Smartphone Applications to Prevent Type 2 Diabetes: A Systematic Review and Meta-Analysis.

INTRODUCTION: Evidence supporting the use of apps for lifestyle behavior change and diabetes prevention in people at high risk of diabetes is lacking. The aim of this systematic review was to determine the acceptability and effectiveness of smartphone applications (apps) for the prevention of type 2 diabetes. METHODS: PubMed, Embase, CINAHL and PsychInfo were searched from 2008 to 2023. Included studies involved adults at high risk of developing diabetes evaluating an app intervention with the aim of preventing type 2 diabetes. Random-effects meta-analyses were conducted for weight loss, body mass index (BMI), glycated hemoglobin, and waist circumference. Narrative synthesis was conducted for all studies, including qualitative studies exploring user perspectives. RESULTS: Twenty-four studies (n=2,378) were included in this systematic review, including 9 randomized controlled trials (RCTs) with an average duration of 6 months, 10 quasi-experimental and 7 qualitative studies. Socially disadvantaged groups were poorly represented. Six RCTs were combined in meta-analyses. Apps were effective at promoting weight loss [mean difference (MD) -1.85; 95% CI -2.90 to -0.80] and decreasing BMI [MD -0.90, 95% CI -1.53 to -0.27], with no effect on glycated hemoglobin and waist circumference. No studies reported on diabetes incidence. Qualitative studies highlighted the need for app personalization. DISCUSSION: Smartphone apps have a promising effect on preventing type 2 diabetes by supporting weight loss. Future robust trials should include diverse populations in co-design and evaluation of apps and explore the role of artificial intelligence in further personalizing interventions for higher engagement and effectiveness.

The burden of psychological distress and unhealthy dietary behaviours among 222,401 school-going adolescents from 61 countries.

We aimed to calculate the sex-specific prevalence of psychological distress and unhealthy eating habits among adolescents across countries and regions, and to explore their potential associations. We used data from the Global School-Based Health Survey (GSHS) for 61 countries. Psychological distress was defined based on the existence of ≥ 2 factors from the following: loneliness, anxiety, suicide ideation, suicide planning, and suicide attempt. Four unhealthy dietary behaviours were examined: inadequate fruit intake, inadequate vegetable intake, daily consumption of soft drinks, and weekly fast-food consumption. We used random-effects meta-analysis to estimate the overall and regional pooled prevalence. Mixed-effect multilevel logistic regressions were used to estimate adjusted odds ratios (aORs) of unhealthy dietary behaviours in relation to psychological distress. Among 222,401 school-going adolescents (53.3% girls), the prevalence of psychological distress was 17.9%, with girls reporting higher than boys (20.8% vs. 14.9%). Adolescents in the African region reported the highest prevalence (22.5%), while those in the South-East Asia region reported the lowest (11.3%). The prevalence of inadequate fruit intake, inadequate vegetable intake, daily soft drink consumption, and weekly fast-food consumption was 37.0%, 28.5%, 50.0%, and 57.4% respectively. Psychological distress was associated with inadequate fruit intake (pooled aOR = 1.19, 95% CI 1.17-1.23), inadequate vegetable intake (pooled OR = 1.19, 1.16-1.22), daily consumption of soft drinks (pooled aOR = 1.14, 1.12-1.17), and weekly consumption of fast food (pooled aOR = 1.12, 1.09-1.15). Our findings indicate a substantial variance in the burden of psychological distress and unhealthy dietary behaviours across different regions. Adolescents experiencing psychological distress were more likely to have unhealthy dietary habits.

Psychological distress and unhealthy dietary behaviours among adolescents aged 12-15 years in nine South-East Asian countries: a secondary analysis of the Global School-Based Health Survey data.

