The dietary supplements effect on metabolic markers in non-pharmacologically managed gestational diabetes mellitus patients: a systematic review and meta-analysis and meta-regression of randomized controlled trials.

Background: Although several randomized clinical trials have tested the effect of prenatal dietary supplements on plasma glucose and lipid levels in non-pharmacologically managed gestational diabetes mellitus patients (GDM), a rigorous meta-analytic compendium lacks in the context. Therefore, this study aims to address this evidence gap. Method: Eligible trials retrieved from searches in the PubMed, Embase, and Scopus databases were appraised using the Revised Cochrane risk-of-bias tool for randomized trials (RoB 2). The weighted mean differences (WMD) between dietary supplements and placebo were estimated using random-effect meta-analysis models for plasma glycemic and lipid markers. Meta-regression analysis ensued for effect modifier identification. The statistical significance estimation happened at p < 0.05 (95% confidence interval). Results: This review included 19 trials (mostly Iranian and of low risk of bias primarily) of > 8000 GDM patients. Meta-analysis showed favorable effects of dietary supplementation on fasting plasma glucose (WMD: -5.42 mg/dL, p < 0.001), homeostasis model assessment indexes- insulin resistance (HOMA-IR; WMD: -1.02, p < 0.001), quantitative insulin sensitivity check index (WMD: 0.01, p < 0.001), total cholesterol (TC; WMD: -7.70 mg/dL, p = 0.006), triglycerides (WMD: -10.23 mg/dL, p = 0.0083), TC/high-density lipoprotein (WMD: -0.31 mg/dL, p < 0.001), low-density lipoprotein (WMD: -5.79 mg/dL; p < 0.001) and very-low-density lipoprotein (WMD: -5.67 mg/dL, p < 0.001) levels. However, the HOMA- ß-cell function didn't increase (WMD: -17.91, p < 0.001). Baseline maternal age (ß = 0.28, p = 0.014) and GDM diagnostic criteria (ß = 0.90, p = 0.012) were effect moderators of HOMA-IR and body mass index (BMI) (ß = 6.07, p = 0.022) and supplement type (solo versus combined) (ß = 14.99, p = 0.006) were effect moderators of triglyceride levels. Conclusion: Altogether, antenatal dietary supplements achieved control over plasma glycemic and lipid profiles in non-pharmacologically treated GDM patients. Maternal age and GDM diagnostic criteria moderated HOMA-IR levels. BMI and supplement-type moderated triglyceride levels. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01369-0.

Comparison of the effect of dietary and herbal supplements on anthropometric, metabolic and androgenic profiles of women with polycystic ovary syndrome: a systematic review and network meta-analysis protocol.

Polycystic ovarian syndrome (PCOS) is characterized by obesity, glucose intolerance, dyslipidemia, and hyperandrogenemia. Although several, placebo-controlled 2x2 factorial design, randomized controlled trials have tested the efficacy of dietary and herbal supplements in controlling these parameters in PCOS patients, these studies are not suitable for a comparative efficacy assessment across these supplements. Herein, a protocol for systematic review and network meta-analysis (NMA) is presented to make such a comparison. PubMed, Embase, and Scopus, were interrogated to identify relevant trials, published in English, factors to be investigated will include dietary factors, micronutrients, choline, essential fatty acids, and herbal extracts. Other factors to be considered include trial design, population characteristics, interventions compared, and outcomes of interest. The revised Cochrane tool was used for the appraisal of eligible trials. NMA (frequentist method) will be used for respective outcomes to compare effect sizes (weighted or standardized mean difference) among the interventions. Both logical and statistical (inconsistency assessment) approaches will be used to minimize intransitivity risk. The surface under the cumulative ranking curve values will be used to gauge the best intervention for outcomes with a statistically significant effect size suggesting a favorable outcome. Additionally, the exploration of interrelation among interventions and the small study effect in respective NMA models will be investigated using network maps and comparison-adjusted funnel plots, respectively. Statistical significance is assumed at p<0.05 with 95% confidence interval. Stata statistical software (v16) was used for analysis. The study was registered with PROSPERO, registration number: CRD42022301530.

Treatment-duration-wise harm profile of insulin-sodium-glucose co-transporter inhibitor co-treatment in type 1 diabetes mellitus patients.

