The Effects of mHealth-Based Gamification Interventions on Participation in Physical Activity: Systematic Review.

BACKGROUND: It is well known that regular physical exercise has associated benefits; yet, participation remains suboptimal. Mobile health (mHealth) has become an indispensable medium to deliver behavior change interventions, and there is a growing interest in the gamification apps in mHealth to promote physical activity (PA) participation. Gamification could use game design elements (such as points, leaderboards, and progress bars), and it has the potential to increase motivation for PA and engagement. However, mHealth-based gamification interventions are still emerging, and little is known about the application status and efficacy of such interventions. OBJECTIVE: This systematic review aims to investigate gamification apps in mHealth for improving PA levels and simultaneously summarize the impact of gamification interventions on PA participation. METHODS: We searched PubMed, Scopus, Web of Science, Embase, CINAHL (EBSCO host), and IEEE Xplore from inception to December 20, 2020. Original empirical research exploring the effects of gamification interventions on PA participation was included. The papers described at least one outcome regarding exercise or PA participation, which could be subjective self-report or objective indicator measurement. Of note, we excluded studies about serious games or full-fledged games. RESULTS: Of 2944 studies identified from the database search, 50 (1.69%) were included, and the information was synthesized. The review revealed that gamification of PA had been applied to various population groups and broadly distributed among young people but less distributed among older adults and patients with a disease. Most of the studies (30/50, 60%) combined gamification with wearable devices to improve PA behavior change, and 50% (25/50) of the studies used theories or principles for designing gamified PA interventions. The most frequently used game elements were goal-setting, followed by progress bars, rewards, points, and feedback. This review demonstrated that gamification interventions could increase PA participation; however, the results were mixed, and modest changes were attained, which could be attributed to the heterogeneity across studies. CONCLUSIONS: Overall, this study provides an overview of the existing empirical research in PA gamification interventions and provides evidence for the efficacy of gamification in enhancing PA participation. High-quality empirical studies are needed in the future to assess the efficacy of a combination of gamification and wearable activity devices to promote PA, and further exploration is needed to investigate the optimal implementation of these features of game elements and theories to enhance PA participation.

Hyposmia as a Predictive Marker of Parkinson's Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Hyposmia is one of the most common and best-characterized conditions that is also one of the first nonmotor features of Parkinson's disease (PD). The association of hyposmia with PD is widely accepted; however the likelihood of developing PD is unclear. Our meta-analysis aimed to investigate the risk of PD in individuals with hyposmia. METHODS: Prospective studies on humans published before December 4th, 2018, were searched for in PubMed, Embase, Web of Science, and Cochrane Library databases. Two independent reviewers screened studies for inclusion and extracted data. We assessed the quality of studies using the Newcastle-Ottawa Scale and pooled data for analysis using random-effects models. RESULTS: Of the 1774 studies retrieved, seven met the inclusion criteria for this review. A total of 3272 hyposmia and 176 PD events were reported over follow-up periods ranging from 3 to 17 years. Hyposmia was associated with a 3.84-fold risk of developing PD (pooled relative risk: 3.84, 95% CI 2.12-6.95). Subgroup analyses identified few differences between different hyposmia assessment methodologies and follow-up periods. CONCLUSIONS: Our findings suggest that deficiencies in olfaction are associated with an increased risk of developing PD. Future studies are needed to investigate whether hyposmia is a promising and feasible biomarker for the early diagnosis of PD.

A liquid chromatography-tandem mass spectrometry method for preclinical pharmacokinetics and tissue distribution of hydrolyzable tannins chebulinic acid and chebulagic acid in rats.