It is unclear whether there is any association between psychological distress and unhealthy dietary habits among adolescents in low- and middle-income countries. We aimed to estimate the prevalence of these factors in South-East Asia region and investigate their associations. We used data from the Global School-based Health Survey for nine South-East Asian countries. Psychological distress was defined by presence of ≥ 2 factors from loneliness, anxiety, suicide ideation, suicide planning and suicide attempt. We assessed inadequate fruit intake, inadequate vegetable intake, daily soft drink and weekly fast-food consumption. We used random-effects meta-analysis to estimate pooled prevalence. Logistic regressions were used to estimate OR of unhealthy dietary behaviours for psychological distress. Among 30 013 adolescents (56 % girls) aged 12-15 years, the prevalence of psychological distress was 11·0 %, with girls reporting slightly higher than boys (11·8 % v. 10·1 %). The prevalence of inadequate fruit intake, inadequate vegetable intake, daily soft drink consumption and weekly fast-food consumption was 42 %, 26 %, 40 % and 57 %, respectively. Psychological distress was associated with inadequate fruit intake (pooled OR = 1·20, 95 % CI 1·03, 1·40), inadequate vegetable intake (pooled OR = 1·17, 1·05, 1·31) and daily soft drink consumption (pooled OR = 1·14, 1·03, 1·26); but not with weekly fast-food consumption (pooled OR = 1·13, 0·96, 1·31). We observed substantial cross-country variations in prevalence and OR estimates. In conclusion, South-East Asian adolescents have significant burden of psychological distress and unhealthy dietary behaviours, with those having psychological distress are more likely to have unhealthy dietary behaviours. Our findings will guide preventative interventions and inform relevant policies around adolescent nutrition in the region.

Rutin hydrate and extract from Castanopsis tribuloides reduces pyrexia via inhibiting microsomal prostaglandin E synthase-1.

Castanopsis tribuloides belongs to the oak species (Fagaceae) and it is commonly distributed in evergreen forests of Bangladesh, India, Myanmar, Nepal, China, and Thailand. Our present study aimed at uncovering the antipyretic potential of methanol extract of C. tribuloides bark (CTB) in the mice models. Baker's yeast pyrexia model was employed to determine the antipyretic potentials of the extract. Besides, molecular docking and dynamics simulation of CTB phenolic compounds were explored to validate the experimental results and gain insight into the possible antipyretic mechanism of action that can lead to the design and discovery of novel drugs against mPGES-1. The results revealed that CTB (400 mg/kg) significantly inhibited (P < 0.001) the elevated body temperature of mice since 0.5 h, which is more prominent than the standard. At dose 200 mg/kg, the bark extract also produced significant (P < 0.05) antipyretic activity since 2 h. HPLC-DAD analysis identified and quantified nine polyphenolic compounds from the extract, including rutin hydrate, (-) epicatechin, caffeic acid, catechin hydrate, catechol, trans-ferulic acid, p-coumaric acid, vanillic acid, and rosmarinic acid. Molecular docking study suggested probable competition of these phenolic compounds with glutathione, an essential cofactor for microsomal prostaglandin E synthase-1 (mPGES-1) activity. Additionally, RMSF, RMSD, Rg, and hydrogen bonds performed during MD simulations revealed that rutin hydrate (rich in CTB) bound to the mPGES-1 active site in a stable manner and thus inactivating mPGES-1. Therefore, it can be concluded that rutin hydrate reduces pyrexia in mice via downregulating PGE2 synthesis by inhibiting mPGES-1 activity.

Phenolic compounds and extracts from Crotalaria calycina Schrank potentially alleviate pain and inflammation through inhibition of cyclooxygenase-2: An in vivo and molecular dynamics studies.

Crotalaria calycina Schrank is a local Bangladeshi plant well-accepted by the tribal population for its medicinal properties. The primary approach of our study was to uncover the analgesic and anti-inflammatory potential of methanol extract of C. calycina stem in mice model with in silico molecular docking and molecular dynamics simulation approach. Phenolic compounds were identified and quantified from the extract through high-performance liquid chromatography-diode array detector (HPLC-DAD) analysis. Writhing assay through injection of acetic acid, licking assay through formalin injection, and finally, hot plate assay was employed to observe the analgesic activity. The carrageenan-induced paw edema model was employed to determine the anti-inflammatory potential of the extract. In silico molecular docking and molecular dynamics were also run to validate the in vivo study results. Eight polyphenolic compounds from the extract were identified and quantified via HPLC-DAD analysis, and (-) epicatechin was most abundantly distributed (87.15 ± 0.24 mg/100 g dry extract). In vivo study revealed that 400 mg/kg dose significantly inhibited (P < 0.01) the writhing response in the writhing assay and demonstrated the highest percent of inhibition of licking (70.67%) in the late part of the licking test. The same extract dose produced the highest (74.71%) percent of maximal effect (% MPE) in the hot plate assay. It demonstrated the highest percent of edema inhibition (68.00%) in the fourth hour of the paw edema assay. Molecular docking and molecular dynamics simulation of (-) epicatechin, caffeic acid, and kaempferol with cyclooxygenase-2 revealed that they have similar interactions to the standard inhibitor celecoxib. These valuable bioactive compounds may induce significant analgesic and anti-inflammatory properties in MECCS. Therefore, based on the findings of this study, it can be concluded that C. calycina stem can be a prospect in the medicinal field due to its remarkable analgesic and anti-inflammatory effect.