Background: The treatment duration of insulin-sodium-glucose co-transporter inhibitors (SGLTis) co-treatment of type 1 diabetes mellitus (T1DM) patients in randomized controlled trials (RCTs) varies by 1-52 weeks. Henceforth, treatment duration-wise, we compared the following insulin-treatment adjuncts- mega- versus low-dose SGLTis, SGLTis versus placebo, and different SGLTi dosages. Method: Double-blinded RCTs reporting the above were searched (using terms like insulin-dependent, "juvenile-onset diabetes," and "sodium glucose cotransport*") in the PubMed, Embase, and Scopus databases and appraised using a Cochrane tool. The risks across different SGLTi-dosages were compared using network meta-analysis. Random-effect pairwise meta-analysis was performed for the remaining harm juxtapositions. Meta-analyses were performed for the following treatment durations- < 4 weeks, 4 to < 24 weeks, and ≥ 24 weeks. For meta-analysis and certainty of evidence assessment, we used the Stata statistical software and the GRADE method, respectively. Results: A total of 15 (low risks of bias) studies sourcing data from about 7,330 T1DM patients were reviewed. Meta-analysis findings of ≥ 24 weeks long trials were- a. SGLTi-insulin co-treatment increased the genital infection (GI) (RR: 3.51; 95% CI: 2.59, 4.77), diabetic ketoacidosis (DKA) and (RR: 3.25; 95% CI:1.29, 8.16), and serious side effects (RR: 1.43; 95% CI: 1.05, 1.94) risk. b. SGLT2i-insulin increased the GI risk (RR: 3.77; 95% CI: 2.31, 6.16; high-quality evidence). c. Sotagliflozin-insulin increased the GI (RR: 3.36; 95% CI: 2.28, 4.96) and DKA (RR: 6.69; 95% CI: 2.75, 16.32) risk (both high-quality evidence). Compared to low-dose, megadose SGLTi treatment for 4 to < 24 weeks increased the GI risk. The remaining analyses were not statistically significantly different. Conclusion: On moderate to long-term treatment (24-52 weeks) of T1DM patients, insulin-SGLT2i co-treatment was associated with GI risk, and insulin-sotagliflozin co-treatment was associated with DKA and GI risk. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01192-7.

Efficient Synergistic Antibacterial Activity of α-MSH Using Chitosan-Based Versatile Nanoconjugates.

The application of antimicrobial peptides has emerged as an alternative therapeutic tool to encounter against multidrug resistance of different pathogenic organisms. α-Melanocyte stimulating hormone (α-MSH), an endogenous neuropeptide, is found to be efficient in eradicating infection of various kinds of Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA). However, the chemical stability and efficient delivery of these biopharmaceuticals (i.e., α-MSH) to bacterial cells with a significant antibacterial effect remains a key challenge. To address this issue, we have developed a chitosan-cholesterol polymer using a single-step, one-pot, and simple chemical conjugation technique, where α-MSH is loaded with a significantly high amount (37.7%), and the final product is obtained as chitosan-cholesterol α-MSH polymer-drug nanoconjugates. A staphylococcal growth inhibition experiment was performed using chitosan-cholesterol α-MSH and individual controls. α-MSH and chitosan-cholesterol both show bacterial growth inhibition by a magnitude of 50 and 79%, respectively. The killing efficiency of polymer-drug nanoconjugates was very drastic, and almost no bacterial colony was observed (∼100% inhibition) after overnight incubation. Phenotypic alternation was observed in the presence of α-MSH causing changes in the cell structure and shape, indicating stress on Staphylococcus aureus. As a further consequence, vigorous cell lysis with concomitant release of the cellular material in the nearby medium was observed after treatment of chitosan-cholesterol α-MSH nanoconjugates. This vigorous lysis of the cell structure is associated with extensive aggregation of the bacterial cells evident in scanning electron microscopy (SEM). The dose-response experiment was performed with various concentrations of chitosan-cholesterol α-MSH nanoconjugates to decipher the degree of the bactericidal effect. The concentration of α-MSH as low as 1 pM also shows significant inhibition of bacterial growth (∼40% growth inhibition) of Staphylococcus aureus. Despite playing an important role in inhibiting bacterial growth, our investigation on hemolytic assay shows that chitosan-cholesterol α-MSH is significantly nontoxic at a wide range of concentrations. In a nutshell, our analysis demonstrated novel antimicrobial activity of nanoparticle-conjugated α-MSH, which could be used as future therapeutics against multidrug-resistant Staphylococcus aureus and other types of bacterial cells.