A simple and sensitive liquid chromatography-tandem mass spectrometry method was developed for the simultaneous determination of chebulinic acid and chebulagic acid in rat plasma and tissues and well used in the pharmacokinetic and tissue distribution studies after intraperitoneal injection administration. Samples were processed with methanol by protein precipitation, and chromatographic separation was performed on an Agilent Zorbax SB-C18 column (50 × 2.1 mm, 1.8 µm) with a mobile phase consisting of methanol and water containing 0.1% formic acid (60:40, v/v). Quantification was performed by selected reaction monitoring with m/z 977.1 → 806.8 for chebulagic acid, m/z 979.0 → 808.7 for chebulinic acid and m/z 851.2 → 704.9 for the internal standard. Good linearity was observed over their respective concentration range. The pharmacokinetic study showed that both compounds reached their peak concentration values (605.8 ± 35.6 ng/mL for chebulinic acid and 1327.1 ± 118.6 ng/mL for chebulagic acid) at the same time of 0.9 h following intraperitoneal injection administration. The two compounds could be detected in blood-abundant tissues. The kidney had the highest concentrations (462.6 ± 138.5 ng/g for chebulinic acid and 1651.7 ± 167.7 ng/g for chebulagic acid) at 1 h post-dose, followed by the heart, liver, spleen and lung.

Physical activity can improve cognition in patients with Alzheimer's disease: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND/OBJECTIVE: Alzheimer's disease (AD) is mainly characterized by decline of cognitive functions such as memory and learning, which has a high prevalence and poor drug efficacy in treatment regimes. A systematic review and meta-analysis of randomized controlled trials (RCTs) were conducted to evaluate the effectiveness of exercise on cognitive function in patients diagnosed with AD. METHODS: The bibliographic databases (PubMed, Cochrane Library and Embase, and Web of Science) and four Chinese databases (Wanfang data, CBM, CNKI, and VIP) were searched to identify RCTs published in any language between January 1, 1960, and January 1, 2018. Only peer-reviewed articles and RCTs were included. The collected data were analyzed by Review Manager (5.3). RESULTS: Overall, 869 patients diagnosed with AD were included from 13 RCTs. Patients in the intervention group received pure exercise interventions and a cognitive test. Although there was heterogeneity in intervention methods and cognitive measures among studies, meta-analysis (seven studies) supports positive effects of physical activity on cognitive function of patients with AD (mean difference [MD] =2.53, the 95% CI=0.84 to 4.22, test for overall effect: Z=2.93 [P=0.003]). Eight studies demonstrated that exercise improves cognitive function for individuals with AD. However, the remaining five studies did not display a beneficial effect of exercise on cognitive function in patients with AD. CONCLUSION: This meta-analysis and systematic review indicated that exercise intervention might improve the cognitive function of AD or slow down the decline of cognition; however, this relationship was not always true across studies. RCTs with clear intervention criteria, large samples, and long-term follow-up are needed in the future to demonstrate the benefits of exercise for cognitive function in AD patients.

Sarcodon imbricatus polysaccharides protect against cyclophosphamide-induced immunosuppression via regulating Nrf2-mediated oxidative stress.

Sarcodon imbricatus, a rare medicinal and edible fungus, has various pharmacological bioactivities. The present study systematically investigated the protective effects of S. imbricatus polysaccharides (SIPS) against cyclophosphamide (CTX)-induced immunosuppression in Balb/c mice model. Compared with the CTX-induced immunosuppressive mice, the spleen and thymus indexes in the mice with 28-day SIPS orally administration were significantly increased, bodyweight loss was alleviated, and the natural killer (NK) cytotoxicity and the proliferative activities of lymphocytes were elevated. SIPS regulated the production of immunoglobulins including IgA, IgG and IgM in the serum and spleen. Notably, SIPS promoted the secretion of interleukin-2 (IL-2), IL-6, IL-10, IL-12 and interferon-γ (IFN-γ) of serum and spleen in CTX-induced immunosuppressive mice. Additionally, SIPS inhibited reactive oxygen species (ROS) levels and increased total antioxidant capacity, including superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities of spleen and thymus, as well as enhanced acid phosphatase (ACP) and lysozyme (LZM) levels of thymus in CTX-induced immunosuppressive mice. Histopathological analysis of spleen revealed the protective effect of SIPS against CTX-induced immunosuppression. More importantly, SIPS promoted the expression of nuclear factor-erythroid 2-related factor 2 (Nrf2) and its downstream target genes encoding antioxidant enzymes: SOD1, SOD2, haem oxygenase-1 (HO-1), CAT and quinone oxidoreductase 1 (NQO1). Altogether, SIPS reversed CTX-induced immunosuppression effectively and predominantly through Nrf2-mediated oxidative stress, which provided the useful evidence that SIPS can be served as a novel natural immunomodulator in health foods or medicine.