Histomorphometric analysis of the epithelial lumen, mesenchyme, smooth muscle cell layers, and mesentery of the mouse developing duodenum in relation with the macroscopic morphogenesis.

Integral analysis of the development of the epithelium, mesenchyme, and smooth muscle cell (SMC) layers, i.e., the inner circular (IC) and outer longitudinal layers, as well as their relation with the mesentery is necessary to understand macroscopic gut development. We here focused on the proximal duodenum with the characteristic "C"-shaped loop and analyzed the duodenum down to the duodenojejunal flexure in C57BL/6J mouse embryos at embryonic days (E) 13.5, 15.5, and 17.5 by histomorphometric analysis. We examined the angle of the axis of the epithelial lumen, which was oval at E13.5 against the mesentery, along with the epithelial cell nuclear shape, the adjacent mesenchymal cell density in relation to the epithelial lumen axis, and the development of SMC layers. The luminal axis of the oval epithelial lumen at E13.5 rotated clockwise against the mesentery in the proximal duodenum. The shape of epithelial nuclei was longer and thinner at the long axis but shorter and broader at the short axis, whereas mesenchymal density was significantly lower in the area on the luminal long axis than that on the short axis. The number of SMC layers in the IC at E13.5, E15.5, and E17.5 showed a regional difference in relation to the mesentery, but no regional difference along the long axis of the duodenum. These findings suggest that epithelial lumen winding against the mesentery and the corresponding changes in the epithelial cell shape and surrounding mesenchymal density may be involved in the formation of the "C" loop of the proximal duodenum.

Development of the smooth muscle layer in the ileum of mouse embryos.

The smooth muscle layer (SML) comprises a significant portion of the intestines and other tubular organs. Whereas epithelial development has recently been extensively studied, SML development has drawn relatively less attention. Previous morphological reports revealed that the inner circular layer (IC) differentiates earlier than the outer longitudinal layer (OL), but detailed development of the SML, including chronological changes in the cell layer number, precise cell orientation, and regional differences in relation to the mesentery, has not been reported. We here observed the development of the SML in the C57BL/6J mouse ileum near the ileocecal junction at embryonic day (E) 13.5, 15.5, and 17.5. By histo-morphometric analyses, in IC, smooth muscle cells (SMCs) were oval-shaped and irregularly arranged in 3-4 layers at E13.5, then adopted an elongated spindle shape and decreased to two cell layers at E15.5 and E17.5. The IC SMC nuclear angle was not vertical, but oriented at 60-80° against the mid-axis of the intestinal lumen. The single SMC layer in OL was observed at E17.5, and the SMC nuclear angle was parallel to the luminal mid-axis. No clear regional difference against the mesentery was observed. Collectively, the findings suggest that development and differentiation of the ileal SML is not simple but regulated in a complex manner and possibly related to the macroscopic organogenesis.

Interkinetic nuclear migration in the tracheal and esophageal epithelia of the mouse embryo: Possible implications for tracheo-esophageal anomalies.

Interkinetic nuclear migration (INM) is a cell polarity-based phenomenon in which progenitor cell nuclei migrate along the apico-basal axis of the pseudostratified epithelium in synchrony with the cell cycle. INM is suggested to be at least partially cytoskeleton-dependent and to regulate not only the proliferation/differentiation of stem/progenitor cells but also the localized/overall size and shape of organs/tissues. INM occurs in all three of the germ-layer derived epithelia, including the endoderm-derived gut. However, INM has not been documented in the esophagus and respiratory tube arising from the anterior foregut. Esophageal atresia with or without trachea-esophageal fistula (EA/TEF) is a relatively common developmental defect. Transcription factors and signaling molecules have been implicated in EA/TEF, but the etiology of EA/TEF-which has been suggested to involve cell polarity-related mechanisms-remains highly controversial. In the present study, we first examined whether INM exists in the trachea and esophagus of mouse embryos at embryonic day 11.5 (E11.5), just after separation of the two tubes from the anterior foregut. By labeling the DNA-synthesizing stem cell nuclei with 5-ethynyl-2'-deoxyuridine, a nucleotide analogue, and statistically analyzing chronological changes in the distribution pattern of the labeled nuclei by using multidimensional scaling, we showed the existence of INM in both the esophagus and trachea, with differences in the INM magnitude and cycle pattern. We further showed morphological changes from the INM-based pseudostratified single layer to the stratified multilayer in the esophageal epithelium in association with a temporal loss/perturbation of AB polarity, suggesting a possible relation with the pathogenesis of EA/TEF.