Associations Between Multidimensional Sleep Health Parameters and Adolescents' Self-reported Light Exposure in the Free-living Environment.

The objective of this study was to characterize the associations between light exposure in the free-living environment and multiple dimensions of sleep health of typically developing adolescents. Fifty-six (29 girls, 27 boys) typically developing adolescents (mean age = 13.59, SD = 0.89, range = 12-17 years) participated. For six consecutive nights, sleep was assessed in the home environment using actigraphy. During the same period, participants were asked to fill out a daily sleep log and a daily light exposure log, and to complete questionnaires regarding their alertness and subjective sleep satisfaction. Longer self-reported exposure to daylight in the morning was associated with longer objectively measured sleep duration. Longer self-reported exposures to electronic devices in the evening were associated with later objectively measured sleep onset and offset times, shorter sleep duration, and greater day-to-day sleep variability. Longer morning exposure to outdoor light was associated with a longer sleep duration. Self-reported light exposure was not associated with sleep satisfaction, alertness/sleepiness, or sleep efficiency. Among the covariates, circadian preference accounted for the highest percentage of variance. Adolescents' sleep health is associated with the self-reported duration of exposure to daylight in the morning and to electronic devices in the evening.

C11 choline PET/CT succeeds when conventional imaging for primary hyperparathyroidism fails.

BACKGROUND: Focused parathyroidectomy in primary hyperparathyroidism is possible with accurate preoperative localization. A growing body of data exists regarding the role of radio-labeled C11 choline positron emission tomography/computed tomography. In cases of nonlocalized disease, it may be a useful adjunct to ultrasound, (123)I/(99)Tc-sestamibi (I-123 sestamibi), or 4-dimensional computed tomography imaging. METHODS: Patients who received a neck and chest limited coverage C11 choline positron emission tomography/computed tomography for evaluation of primary hyperparathyroidism from 2017 to 2021 at a single institution were retrospectively reviewed. We assessed the sensitivity, positive predictive value, and false negative rate. We also compared these rates to the standard modalities of ultrasound, I-123 sestamibi, 4-dimensional computed tomography, and examined concordance rates. RESULTS: We identified 43 patients, of whom 33 had a positive C11 choline positron emission tomography/computed tomography finding. This cohort of patients had failed to localize on multiple standard imaging modalities. Twenty-five patients proceeded to surgery, 72% of whom were reoperative cases. Twenty (80%) achieved an intraoperative cure. Analysis showed that C11 choline positron emission tomography/computed tomography achieved a sensitivity of 64% (95% confidence interval 47%-82%) and positive predictive value of 72% (95% confidence interval 54%-90%). There were 5/25 (20%) false positive positron emission tomography C11 choline results found to be lymph nodes, normal parathyroid, and 1 recurrent laryngeal nerve neuroma. CONCLUSION: C11 choline positron emission tomography/computed tomography is a useful adjunct for parathyroid localization in a complex population of patients who have failed standard localization techniques including ultrasound, I-123 sestamibi, or 4-dimensional computed tomography and/or prior operations. Although routine inclusion of C11 choline positron emission tomography/computed tomography imaging may not be necessary, it may aid in preoperative localization in the reoperative setting.

Participant attrition and perinatal outcomes in prenatal vitamin D-supplemented gestational diabetes mellitus patients in Asia: A meta-analysis.