Chitosan Oligosaccharide Reduces Propofol Requirements and Propofol-Related Side Effects.

Propofol is one of the main sedatives but its negative side effects limit its clinical application. Chitosan oligosaccharide (COS), a kind of natural product with anti-pain and anti-inflammatory activities, may be a potential adjuvant to propofol use. A total of 94 patients receiving surgeries were evenly and randomly assigned to two groups: 10 mg/kg COS oral administration and/or placebo oral administration before being injected with propofol. The target-controlled infusion of propofol was adjusted to maintain the values of the bispectral index at 50. All patients' pain was evaluated on a four-point scale and side effects were investigated. To explore the molecular mechanism for the functions of COS in propofol use, a mouse pain model was established. The activities of Nav1.7 were analyzed in dorsal root ganglia (DRG) cells. The results showed that the patients receiving COS pretreatment were likely to require less propofol than the patients pretreated with placebo for maintaining an anesthetic situation (p < 0.05). The degrees of injection pain were lower in a COS-pretreated group than in a propofol-pretreated group. The side effects were also more reduced in a COS-treated group than in a placebo-pretreated group. COS reduced the activity of Nav1.7 and its inhibitory function was lost when Nav1.7 was silenced (p > 0.05). COS improved propofol performance by affecting Nav1.7 activity. Thus, COS is a potential adjuvant to propofol use in surgical anesthesia.

Moment-flux models for bacterial chemotaxis in large signal gradients.

Chemotaxis is a fundamental process in the life of many prokaryotic and eukaryotic cells. Chemotaxis of bacterial populations has been modeled by both individual-based stochastic models that take into account the biochemistry of intracellular signaling, and continuum PDE models that track the evolution of the cell density in space and time. Continuum models have been derived from individual-based models that describe intracellular signaling by a system of ODEs. The derivations rely on quasi-steady state approximations of the internal ODE system. While this assumption is valid if cell movement is subject to slowly changing signals, it is often violated if cells are exposed to rapidly changing signals. In the latter case current continuum models break down and do not match the underlying individual-based model quantitatively. In this paper, we derive new PDE models for bacterial chemotaxis in large signal gradients that involve not only the cell density and flux, but also moments of the intracellular signals as a measure of the deviation of cell's internal state from its steady state. The derivation is based on a new moment closure method without calling the quasi-steady state assumption of intracellular signaling. Numerical simulations suggest that the resulting model matches the population dynamics quantitatively for a much larger range of signals.

A High Frequency of Peripheral Blood IL-22(+) CD4(+) T Cells in Patients With New Onset Type 2 Diabetes Mellitus.

BACKGROUND: This study is aimed at investigating the frequency of different functional IL-22(+) CD4(+) T cells in Chinese patients with type 2 diabetes mellitus (T2DM). METHODS: The frequency of circulating IFN-γ+IL-17-IL-22-CD4(+) (Th1), IFN-γ-IL-17A+IL-22-CD4(+) (Th17), and IFN-γ-IL-17A-IL-22(+) CD4(+) (Th22), and other subsets of IL-22(+) CD4(+) T cells in 31 patients with new onset T2DM and 16 healthy controls was characterized by flow cytometry. The levels of serum IL-22, IL-17, IFN-γ, insulin C-peptide, hemoglobin A1c (HbA1c), fasting plasma glucose, and insulin were examined. RESULTS: The frequency of Th1, Th17, Th22, IFN-γ(+) IL-17(-) IL-22(+) , and IFN-γ(-) IL-17(+) IL-22(+) CD4(+) T cells and the concentrations of IL-22, but not IL-17 and IFNγ, in the patients were significantly higher than controls. The percentages of Th22 cells were correlated positively with the frequency of IFN-γ(-) IL-17(+) IL-22(+) CD4(+) T cells, the values of body mass index (BMI) and homeostatic model assessment insulin resistance (HOMA-IR), and the levels of serum IL-22 in those patients. CONCLUSION: Our data suggest that IL-22(+) CD4(+) T cells may contribute to the early process of T2DM.

