Short-term physical exercise controls age-related hyperinsulinemia and improves hepatic metabolism in aged rodents.

PURPOSE: Aging is associated with changes in glucose homeostasis related to both decreased insulin secretion and/or impaired insulin action, contributing to the high prevalence of type 2 diabetes (T2D) in the elderly population. Additionally, studies are showing that chronically high levels of circulating insulin can also lead to insulin resistance. In contrast, physical exercise has been a strategy used to improve insulin sensitivity and metabolic health. However, the molecular alterations resulting from the effects of physical exercise in the liver on age-related hyperinsulinemia conditions are not yet fully established. This study aimed to investigate the effects of 7 days of aerobic exercise on hepatic metabolism in aged hyperinsulinemic rats (i.e., Wistar and F344) and in Slc2a4+/- mice (hyperglycemic and hyperinsulinemic mice). RESULTS: Both aged models showed alterations in insulin and glucose tolerance, which were associated with essential changes in hepatic fat metabolism (lipogenesis, gluconeogenesis, and inflammation). In contrast, 7 days of physical exercise was efficient in improving whole-body glucose and insulin sensitivity, and hepatic metabolism. The Slc2a4+/- mice presented significant metabolic impairments (insulin resistance and hepatic fat accumulation) that were improved by short-term exercise training. In this scenario, high circulating insulin may be an important contributor to age-related insulin resistance and hepatic disarrangements in some specific conditions. CONCLUSION: In conclusion, our data demonstrated that short-term aerobic exercise was able to control mechanisms related to hepatic fat accumulation and insulin sensitivity in aged rodents. These effects could contribute to late-life metabolic health and prevent the development/progression of age-related T2D.

Inspiratory muscle training on quality of life in individuals with spinal cord injury: A systematic review and meta-analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVES: The objective was to summarize the effectiveness of Inspiratory Muscle Training (IMT) on the quality of life in individuals with Spinal Cord Injury (SCI). METHODS: An online systematic literature search was conducted in the following databases: PubMed/MEDLINE, PubMed CENTRAL, EMBASE, ISI Web of Science, SciELO, CINAHL/SPORTDiscus, and PsycINFO. Randomized and non-randomized clinical studies investigating the effectiveness of IMT in quality of life were included in the present study. The results used the mean difference and 95% confidence interval for maximal inspiratory pressure (MIP), forced expiratory volume in 1 s (FEV1), maximal expiratory pressure (MEP), and the standardized mean differences for the quality of life and maximum ventilation volume. RESULTS: The search found 232 papers, and after the screening, four studies met the inclusion criteria and were included in the meta-analytical procedures (n = 150 participants). No changes were demonstrated in the quality of life domains (general health, physical function, mental health, vitality, social function, emotional problem, and pain) after IMT. The IMT provided a considerable effect over the MIP but not on FEV1 and MEP. Conversely, it was not able to provide changes in any of the quality of life domains. None of the included studies evaluated the IMT effects on the expiratory muscle maximal expiratory pressure. CONCLUSION: Evidence from studies shows that inspiratory muscle training improves the MIP; however, this effect does not seem to translate to any change in the quality of life or respiratory function outcomes in individuals with SCI.

Medical imaging call centre: a communication success story.

AIM: To evaluate utilisation of a medical imaging call centre (MICC) at a multi-site, academic radiology department, focusing on communication of critical, urgent, or significant unexpected findings. MATERIALS AND METHODS: Institutional research ethics board approval was obtained. All calls made to MICC from 1 January to 31 December 2019 were reviewed retrospectively. The total number of calls, date, and reason of each call, level of report alert, and turnaround time (TAT) were recorded. Level 1, 2, and 3 alerts were defined as "potentially life-threatening new/unexpected findings", "could result in morbidity/mortality", or "not immediately life-threatening or urgent", respectively. TAT was defined as the time from alert request received by the MICC until acknowledgement of receipt by the referring physician, with a desired TAT of 60 min, 3 h, and 3 days for each level, respectively. RESULTS: The MICC received 29,799 calls in 2019, on average 2,483 (range 1,989-3,098) calls per month. The most common indications for contacting the MICC were to request imaging reports to be expedited (14,916 calls, 50%) and issuing report alerts to communicate unexpected or urgent findings (7,060 calls, 24%). Average number and range of calls for Level 1, 2, and 3 alerts were 57 (39-80), 345 (307-388), and 187 (127-215) per month, respectively. Average TAT for Level 1, 2, and 3 report alerts were 59 min, 2 h 26 min, and 19 h 39 min, respectively. CONCLUSION: The MICC received a large volume of calls and was a successful method for timely communication of unexpected or urgent imaging findings using a three-tiered alert system.

