Exercise as a tool to mitigate metabolic disease.

Metabolic diseases, notably obesity and type 2 diabetes, have reached alarming proportions and constitute a significant global health challenge, emphasizing the urgent need for effective preventive and therapeutic strategies. In contrast, exercise training emerges as a potent intervention, exerting numerous positive effects on metabolic health through adaptations to the metabolic tissues. Here, we reviewed the major features of our current understanding with respect to the intricate interplay between metabolic diseases and key metabolic tissues, including adipose tissue, skeletal muscle, and liver, describing some of the main underlying mechanisms driving pathogenesis, as well as the role of exercise to combat and treat obesity and metabolic disease.

Maternal exercise preserves offspring cardiovascular health via oxidative regulation of the ryanodine receptor.

OBJECTIVE: The intrauterine environment during pregnancy is a critical factor in the development of obesity, diabetes, and cardiovascular disease in offspring. Maternal exercise prevents the detrimental effects of a maternal high fat diet on the metabolic health in adult offspring, but the effects of maternal exercise on offspring cardiovascular health have not been thoroughly investigated. METHODS: To determine the effects of maternal exercise on offspring cardiovascular health, female mice were fed a chow (C; 21% kcal from fat) or high-fat (H; 60% kcal from fat) diet and further subdivided into sedentary (CS, HS) or wheel exercised (CW, HW) prior to pregnancy and throughout gestation. Offspring were maintained in a sedentary state and chow-fed throughout 52 weeks of age and subjected to serial echocardiography and cardiomyocyte isolation for functional and mechanistic studies. RESULTS: High-fat fed sedentary dams (HS) produced female offspring with reduced ejection fraction (EF) compared to offspring from chow-fed dams (CS), but EF was preserved in offspring from high-fat fed exercised dams (HW) throughout 52 weeks of age. Cardiomyocytes from HW female offspring had increased kinetics, calcium cycling, and respiration compared to CS and HS offspring. HS offspring had increased oxidation of the RyR2 in cardiomyocytes coupled with increased baseline sarcomere length, resulting in RyR2 overactivity, which was negated in female HW offspring. CONCLUSIONS: These data suggest a role for maternal exercise to protect against the detrimental effects of a maternal high-fat diet on female offspring cardiac health. Maternal exercise improved female offspring cardiomyocyte contraction, calcium cycling, respiration, RyR2 oxidation, and RyR2 activity. These data present an important, translatable role for maternal exercise to preserve cardiac health of female offspring and provide insight on mechanisms to prevent the transmission of cardiovascular diseases to subsequent generations.

Antimicrobial and Antibiofilm Coating of Dental Implants-Past and New Perspectives.

Regarded as one of the best solutions to replace missing teeth in the oral cavity, dental implants have been the focus of plenty of studies and research in the past few years. Antimicrobial coatings are a promising solution to control and prevent bacterial infections that compromise the success of dental implants. In the last few years, new materials that prevent biofilm adhesion to the surface of titanium implants have been reported, ranging from improved methods to already established coating surfaces. The purpose of this review is to present the developed antimicrobial and antibiofilm coatings that may have the potential to reduce bacterial infections and improve the success rate of titanium dental implants. All referred coating surfaces showed high antimicrobial properties with effectiveness in biofilm control, while maintaining implant biocompatibility. We expect that by combining the use of oligonucleotide probes as a covering material with novel peri-implant adjuvant therapies, we will be able to avoid the downsides of other covering materials (such as antibiotic resistance), prevent bacterial infections, and raise the success rate of dental implants. The existing knowledge on the optimal coating material for dental implants is limited, and further research is needed before more definitive conclusions can be drawn.

Monoclonal Gammopathy of Renal Significance and Thrombotic Microangiopathy: A Case Report.

Monoclonal gammopathy of renal significance (MGRS) is a group of pathologies that includes all kidney disorders related to a monoclonal protein in patients without diagnostic criteria for B-cell malignancies. There are multiple MGRS-associated kidney disorders, and more are still being discovered, which makes this diagnosis challenging. The relationship between monoclonal gammopathies and thrombotic microangiopathy (TMA) is of growing interest in literature. This article describes the case of a patient with newly diagnosed MGRS, presenting with rapidly progressing kidney failure and with histologic characteristics of TMA. The patient progressed to end-stage renal disease (ESRD) despite treatment with plasmapheresis and clone-directed therapy, as is currently advised in the literature. Although rare, the association between these two entities should not be unnoticed because of patients' renal and vital prognosis.

Skeleton Driven Action Recognition Using an Image-Based Spatial-Temporal Representation and Convolution Neural Network.

