Association of Sedentary Lifestyle with Risk of Acute and Post-Acute COVID-19 Sequelae: A Retrospective Cohort Study.

BACKGROUND: Evidence suggests that coronavirus disease 2019 (COVID-19) survivors could experience COVID-19 sequelae. Although various risk factors for COVID-19 sequelae have been identified, little is known about whether a sedentary lifestyle is an independent risk factor. METHODS: In this retrospective cohort study, 4850 participants self-reported their COVID-19 sequelae symptoms between June and August 2022. A sedentary lifestyle included physical inactivity (<150 min/week of moderate-to-vigorous intensity physical activity) and prolonged sedentary behavior (≥10 h/day) before the fifth COVID-19 wave was recorded. Logistic regression analysis was performed to determine the relationships between sedentary lifestyle and risk of acute and post-acute (lasting ≥2 months) COVID-19 sequelae. RESULTS: A total of 1443 COVID-19 survivors and 2962 non-COVID-19 controls were included. Of the COVID-19 survivors, >80% and >40% self-reported acute and post-acute COVID-19 sequelae, respectively. In the post-acute phase, COVID-19 survivors who were physically inactive had a 37% lower risk of insomnia, whereas those with prolonged sedentary behavior had 25%, 67%, and 117% higher risks of at least one symptom, dizziness, and "pins and needles" sensation, respectively. For the acute phase, prolonged sedentary behavior was associated with a higher risk of fatigue, "brain fog," dyspnea, muscle pain, joint pain, dizziness, and "pins and needles" sensation. Notably, sedentary behavior, rather than physical inactivity, was correlated with a higher risk of severe post-COVID-19 sequelae in both acute and post-acute phases. CONCLUSIONS: Prolonged sedentary behavior was independently associated with a higher risk of both acute and post-acute COVID-19 sequelae, whereas physical inactivity played contradictory roles in COVID-19 sequelae.

Effect of game-based high-intensity interval training program on the executive function of children with ADHD: Protocol of a randomized controlled trial.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common developmental disorder in childhood, with a 5%-6% worldwide prevalence. Children with ADHD often demonstrate impaired executive function, which is closely related to the development of the commonly observed behavioral problems such as inattention, impaired inhibition, and hyperactivity. The purpose of this study is to examine whether a game-based high-intensity interval training (HIIT) program can improve the executive function of children with ADHD, compared with a traditional structured aerobic exercise program and a non-treatment control group. METHODS/DESIGN: A total of 42 children with ADHD will be recruited to participate in this three-arm school-based randomized controlled trial. An 8-week specially designed game-based HIIT (GameHIIT) program and a traditional game-based structured aerobic exercise (GameSAE) program will be delivered to those children randomly assigned to these two intervention groups, while the children in the control group will maintain their regular physical activity over the same period. A number of outcome measures including executive function, cerebral hemodynamic response, physical activity, physical fitness, and enjoyment and adherence to the intervention will be assessed for both groups at baseline (T0), immediately after the intervention period (T1), and after the follow-up period (T2). DISCUSSION: HIIT has recently emerged as a feasible and efficacious strategy for increasing physical health outcomes and cognitive function, including executive function, in healthy young people. However, research has yet to investigate whether the executive function of children with ADHD can be effectively enhanced through HIIT. If, as hypothesized, GameHIIT program improves outcomes for children with ADHD, the present research will inform the development of targeted exercise programs that can be more broadly used with this particular population.

Alternating high-intensity interval training and continuous training is efficacious in improving cardiometabolic health in obese middle-aged men.

