Effects of one-year once-weekly high-intensity interval training on body adiposity and liver fat in adults with central obesity: Study protocol for a randomized controlled trial.

Objective: This study aims to examine the effects of one-year, once-weekly high-intensity interval training (HIIT) on body adiposity and liver fat in adults with central obesity. Methods: One-hundred and twenty adults aged 18-60 years with central obesity (body mass index ≥25, waist circumference ≥90 cm for men and ≥80 cm for women). This is an assessor-blinded randomized controlled trial. Participants will be randomly assigned to the HIIT group or the usual care control group. Each HIIT session will consist of 4 × 4-min bouts at 85%-95% maximal heart rate, interspersed with 3-min bouts at 50%-70% maximal heart rate. The HIIT group will complete one session per week for 12 months, whereas the usual care control group will receive health education. The primary outcomes of this study are total body adiposity and intrahepatic triglyceride content. The secondary outcomes include abdominal visceral adipose tissue, subcutaneous adipose tissue, body mass index, waist circumference, hip circumference, cardiorespiratory fitness, lean body mass, bone mineral density, blood pressure, fasting blood glucose, insulin, triglycerides, glycated hemoglobin, cholesterol profile, liver function enzymes, medications, adherence to exercise, adverse events, quality of life, and mental health. Outcome measure will be conducted at baseline, 12 months (post-intervention), and 24 months (one-year follow-up). Impact of the project: This study will explore the benefits of long-term once-weekly HIIT with a follow-up period to assess its effectiveness, adherence, and sustainability. We expect this intervention will enhance the practical suitability of HIIT in inactive adults with central obesity, and provide insights on low-frequency HIIT as a novel exercise option for the management of patients with central obesity and liver fat. Trial registration: ClinicalTrials.gov (NCT03912272) registered on 11 April 2019.

Multimodal Patient-Specific Registration for Breast Imaging Using Biomechanical Modeling with Reference to AI Evaluation of Breast Tumor Change.

BACKGROUND: The strategy to combat the problem associated with large deformations in the breast due to the difference in the medical imaging of patient posture plays a vital role in multimodal medical image registration with artificial intelligence (AI) initiatives. How to build a breast biomechanical model simulating the large-scale deformation of soft tissue remains a challenge but is highly desirable. METHODS: This study proposed a hybrid individual-specific registration model of the breast combining finite element analysis, property optimization, and affine transformation to register breast images. During the registration process, the mechanical properties of the breast tissues were individually assigned using an optimization process, which allowed the model to become patient specific. Evaluation and results: The proposed method has been extensively tested on two datasets collected from two independent institutions, one from America and another from Hong Kong. CONCLUSIONS: Our method can accurately predict the deformation of breasts from the supine to prone position for both the Hong Kong and American samples, with a small target registration error of lesions.

Obestatin and growth hormone reveal the interaction of central obesity and other cardiometabolic risk factors of metabolic syndrome.

Metabolic syndrome (MetS) is a multi-factorial disorder including central obesity (CO), insulin resistance, hyperglycemia, dyslipidemia and hypertension which increases the risk of diabetes mellitus and cardiovascular diseases. CO is considered as an essential component of MetS according to International Diabetes Federation (IDF), which may further modulate distinct signalling pathways compared with the other four MetS risk factors. Given that ghrelin signalling and the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis regulates energy balance and metabolic homeostasis, this study examined the changes in various ghrelin products and circulating hormones in response to the interaction between CO and other MetS components including blood pressure, fasting blood glucose, triglycerides, and high-density lipoprotein cholesterol in 133 Hong Kong Chinese adults. Circulating obestatin and GH were increased and reduced, respectively, by either CO or the other 4-risk factor cluster. These changes were further augmented by the presence of all MetS risk factors. However, changes of ghrelin levels were not mediated by CO but the other MetS risk factors. Our findings suggest that CO does not predict all the dysregulation of signalling pathways in individuals with MetS. Although CO and other MetS may share common signalling targets (i.e., obestatin and GH), CO does not contribute to the perturbation of ghrelin signalling.

Low-Frequency HIIT Improves Body Composition and Aerobic Capacity in Overweight Men.