Individuals with Autism Spectrum Disorder (ASD) typically present difficulties in engaging and interacting with their peers. Thus, researchers have been developing different technological solutions as support tools for children with ASD. Social robots, one example of these technological solutions, are often unaware of their game partners, preventing the automatic adaptation of their behavior to the user. Information that can be used to enrich this interaction and, consequently, adapt the system behavior is the recognition of different actions of the user by using RGB cameras or/and depth sensors. The present work proposes a method to automatically detect in real-time typical and stereotypical actions of children with ASD by using the Intel RealSense and the Nuitrack SDK to detect and extract the user joint coordinates. The pipeline starts by mapping the temporal and spatial joints dynamics onto a color image-based representation. Usually, the position of the joints in the final image is clustered into groups. In order to verify if the sequence of the joints in the final image representation can influence the model's performance, two main experiments were conducted where in the first, the order of the grouped joints in the sequence was changed, and in the second, the joints were randomly ordered. In each experiment, statistical methods were used in the analysis. Based on the experiments conducted, it was found statistically significant differences concerning the joints sequence in the image, indicating that the order of the joints might impact the model's performance. The final model, a Convolutional Neural Network (CNN), trained on the different actions (typical and stereotypical), was used to classify the different patterns of behavior, achieving a mean accuracy of 92.4% ± 0.0% on the test data. The entire pipeline ran on average at 31 FPS.

Dual SGLT1/SGLT2 Inhibitor Phlorizin Ameliorates Non-Alcoholic Fatty Liver Disease and Hepatic Glucose Production in Type 2 Diabetic Mice.

PURPOSE: NAFLD is a hepatic component of type 2 diabetes mellitus (T2D), in which impaired hepatic glucose production plays an important role. Inhibitors of sodium glucose transporter 2 (SGLT2) reduce glycemia and exert beneficial effects on diabetic complications. Recently, dual SGLT1/2 inhibition has been proposed to be more effective in reducing glycemia. We hypothesized that improving hepatic glucose metabolism induced by SGLT1/2 inhibition could be accompanied by beneficial effects on NAFLD progression. METHODS: Glycemic homeostasis, hepatic glucose production and NAFLD features were investigated in obese T2D mice, treated with SGLT1/2 inhibitor phlorizin for 1 week. RESULTS: T2D increased glycemia; insulinemia; hepatic expression of phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase) and glucose transporter 2 (Slc2a2 gene); hepatocyte nuclear factors 1A/4A/3B-binding activity in Slc2a2; endogenous glucose production; liver weight, plasma transaminase concentration as well as hepatic inflammation markers, and induced histological signals of non-alcoholic steatohepatitis (NASH, according to NASH-CRN Pathology Committee System). Phlorizin treatment restored all these parameters (mean NASH score reduced from 5.25 to 2.75 P<0.001); however, plasma transaminase concentration was partially reverted and some hepatic inflammation markers remained unaltered. CONCLUSION: NAFLD accompanies altered hepatic glucose metabolism in T2D mice and that greatly ameliorated through short-term treatment with the dual SGLT1/2 inhibitor. This suggests that altered hepatic glucose metabolism participates in T2D-related NAFLD and highlights the pharmacological inhibition of SGLTs as a useful approach not only for controlling glycemia but also for mitigating development and/or progression of NAFLD.

Surgical Treatment for Congenital Dislocation of the Patella in a Young Adult: A Case Report.

CASE: We present an 18-year-old man with poor alignment of the lower limbs, marked by congenital dislocation of the left patella, with gait impairment, and an associated 20° flexion contracture. Surgical treatment was performed with a single complex procedure with the release of the lateral retinaculum, capsule, and iliotibial tract, followed by a subtraction trochleoplasty, tibial tubercle transfer, elongation of the quadriceps tendon, and anatomical reconstruction of the medial patellofemoral ligament. At the 5-year follow-up, the patient had a significant improvement in gait pattern, with the patella centered on the new trochlear groove without any signs of patellar instability. CONCLUSIONS: The approach of congenital dislocation of the patella is controversial, and although numerous procedures have been described in children, the approach in adults should be individually tailored. In this case, trochlear deepening and preserving the trochlear cartilage proved to be an effective option for treating a congenital dislocation.

Effects of walk training with self-selected intensity on biochemical markers and anthropometric variables in women with obesity.

To evaluate the effects of 12-weeks of walk training with self-selected intensity on lipid profile and anthropometric variables in women with obesity. Forty-eight women volunteers with obesity were randomly assigned into two training groups: self-selected walking group (SSWG; n=25) and control group (CG; n=23). There was improvement in biochemical markers only in the SSWG post-intervention (p<0.05), however no changes were verified in anthropometric variables (p>0.05). This study demonstrates that walking at self-selected intensity improved the lipid profile in women with obesity.

Energy System Contributions in Upper and Lower Body Wingate Tests in Highly Trained Athletes.