Effect of penehyclidine hydrochloride on heart rate variability in hysteroscopy.

In order to evaluate the effect of different doses of penehyclidine hydrochloride (penehyclidine) on heart rate (HR) and HR variability (HRV) in hysteroscopy, 180 patients (American Society of Anesthesiologists grade I-II) were randomized equally to three groups: 0.5 mg penehyclidine and intravenous anesthesia (group I), 1.0 mg penehyclidine and intravenous anesthesia (group II) and saddle anesthesia combined with intravenous anesthesia (control group). HR and HRV, including total power (TP), low-frequency power (LF), high-frequency power (HF) and the LF to HF ratio (LF/HF), were recorded prior and subsequent to the induction of anesthesia (T0 and T1, respectively), following the start of surgery (T2) and following completion of surgery (T3). HR was lower at T2 than at T0 in the control patients, but no differences were observed in groups I and II. The HR at T2 was increased in group II compared with that in group I. TP in group II was significantly higher compared with that in group I at T2. At T1 and at T2, the LF and HF values were lower in group I than those in the controls. Patients in group II also had higher LF and HF at T2 than patients in group I. The HF was higher at T2 than that at T0 in the controls; however, the HF and LF did not change significantly within groups I and II. No significant differences were observed in the LF/HF ratio among the three groups. At a dose of 0.5 mg, penehyclidine stabilized HRV and did not alter the autonomic nervous modulation of HR. A penehyclidine dose of 1.0 mg may be superior to a dose of 0.5 mg in maintaining HR, but is less effective at balancing sympathetic and parasympathetic activity.

NKG2A expression and impaired function of NK cells in patients with new onset of Graves' disease.

BACKGROUND: Graves' disease (GD) is an organ-specific autoimmune disease. A significant decrease of the distribution of NK cells in the peripheral blood in children and adolescents with untreated GD has been observed. However, the role of NK and its subsets in adults with GD remains unclear. METHODS: A total of 28 adult patients with new onset of GD and 23 healthy controls (HC) were recruited. The number of activated inhibitory NK cells in peripheral blood of individual subjects was determined by flow cytometry. RESULTS: The number of CD3(-)CD56(+) and CD3(-)CD16(+)NK cells in peripheral blood was significantly decreased in the GD patients than the HC. Compared to the HCs, decreased number of NKG2D(+), NKG2C(+), NKp30(+) and NKG2A(+) NK cells and increased number of KIR3DL1(+) NK cells were detected in the GD patients. Moreover, the number of inducible CD107a(+) and IFN-γ-secreting NK cells in GD patients significantly decreased than those in HC. Interestingly, the number of NKG2A(+)NK cells was negatively correlated with the level of serum TRAb in GD patients. CONCLUSION: Our data indicate that decreased number and impaired function of NK cells may contribute to the pathogenesis of GD.

Lidocaine attenuates lipopolysaccharide-induced inflammatory responses in microglia.

BACKGROUND: Lidocaine has been used as a local anesthetic with anti-inflammatory properties, but its effects on neuroinflammation have not been well defined. In the present study, we investigated the prophylactic effects of lidocaine on lipopolysaccharide (LPS)-activated microglia and explored the underlying mechanisms. MATERIALS AND METHODS: Microglial cells were incubated with or without 1 µg/mL LPS in the presence or absence of lidocaine, a p38 mitogen-activated protein kinase (p38 MAPK) inhibitor (SB203580), a nuclear factor-kappa B (NF-κB) inhibitor (pyrrolidine dithiocarbamate), or small interfering RNA. The protein and expression levels of inflammatory mediators, such as monocyte chemotactic protein 1, nitric oxide, prostaglandin E2, interleukin 1ß, and tumor necrosis factor α were measured using enzyme-linked immunosorbent assays and real-time polymerase chain reaction. The effect of lidocaine on NF-κB and p38 MAPK activation was evaluated using enzyme-linked immunosorbent assays, Western blot analysis, and electrophoretic mobility shift assay. RESULTS: Lidocaine (≥2 µg/mL) significantly inhibited the release and expression of nitric oxide, monocyte chemotactic protein 1, prostaglandin E2, interleukin 1ß, and tumor necrosis factor α in LPS-activated microglia. Treatment with lidocaine also significantly inhibited the phosphorylation of p38 MAPK and the nuclear translocation of NF-κB p50/p65, increased the protein levels of inhibitor kappa B-α. Furthermore, our study shows that the LPS-induced release of inflammatory mediators was suppressed by SB203580, pyrrolidine dithiocarbamate, and small interfering RNA. CONCLUSIONS: Prophylactic treatment with lidocaine inhibits LPS-induced release of inflammatory mediators from microglia, and these effects may be mediated by blockade of p38 MAPK and NF-κB signaling pathways.