BACKGROUND: The relationship between the frequency of high-intensity interval training (HIIT) and the resultant adaptations is largely unclear. PURPOSE: This study compared the effects of different frequencies of HIIT with those of moderate-intensity continuous training (MICT) on body composition in overweight or obese adults. METHODS: Fifty-six overweight or obese (body mass index = 26.4 ± 2.9) men between 18 and 30 yr old (age = 22.8 ± 3.1 yr) were randomly assigned to the following groups: no-intervention control (CON; n = 14), MICT performed thrice weekly (MICT×3/wk; n = 9), HIIT performed thrice weekly (HIIT×3/wk; n = 14), HIIT performed twice weekly (HIIT×2/wk; n = 10), and HIIT performed once weekly (HIIT×1/wk; n = 9). Each HIIT session consisted of 12 × 1-min bouts at 90% heart rate reserve, interspersed with 11 × 1-min bouts at 70% heart rate reserve. Aerobic capacity, body composition, resting heart rate, vascular function, insulin resistance, and biomarkers of metabolic syndrome risk factor were examined at baseline, after 4 wk, and after 8 wk of intervention. RESULTS: Aerobic capacity and percent fat-free mass significantly increased in all exercise groups compared with those in the CON group (CON vs all exercise groups, P < 0.05), whereas body fat mass and systolic blood pressure significantly decreased after 8 wk of intervention in all exercise groups compared with those in the CON group (CON vs all exercise groups, P < 0.05). Body fat mass significantly decreased after 4 wk in all HIIT groups compared with those in the CON group (CON vs all HIIT groups, P < 0.05) but not in the MICT×3/wk group. CONCLUSION: These novel results demonstrated that performing HIIT once weekly, even with a lower weekly volume of exercise, improved cardiorespiratory fitness, body composition, and blood pressure in overweight/obese adults. Low-frequency HIIT might be a feasible and effective strategy for the prescription of an initial exercise program for inactive, overweight, or obese young men.

One Year of Yoga Training Alters Ghrelin Axis in Centrally Obese Adults With Metabolic Syndrome.

Introduction: Metabolic syndrome (MetS) is a multiplex cardiometabolic manifestation associated with type 2 diabetes mellitus and cardiovascular diseases. Yoga training has been shown to alleviate MetS. Recently, circulatory ghrelin profile was demonstrated to be associated with MetS. This study examined the effects of 1 year of yoga training on ß-cell function and insulin resistance, and the involvement of metabolic peptides, including unacylated ghrelin (UnAG), acylated ghrelin (AG), obestatin, growth hormone (GH), and insulin, in the beneficial effects of yoga training in centrally obese adults with MetS. Methods: This was a follow up study, in which data of risk factors of MetS, physical performance tests [resting heart rate (HR), chair stand test (CS), chair sit and reach test (CSR), back scratch test (BS), and single leg stand tests (SLS)] and serum samples of 79 centrally obese MetS subjects aged 58 ± 8 years (39 subjects received 1-year yoga training and 40 subjects received no training) were retrieved for analyses. ß-cell function and insulin resistance were examined by Homeostasis Model Assessment (HOMA). Circulating levels of UnAG, AG, obestatin, GH, and insulin were determined by enzyme-linked immunosorbent assay using fasting serum samples. Generalized estimating equation analysis and Mann-Whitney U-test were used to detect statistically significant differences between groups. Results: Waist circumference (WC) was significantly decreased after yoga intervention (control: +2%; yoga: -4%). Significant improvements in HR (control: +2%; yoga: -5%), CS (control: -1%; yoga: +24%), CSR left (control: worsen by 0.90 cm; yoga: improved by 4.21 cm), CSR right (control: worsen by 0.75 cm; yoga: improved by 4.28 cm), right side of BS (control: improved by 0.19 cm; yoga: improved by 4.31 cm), SLS left (control: -10%; yoga: +86%), and SLS right (control: -6%; yoga: +47%) were observed after 1-year yoga training. No significant difference was found between the two groups in insulin, HOMA indices, and disposition index. Yoga training significantly increased circulating GH (control: -3%; yoga: +22%), total circulating ghrelin (control: -26%; yoga: +13%), and UnAG (control: -27%; yoga: +14%), whereas decreased AG (control: -7%; yoga: -33%) and obestatin (control: +24%; yoga: -29%). Conclusion: One-year of yoga training modulated total ghrelin, UnAG, AG, obestatin, and GH while exerting beneficial effects on physical functions and central obesity in adults with MetS. The beneficial effects of yoga may be associated with the alteration of ghrelin gene product and GH.