BACKGROUND: The role of vitamin D supplementation in gestational diabetes mellitus (GDM) patients is unclear. AIM: To determine the burden and risk of post-randomization GDM patient attrition from vitamin D-supplemented arms of randomized controlled trials (RCTs). The auxiliary aim was to compare the effects of nutritional supplements on their fasting blood glucose (FPG) levels and perinatal outcomes. METHODS: RCTs were searched in the PubMed, Embase, and Scopus databases. Random-effect prevalence and pairwise meta-analysis were performed for the primary objective. The auxiliary aim was to compare the effects of nutritional supplements on their fasting blood glucose (FPG) levels and perinatal outcomes. Fixed-effect network meta-analyses were undertaken for the secondary goals. All analyses were performed using Stata software, and statistical significance was determined at P < 0.05. RESULTS: Thirteen RCTs from Iran and China were reviewed. The participant attrition burden in vitamin D recipients was 6% [95% confidence interval (CI): 0.03, 0.10], and its risk did not vary from non-recipients. Vitamin D and calcium co-supplementation reduced the cesarean section incidence in GDM patients [risk ratio (RR): 0.37; 95%CI: 0.18, 0.74]. The hyperbilirubinemia or hospitalization risk in their newborns decreased with vitamin D supplementation (RR: 0.47; 95%CI: 0.27, 0.83) and co-supplementation with calcium (RR: 0.35; 95%CI: 0.16, 0.77) or omega-3 fatty acids (RR: 0.25; 95%CI: 0.08, 0.77). Vitamin D and probiotics co-supplementation decreased newborn hyperbilirubinemia risk (RR: 0.28; 95%CI: 0.09, 0.91). FPG levels and macrosomia risk did not vary across interventions. CONCLUSION: In RCTs, vitamin D supplementation or co-supplementation in GDM patients showed a low participant attrition burden and low risk of cesarean section, newborn hyperbilirubinemia, and newborn hospitalization.

The structure-function analysis of Obg-like GTPase proteins along the evolutionary tree from bacteria to humans.

Obg proteins belong to P-loop guanine triphosphatase (GTPase) that are conserved from bacteria to humans. Like other GTPases, Obg cycles between guanine triphosphate (GTP) bound "on" state and guanine diphosphate (GDP)-bound "off" state, thereby controlling various cellular processes. Different members of this group have unique structural characteristics; a conserved glycine-rich N-terminal domain known as obg fold, a central conserved nucleotide binding domain, and a less conserved C-terminal domain of other functions. Obg is a ribosome dependent GTPase helps in ribosome maturation by interacting with several proteins of the 50S subunit of the ribosome. Obg proteins have been widely considered as a regulator of cellular functions, helping in DNA replication, cell division. Apart from that, this protein also takes part in various stress adaptation pathways like a stringent response, sporulation, and general stress response. In this particular review, the structural features of ObgE have been highlighted and how the structure plays important role in interacting with regulators like GTP, ppGpp that are crucial for executing biological function has been orchestrated. In particular, we believe that Obg-like proteins can provide a link between different global pathways that are necessary for fine-tuning cellular processes to maintain the cellular energy status.

The effects of prenatal dietary supplements on blood glucose and lipid metabolism in gestational diabetes mellitus patients: A systematic review and network meta-analysis protocol of randomized controlled trials.

BACKGROUND: Several randomized controlled trials (RCT) investigated antenatal dietary supplements' effect on gestational diabetes mellitus patients' fasting plasma glucose levels, glycated hemoglobin levels, homeostasis model assessment of- insulin resistance and ß-cell function, quantitative insulin sensitivity check index for glucose, high-, low-, and very-low-density lipoprotein cholesterol levels, total cholesterol levels, triglyceride levels, and triglyceride to high-density lipoprotein ratio. However, an efficacy comparison across various dietary supplements and their co-supplements are unavailable for these outcomes. Therefore, a systematic review protocol is proposed here to make a network meta-analysis (NMA)-based juxtaposition across the following dietary supplements- vitamins, Myo-inositol, choline, minerals, probiotics, prebiotics, synbiotics, and omega-3 fatty acids. MATERIALS AND METHODS: A database search will ensue in the PubMed, Embase, and Scopus databases for RCTs testing the above, irrespective of their geographical origin. Data on population characteristics, compared interventions, and outcomes of interest will get abstracted from the studies included in the proposed review. Each of the reviewed studies will get appraised using the revised Cochrane tool. For each outcome, the comparative efficacy across interventions will be estimated in weighted or standardized mean difference using the frequentist method NMA and presented with their 95% confidence interval using league tables. By constructing network maps and comparison-adjusted funnel plots, a visual assessment of the inter-interventional relation and publication bias in each NMA model will happen, respectively. The best-ranked intervention prediction for respective outcomes will transpire using the surface under the cumulative ranking curve values. The Stata statistical software (version 16) will be used for analysis, and statistical significance will be determined at p<0.05 and 95% confidence interval. TRIAL REGISTRATION: PROSPERO registration number: CRD42020214378.