Interkinetic nuclear migration in the mouse embryonic ureteric epithelium: Possible implication for congenital anomalies of the kidney and urinary tract.

Interkinetic nuclear migration (INM) is a phenomenon in which progenitor cell nuclei migrate along the apico-basal axis of the pseudostratified epithelium, which is characterized by the presence of apical primary cilia, in synchrony with the cell cycle in a manner of apical mitosis. INM is suggested to regulate not only stem/progenitor cell proliferation/differentiation but also organ size and shape. INM has been reported in epithelia of both ectoderm and endoderm origin. We examined whether INM exists in the mesoderm-derived ureteric epithelium. At embryonic day (E) 11.5, E12.5 and E13.5, C57BL/6J mouse dams were injected with 5-bromo-2'-deoxyuridine (BrdU) and embryos were killed 1, 2, 4, 6, 8, 10 and 12 h later. We immunostained transverse sections of the ureter for BrdU, and measured the position of BrdU (+) nuclei in the ureteric epithelia along the apico-basal axis at each time point. We analyzed the distribution patterns of BrdU (+) nuclei in histograms using the multidimensional scaling. Changes in the nucleus distribution patterns suggested nucleus movement characteristic of INM in the ureteric epithelia, and the mode of INM varied throughout the ureter development. While apical primary cilia are related with INM by providing a centrosome for the apical mitosis, congenital anomalies of the kidney and urinary tract (CAKUT) include syndromes linked to primary ciliary dysfunction affecting epithelial tubular organs such as kidney, ureter, and brain. The present study showed that INM exists in the ureteric epithelium and suggests that INM may be related with the CAKUT etiology via primary ciliary protein function.

Fetal jaw movement affects Ihh signaling in mandibular condylar cartilage development: the possible role of Ihh as mechanotransduction mediator.

OBJECTIVE: Jaw movement is an important mechanical factor for prenatal development of the condylar cartilage of mandible. Fetal jaw movement restriction has been shown to cause deformity of the mandibular condyle. We hypothesized that this treatment affects the expression of mechanosensitive molecules, namely Indian hedgehog (Ihh) and Parathyroid hormone related protein (PTHrP) in the condyle. EXPERIMENTAL METHODS: We restrained jaw movement by suturing the jaw of E15.5 mouse embryos and allowed them to develop until E18.5 using exo utero system, and analyzed them by immunohistochemistry and in situ hybridization methods. RESULTS: Morphological, histomorphometric and immunohistochemical study showed that the mandibular condylar cartilage was reduced and deformed, the volume and total cell numbers in the condylar cartilage were also reduced, and number and/or distribution of 5-bromo-2'-deoxyuridine-positive cells, Ihh-positive cells in the mesenchymal and pre-hypertrophic zones were significantly and correspondingly decreased in the sutured group. Using in situ hybridization, reduced expression of Ihh, PTHrP and their related receptors were observed in condylar cartilage of the sutured embryos. CONCLUSIONS: Our results revealed that the altered mechanical stress induced by prenatal jaw movement restriction decreased proliferating cells, the amount of cartilage, and altered expression of the Ihh and PTHrP, suggesting that Ihh act as mechanotransduction mediators in the development of mandibular condylar cartilage.

In vivo analysis of Arg-Gly-Asp sequence/integrin α5ß1-mediated signal involvement in embryonic enchondral ossification by exo utero development system.