Spotting intruders: Species distribution models for managing invasive intertidal macroalgae.

Invasive macroalgae represent one of the major threats to marine biodiversity, ecosystem functioning and structure, as well as being important drivers of ecosystem services depletion. Many such species have become well established along the west coast of the Iberian Peninsula. However, the lack of information about the distribution of the invaders and the factors determining their occurrence make bioinvasions a difficult issue to manage. Such information is key to enabling the design and implementation of effective management plans. The present study aimed to map the current probability of presence of six invasive macroalgae: Grateloupia turuturu, Asparagopsis armata, Colpomenia peregrina, Sargassum muticum, Undaria pinnatifida, and Codium fragile ssp. fragile. For this purpose, an extensive field survey was carried out along the coast of the north-western Iberian Peninsula. Species distribution models (SDMs) were then used to map the presence probability of these invasive species throughout the study region on the basis of environmental and anthropogenic predictor variables. The southern Galician rias were identified as the main hotspots of macroalgal invasion, with a high probability of occurrence for most of the species considered. Conversely, the probability of presence on the Portuguese coast was generally low. Physico-chemical variables were the most important factors for predicting the distribution of invasive macroalgae contributing between 57.27 and 85.24% to the ensemble models. However, anthropogenic factors (including size of vessels, number of shipping lines, distance from ports, population density, etc.) considerably improved the estimates of the probability of occurrence for most of the target species. This study is one of the few to include anthropogenic factors in SDMs for invasive macroalgae. The findings suggest that management actions aimed at controlling these species should strengthen control and surveillance at ports, particularly in southern Galician rias. Early detection should be of main concern for risk assessment plans on the Portuguese coast.

Resistance exercise enhances oxygen uptake without worsening cardiac function in patients with systolic heart failure: a systematic review and meta-analysis.

Recent literature suggests that resistance training (RT) improves peak oxygen uptake ([Formula: see text] peak), similarly to aerobic exercise (AE) in patients with heart failure (HF), but its effect on cardiac remodeling is controversial. Thus, we examined the effects of RT and AE on [Formula: see text] peak and cardiac remodeling in patients with heart failure (HF) via a systematic review and meta-analysis. MEDLINE, EMBASE, Cochrane Library and CINAHL, AMEDEO and PEDro databases search were extracted study characteristics, exercise type, and ventricular outcomes. The main outcomes were [Formula: see text] peak (ml kg-1 min-1), LVEF (%) and LVEDV (mL). Fifty-nine RCTs were included. RT produced a greater increase in [Formula: see text] peak (3.57 ml kg-1 min-1, P < 0.00001, I 2 = 0%) compared to AE (2.63 ml kg-1 min-1, P < 0.00001, I 2 = 58%) while combined RT and AE produced a 2.48 ml kg-1 min-1 increase in [Formula: see text]; I 2 = 69%) compared to control group. Comparison among the three forms of exercise revealed similar effects on [Formula: see text] peak (P = 0.84 and 1.00, respectively; I 2 = 0%). AE was associated with a greater gain in LVEF (3.15%; P < 0.00001, I 2 = 17%) compared to RT alone or combined exercise which produced similar gains compared to control groups. Subgroup analysis revealed that AE reduced LVEDV (- 10.21 ml; P = 0.007, I 2 = 0%), while RT and combined RT and AE had no effect on LVEDV compared with control participants. RT results in a greater gain in [Formula: see text] peak, and induces no deleterious effects on cardiac function in HF patients.

Effects of newly synthetized isoquinoline derivatives on rat uterine contractility and ROCK II activity.