BACKGROUND: High-intensity interval training (HIIT) or moderate-intensity continuous training (MICT) alone has been shown to improve metabolic health, but the effects of alternating the two training approaches as often practiced in real life remained unclear. PURPOSE: To examine the effects of HIIT or MICT alone or alternating HIIT-MICT on cardiometabolic responses in inactive obese middle-aged men. METHODS: Forty-two participants (age: 42 ± 5 y; BMI: 26.3 ± 2.1 kg m-2) were randomly assigned to four groups: HIIT (12 x 1-min running bouts at 80-90% HRmax interspersed with 1-min active recovery at 50% HRmax), MICT (40-min brisk walk at 65-70% HRmax), alternating HIIT-MICT or a non-exercise control group (CON). Exercise sessions were conducted three times per week for 16 weeks. Maximal oxygen uptake (VO2max), body composition (by bioelectrical impedance analysis), blood pressure, fasting blood glucose, insulin resistance (HOMA-IR) and lipid profile were assessed at baseline and after the 16-week intervention. Enjoyment and self-efficacy were also assessed at the end of intervention. RESULTS: All exercise groups showed a similar VO2max increase of ∼15% (HIIT: 34.3 ± 4.4 vs 39.1 ± 5.4; MICT: 34.9 ± 5.0 vs 39.4 ± 7.2; and alternating HIIT-MICT: 34.4 ± 5.0 vs 40.3 ± 4.6 mL kg-1min-1) compared to baseline and CON (all p < 0.05). Weight, BMI, % fat and waist circumference also showed similar reductions in all exercise groups compared to baseline and CON (all p < 0.05). No significant group difference was observed for all blood markers. Compared to baseline, total cholesterol decreased after HIIT-MICT, while HIIT significantly decreased fasting insulin level and improved insulin resistance (p < 0.05). Enjoyment, self-efficacy and adherence were similar among all exercise groups. CONCLUSION: HIIT or MICT alone or alternating HIIT-MICT similarly improve cardiovascular fitness and body composition in obese middle-aged men despite differences in total training volume and time commitment.

The APPL1-Rab5 axis restricts NLRP3 inflammasome activation through early endosomal-dependent mitophagy in macrophages.

Although mitophagy is known to restrict NLRP3 inflammasome activation, the underlying regulatory mechanism remains poorly characterized. Here we describe a type of early endosome-dependent mitophagy that limits NLRP3 inflammasome activation. Deletion of the endosomal adaptor protein APPL1 impairs mitophagy, leading to accumulation of damaged mitochondria producing reactive oxygen species (ROS) and oxidized cytosolic mitochondrial DNA, which in turn trigger NLRP3 inflammasome overactivation in macrophages. NLRP3 agonist causes APPL1 to translocate from early endosomes to mitochondria, where it interacts with Rab5 to facilitate endosomal-mediated mitophagy. Mice deficient for APPL1 specifically in hematopoietic cell are more sensitive to endotoxin-induced sepsis, obesity-induced inflammation and glucose dysregulation. These are associated with increased expression of systemic interleukin-1ß, a major product of NLRP3 inflammasome activation. Our findings indicate that the early endosomal machinery is essential to repress NLRP3 inflammasome hyperactivation by promoting mitophagy in macrophages.

Effects and dose-response relationship of high-intensity interval training on cardiorespiratory fitness in overweight and obese adults: a systematic review and meta-analysis.

This study aims to quantify the effects of high-intensity interval training (HIIT) on cardiorespiratory fitness (CRF) by considering potential moderators and to characterise dose-response relationships of HIIT variables that could maximise CRF improvements in overweight and obese adults. Following a comprehensive search through four electronic databases, 19 studies met eligibility criteria. Random-effects models were applied to weight all included studies and to compute the weighted mean standardised mean differences (SMDwm). Meta-analysis showed that HIIT was a highly effective approach for improving CRF in overweight and obese adults (SMDwm = 1.13). Effects were modified by sex and baseline CRF level. Dose-response relationship analysis provided some preliminary data regarding the training period, training intensity, and session duration. However, it is still not possible to provide accurate recommendations currently. Further studies are still needed to identify the most appropriate training variables to prescribe effective HIIT programmes for improving CRF in overweight and obese adults.

Chronic AdipoRon Treatment Mimics the Effects of Physical Exercise on Restoring Hippocampal Neuroplasticity in Diabetic Mice.