PURPOSE: This study compared the energy system contributions and relationship between mechanical and energy system variables in upper and lower body Wingate tests (WAnT) in judo athletes. METHOD: Eleven male judo athletes (18 ± 1 years, 174.3 ± 5.3 cm, 72.6 ± 9.9 kg, 11.8 ± 1.7% body fat) attended two laboratory sessions to perform two WAnT (upper and lower body) and two incremental tests (upper and lower body). The energy contributions of the oxidative, glycolytic, and phosphagen (ATP-PCr) systems were estimated based on oxygen consumption ( V˙O2 ) during WAnT, delta of lactate, and the fast phase of excess V˙O2 , respectively. RESULTS: The upper and lower body presented similar results of oxidative (21 ± 4% vs 23 ± 3%) and ATP-PCr system contributions (29 ± 6% vs 32 ± 5%). The glycolytic system contribution (50 ± 5% vs 45 ± 4%) was higher in the upper body. The variance of mechanical variables in upper body was explained by glycolytic (R2 = 0.49-0.62) and oxidative systems (R2 = 0.44-0.49), whereas the variance of mechanical variables in lower body was explained by ATP-PCr (R2 = 0.41-0.55) and glycolytic systems (R2 = 0.62-0.94). CONCLUSIONS: During WAnT, the glycolytic system presented the major energy contribution, being higher in the upper body. Moreover, mechanical and energy system variables presented a distinct relationship when comparing upper and lower body WAnT.

Early Debridement, antibiotics and implant retention (DAIR) in patients with suspected acute infection after hip or knee arthroplasty - safe, effective and without negative functional impact.

Introduction: Debridement, antibiotics and implant retention (DAIR) is known to be effective in treating acute periprosthetic joint infection (PJI). However, deciding to perform additional surgery in the early postoperative period may be challenging as there is the concern of adding morbidity and clinical presentation is often subtle. We mean to assess the impact of early DAIR on final functional outcome. Methods: A case-control comparison was performed between patients that underwent DAIR for suspected PJI between 2010-2016 and controls randomly selected (1:2 ratio) from a list of primary joint replacements. Patients were matched for anatomic site, age, gender, American Society of Anesthesiologists (ASA) classification, body mass index and follow-up time. The outcome of surgical treatment and complications were assessed and Hip disability and Osteoarthritis Outcome Score (HOOS) or Knee injury and Osteoarthritis Outcome Score (KOOS) were performed. Results: Thirty-eight cases were included at a mean follow-up of 42 months. Infection was not confirmed in one patient. There was one infection related-death and three other cases of treatment failure that required a two-stage revision. Overall success rate was 89.2%. There were no significant patient reported differences regarding final functional outcome between both groups: pain 91±6 vs. 87±13; other symptoms 90±8 vs. 90±9; activities of day living 86±8 vs. 85±14; sport 63±13 vs. 57±16; quality of life 78±17 vs. 76±16. Discussion: These findings support that DAIR for suspected acute PJI is safe, effective and causes no impact on final functional results. Thus, a low threshold for assuming infection and subsequent DAIR may safely be adopted in the early postoperative period.

Does moderate-intensity continuous training result in greater total energy expenditure compared to high-intensity interval training?

Recently in the Journal of Sports Sciences, Schaun et al. published a study on the comparison of energy expenditure between high-intensity interval training and moderate continuous training performed in water. With this Letter to the Editor, we would like to comment on the methodological aspects that should be considered to analyze the results presented, as well as the conclusions. Abbreviations: CONT, moderate-intensity continuous training; EPOC, excess post-exercise oxygen consumption; HIIT, high-intensity interval training; VO2max, maximal oxygen consumption.

Diabetes induces tri-methylation at lysine 9 of histone 3 at Slc2a4 gene in skeletal muscle: A new target to improve glycemic control.

Expression of the glucose transporter GLUT4, encoded by Slc2a4 gene, is reduced in both type 1 and type 2 diabetes (T1D and T2D), contributing to glycemic impairment. The present study investigated epigenetic regulations at the Slc2a4 promoter in skeletal muscle of T1D- and T2D-like experimental models. Slc2a4/GLUT4 repression was observed in T1D and T2D and that was reversed by insulin and resveratrol treatments, respectively. In both T1D-like and T2D-like animals, tri-methylation at lysine 9 of histone 3 (H3K9me3) increased in the Slc2a4 enhancer segment, whereas MEF2A/D binding into this segment was reduced; all effects were reversed by respective treatments. This study reveals that increased H3K9me3 in the Slc2a4 promoter enhancer segment contributes to reduce GLUT4 expression in skeletal muscle and to worse glycemic control in diabetes, pointing to the H3K9me3 of Slc2a4 promoter as a potential target for development of new approaches for treating diabetes.