Protein kinases have an important role in signal transduction in the cellular system via protein phosphorylation. RhoA activated Rho-kinases have a pivotal role in the regulation of smooth muscle contraction. ROCK I and ROCK II phosphorylate myosin-phosphatase and myosin-kinase, which induces contraction in the myometrium. Several studies have investigated the affinity of isoquinoline alkaloids (HA-1077, H1152P) to Rho-kinases, and these compounds notably inhibited the Ca2+-independent process. We measured the efficiency of 25 original, newly synthesized isoquinoline derivatives for the Rho-kinase activity using Rho-associated kinase activity assay and determined their effects on the non-pregnant, 20-day pregnant and parturient rat myometrial contraction in vitro. The IC50 values of 11 from among the 25 derivatives were significantly lower on the oxytocin-induced non-pregnant rat uterine contraction compared with Y-27632 and fasudil, although their maximal inhibitory effects were weaker than those of Y-27632 and fasudil. We measured the effects of 11 isoquinoline molecules with significant IC50 values on ROCK II activity. We found two isoquinolines out of 11 compounds (218 and 852) which decreased the active ROCK II level similarly as Y-27632. Then we found that 218 and 852 relaxed the 20th-day pregnant and parturient rat uterus with greater potency as compared with fasudil. The majority of the synthesized isoquinoline derivatives have uterus relaxant effects and two of them significantly suppress the Rho-kinase mediated myosin light chain phosphorylation. Our results may suggest that the isoquinoline structure has a promising prospect for the development of new and effective inhibitors of uterine contractions in preterm birth.

Anti-Tumor Necrosis Factor-α-Induced Dermatological Complications in a Large Cohort of Inflammatory Bowel Disease Patients.

BACKGROUND/AIMS: The broader use of anti-tumor necrosis factor (TNF) agents in inflammatory bowel disease (IBD) has been associated with a high rate of adverse reactions. Dermatological complications are among the most common adverse events. We assessed the incidence, risk factors, management, and outcome of anti-TNF-induced dermatological complications in a large cohort of IBD patients. METHODS: This was an observational retrospective study at a single tertiary referral center. All consecutive adult IBD patients treated with anti-TNF agents between 2005 and 2015 were identified. Patients who developed at least one dermatological complication while on anti-TNF therapy were included. RESULTS: From the 732 patients treated with anti-TNF agents, 211 (29%) developed at least one dermatological complication: 52% women (mean age of 42 ± 13 years), 85% with Crohn's disease, 67% were under infliximab. Median follow-up time under anti-TNF therapy was 53 (27-77) months. Dermatological complications recorded were: infections (13.5%), psoriasiform lesions (5.3%), injection/infusion reactions (3.8%), skin cancer (0.5%), and miscellaneous (5.6%). Overall, female gender (OR = 1.658, p = 0.029), smoking (OR = 2.021, p = 0.003), and treatment with an infliximab dose of 10 mg/kg (OR = 2.012, p = 0.007) were independent risk factors for dermatological complications in multivariable analysis. Female gender (OR = 3.63, p = 0.017), smoking (OR = 2.846, p = 0.041), and treatment with adalimumab (OR = 8.894, p < 0.001) were independently associated with development of psoriasiform lesions. Three (3%) patients with infectious complications and 12 (31%) patients with psoriasiform lesions discontinued anti-TNF therapy definitively. CONCLUSIONS: Dermatological manifestations occurred in almost one-third of our population. Infections were the most common complication, but anti-TNF-induced psoriasiform lesions were the most common cause for anti-TNF therapy definitive discontinuation.

Liver transplant recipients have a higher prevalence of anal squamous intraepithelial lesions.

BACKGROUND: Anal squamous intraepithelial lesions (ASIL) are precancerous lesions of anal squamous cell carcinoma, with a higher prevalence in immunosuppressed patients. There are some studies in kidney transplant recipients, but there is no information regarding prevalence in liver transplantation. Our aim was to evaluate the prevalence of ASIL in this setting. METHODS: Prospective case-control study involving liver transplant recipients without any other known risk factor for ASIL (n=59), which were compared with a healthy control group (n=57). All were submitted to anal cytology and high-resolution anoscopy was performed in those with abnormal results. RESULTS: Ten (17%) of liver transplant recipients had abnormal cytological results, seven patients had atypical squamous cells of undetermined significance (ASC-US), one patient had atypical squamous cells that cannot exclude high-grade (ASC-H) and two patients had high-grade squamous intraepithelial lesions (HSIL). In the control group, one patient (2%) had an ASC-US result (P=0.005). Anal squamous intraepithelial lesions were confirmed in 7 out of 10 of liver transplant patients and 0 out of 1 in the controls (P=0.013) by high-resolution anoscopy with biopsies. Current smoking was the only risk factor for abnormal cytology (odds ratio=5.87, 95% confidence intervals=1.22-28.12, P=0.027). CONCLUSIONS: Liver transplant patients have a higher risk of ASIL. Screening should be considered, especially in smokers.