Pre-pandemic sleep behavior and adolescents' stress during Covid-19: a prospective longitudinal study.

OBJECTIVE: To prospectively document changes in adolescents' sleep before versus during the COVID-19 pandemic, and to examine their impact on adolescents' perceived stress. METHODS: Sixty-two typically developing adolescents participated in the study before (Time 1: January 15 to March 13, 2020) and during (Time 2: May 15 to June 30, 2020) the COVID-19 pandemic in Canada. At Time 1, each participant's sleep pattern was assessed in the home environment using actigraphy and sleep logs for seven consecutive nights. Adolescents completed a battery of questionnaires in which they reported on their sleep schedule, duration, and quality, as well as their activities at bedtime, their daytime sleepiness, and their social/emotional behavior. The participants' parents provided demographic information. At Time 2, each participant completed a sleep log, the same battery of questionnaires regarding sleep, and the Perceived Stress Scale. RESULTS: (1) Adolescents' reported sleep was of longer duration and on a delayed schedule during the COVID-19 pandemic compared to pre-pandemic. (2) A larger proportion of adolescents reported meeting or exceeding the recommended amount of sleep during the COVID-19 pandemic compared to pre-pandemic sleep. (3) "Social jet lag" disappeared during the COVID-19 pandemic. (4) A shorter reported sleep duration and higher level of arousal at bedtime at Time 1 were significant predictors of adolescents' perceived stress at Time 2-during the COVID-19 pandemic. (5) A higher levels of arousal at bedtime and lower reported sleep quality at Time 2 were concurrently associated with higher levels of perceived stress among adolescents, even when we controlled for the levels of pre-pandemic emotional or behavioral issues, sleep duration, or sleep quality. CONCLUSION: Sleep duration and cognitive-emotional arousal, which are both modifiable behaviors, were associated with adolescents' perceived stress during the COVID-19 pandemic. These behaviors could be useful targets for preventive interventions aiming to reduce adolescents' stress in the face of stressogenic situations, such as the COVID-19 pandemic.

Diabetes prevalence and mortality in COVID-19 patients: a systematic review, meta-analysis, and meta-regression.

BACKGROUND: The coronavirus disease 2019 (COVID-19) patients with diabetes mellitus (DM) are at high risk of fatal outcomes. This meta-analysis quantifies the prevalence of mortality among (1) diabetic and (2) non-diabetic, and (3) the prevalence of DM, in hospitalized COVID-19 patients. METHODS: Published studies were retrieved from four electronic databases (PubMed, Embase, Scopus, and medRxiv) and appraised critically utilizing the National Heart, Lung, and Blood Institute's tool. Meta-analyses were performed using the random-effects model. The measures of heterogeneity were ascertained by I- squared (I 2 ) and Chi-squared (Chi 2 ) tests statistics. Predictors of heterogeneity were quantified using meta-regression models. RESULTS: Of the reviewed 475 publications, 22 studies (chiefly case series (59.09 %)), sourcing data of 45,775 hospitalized COVID-19 patients, were deemed eligible. The weighted prevalence of mortality in hospitlized COVID-19 patients with DM (20.0 %, 95 % CI: 15.0-26.0; I 2 , 96.8 %) was 82 % (1.82-time) higher than that in non-DM patients (11.0 %, 95 % CI: 5.0-16.0; I 2 , 99.3 %). The prevalence of mortality among DM patients was highest in Europe (28.0 %; 95 % CI: 14.0-44.0) followed by the United States (20.0 %, 95 % CI: 11.0-32.0) and Asia (17.0 %, 95 % CI: 8.0-28.0). Sample size and severity of the COVID-19 were associated (p < 0.05) with variability in the prevalence of mortality. The weighted prevalence of DM among hospitalized COVID-19 patients was 20 % (95 % confidence interval [CI]: 15-25, I 2 , 99.3 %). Overall, the quality of the studies was fair. CONCLUSIONS: Hospitalized COVID-19 patients were appreciably burdened with a high prevalence of DM. DM contributed to the increased risk of mortality among hospitalized COVID-19 patients compared to non-DM patients, particularly among critically ill patients. Registration: PROSPERO (registration no. CRD42020196589). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-021-00779-2.