A higher frequency of circulating IL-22(+)CD4(+) T cells in Chinese patients with newly diagnosed Hashimoto's thyroiditis.

BACKGROUND: IL-22 and IL-17A are implicated in the pathogenesis of autoimmune diseases. However, the role of IL-22(+) and IL-17A(+) CD4(+) T cells in the pathogenesis of Hashimoto's thyroiditis (HT) is not fully understood. This study investigates serum IL-22 and IL-17A levels and determines the frequency of circulating IL-22(+) CD4(+) T cells in HT patients to understand their roles in the pathogenesis of HT. METHODS: The levels of serum IL-22, IL-17A and IFN-γ and the frequency of circulating IL-22(+)CD4(+) and IL-17A(+)CD4(+) T cells in 17 HT patients and 17 healthy controls (HC) were determined by enzyme-linked immunosorbent assay (ELISA) and flow cytometry. The levels of serum free triiodothyronine (FT4), free thyroxine (FT3), thyroid stimulating hormone (TSH), anti-thyroid peroxidase (TPO) and anti-thyroglobulin antibodies (TgAb) by chemiluminescent enzyme immunoassay and radioimmunoassay. RESULTS: The percentages of circulating IL-22(+)CD4(+) and IL-17(+)CD4(+) T cells (p<0.0001, p<0.0001) and the levels of serum IL-22, IL-17A and IFN-γ (p<0.0001, p<0.0001, p = 0.0210) in the HT patients were significantly higher than that in the HC. The percentages of IL-22(+)CD4(+) T cells were positively correlated with Th17 cells (r = 0.8815, p<0.0001) and IL-17A(+)IL-22(+)CD4(+) T cells (r = 0.8914, p<0.0001), but were negatively correlated with Th1 cells (r = -0.6110, p<0.0092) in the HT patients. The percentages of Th22 cells, Th17 cells and IL-17A(+)IL-22(+)CD4(+) T cells were negatively correlated with the levels of serum TSH in the HT patients (r = -0.8402, p<0.0001; r = -0.8589, p<0.0001; r = -0.8289 p<0.0001, respectively). CONCLUSIONS: A higher frequency of circulating IL-22(+)CD4(+) and IL-17A(+)CD4(+) T cells may be associated with the development of HT in Chinese patients.

A high frequency of peripheral blood NKG2D+NK and NKT cells in euthyroid patients with new onset hashimoto's thyroiditis--a pilot study.

Hashimoto's thyroiditis (HT) is a T cell-mediated autoimmune disease. However, little is known about the role of different subsets of natural killer (NK) and natural killer T (NKT) cells at the early stage of the HT process. A total of 45 euthyroid patients with new onset HT and 40 age/gender-matched healthy controls (HC) were examined for the frequency of different subsets of NK and NKT cells and their function by flow cytometry. In comparison with that in HC, significantly higher percentages of peripheral blood CD3-CD56+ NK, NKG2D+, NKp30+ NK and NKT cells, but significantly lower percentages of NKG2A+, KIR2DL3+ inhibitory NK and NKT cells were detected in the HT patients. Furthermore, the percentages of NKG2D+ NK cells were correlated positively with the concentrations of serum anti-thyroid peroxidase antibody (TPOAb) in the HT patients. Moreover, the percentages of inducible IFN-γ and CD107a+ NK cells in the HT patients were significantly higher than those in HC. Our data suggest that activated NK cells may participate in the early pathogenic process of HT.