Hemodynamic Effects Induced by Transcutaneous Electrical Nerve Stimulation in Apparently Healthy Individuals: A Systematic Review With Meta-Analysis.

OBJECTIVE: To determine the immediate effects of transcutaneous electrical nerve stimulation (TENS) on heart rate, systolic blood pressure (SBP), and diastolic blood pressure (DBP) in apparently healthy adults (age ≥18y). DATA SOURCES: The Cochrane Library (online version 2014), PubMed (1962-2014), EMBASE (1980-2014), and LILACS (1980-2014) electronic databases were searched. STUDY SELECTION: Randomized controlled trials were included when TENS was administered noninvasively with surface electrodes during rest, and the effect of TENS was compared with that of control or placebo TENS. A sensitive search strategy for identifying randomized controlled trials was used by 2 independent reviewers. The initial search led to the identification of 432 studies, of which 5 articles met the eligibility criteria. DATA EXTRACTION: Two independent reviewers extracted data from the selected studies. Quality was evaluated using the PEDro scale. Mean differences or standardized mean differences in outcomes were calculated. DATA SYNTHESIS: Five eligible articles involved a total of 142 apparently healthy individuals. Four studies used high-frequency TENS and 3 used low-frequency TENS and evaluated the effect on SBP. Three studies using high-frequency TENS and 2 using low-frequency TENS evaluated the effect on DBP. Three studies using high-frequency TENS and 1 study using low-frequency TENS evaluated the effect on heart rate. A statistically significant reduction in SBP (-3.00mmHg; 95% confidence interval [CI], -5.02 to -0.98; P=.004) was found using low-frequency TENS. A statistically significant reduction in DBP (-1.04mmHg; 95% CI, -2.77 to -0.03; I(2)=61%; P=.04) and in heart rate (-2.55beats/min; 95% CI, -4.31 to -0.78; I(2)=86%; P=.005]) was found using both frequencies. The median value on the PEDro scale was 7 (range, 4-8). CONCLUSIONS: TENS seems to promote a discrete reduction in SBP, DBP, and heart rate in apparently healthy individuals.

Intraoperative diagnosis of nonpigmented nail tumours with ex vivo fluorescence confocal microscopy: 10 cases.

BACKGROUND: Ex vivo fluorescence confocal microscopy (FCM) permits real-time imaging of freshly excised skin tissues. Its usefulness as a time-sparing alternative to frozen sections in Mohs surgery of basal cell carcinoma is well documented. OBJECTIVES: The purpose of this study was to describe the ex vivo FCM features of a series of benign and malignant nonpigmented tumours of the nail unit, and to correlate them with conventional histopathology. PATIENTS AND METHODS: Nail apparatus tumours from 10 patients were imaged during surgical exploration using ex vivo FCM after immersion in acridine orange. Confocal mosaics of the freshly performed biopsies were evaluated in real time and retrospectively compared with haematoxylin and eosin sections. RESULTS: Our series included two invasive epithelial tumours (Group 1), four in situ or minimally invasive squamous cell carcinomas (SCC) (Group 2), three benign epithelial tumours (Group 3) and one nodular melanoma (Group 4). The correlation was excellent for malignant epithelial tumours exhibiting marked cytological and architectural atypias (Bowen disease, invasive SCC and onycholemmal carcinoma). Onychomatricomas exhibited a very peculiar aspect with densely cellular papillae. The correlation was less favourable for minimally invasive well-differentiated SCCs with slight cytological atypias. The correlation was poor for our case of amelanotic invasive subungual melanoma. CONCLUSIONS: Ex vivo FCM could be a useful tool to shorten management of nonpigmented nail tumours: in the case of a malignant tumour, it could indeed lead to performing wide excision during the same surgical procedure and possibly assessing the surgical margins.

Aerobic exercise effect on prognostic markers for systolic heart failure patients: a systematic review and meta-analysis.