Ghrelin Axis Reveals the Interacting Influence of Central Obesity and Hypertension.

Objective: This study aimed to investigate how central obesity and hypertension modulate unacylated ghrelin (UnAG), acylated ghrelin (AG), obestatin, growth hormone (GH), and the ratios of UnAG/obestatin, AG/obestatin, and total ghrelin/obestatin. Methods: Circulatory abundances of UnAG, AG, obestatin and GH were determined in 387 Hong Kong Chinese female adults with age between 24 to 86 years based on a 2 × 2 factorial design of hypertension (blood pressure ≥140/90 mmHg) and central obesity (waist circumference or WC ≥80 cm). Participants were categorized as neither hypertensive nor centrally obese (NHNO; n = 105), hypertensive but not centrally obese (HNO; n = 102), centrally obese but not hypertensive (NHO; n = 74) and hypertensive and centrally obese (NO; n = 106). Pearson's correlation analyses were performed to detect the association between the peptides examined with WC and blood pressure. The main and interaction effects of hypertension and central obesity were examined by generalized estimating equations analyses. Results: Correlation analyses revealed that systolic blood pressure was negatively correlated with AG/obestatin, UnAG/obestatin and total ghrelin/obestatin ratios, AG, total ghrelin, and GH, while diastolic blood pressure was negatively correlated with UnAG/obestatin, total ghrelin/obestatin ratios, and GH. WC was negatively correlated with AG/obestatin, UnAG/obestatin, and total ghrelin/obestatin ratios, UnAG, AG, total ghrelin, GH, and obestatin. Interaction effects of hypertension and central obesity were observed on UnAG/obestatin, AG/obestatin and total ghrelin/obestatin ratios, and obestatin. Obestatin in NHO group was significantly higher compared to NHNO and HO groups. UnAG/obestatin, AG/obestatin, and total ghrelin/obestatin ratios were higher in NHNO group compared to HNO and HO groups. Main effects of central obesity and hypertension were observed in UnAG, total ghrelin and GH. The HO group manifested the lowest level of UnAG, total ghrelin and GH among all the groups studied. Main effect of hypertension was observed on AG, suggesting that hypertensive individuals exhibited lower levels of AG regardless of central obesity. Conclusion: Circulatory ghrelin gene products and GH exhibit different modes of modulation in response to the co-manifestation of multiple cardiovascular risk factors compared with a single risk factor alone.

Adipokines demonstrate the interacting influence of central obesity with other cardiometabolic risk factors of metabolic syndrome in Hong Kong Chinese adults.

OBJECTIVE: Metabolic syndrome (MetS) or prediabetes is a complex disorder that is defined by a clustering of cardiometabolic risk factors, including obesity, hypertriglyceridemia, reduced high-density lipoprotein (HDL) cholesterol, hypertension, and insulin resistance. Among cardiometabolic risk factors, central obesity plays a key role in the development of MetS through alterations in the secretion of adipokines and interacts with other MetS risk factors to unfavorably influence overall cardiometabolic risk. Obesity has grasped epidemic proportions in Asia, which has the highest number of people with diabetes in the world. But, the importance of central obesity in the clustering of all four MetS risk factors or vice versa in predicting severity of MetS has not yet been investigated in Asian population. Therefore, the present study examined the influence of central obesity on circulating levels of adipokines through its interaction with the clustering of cardiometabolic risk factors of MetS including hyperglycemia, hypertriglyceridemia, dyslipidemia and hypertension in Hong Kong Chinese adults. SUBJECTS: Blood samples from 83 Hong Kong Chinese adults, who were previously screened for MetS according to the guideline of the United States National Cholesterol Education Program Expert Panel Adult Treatment Panel III criteria were selected. Insulin and adipokines, including visfatin, chemerin, plasminogen activator inhibitor-1 (PAI-1), resistin, C-C motif chemokine ligand 2 (CCL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), tumour necrosis factor-α (TNF-α), leptin and adiponectin were assessed. RESULTS: The interacting effect of central obesity with all of the other four MetS risk factors increased the proinflammatory status of adipokines (TNF-α, leptin) and decreased the anti-inflammatory status of adipokine (adiponectin). CONCLUSION: Our results indicate that the inflammatory status of MetS may be more severe in the presence of central obesity. Adipokines, as biomarkers for pathophysiological changes, may help to improve early patient identification and to predict MetS-associated morbidity and mortality.