Changes in anthropometric and blood 25-hydroxyvitamin D measurements in antenatal vitamin supplemented gestational diabetes mellitus patients: a systematic review and meta-analysis of randomized controlled trials

Objective: Gestation weight (GW), body mass index (BMI), and blood 25-hydroxyvitamin D [25(OH)D] level during pregnancy are important determinants of the gestational outcomes. This study aimed to study how these parameters vary between antenatal vitamin D recipients and non-recipients in gestational diabetes mellitus (GDM) patients. Material and Methods: The randomized controlled trials comparing these outcomes between vitamin D recipient and non-recipient GDM patients were searched in electronic databases (PubMed, Embase, and Scopus). The reviewed studies' data were abstracted and critically appraised using the Cochrane tool. The estimation of the weighted mean difference for GW and BMI and standardized mean difference (SMD) for 25(OH)D levels occurred by juxtaposing the interventions meta-analytically (random-effect model). The statistical inconsistency was determined by Chi2 and I2 method. The statistical significance was estimated at p<0.05 and 95% confidence interval (CI). Results: Eleven eligible trials (all Iran-based, except one), sourcing data from about 875 GDM patients, were reviewed. Overall, the risk of bias was low, except for selection and performance bias. On random-effect model meta-analysis, the 25(OH)D levels of the GDM patients favored the vitamin D recipients when compared to non-vitamin D (SMD 1.97, 95% CI: 1.06-2.88, p<0.001; I2 96.2%, p of Chi2 <0.001) and placebo (SMD 1.86, 95% CI: 0.95-2.77, p<0.001; I2 95.3%, p of Chi2 <0.001) recipients, respectively. On meta-regression, sample size was a predictor of the observed heterogeneity. For GW and BMI the interventions did not differ statistically significantly. Conclusion: In GDM patients, antenatal use of vitamin D aids in the rise of blood 25(OH)D levels. However, vitamin D supplementation did not affect change in GW or BMI.

Epidemiological burden of parents being the index cases of COVID-19 infected children.

BACKGROUND: In the ongoing coronavirus disease 2019 (COVID-19) pandemic, when children remain home-confined secondary to the closure of schools, little is known of the burden of the parents being their index case. AIM: To determine the prevalence of parents being the index case of COVID-19 infected children. METHODS: A database search in PubMed and Scopus ensued to recruit studies reporting the index case information of COVID-19 infected individuals aged ≤ 18. The reviewed articles' quality evaluation included the use of the National Heart, Lung, and Blood Institute's tool. A random-effect meta-analysis ensued to determine the prevalence of the parent being and not-being the index case. Heterogeneity was assessed by I 2 and Chi 2 statistics. The publication bias was evaluated by funnel plots and Egger's test. RESULTS: Overall, this review included 13 eligible studies sourcing data from 622 children of 33 nations. Study designs were heterogeneous and primarily included descriptive reports (38.4%). The prevalence of parent being the index case was 54% (95%CI: 0.29-0.79; I 2: 62.3%, Chi 2 P < 0.001). In > 70% of children, their index-case parent was symptomatic due to COVID-19 at the time of infection transmitting. Studies for which a risk of bias assessment was possible were of fair quality. CONCLUSION: There is a substantial global burden of parents being the index case of COVID-19 infected children, and frequently these parents are symptomatic. Therefore, from a public health perspective, early detection of these parents is crucial.

The impact of COVID-19 related school shutdown on sleep in adolescents: a natural experiment.

OBJECTIVE: During the outbreak of the COVID-19 pandemic in 2020, high schools closed or transitioned to remote teaching. The aim of this study was to describe how the COVID-19 related school shutdown impacted the sleep behaviors of typically developing adolescents. METHODS: A qualitative study was conducted between April 28 and June 3, 2020 with 45 adolescents using one-on-one semi-structured phone interviews. RESULTS: The "natural experiment" caused by the shutdown of schools due to the COVID-19 pandemic led to a 2-h shift in the sleep of typically developing adolescents, longer sleep duration, improved sleep quality, and less daytime sleepiness compared to those experienced under the regular school-time schedule. DISCUSSION: These findings are consistent with previous studies showing that delaying high school start times could be an effective way to extend sleep duration, improve sleep quality, reduce daytime sleepiness and lower adolescents' stress during the school year. As many countries look for ways to reduce the number of interactions between students in schools so that physical distancing is feasible, following teens' delayed sleep biology could offer an affordable solution. For example, staggering arrival times by delaying school start time for older adolescents compared with younger adolescents can reduce the total number of students attending school at the same time. This strategy offers a practical means to reduce school density and the number of interactions between students which are needed to reduce the potential transmission of COVID-19 in schools, while improving adolescents sleep health.