From previous systematic reviews and meta-analyses, there is consensus about the positive effect of exercise training on exercise capacity for systolic heart failure (HF); however, the effect on actual prognostic markers such as NTproBNP and minute ventilation/carbon dioxide production (VE/VCO2) slope has not been evaluated. The primary aim of the proposed study is to determine the effect of aerobic exercise training (AEX) on the VE/VCO2 slope and NTproBNP. The following databases (up to February 30, 2013) were searched with no language limitations: CENTRAL (The Cochrane Library 2013, issue 2), MEDLINE (from January 1966), EMBASE (from January 1980), and Physiotherapy Evidence Database (PEDro) (from January 1929). We screened reference lists of articles and also conducted an extensive hand search of the literature. Randomized controlled trials of exercise-based interventions with 2-month follow-up or longer compared to usual medical care or placebo were included. The study population comprised adults aged between 18 and 65 years, with evidence of chronic systolic heart failure (LVEF < 45 % and baseline NTproBNP > 300 pg/ml). Two review authors independently extracted data on study design, participants, interventions, and outcomes. We assessed the risk of bias using PEDro scale. We calculated mean differences (MD) or standardized mean differences between intervention and control groups for outcomes with sufficient data; for other outcomes, we described findings from individual studies. Eight studies involving a total of 408 participants met the inclusion criteria across the NTproBNP (5 studies with 191 patients) and VE/VCO2 slope (4 studies with 217 patients). Aerobic exercise significantly improved NTproBNP by a MD of -817.75 [95 % confidence interval (CI) -929.31 to -706.19]. Mean differences across VE/VCO2 slope were -6.55 (95 % CI -7.24 to -5.87). Those patients' characteristics and exercise were similar (frequency = 3-5 times/week; duration = 20-50 min/day; intensity = 60-80 % of VO2 peak) on the included studies. Moreover, the risk of bias across all studies was homogeneous (PEDro scale = 7-8 points). However, based on the statistical analysis, the heterogeneity among the studies was still high, which is related to the variable characteristics of the studies. Aerobic exercise may be effective at improving NTproBNP and the VE/VCO2 slope in systolic HF patients, but these effects are limited to a specific HF population meeting specific inclusion criterion in a limited number of studies. Future randomized controlled studies including diastolic and HF overleap with pulmonary diseases are needed to better understand the exact influence of AEX.

Preclinical development of siRNA therapeutics: towards the match between fundamental science and engineered systems.

The evolution of synthetic RNAi faces the paradox of interfering with the human biological environment. Due to the fact that all cell physiological processes can be target candidates, silencing a precise biological pathway could be challenging if target selectivity is not properly addressed. Molecular biology has provided scientific tools to suppress some of the most critical issues in gene therapy, while setting the standards for siRNA clinical application. However, the protein down-regulation through the mRNA silencing is intimately related to the sequence-specific siRNA ability to interact accurately with the potential target. Moreover, its in vivo biological fate is highly dependent on the successful design of a vehicle able to overcome both extracellular and intracellular barriers. Anticipating a great deal of innovation, crucial to meet the challenges involved in the RNAi therapeutics, the present review intends to build up a synopsis on the delivery strategies currently developed. FROM THE CLINICAL EDITOR: This review discusses recent progress and pertinent limiting factors related to the use of siRNA-s as efficient protein-specific "silencing" agents, focusing on targeted delivery not only to cells of interest, but to the proper intracellular destination.

Comparable Ventilatory Inefficiency at Maximal and Submaximal Performance in COPD vs. CHF subjects: An Innovative Approach. / Ineficiência Ventilatória Comparável no Desempenho Máximo e Submáximo em Indivíduos com DPOC e ICC: Uma Abordagem Inovadora.