Adipokine Profiling in Adult Women With Central Obesity and Hypertension.

Central obesity and hypertension are common risk factors for the metabolic syndrome, cardiovascular and renal diseases. Studies have shown that it is more difficult to control blood pressure and prevent end-organ damage in obese individuals with hypertension compared to their non-obese counterparts, especially among women. Obese females have a 6 times higher risk of developing hypertension than non-obese females while obese males are at a 1.5 times higher risk of developing hypertension, compared to their non-obese counterparts. Indeed, the inter-relationship between obesity and hypertension is unclear. Adipokines have been proposed to play a mediating role in the relationship between obesity and hypertension and are involved in the pathogenesis of metabolic diseases. Therefore, this study sought to determine the role of adipokines (adiponectin, plasminogen activator inhibitor-1, leptin, and tumor necrosis factor-α) in hypertensive Hong Kong Chinese women with central obesity. A total of 387 women aged 58 ± 11 years who were examined with a 2 × 2 factorial design for central obesity (waist circumference ≥ 80 cm) and hypertension (blood pressure ≥ 140/90 mmHg), were recruited from a pool of 1,492 Hong Kong Chinese adults who were previously screened for metabolic syndrome. Subjects with hyperglycemia, hypertriglyceridemia, and dyslipidemia were excluded to eliminate confounding effects. Our findings revealed that hypertensive women with central obesity had a lower anti-inflammatory status (adiponectin) and a higher pro-inflammatory status (TNF-α) than obese alone or hypertensive alone women. Also, women with central obesity had higher circulatory PAI-1 and leptin concentrations than their non-obese counterparts. We conclude that obesity may shift toward a more pro-inflammatory state and may become more severe in the presence of hypertension or vice versa.

Association of Markers of Proinflammatory Phenotype and Beige Adipogenesis with Metabolic Syndrome in Chinese Centrally Obese Adults.

BACKGROUND: Visceral adiposity is associated with higher productions of C-reactive protein (CRP) and interleukin-6 (IL-6). Inflammation of obese adipose tissues could contribute to systemic metabolic dysregulation, especially thermogenic activity of white adipose tissues, namely, beige adipogenesis, characterized by altered irisin expression. Thus, we investigated the roles of inflammation and adipocyte beiging in Chinese centrally obese (CO) adults with metabolic syndrome (MetS). METHODS: This cross-sectional study was conducted on 54 CO and 58 non-CO subjects drawn from 1492 Chinese people with age and sex matched during November 2010 and August 2013. Twenty (37.0%) of the CO subjects fulfilled the IDF worldwide definition of MetS. Serum CRP, IL-6, and irisin levels were examined. RESULTS: Higher CRP and IL-6, but lower irisin, levels were manifested in MetS versus non-MetS subjects with or without CO. Multiple linear regression identified high-density lipoprotein cholesterol level as the only independent risk factor for irisin level. Categorized by median of CRP and IL-6 levels, a lower irisin level was only observed in high CRP group. CONCLUSION: Under the condition of central obesity, chronic inflammation and impaired beige adipogenesis are associated with MetS in Chinese adults.

Noninvasive Real-Time Characterization of Renal Clearance Kinetics in Diabetic Mice after Receiving Danshensu Treatment.

Danshensu (DSS) is an active ingredient extracted from the root of the Danshen that could ameliorate oxidative stress via upregulation of heme oxygenase- (HO-) 1. Little is known about the treatment effects of DSS on kidney function in diabetic mice. Therefore, the primary aim of the present study was to characterize the renal clearance kinetics of IRdye800CW in db/db mice after DSS treatment. The secondary aim was to measure several biomarkers of renal function and oxidative stress (urinary F2-isoprostane, HO-1 in kidney and serum bilirubin). Fourteen db/db diabetic mice were randomly assigned into two groups and received either DSS treatment (DM + DSS) or vehicle treatment (DM). A third group that comprised of db/+ nondiabetic mice (non-DM control) received no DSS treatment and served as the nondiabetic control. At the end of a 3-week intervention period, serum and urinary biomarkers of renal function and oxidative stress were assessed and the renal clearance of IRdye800CW dye in all mice was determined noninvasively using Multispectral Optoacoustic Tomography. The major finding from this study suggested that DSS treatment in db/db mice improved renal clearance. Increased expression of HO-1 after DSS treatment also suggested that DSS might represent a potential therapeutic avenue for clinical intervention in diabetic nephropathy.