The risk of morbidities in newborns of antenatal vitamin D supplemented gestational diabetes mellitus patients.

BACKGROUND: There is no established antenatal intervention that reduces the risk of preeclampsia and preterm delivery in gestational diabetes mellitus (GDM) mothers and hyperbilirubinemia, hypoglycemia, and hospitalization in their newborns. Henceforth, this study aims to study how these risks change on prenatal vitamin D supplementation. METHODS: Randomized parallel arm trials comparing these interventions' effect on the above outcomes were searched in the PubMed, Embase, and Scopus, irrespective date, and language of publication. Each eligible trial's risk of bias was assessed using the Cochrane collaboration tool. Using random-effects meta-analysis, the risk of the outcomes was compared. RESULTS: Six eligible Iran-based trials of about 476 participants were included in this review. Four trials complemented vitamin D along with other nutrients. Overall, the risk of bias was low in these trials. The newborns of antenatal vitamin D recipients have a reduced risk of hyperbilirubinemia (relative risk [RR] = 0.46; 95% confidence interval [CI]: 0.33, 0.64; I2 = 0%) and hospitalization (RR = 0.46; 95% CI: 0.32, 0.65; I2 = 0%) than those who did not receive the supplement. The rest of the outcomes did not vary between the compared interventions. The results remained unchanged on using a fixed-effect meta-analysis, repeating the meta-analysis while eliminating a trial each time, and on imputation analysis. An auxiliary meta-analysis comparing the intervention with placebo also suggested a decreased risk of hyperbilirubinemia (RR = 0.43; 95% CI: 0.30, 0.62; I2 = 0%) and hospitalization (RR = 0.44; 95% CI: 0.30, 0.62; I2 = 0%). CONCLUSION: Newborns of GDM mothers who received vitamin D as a sole or co-supplement antenatally have a decreased risk of hyperbilirubinemia and hospitalization.

The comparison of efficacy and safety between different doses of empagliflozin in insulin-treated type 1 diabetes mellitus patients: a systematic review and meta-analysis protocol.

OBJECTIVES: The proposed review aims to compare the efficacy and safety profile of empagliflozin 25 mg with its lower dosages and placebo, respectively, in insulin-treated type 1 diabetes mellitus (T1DM) patients. METHODS: Double-blinded randomized controlled trials comparing the above outcomes will be searched primarily in three electronic databases (PubMed, Embase, and Scopus) and eligible trials will be included in the proposed review. Then, from the trials recruited in the review, data of the study design, participants, interventions compared, and outcomes of interest will be extracted. Subsequently, the trials' risk of bias will be assessed using the Cochrane Collaboration's tool. The meta-analysis will be conducted with a fixed-effect or a random-effect model to estimate the mean differences (weighted or standardized) and risk ratios for the efficacy and safety-related comparable outcome data, respectively. Statistical heterogeneity will be assessed by the p-value of chi-squared statistics and I2 statistics and explained by subgroup analysis and meta-regression. Publication bias will be assessed by funnel plots and Egger's test. The sensitivity analysis will repeat the meta-analysis for respective outcomes using assumptions alternative to that used in the preliminary meta-analysis and by dropping each study at a time. RESULTS: A narrative reporting will ensue if a meta-analytic comparison is not possible. CONCLUSIONS: Based on the contemporary literature, the proposed review will synthesize the evidence on how the efficacy and safety profile of high dose empagliflozin varies with its lower doses and placebo, respectively, in insulin-treated T1DM patients.