Administration of exercise mimetic drugs could be a novel therapeutic approach to combat comorbid neurodegeneration and metabolic syndromes. Adiponectin is an adipocyte-secreted hormone. In addition to its antidiabetic effect, adiponectin mediates the antidepressant effect of physical exercise associated with adult hippocampal neurogenesis. The antidiabetic effect of the adiponectin receptor agonist AdipoRon has been demonstrated, but its potential pro-cognitive and neurotrophic effects in the hippocampus under diabetic condition are still unclear. This study reported that chronic AdipoRon treatment for 2 weeks improved hippocampal-dependent spatial recognition memory in streptozotocin-induced diabetic mice. Besides, AdipoRon treatment increased progenitor cell proliferation and neuronal differentiation in the hippocampal dentate gyrus (DG) of diabetic mice. Furthermore, AdipoRon treatment significantly increased dendritic complexity, spine density, and N-methyl-D-aspartate receptor-dependent long-term potentiation (LTP) in the dentate region, and increased BDNF levels in the DG of diabetic mice. AdipoRon treatment activated AMPK/PGC-1α signalling in the DG, whereas increases in cell proliferation and LTP were not observed when PGC-1α signalling was pharmacologically inhibited. In sum, chronic AdipoRon treatment partially mimics the benefits of physical exercise for learning and memory and hippocampal neuroplasticity in the diabetic brain. The results suggested that AdipoRon could be a potential physical exercise mimetic to improve hippocampal plasticity and hence rescue learning and memory impairment typically associated with diabetes.

AdipoRon Treatment Induces a Dose-Dependent Response in Adult Hippocampal Neurogenesis.

AdipoRon, an adiponectin receptor agonist, elicits similar antidiabetic, anti-atherogenic, and anti-inflammatory effects on mouse models as adiponectin does. Since AdipoRon can cross the blood-brain barrier, its chronic effects on regulating hippocampal function are yet to be examined. This study investigated whether AdipoRon treatment promotes hippocampal neurogenesis and spatial recognition memory in a dose-dependent manner. Adolescent male C57BL/6J mice received continuous treatment of either 20 mg/kg (low dose) or 50 mg/kg (high dose) AdipoRon or vehicle intraperitoneally for 14 days, followed by the open field test to examine anxiety and locomotor activity, and the Y maze test to examine hippocampal-dependent spatial recognition memory. Immunopositive cell markers of neural progenitor cells, immature neurons, and newborn cells in the hippocampal dentate gyrus were quantified. Immunosorbent assays were used to measure the serum levels of factors that can regulate hippocampal neurogenesis, including adiponectin, brain-derived neurotrophic factor (BDNF), and corticosterone. Our results showed that 20 mg/kg AdipoRon treatment significantly promoted hippocampal cell proliferation and increased serum levels of adiponectin and BDNF, though there were no effects on spatial recognition memory and locomotor activity. On the contrary, 50 mg/kg AdipoRon treatment impaired spatial recognition memory, suppressed cell proliferation, neuronal differentiation, and cell survival associated with reduced serum levels of BDNF and adiponectin. The results suggest that a low-dose AdipoRon treatment promotes hippocampal cell proliferation, while a high-dose AdipoRon treatment is detrimental to the hippocampus function.

Promoting healthy ageing through light volleyball intervention in Hong Kong: study protocol for a randomised controlled trial.