Ablation of Bax and Bak protects skeletal muscle against pressure-induced injury.

Pressure-induced injury (PI), such as a pressure ulcer, in patients with limited mobility is a healthcare issue worldwide. PI is an injury to skin and its underlying tissue such as skeletal muscle. Muscle compression, composed of mechanical deformation of muscle and external load, leads to localized ischemia and subsequent unloading reperfusion and, hence, a pressure ulcer in bed-bound patients. Although the gross factors involved in PI have been identified, little is known about the exact disease mechanism or its links to apoptosis, autophagy and inflammation. Here, we report that PI is mediated by intrinsic apoptosis and exacerbated by autophagy. Conditional ablation of Bax and Bak activates the Akt-mTOR pathway and Bnip3-mediated mitophagy and preserves mitochondrial contents in compressed muscle. Moreover, we find that the presence/absence of Bax and Bak alters the roles and functions of autophagy in PI. Our results suggest that manipulating apoptosis and autophagy are potential therapeutic targets for treatment and prevention of PI.

Revealing the Neural Mechanisms Underlying the Beneficial Effects of Tai Chi: A Neuroimaging Perspective.

Tai Chi Chuan (TCC), a traditional Chinese martial art, is well-documented to result in beneficial consequences in physical and mental health. TCC is regarded as a mind-body exercise that is comprised of physical exercise and meditation. Favorable effects of TCC on body balance, gait, bone mineral density, metabolic parameters, anxiety, depression, cognitive function, and sleep have been previously reported. However, the underlying mechanisms explaining the effects of TCC remain largely unclear. Recently, advances in neuroimaging technology have offered new investigative opportunities to reveal the effects of TCC on anatomical morphologies and neurological activities in different regions of the brain. These neuroimaging findings have provided new clues for revealing the mechanisms behind the observed effects of TCC. In this review paper, we discussed the possible effects of TCC-induced modulation of brain morphology, functional homogeneity and connectivity, regional activity and macro-scale network activity on health. Moreover, we identified possible links between the alterations in brain and beneficial effects of TCC, such as improved motor functions, pain perception, metabolic profile, cognitive functions, mental health and sleep quality. This paper aimed to stimulate further mechanistic neuroimaging studies in TCC and its effects on brain morphology, functional homogeneity and connectivity, regional activity and macro-scale network activity, which ultimately lead to a better understanding of the mechanisms responsible for the beneficial effects of TCC on human health.

Yoga training modulates adipokines in adults with high-normal blood pressure and metabolic syndrome.

Metabolic syndrome (MetS) is associated with diabetes mellitus and cardiovascular diseases. Our previous study indicated that people with MetS showed a decrease in waist circumference and a decreasing trend in blood pressure after 1-year yoga. This study investigated the effect of yoga on MetS people with high-normal blood pressure by exploring modulations in proinflammatory adipokines (leptin, chemerin, visfatin, and plasminogen activator inhibitor-1 or PAI-1) and an anti-inflammatory adipokine (adiponectin). A total of 97 Hong Kong Chinese individuals aged 57.6 ± 9.1 years with MetS and high-normal blood pressure were randomly assigned to control (n = 45) and yoga groups (n = 52). Participants in the control group were not given any intervention but were contacted monthly to monitor their health status. Participants in the yoga group underwent a yoga training program with three 1-hour yoga sessions weekly for 1 year. The participants' sera were harvested and assessed for adipokines. Generalized estimating equation (GEE) was used to examine the interaction effect between 1-year time (pre vs post), and intervention (control vs yoga). GEE analyses revealed significant interaction effects between 1-year time and yoga intervention for the decreases in leptin and chemerin and the increase in adiponectin concentration in the sera examined. These results demonstrated that 1-year yoga training decreased proinflammatory adipokines and increased anti-inflammatory adipokine in adults with MetS and high-normal blood pressure. These findings support the beneficial role of yoga in managing MetS by favorably modulating adipokines.