A comparison of the risk of cesarean section in gestational diabetes mellitus patients supplemented antenatally with vitamin D containing supplements versus placebo: A systematic review and meta-analysis of double-blinded randomized controlled trials

The aim of this study was to study the role of vitamin D containing supplements in the risk of cesarean section (CS), a common complication in gestational diabetes mellitus (GDM) patients. An additional objective was to assess the risk of developing pre-eclampsia, preterm delivery, macrosomia, and polyhydramnios in these participants. Various electronic databases were searched for double-blinded parallel-arm randomized controlled trials that reported the incidence of CS in adult, non-insulin treated GDM patients who received vitamin D and placebo in different treatment arms, respectively. Next, each eligible trial's risk of bias was assessed, and the effects of the above interventions on the respective outcomes were compared meta-analytically across the trials. This review included five Iranian trials sourcing data from nearly 380 participants. The risk of bias in the trials was primarily low. In contrast to the placebo group, the risk of CS [risk ratio (RR): 0.61, p=0.002, 95% confidence interval (CI): 0.44,0.83; I2=0%, p-value of Cochrane's Q: 0.373) and macrosomia (RR: 0.31, p=0.006, 95% CI: 0.13,0.72; I2=0%, p-value of Cochrane's Q: 0.935] was less in the vitamin D supplemented group. The remaining outcomes did not differ between the intervention groups. The antenatal use of vitamin D containing supplements in non-insulin treated GDM patients might reduce the risk of CS and macrosomia.

A systematic review and meta-analysis of randomized controlled trials, juxtaposing the control of glycemia and blood pressure between large dose empagliflozin and placebo among type 1 diabetes patients.

OBJECTIVES: While empagliflozin (25 mg) is used to treat type-2 diabetes mellitus patients with optimum renal functioning, its efficacy and safety in type-1 diabetes mellitus (T1DM) is not yet established. Therefore, this study aimed to compare insulin-treated T1DM patients' (with adequate renal functioning) glycemic and blood pressure control between the 25 mg empagliflozin recipients and placebo recipients. METHODS: Parallel-arm randomized controlled trials comparing the effect of daily administered 25 mg empagliflozin tablets in adjunct to insulin treatment with placebo and insulin treatment in T1DM patients with an estimated glomerular filtration rate of 45 mL/min/1.73 m2 or more were eligible for inclusion. Trials were searched in PubMed, EMBASE, SCOPUS, and CENTRAL with no restriction on date and language. Risk of bias of trials was assessed and mean and standard deviation of glycated hemoglobin (HbA1c, in %), systolic blood pressure (mmHg), and diastolic blood pressure (mmHg) at the end of the trial period were collected, and random-effects meta-analysis was done to estimate the weighted mean difference (WMD). The meta-analysis was done in Stata statistical software. This study was conducted in June 2019. RESULTS: Three relatively small-sized trials published between 2015 and 2018 were eligible for review and analyses. The trials suffered from unclear risk of performance and detection bias. The HbA1c reduction favored the intervention group (WMD = -0.478, 95% confidence intervals = -0.766--0.189, P = 0.001; I2 = 0%). The WMD of blood pressure (systolic and diastolic) did not vary between the treatment groups. CONCLUSION: Evidence (of moderate quality) suggests that daily administration of empagliflozin 25 mg tablets in adjunct to insulin in T1DM patients with optimum kidney functioning is useful to achieve glycemic control compared to placebo and insulin therapy. However, the effect on blood pressure remained indistinguishable between the compared interventions.

Shoulder joint mobility in patients with primary adhesive capsulitis after treatment with continuous mode of ultrasound: A systematic review of randomized controlled trials.

Background: Although the continuous mode of ultrasound therapy improves joint mobility, its role in primary adhesive capsulitis (AC) remains unclear. Therefore, this systematic review aims to address this evidence gap. Methods: The literature search included databases (SCOPUS, CINAHL, EMBASE, and PubMed) and in-text references of articles read full-text. Randomized controlled trials (RCT) on primary AC patients (published in the English language between 1979-2019) comparing the ROM changes (in degrees) mainly between continuous mode of US therapy with any other non-electrotherapeutic treatment were eligible for inclusion. The trials were reviewed narratively along with an assessment of the risk of bias. Results: Out of 174 search results, two eligible single-center trials comprising of 100 participants compared ROM in four separate directions at the 10th session and after three months post-intervention. The risk of selection bias, performance bias, and attrition bias was unclear among the trials. While in both the trials ROM (in all directions) improved in the respective intervention groups at follow up, most of these changes varied between the intervention groups in one trial. However, in the latter trial, participants in the treatment group had the worst ROM values at baseline with poor compliance to the adjunct exercise therapy. Conclusion: The contemporary evidence in the context remains inconclusive due to a lack of large multicentric well-conducted RCTs.