BACKGROUND: Currently, excess ventilation has been grounded under the relationship between minute-ventilation/carbon dioxide output ( V ˙ E - V ˙ CO 2 ). Alternatively, a new approach for ventilatory efficiency ( η E V ˙ ) has been published. OBJECTIVE: Our main hypothesis is that comparatively low levels of η E V ˙ between chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) are attainable for a similar level of maximum and submaximal aerobic performance, conversely to long-established methods ( V ˙ E - V ˙ CO 2 slope and intercept). METHODS: Both groups performed lung function tests, echocardiography, and cardiopulmonary exercise testing. The significance level adopted in the statistical analysis was 5%. Thus, nineteen COPD and nineteen CHF-eligible subjects completed the study. With the aim of contrasting full values of V ˙ E - V ˙ CO 2 and η V ˙ E for the exercise period (100%), correlations were made with smaller fractions, such as 90% and 75% of the maximum values. RESULTS: The two groups attained matched characteristics for age (62±6 vs. 59±9 yrs, p>.05), sex (10/9 vs. 14/5, p>0.05), BMI (26±4 vs. 27±3 Kg m2, p>0.05), and peak V ˙ O 2 (72±19 vs. 74±20 %pred, p>0.05), respectively. The V ˙ E - V ˙ CO 2 slope and intercept were significantly different for COPD and CHF (27.2±1.4 vs. 33.1±5.7 and 5.3±1.9 vs. 1.7±3.6, p<0.05 for both), but η V ˙ E average values were similar between-groups (10.2±3.4 vs. 10.9±2.3%, p=0.462). The correlations between 100% of the exercise period with 90% and 75% of it were stronger for η V ˙ E (r>0.850 for both). CONCLUSION: The η V ˙ E is a valuable method for comparison between cardiopulmonary diseases, with so far distinct physiopathological mechanisms, including ventilatory constraints in COPD.

FUNDAMENTO: Atualmente, o excesso de ventilação tem sido fundamentado na relação entre ventilação-minuto/produção de dióxido de carbono ( V ˙ E − V ˙ CO 2 ). Alternativamente, uma nova abordagem para eficiência ventilatória ( η E V ˙ ) tem sido publicada. OBJETIVO: Nossa hipótese principal é que níveis comparativamente baixos de η E V ˙ entre insuficiência cardíaca crônica (ICC) e doença pulmonar obstrutiva crônica (DPOC) são atingíveis para um nível semelhante de desempenho aeróbico máximo e submáximo, inversamente aos métodos estabelecidos há muito tempo (inclinação V ˙ E − V ˙ CO 2 e intercepto). MÉTODOS: Ambos os grupos realizaram testes de função pulmonar, ecocardiografia e teste de exercício cardiopulmonar. O nível de significância adotada na análise estatística foi 5%. Assim, dezenove indivíduos elegíveis para DPOC e dezenove indivíduos elegíveis para ICC completaram o estudo. Com o objetivo de contrastar valores completos de V ˙ E − V ˙ CO 2 e η E V ˙ para o período de exercício (100%), correlações foram feitas com frações menores, como 90% e 75% dos valores máximos. RESULTADOS: Os dois grupos tiveram características correspondentes para a idade (62±6 vs 59±9 anos, p>.05), sexo (10/9 vs 14/5, p>0,05), IMC (26±4 vs 27±3 Kg m2, p>0,05), e pico V ˙ O 2 (72±19 vs 74±20 % pred, p>0,05), respectivamente. A inclinação V ˙ E − V ˙ CO 2 e intercepto foram significativamente diferentes para DPOC e ICC (207,2±1,4 vs 33,1±5,7 e 5,3±1,9 vs 1,7±3,6, p<0,05 para ambas), mas os valores médios da η E V ˙ foram semelhantes entre os grupos (10,2±3,4 vs 10,9±2,3%, p=0,462). As correlações entre 100% do período do exercício com 90% e 75% dele foram mais fortes para η E V ˙ (r>0,850 para ambos). CONCLUSÃO: A η E V ˙ é um método valioso para comparação entre doenças cardiopulmonares, com mecanismos fisiopatológicos até agora distintos, incluindo restrições ventilatórias na DPOC.

Comparative analysis of the performance of commonly available density functionals in the determination of geometrical parameters for copper complexes.

In this study, a set of 50 transition-metal complexes of Cu(I) and Cu(II), were used in the evaluation of 18 density functionals in geometry determination. In addition, 14 different basis sets were considered, including four commonly used Pople's all-electron basis sets; four basis sets including popular types of effective-core potentials: Los Alamos, Steven-Basch-Krauss, and Stuttgart-Dresden; and six triple-ζ basis sets. The results illustrate the performance of different methodological alternatives for the treatment of geometrical properties in relevant copper complexes, pointing out Double-Hybrid (DH) and Long-range Correction (LC) Generalized Gradient Approximation (GGA) methods as better descriptors of the geometry of the evaluated systems. These however, are associated with a computational cost several times higher than some of the other methods employed, such as the M06 functional, which has also demonstrated a comparable performance. Regarding the basis sets, 6-31+G(d) and 6-31+G(d,p) were the best performing approaches. In addition, the results show that the use of effective-core potentials has a limited impact, in terms of the accuracy in the determination of metal-ligand bond-lengths and angles in our dataset of copper complexes. Hence, these could become a good alternative for the geometrical description of these systems, particularly CEP-121G and SDD basis sets, if one is considering larger copper complexes where the computational cost could be an issue.