Protective Effect of Unacylated Ghrelin on Compression-Induced Skeletal Muscle Injury Mediated by SIRT1-Signaling.

Unacylated ghrelin, the predominant form of circulating ghrelin, protects myotubes from cell death, which is a known attribute of pressure ulcers. In this study, we investigated whether unacylated ghrelin protects skeletal muscle from pressure-induced deep tissue injury by abolishing necroptosis and apoptosis signaling and whether these effects were mediated by SIRT1 pathway. Fifteen adult Sprague Dawley rats were assigned to receive saline or unacylated ghrelin with or without EX527 (a SIRT1 inhibitor). Animals underwent two 6-h compression cycles with 100 mmHg static pressure applied over the mid-tibialis region of the right limb whereas the left uncompressed limb served as the intra-animal control. Muscle tissues underneath the compression region, and at the similar region of the opposite uncompressed limb, were collected for analysis. Unacylated ghrelin attenuated the compression-induced muscle pathohistological alterations including rounding contour of myofibers, extensive nucleus accumulation in the interstitial space, and increased interstitial space. Unacylated ghrelin abolished the increase in necroptosis proteins including RIP1 and RIP3 and attenuated the elevation of apoptotic proteins including p53, Bax, and AIF in the compressed muscle. Furthermore, unacylated ghrelin opposed the compression-induced phosphorylation and acetylation of p65 subunit of NF-kB. The anti-apoptotic effect of unacylated ghrelin was shown by a decrease in apoptotic DNA fragmentation and terminal dUTP nick-end labeling index in the compressed muscle. The protective effects of unacylated ghrelin vanished when co-treated with EX527. Our findings demonstrated that unacylated ghrelin protected skeletal muscle from compression-induced injury. The myoprotective effects of unacylated ghrelin on pressure-induced tissue injury were associated with SIRT1 signaling.

Cardiovascular Protective Effects of Salvianic Acid A on db/db Mice with Elevated Homocysteine Level.

The onsets of left ventricular hypertrophy (LVH) and endothelial dysfunction (ED) in diabetics, especially in those with elevated homocysteine (Hcy), precede the development of cardiovascular (CV) events. Salvianic acid A (SAA) is a renowned Traditional Chinese Medicine (TCM) that has been applied in the treatment of cardiovascular disease for many decades. In this study, we aimed (1) to investigate the CV protective effects of SAA on ameliorating LVH and ED in db/db mice with elevated blood Hcy level and (2) to decipher whether the observed CV protective effects of SAA are associated with Hcy metabolism by modulating the methylation potential and redox status in the liver of the db/db mice with elevated blood Hcy level. Our results found that the administration of SAA could significantly slow down the build-up of left ventricular mass and ameliorate ED. Immunological assay analysis on the mouse liver tissue also indicated that SAA treatment on db/db mice with elevated Hcy was associated with reduced methylation potential but improved redox status. In conclusion, we revealed that SAA has the potential to protect against the hyperglycemia- and hyperhomocysteinemia-induced oxidative stress on diabetic mice via modulation in Hcy metabolism.

Role of free fatty acids in endothelial dysfunction.

Plasma free fatty acids levels are increased in subjects with obesity and type 2 diabetes, playing detrimental roles in the pathogenesis of atherosclerosis and cardiovascular diseases. Increasing evidence showing that dysfunction of the vascular endothelium, the inner lining of the blood vessels, is the key player in the pathogenesis of atherosclerosis. In this review, we aimed to summarize the roles and the underlying mechanisms using the evidence collected from clinical and experimental studies about free fatty acid-mediated endothelial dysfunction. Because of the multifaceted roles of plasma free fatty acids in mediating endothelial dysfunction, elevated free fatty acid level is now considered as an important link in the onset of endothelial dysfunction due to metabolic syndromes such as diabetes and obesity. Free fatty acid-mediated endothelial dysfunction involves several mechanisms including impaired insulin signaling and nitric oxide production, oxidative stress, inflammation and the activation of the renin-angiotensin system and apoptosis in the endothelial cells. Therefore, targeting the signaling pathways involved in free fatty acid-induced endothelial dysfunction could serve as a preventive approach to protect against the occurrence of endothelial dysfunction and the subsequent complications such as atherosclerosis.

