min. 2. The results showed no significant effect of age on the febrile response induced by bacterial endotoxins, but a slight tendency towards a reduced fever peak was observed with increasing age. The response latency also increased with age.

Purified C3a, a cleavage product of the third component of complement,was incubated with various cell types of human and mouse origin. All the tumour cell types tested were lysed by low concentrations of C3a, whereas normal human lymphocytes were relatively resistant. No lysis was produced by C3 or C3b. The possible role of C3a in immunity against tumours is discussed.

Clonal assays for erythroid progenitors (BFU-e and CFU-e) were used to study 20 patients with rheumatoid arthritis, 15 of whom had anaemia of chronic disease and five of whom were haematologically normal. The numbers of bone marrow BFU-e and CFU-e in the anaemic patients did not differ significantly from those in normal controls. Macrophages were removed from the bone marrow by a combination of adherence and buoyant density centrifugation over a sucrose gradient and the resulting fractions were cultured alone or together with autologous adherent cells in BFU-e assays. Co-culture with adherent cells significantly increased colony growth in both the controls and in seven of eight anaemic patients studied. Serum from 14 anaemic patients and from five non-anaemic patients was added to cultures of bone marrow or to control peripheral blood 'null' cells. Anaemic serum uniformly either inhibited or failed to stimulate BFU-e growth under these conditions. Serum from non-anaemic patients and from 10 healthy controls stimulated BFU-e growth from 'null' cells to an equal degree.

The morphology of stained preparations of cells from human bone marrow and peripheral blood erythroid colonies cultured in methylcellulose, were examined by light microscopy. Although the morphology of 7 d erythroid colonies (CFU-E) was largely normoblastic, bone marrow and peripheral blood erythroid burst (BFU-E) showed a variable degree of megaloblastic and culture system and the deoxyuridine suppression test demonstrated active thymidine synthesis. Megaloblastic morphology was correlated with the growth induced by the addition of monocytes to erythroid progenitors. It was concluded that megaloblastosis was a feature of the erythroblasts derived from an early BFU-E which required monocytes for their development.

Globin chain synthesis was studied in mature erythroid bursts cultured from the peripheral blood null cells of 21 normal individuals. Although coculture of autologous T-lymphocytes with null cells resulted in a fivefold increase in the yield of erythroid bursts, the proportion of gamma chains synthesized (gamma/gamma + beta) was not significantly different from that seen without T cells. Coculture with autologous monocytes also resulted in increased burst-forming unit (BFU-e) proliferation but the ratio gamma/gamma + beta (0.25 +/- 0.03) was significantly higher than that seen with null cells alone (0.08 +/- 0.006) or with T cells (0.10 +/- 0.008). The relative increase in gamma-chain synthesis correlated with the severity of megaloblastic changes in erythroid progeny of BFU-e (P less than 0.01) but showed no significant relationship to the extent of colony maturation assessed by erythroblast maturity.

Colony assays in methylcellulose of primitive erythroid precursors (BFU-E) were carried out from the null cell fraction of normal human peripheral blood lymphoid cells. There was little proliferation or maturation of BFU-E as assessed by both the number and the size of colonies formed, when null cells alone were cultured. Culture of null cells with up to 8 X 10(5) autologous T-lymphocytes per ml led to considerable stimulation of colony growth and maturation. Culture of null cells with peripheral blood monocytes also resulted in the indication of BFU-E growth, although the response was inferior to the seen with T-cells. Co-culture of null cells together with both T-cells and monocytes resulted in a uniformly greater response than with either alone, and this was shown to be due to a positive interaction between these two cell types.

Mouse peritoneal macrophages were activated in serum-free culture with lipopolysaccharide, dextran sulphate or C3b. They were found to liberate into the culture medium a cytolytic factor and a factor which was pharmacologically indistinguishable from C3a. The cytolytic activity was neutralized by antiserum against C3a. These results suggest that macrophages can be activated by C3b (or agents that generate C3b) to cleave C3, which they themselves produce. In this way the activated macrophages form C3a, which appears to be a major factor in macrophage-mediated cytolysis. These findings have implications in tumour immunity and in the pathogenesis of inflammatory reactions.