Comparison of fine needle aspiration and core needle biopsy in the diagnosis of bone tumours.

Much literature exists regarding the diagnostic yield and accuracy of core needle biopsy (CNB) and fine needle aspiration (FNA) but none compares both in the same tumour. Ninety-four patients were prospectively studied using a FNA and CNB. With FNA 70 diagnoses were possible (74,5%). Accurate diagnosis rate was 97,1%. In 92 patients (97,9%) a diagnosis was obtained with CNB and 91 (98,9%) were accurate.. The diagnostic yield was 74,5% for FNA and 97,9% for CNB (p < 0.0001). The diagnostic accuracy was 97,1% for FNA and 98,9% for CNB (p = 0.5787). Regarding determining malignancy FNA and CNB had 98,3% and 98,5% sensibility, 100% and 100% specificity, 100% and 100% positive predictive value and 95,2% and 96,2% negative predictive value, respectively. In conclusion FNA is as accurate as CNB on all accounts. Despite the reliability of FNA, the number of inconclusive cases makes it an inferior technique when compared with CNB.

Diabetes Modulates MicroRNAs 29b-3p, 29c-3p, 199a-5p and 532-3p Expression in Muscle: Possible Role in GLUT4 and HK2 Repression.

The reduced expression of solute carrier family 2, facilitated glucose transporter member 4 (GLUT4) and hexokinase-2 (HK2) in skeletal muscle participates in insulin resistance of diabetes mellitus (DM). MicroRNAs (miRNAs) have emerged as important modulators of mRNA/protein expression, but their role in DM is unclear. We investigated miRNAs hypothetically involved in GLUT4/HK2 expression in soleus muscle of type 1 diabetes-like rats. In silico analysis revealed 651 miRNAs predicted to regulate solute carrier family 2 member 4 (Slc2a4) mRNA, several of them also predicted to regulate Hk2 mRNA, and 16 miRNAs were selected for quantification. Diabetes reduced Slc2a4/GLUT4 and Hk2/HK2 expression (50-77%), upregulated miR-29b-3p and miR-29c-3p (50-100%), and downregulated miR-93-5p, miR-150-5p, miR-199a-5p, miR-345-3p, and miR-532-3p (~30%) expression. Besides, GLUT4 and HK2 proteins correlated (P < 0.05) negatively with miR-29b-3p and miR-29c-3p and positively with miR-199a-5p and miR-532-3p, suggesting that these miRNAs could be markers of alterations in GLUT4 and HK2 expression. Additionally, diabetes increased the nuclear factor kappa B subunit 1 protein (p50) expression, a repressor of Slc2a4, which was also predicted as a target for miR-199a-5p and miR-532-3p. Correlations were also detected between these miRNAs and blood glucose, 24-h glycosuria and plasma fructosamine, and insulin therapy reversed most of the alterations. In sum, we report that diabetes altered miR-29b-3p, miR-29c-3p, miR-199a-5p and miR-532-3p expression in muscle of male rats, where their predicted targets Slc2a4/GLUT4 and Hk2/HK2 are repressed. These data shed light on these miRNAs as a markers of impaired skeletal muscle glucose disposal, and, consequently, glycemic control in diabetes.

Advanced glycation end products-induced insulin resistance involves repression of skeletal muscle GLUT4 expression.

Little is known about advanced glycation end products (AGEs) participation in glucose homeostasis, a process in which skeletal muscle glucose transporter GLUT4 (Scl2a4 gene) plays a key role. This study investigated (1) the in vivo and in vitro effects of AGEs on Slc2a4/GLUT4 expression in skeletal muscle of healthy rats, and (2) the potential involvement of endoplasmic reticulum and inflammatory stress in the observed regulations. For in vivo analysis, rats were treated with advanced glycated rat albumin (AGE-albumin) for 12 weeks; for in vitro analysis, soleus muscles from normal rats were incubated with bovine AGE-albumin for 2.5 to 7.5 hours. In vivo, AGE-albumin induced whole-body insulin resistance; decreased (~30%) Slc2a4 mRNA and GLUT4 protein content; and increased (~30%) the nuclear content of nuclear factor NF-kappa-B p50 subunit (NFKB1), and cellular content of 78 kDa glucose-regulated protein (GRP78). In vitro, incubation with AGE-albumin decreased (~50%) the Slc2a4/GLUT4 content; and increased cellular content of GRP78/94, phosphorylated-IKK-alpha/beta, nuclear content of NFKB1 and RELA, and the nuclear protein binding into Slc2a4 promoter NFKB-binding site. The data reveal that AGEs impair glucose homeostasis in non-diabetic states of increased AGEs concentration; an effect that involves activation of endoplasmic reticulum- and inflammatory-stress and repression of Slc2a4/GLUT4 expression.