Musculoskeletal impact of the use of various types of electronic devices on university students in Hong Kong: An evaluation by means of self-reported questionnaire.

INTRODUCTION: Despite the increasingly widespread popularity of electronic devices, there are limited comprehensive studies on the effects of usage and exposure to multiple electronic devices over extended periods of time. Therefore, this study explored the cumulative musculoskeletal implications of exposure to various electronic devices among university students. METHODS: A self-reported questionnaire was administered in the university in Hong Kong and students provided information about the frequency and duration of electronic devices use, including computers, mobile phones and game consoles, and reported on any musculoskeletal pain or discomfort that may relate to electronic devices usage in the immediate 12 months prior to the survey date. RESULTS: A total of 503 university students (59% males and 41% females) aged 18-25 years completed the questionnaire. The results showed that 251 (49.9%) respondents reported upper limb musculoskeletal symptoms, particularly in the neck and shoulder regions. Among these, 155 (61.8%) indicated that their discomfort was related to electronic device usage. Statistically significant differences in exposure to electronic devices and musculoskeletal outcomes between genders were found (p < 0.05). CONCLUSION: The use of electronic devices and habitual postures were associated with musculoskeletal problems among university students in Hong Kong. This phenomenon highlights the urgent need for ergonomics education and recommendations to increase students' awareness of musculoskeletal wellbeing.

S100A8 and S100A9 Are Associated with Doxorubicin-Induced Cardiotoxicity in the Heart of Diabetic Mice.

Cardiomyopathy is a clinical problem that occurs in the hearts of type 2 diabetic patients as well as cancer patients undergoing doxorubicin chemotherapy. The number of diabetic cancer patients is increasing but surprisingly the cardiac damaging effects of doxorubicin, a commonly used chemotherapeutic drug, on diabetic hearts have not been well-examined. As the signaling mechanisms of the doxorubicin-induced cardiomyopathy in type 2 diabetic heart are largely unknown, this study examined the molecular signaling pathways that are responsible for the doxorubicin-induced cardiotoxicity in type 2 diabetic hearts. Male 14- to 18-week-old db/db mice were used as the type 2 diabetic model, and age-matched non-diabetic db/+ mice served as controls. The db/+ non-diabetic and db/db diabetic mice were randomly assigned to the following groups: db/+CON, db/+DOX-5d, db/+DOX-7d, db/dbCON, db/dbDOX-5d, and db/dbDOX-7d. Mice assigned to doxorubicin (DOX) group were exposed to an intraperitoneal (i.p.) injection of DOX at a dose of 15 mg/kg to induce cardiomyopathy. Mice in control (CON) groups were i.p. injected with the same volume of saline instead of DOX. Mice were euthanized by overdose of ketamine and xylazine 5 or 7 days after the DOX injection. Microarray analysis was adopted to examine the changes of the whole transcriptional profile in response to doxorubicin exposure in diabetic hearts. Ventricular fractional shortening was examined as an indicator of cardiac function by transthoracic echocardiography. The presence of diabetic cardiomyopathy in db/db mice was evident by the reduction of fractional shortening. There was a further impairment of cardiac contractile function 7 days after the DOX administration in db/db diabetic mice. According to our microarray analysis, we identified a panel of regulatory genes associated with cardiac remodeling, inflammatory response, oxidative stress, and metabolism in the DOX-induced cardiac injury in diabetic heart. The microarray results of selected genes were confirmed by real time PCR. Notably, S100A8 and S100A9 were found to have a unique specific expression pattern that was coincident with the DOX-induced cardiomyopathy in diabetic hearts. Correspondingly, NF-κB expression in diabetic hearts was increased together with the elevation of S100A8/9 and activation of p38 MAPK signaling after DOX administration, which induced cardiac inflammation as demonstrated by the elevation of cardiac IL-6 level. These findings provide novel pre-clinical information for revealing the S100A8/A9-associated molecular signaling pathways that mediate the doxorubicin-induced cardiotoxicity in diabetic hearts.