Hemodynamic responses to resistance exercise with restricted blood flow in young and older men.

Exercise with blood flow restriction promotes significant improvements, and it has been considered an attractive exercise strategy, especially for older individuals. However, the acute cardiovascular responses to resistance exercise with blood flow restriction (BFR) are not fully known. The purpose of this study was to evaluate the hemodynamic responses during resistance exercise with BFR in young and older individuals. We compared hemodynamic responses in 15 young (30 ± 3 years) and 12 older (66 ± 7 years) subjects during low-intensity resistance biceps curl exercise with (BFR-RE) or without (RE) BFR in a random and crossover design. Heart rate (HR), mean blood pressure (MBP), calf blood flow (CBF), and calf vascular resistance (CVR) were evaluated. Both groups presented similar values at baseline. Compared with RE, HR and MBP were higher during BFR-RE for both the groups, and these changes were maintained during the recovery period. In both the groups, BFR-RE elicited larger decreases in CBF and increased CVR. Both groups showed a significant increase in double product during BFR-RE. In conclusion, resistance exercise with BFR elicits greater hemodynamic changes in healthy young and older subjects, with responses of similar magnitudes in both groups. The safety of BFR in clinical practice demands further study in vulnerable populations.

Early Neuromuscular Electrical Stimulation Preserves Muscle Size and Quality and Maintains Systemic Levels of Signaling Mediators of Muscle Growth and Inflammation in Patients with Traumatic Brain Injury: A Randomized Clinical Trial.

Objective: To investigate the effects of an early neuromuscular electrical stimulation (NMES) protocol on muscle quality and size as well as signaling mediators of muscle growth and systemic inflammation in patients with traumatic brain injury (TBI). Design: Two-arm, single-blinded, parallel-group, randomized, controlled trial with a blinded assessment. Setting. Trauma intensive care unit at a university hospital. Participants. Forty consecutive patients on mechanical ventilation (MV) secondary to TBI were prospectively recruited within the first 24 hours following admission. Interventions. The intervention group (NMES; n = 20) received a daily session of NMES on the rectus femoris muscle for five consecutive days (55 min/each session). The control group (n = 20) received usual care. Main Outcome Measures. Muscle echogenicity and thickness were evaluated by ultrasonography. A daily blood sample was collected to assess circulating levels of insulin-like growth factor I (IGF-I), inflammatory cytokines, and matrix metalloproteinases (MMP). Results: Both groups were similar at baseline. A smaller change in muscle echogenicity and thickness (difference between Day 1 and Day 7) was found in the control group compared to the NMES group (29.9 ± 2.1 vs. 3.0 ± 1.2, p < 0.001; -0.79 ± 0.12 vs. -0.01 ± 0.06, p < 0.001, respectively). Circulating levels of IGF-I, pro-inflammatory cytokines (IFN-y), and MMP were similar between groups. Conclusion: An early NMES protocol can preserve muscle size and quality and maintain systemic levels of signaling mediators of muscle growth and inflammation in patients with TBI. This trial is registered with https://www.ensaiosclinicos.gov.br under number RBR-2db.

Effect of transcutaneous electrical nerve stimulation on muscle metaboreflex in healthy young and older subjects.