BACKGROUND: Our pilot study has demonstrated improvements in health outcomes through participation in a new sport, light volleyball (LVB), among older adults. In response to the promising results of the LVB pilot study and the priority of allocating resources to the prevention of age-related fitness degradation by the Hong Kong (HKG) government, the present study aims to investigate the effectiveness of a LVB intervention on physical and psychological health attributes among older adults at a larger scale in HKG. METHODS/DESIGN: This study will apply both quantitative and qualitative methods with a large sample (approximately 315 participants). We will adopt a randomized controlled trial (RCT) design to further evaluate the effectiveness of a LVB intervention on health outcomes against a comparison group, Tai Chi (TC), and a control group (C). Older adults will be eligible to join the intervention if they are (a) aged 65 years and above; (b) living in the community independently; (c) absent of diagnosed cognitive impairment; (d) not regular participants in a structured PA program for two years preceding the study; and (e) able to achieve a passing score on the Timed-up-and-go test (TUG) and Abbreviated Mental Test (AMT).About 315 participants will be randomly assigned into 3 groups in 1:1:1 ratio. LVB group participants will receive 16-week LVB program; TC group will utilize a simplified 24-form Yang Style TC, and C group participants will be instructed to maintain their normal daily activity and join regular non-exercise social gatherings. Measurements will be collected before and after the intervention, and 6 months and 12 months after completion of the intervention. DISCUSSION: This intervention, if effective, will enhance older adult's physical and psychological health, and provide the data and evidence to support policymaking in relation to future PA promotion for older adults. TRIAL REGISTRATION NUMBER: ChiCTR1900026657.

The Novel Perspectives of Adipokines on Brain Health.

First seen as a fat-storage tissue, the adipose tissue is considered as a critical player in the endocrine system. Precisely, adipose tissue can produce an array of bioactive factors, including cytokines, lipids, and extracellular vesicles, which target various systemic organ systems to regulate metabolism, homeostasis, and immune response. The global effects of adipokines on metabolic events are well defined, but their impacts on brain function and pathology remain poorly defined. Receptors of adipokines are widely expressed in the brain. Mounting evidence has shown that leptin and adiponectin can cross the blood-brain barrier, while evidence for newly identified adipokines is limited. Significantly, adipocyte secretion is liable to nutritional and metabolic states, where defective circuitry, impaired neuroplasticity, and elevated neuroinflammation are symptomatic. Essentially, neurotrophic and anti-inflammatory properties of adipokines underlie their neuroprotective roles in neurodegenerative diseases. Besides, adipocyte-secreted lipids in the bloodstream can act endocrine on the distant organs. In this article, we have reviewed five adipokines (leptin, adiponectin, chemerin, apelin, visfatin) and two lipokines (palmitoleic acid and lysophosphatidic acid) on their roles involving in eating behavior, neurotrophic and neuroprotective factors in the brain. Understanding and regulating these adipokines can lead to novel therapeutic strategies to counteract metabolic associated eating disorders and neurodegenerative diseases, thus promote brain health.

Vitamin D status and cardiometabolic risk factors in young adults in Hong Kong: associations and implications.

BACKGROUND AND OBJECTIVES: Vitamin D deficiency is reportedly common, but we lack data from young adults. Such data are of interest because epidemiological data support vitamin D as a possible risk modulator for diabetes and cardiovascular ('cardiometabolic') disease. Our objectives were to assess vitamin D status (as plasma 25(OH)D concentration) and investigate associations between this and biomarkers of cardiometabolic disease risk in a group of still-healthy young adults in Hong Kong. METHODS AND STUDY DESIGN: In this observational study, fasting venous blood was collected from 196 (63 males, 133 females), young (18-26 years) non-smoking, nonobese, consenting adults in good general health. Plasma 25(OH)D was measured by LC-MS/MS. A panel of established cardiometabolic risk factors (HbA1c, plasma glucose, lipid profile, hsCRP) and blood pressure were also measured. RESULTS: Mean (SD) plasma 25(OH)D concentration was 42.1 (13.0), with range 15.7-86.8 nmol/L; 141/196 subjects (72%) had vitamin D deficiency (25(OH)D <50 nmol/L); 13/184 (6.6%) were severely deficient (<25 nmol/L). Inverse association was seen between 25(OH)D and fasting glucose (r=-0.18; p<0.05). Higher HbA1c and TC:HDL-C ratio and lower HDL-C were seen in those with plasma 25(OH)D <25 nmol/L (p<0.05). CONCLUSIONS: Vitamin D deficiency was highly prevalent and associated with poorer cardiometabolic risk profile in these young adults. Public health strategies for addressing vitamin D deficiency are needed urgently. These new data provide support for further study on vitamin D deficiency as a modifiable risk factor for cardiometabolic disease and the ameliorative effects of increased vitamin D intake on cardiometabolic disease risk profile of vitamin D-deficient young adults.