Enchondral ossification is a fundamental mechanism for longitudinal bone growth during vertebrate development. In vitro studies suggested that functional blockade with RGD peptides or with an antibody that interferes with integrin α5ß1-ligand interactions inhibited pre-hypertrophic chondrocyte differentiation. The purpose of this study is to elucidate in vivo the roles of the integrin α5ß1-mediated signal through the Arg-Gly-Asp (RGD) sequence in the cell-extracellular matrix (ECM) interaction in embryonic enchondral ossification by an exo utero development system. We injected Arg-Gly-Asp-Ser (RGDS) peptides and anti-integrin α5ß1 antibody (α5ß1 ab) in the upper limbs of mouse embryos at embryonic day (E) 15.5 (RGDS-injected limbs, α5ß1 ab-injected limbs), and compared the effects on enchondral ossification with those found in the control limbs (Arg-Gly-Glu-Ser peptide-, mouse IgG-, or vehicle-injected, and no surgery) at E16.5. In the RGDS-injected limbs, the humeri were shorter and there were fewer BrdU-positive cells than in the control limbs. The ratios of cartilage length and area to those of the humerus were higher in the RGDS-injected limbs. The ratios of type X collagen to type 2 collagen mRNA and protein (Coll X/Coll 2) were significantly lower in the RGDS-injected limbs. In those limbs, TUNEL-positive cells were hardly observed, and the ratios of fractin to the Coll X/Coll 2 ratio were lower than in the control limbs. Furthermore, the α5ß1 ab-injected limbs showed results similar to those of RGDS-injected limbs. The present in vivo study by exo utero development system showed that RGDS and α5ß1 ab injection decreased chondrocyte proliferation, differentiation, and apoptosis in enchondral ossification, and suggested that the integrin α5ß1-mediated ECM signal through the RGD sequence is involved in embryonic enchondral ossification.

Mathematical analysis of mandibular morphogenesis by micro-CT-based mouse and alizarin red S-stained-based human studies during development.

Prenatal development of the mandible is an important factor in its postnatal function. To examine quantitatively normal and abnormal developmental changes of the mandible, we here evaluated morphological changes in mineralizing mandibles by thin-plate spline (TPS) including bending energy (BE) and Procrustes distance (PD), and by Procrustes analyses including warp analysis, regression analysis, and discriminant function analysis. BE and PD were calculated from lateral views of the mandibles of mice or of human fetuses using scanned micro-computed tomography (CT) images or alizarin red S-stained specimens, respectively. BE and PD were compared (1) between different developmental stages, and further, to detect abnormalities in the data sets and to evaluate the deviation from normal development in mouse fetuses, (2) at embryonic day (E) 18.5 between the normal and deformed mandibles, the latter being caused by suturing the jaw at E15.5, (3) at E15.5 and E18.5 between normal and knockout mutant mice of receptor tyrosine kinase-like orphan receptor (Ror) 2. In mice, BE and PD were large during the prenatal period and small after postnatal day 3, suggesting that the mandibular shape changes rapidly during the prenatal and early postnatal periods. In humans, BE of the mandibles peaked at 16-19 weeks of gestation, suggesting the time-dependent change in the mandibular shape. TPS and Procrustes analyses statistically separated the abnormal mandibles of the sutured or Ror2 mutant mouse fetuses from the normal mandible. These results suggest that TPS and Procrustes analyses are useful for assessing the morphogenesis and deformity of the mandible.

Effects of restriction of fetal jaw movement on prenatal development of the temporalis muscle.

Jaw movement affects masticatory muscles during the postnatal period. Prenatal jaw movement has also been implicated in the development of the temporomandibular joint; however, its effect on prenatal development of the masticatory muscles has not been extensively analysed. In the present study, we examined the effects of the restriction of fetal jaw movement on the temporalis muscle, a major masticatory muscle, in mice by suturing the maxilla and mandible (sutured group) using an exo utero development system. We compared the morphology of the temporalis muscle between sutured, sham-operated and normal in utero groups. At embryonic day (E) 18.5, the volume of muscle fibres, but not that of connective tissue, in the temporalis muscle was decreased in the sutured group. The E18.5 temporalis muscle in the sutured group appeared morphologically similar to that of the E17.5 in utero group, except for frequent muscle fibre irregularities. By transmission electron microscopy, in the sutured group, the myofibrils were immature and scattered, the nuclei appeared comparatively immature, the mitochondria were expanded in volume with fewer cristae, and cytoplasmic inclusion bodies were frequently observed. Expression of Myf-6, a late myogenic transcription factor, by real-time RT-PCR was not significantly different between the sutured and sham-operated groups. These findings demonstrated approximately 1-day delay in the morphological development of the temporalis muscle in the sutured group, and some abnormalities were observed, although Myf-6 level was not affected in the sutured group. The present study revealed that the prenatal jaw movement influences the development of the temporalis muscle.