Transcutaneous electrical nerve stimulation (TENS) increases local blood flow. It is not known whether increase in blood flow may be caused by inhibition of sympathetic activity, mediated by muscle metaboreflex activity. The purpose of this study was to evaluate the effect of TENS on metaboreflex activation and heart rate variability (HRV) in young and older individuals. Eleven healthy young (age 25 ± 1.3 years) and 11 healthy older (age 63 ± 4.2 years) were randomized to TENS (30 min, 80 Hz, 150 µs) or placebo (same protocol without electrical output) applied on the ganglion region. Frequency domain indices of HRV and hemodynamic variables were evaluated during the pressor response to static handgrip exercise at 30% of maximal voluntary contraction, followed by recovery with (PECO+) or without (PECO-) circulatory occlusion, in a randomized order. At the peak exercise, the increase in mean blood pressure was attenuated by TENS (P < 0.05), which was sustained during PECO+ and PECO-. TENS promoted a higher calf blood flow and lower calf vascular resistance during exercise and recovery. Likewise, TENS induced a reduction in the estimated muscle metaboreflex control both in young (placebo: 28 ± 4 units vs. TENS: 6 ± 3, P < 0.01) and in older individuals (placebo: 13 ± 3 units vs. TENS: 5 ± 3, P < 0.01). HRV analysis showed similar improvement in sympatho-vagal balance with TENS in young and older individuals. We conclude that application of TENS attenuates blood pressure and vasoconstrictor responses during exercise and metaboreflex activation, associated with improved sympatho-vagal balance in healthy young and older individuals.

Risk factors and clinical outcomes of acute esophageal necrosis: retrospective case series of a rare disease with "black" prognosis.

Acute esophageal necrosis is a rare syndrome classically characterized by black distal esophagus with a complex pathophysiology that usually involves a combination of esophageal ischemia, gastroesophageal reflux and impaired mucosal reparative mechanisms. We retrospectively analyzed the main risk factors, clinical characteristics and outcome in all patients diagnosed with acute esophageal necrosis between January 2015 and December 2020 at our center. Ten patients were identified in a total of 26854 upper digestive endoscopies (0.04%). Most patients were male (8/10) and the mean age of presentation was 71.1 years. The most common presenting symptoms were melena and hematemesis and half the patients required red blood cell transfusion. The most common risk factors were hypertension, diabetes mellitus, dyslipidemia, chronic kidney disease, peripheral artery disease, coronary artery disease, cerebrovascular disease, heart failure and malignancy. Compromised hemodynamic state was the most common precipitating event in four patients. Other recognized precipitating events included surgical interventions, decompensated heart failure, gastrointestinal bleeding from gastric malignancy and methotrexate. Endoscopic findings revealed diffuse and circumferential black distal esophagus with abrupt transition at gastroesophageal junction and variable proximal extension at presentation. The 1-month mortality rate was 30%, mostly from severe underlying illness. In conclusion, acute esophageal necrosis is a rare cause of upper gastrointestinal bleeding that should be suspected in older patients with multiple comorbidities. Although associated with a high mortality rate, appropriate treatment may result in favorable outcome in most patients.

Acute hemodynamic responses from low-load resistance exercise with blood flow restriction in young and older individuals: A systematic review and meta-analysis of cross-over trials.

OBJECTIVE: To summarize the existing evidence on the acute response of low-load (LL) resistance exercise (RE) with blood flow restriction (BFR) on hemodynamic parameters. DATA SOURCES: MEDLINE (via PubMed), EMBASE (via Scopus), SPORTDiscus, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Web of Science and MedRxiv databases were searched from inception to February 2022. REVIEW METHODS: Cross-over trials investigating the acute effect of LLRE + BFR versus passive (no exercise) and active control methods (LLRE or HLRE) on heart rate (HR), systolic (SBP), diastolic (DBP) and mean (MBP) blood pressure responses. RESULTS: The quality of the studies was assessed using the PEDro scale, risk of bias using the RoB 2.0 tool for cross-over trials and certainty of the evidence using the GRADE method. A total of 15 randomized cross-over studies with 466 participants were eligible for analyses. Our data showed that LLRE + BFR increases all hemodynamic parameters compared to passive control, but not compared to conventional resistance exercise. Subgroup analysis did not demonstrate any differences between LLRE + BFR and low- (LL) or high-load (HL) resistance exercise protocols. Studies including younger volunteers presented higher chronotropic responses (HR) than those with older volunteers. CONCLUSIONS: Despite causing notable hemodynamic responses compared to no exercise, the short-term LL resistance exercise with BFR modulates all hemodynamic parameters HR, SBP, DBP and MBP, similarly to a conventional resistance exercise protocol, whether at low or high-intensity. The chronotropic response is slightly higher in younger healthy individuals despite the similarity regarding pressure parameters.