Doxorubicin Induces Inflammatory Modulation and Metabolic Dysregulation in Diabetic Skeletal Muscle.

Anti-cancer agent doxorubicin (DOX) has been demonstrated to worsen insulin signaling, engender muscle atrophy, trigger pro-inflammation, and induce a shift to anaerobic glycolytic metabolism in skeletal muscle. The myotoxicity of DOX in diabetic skeletal muscle remains largely unclear. This study examined the effects of DOX on insulin signaling, muscle atrophy, pro-/anti-inflammatory microenvironment, and glycolysis metabolic regulation in skeletal muscle of db/db diabetic and db/+ non-diabetic mice. Non-diabetic db/+ mice and diabetic db/db mice were randomly assigned to the following groups: db/+CON, db/+DOX, db/dbCON, and db/dbDOX. Mice in db/+DOX and db/dbDOX groups were intraperitoneally injected with DOX at a dose of 15 mg per kg body weight whereas mice in db/+CON and db/dbCON groups were injected with the same volume of saline instead of DOX. Gastrocnemius was immediately harvested, weighed, washed with cold phosphate buffered saline, frozen in liquid nitrogen, and stored at -80°C for later analysis. The effects of DOX on diabetic muscle were neither seen in insulin signaling markers (Glut4, pIRS1Ser(636∕639), and pAktSer(473)) nor muscle atrophy markers (muscle mass, MuRF1 and MAFbx). However, DOX exposure resulted in enhancement of pro-inflammatory favoring microenvironment (as indicated by TNF-α, HIFα and pNFκBp65) accompanied by diminution of anti-inflammatory favoring microenvironment (as indicated by IL15, PGC1α and pAMPKß1Ser108). Metabolism of diabetic muscle was shifted to anaerobic glycolysis after DOX exposure as demonstrated by our analyses of PDK4, LDH and pACCSer(79). Our results demonstrated that there might be a link between inflammatory modulation and the dysregulation of aerobic glycolytic metabolism in DOX-injured diabetic skeletal muscle. These findings help to understand the pathogenesis of DOX-induced myotoxicity in diabetic muscle.

Development of Kinematic Graphs of Median Nerve during Active Finger Motion: Implications of Smartphone Use.

BACKGROUND: Certain hand activities cause deformation and displacement of the median nerve at the carpal tunnel due to the gliding motion of tendons surrounding it. As smartphone usage escalates, this raises the public's concern whether hand activities while using smartphones can lead to median nerve problems. OBJECTIVE: The aims of this study were to 1) develop kinematic graphs and 2) investigate the associated deformation and rotational information of median nerve in the carpal tunnel during hand activities. METHODS: Dominant wrists of 30 young adults were examined with ultrasonography by placing a transducer transversely on their wrist crease. Ultrasound video clips were recorded when the subject performing 1) thumb opposition with the wrist in neutral position, 2) thumb opposition with the wrist in ulnar deviation and 3) pinch grip with the wrist in neutral position. Six still images that were separated by 0.2-second intervals were then captured from the ultrasound video for the determination of 1) cross-sectional area (CSA), 2) flattening ratio (FR), 3) rotational displacement (RD) and 4) translational displacement (TD) of median nerve in the carpal tunnel, and these collected information of deformation, rotational and displacement of median nerve were compared between 1) two successive time points during a single hand activity and 2) different hand motions at the same time point. Finally, kinematic graphs were constructed to demonstrate the mobility of median nerve during different hand activities. RESULTS: Performing different hand activities during this study led to a gradual reduction in CSA of the median nerve, with thumb opposition together with the wrist in ulnar deviation causing the greatest extent of deformation of the median nerve. Thumb opposition with the wrist in ulnar deviation also led to the largest extent of TD when compared to the other two hand activities of this study. Kinematic graphs showed that the motion pathways of median nerve during different hand activities were complex. CONCLUSION: We observed that the median nerve in the carpal tunnel was rotated, deformed and displaced during the hand activities that people may be performed when using a smartphone, suggesting an increased risk of carpal tunnel syndrome (CTS). In addition, the kinematic graphs of median nerve developed in the present study provide new clues for further studies on the pathophysiology of CTS, and alerting smartphone users to establish proper postural habits when using handheld electronic devices.