Current and future molecular diagnostics in non-small-cell lung cancer.

The molecular investigation of lung cancer has opened up an advanced area for the diagnosis and therapeutic management of lung cancer patients. Gene alterations in cancer initiation and progression provide not only information on molecular changes in lung cancer but also opportunities in advanced therapeutic regime by personalized targeted therapy. EGFR mutations and ALK rearrangement are important predictive biomarkers for the efficiency of tyrosine kinase inhibitor treatment in lung cancer patients. Moreover, epigenetic aberration and microRNA dysregulation are recent advances in the early detection and monitoring of lung cancer. Although a wide range of molecular tests are available, standardization and validation of assay protocols are essential for the quality of the test outcome. In this review, current and new advancements of molecular biomarkers for non-small-cell lung cancer will be discussed. Recommendations on future development of molecular diagnostic services will also be explored.

Muscle mass, structural and functional investigations of senescence-accelerated mouse P8 (SAMP8).

Sarcopenia is an age-related systemic syndrome with progressive deterioration in skeletal muscle functions and loss in mass. Although the senescence-accelerated mouse P8 (SAMP8) was reported valid for muscular ageing research, there was no report on the details such as sarcopenia onset time. Therefore, this study was to investigate the change of muscle mass, structure and functions during the development of sarcopenia. Besides the average life span, muscle mass, structural and functional measurements were also studied. Male SAMP8 animals were examined at month 6, 7, 8, 9, and 10, in which the right gastrocnemius was isolated and tested for ex vivo contractile properties and fatigability while the contralateral one was harvested for muscle fiber cross-sectional area (FCSA) and typing assessments. Results showed that the peak of muscle mass appeared at month 7 and the onset of contractility decline was observed from month 8. Compared with month 8, most of the functional parameters at month 10 decreased significantly. Structurally, muscle fiber type IIA made up the largest proportion of the gastrocnemius, and the fiber size was found to peak at month 8. Based on the altered muscle mass, structural and functional outcomes, it was concluded that the onset of sarcopenia in SAMP8 animals was at month 8. SAMP8 animals at month 8 should be at pre-sarcopenia stage while month 10 at sarcopenia stage. It is confirmed that SAMP8 mouse can be used in sarcopenia research with established time line in this study.

The effect of a pre-exercise carbohydrate meal on immune responses to an endurance performance run.

This study examined the effect of a pre-exercise meal with different glycaemic index (GI) and glycaemic load (GL) on immune responses to an endurance performance run. Eight men completed a preloaded 1 h run at 70 % VO2max on a level treadmill followed by a 10 km performance run on three occasions. In each trial, one of the three prescribed isoenergetic meals, i.e. high GI and high GL (H-H), high GI and low GL (H-L), or low GI and low GL (L-L) was consumed by the subjects 2 h before exercise. Carbohydrate intake (% of energy intake), GI, and GL were 65 %, 79.5, and 82.4 for H-H; 36 %, 78.5, and 44.1 for H-L; 65 %, 40.2, and 42.1 for L-L, respectively. The running time for the three trials was approximately 112 min at 70 % VO2max for the first hour and 76 % VO2max for the last 52 min. Consumption of pre-exercise high-carbohydrate meals (H-H and L-L) resulted in less perturbation of the circulating numbers of leucocytes, neutrophils and T lymphocyte subsets, and in decreased elevation of the plasma IL-6 concentrations immediately after exercise and during the 2 h recovery period compared with the H-L trial. These responses were accompanied by an attenuated increase in plasma IL-10 concentrations at the the end of the 2 h recovery period. The amount of carbohydrate consumed in the pre-exercise meal may be the most important influencing factor rather than the type of carbohydrate in modifying the immunoendocrine response to prolonged exercise.