Characteristics of Interventional Trials for Patients Living With Intestinal Stoma Registered in ClinicalTrials.gov With a Focus on Inflammatory Bowel Disease.

BACKGROUND: This systematic review was performed to characterize the landscape of research conducted in patients with intestinal stoma (IS) and highlight unmet needs for clinical research in Crohn's disease (CD) and IS. METHODS: We searched ClinicalTrials.gov from inception to May 25, 2022, to identify clinical trials assessing interventions in patients with an IS, as well as those with an IS and CD. Studies were grouped according to type of intervention. We excluded observational studies with no treatment arm. RESULTS: A total of 253 studies were included in the final analysis. Most studies investigated devices (n = 122 [48.2%]), or surgical procedures (n = 63 [24.9%]), followed by behavioral interventions (n = 30 [11.8%]), drugs (n = 20 [7.9%]), dietary interventions (n = 2 [0.8%]), skin care products (n = 2 0.8%]), and others (n = 14 [5.5%]). A total of 50.9% (n = 129) of studies had completed recruitment, enrolling 11 116 participants. Only 6 studies (surgery: n = 3; physiological studies: n = 2; drugs: n = 1) exclusively included patients with inflammatory bowel disease (IBD), and 16 studies commented that patients with IBD were excluded in their eligibility criteria. No study assessed efficacy of drugs in patients with CD and IS. Approximately one-quarter of studies (n = 65 of 253) included quality of life as an outcome measure. CONCLUSION: There is a paucity of research in IBD patients with IS, with the majority focusing on devices and surgical procedures. There have been no drug trials evaluating efficacy in patients with CD and IS. There is an urgent need to identify barriers to enrollment and develop eligibility and outcome measures that enable the inclusion of patients with CD with stoma into clinical trials.

We analyzed registered trials for patients with intestinal stoma with special focus on Crohn's disease patients to explore research and unmet needs. Our results indicate a scarcity of studies in this area with most studies limited to surgical procedures and devices.

Predictors of triage pain assessment and subsequent pain management among pediatric patients presenting to the emergency department.

BACKGROUND: Pediatric patients with pain of various causes present to the emergency department. Appropriate assessment and management of pain are important aspects of emergency department treatment. However, only a few studies have identified the predictors of both outcomes. This study aimed to evaluate the rate of pain assessment at triage and subsequent management and to identify the predictors of each outcome. METHODS: This was a multi-center retrospective study based at five community emergency departments. Pediatric patients (< 18 years) with pain or injury who presented to the emergency department between February 2018 and May 2018 were included. In addition to patient demographics, the initial pain assessment at triage, reason for visit, and time to analgesia were determined. Further, the type and route of analgesia were identified in patients who received analgesia. Univariate and multivariable regression models were used to identify predictors of pain assessment and management. RESULTS: There were 4,128 patients with an average age of 9.6 years, and 49.1% of them were female. Only 74.2% of the patients underwent assessment for pain at triage, and 18.3% received analgesia. The median time to analgesia was 95 (IQR: 49-154) min. Most patients presented with head/neck (36.1%), upper limb (21.6%), and lower limb (19.9%) pain. The oral route was the most common analgesia delivery method (67.4%), and ibuprofen and acetaminophen were the primary agents used. Younger age, higher acuity, and presenting with head or neck pain were independent predictors of pain assessment at triage, while children 3-5 years and those with lower extremity pain were more likely to receive analgesia. CONCLUSION: Although pain assessment at triage has improved in pediatric patients, there is still a major deficiency in adequate pain management. Our study highlights predictors of pain assessment and management that can be considered for improved pediatric care.

Placebo Response Rates in Randomized Controlled Trials for Perianal Crohn's Disease: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Perianal fistulizing disease is a common complication of Crohn's disease [CD], for which new therapies are urgently needed. To assist the design of clinical trials for novel therapeutics, we conducted a systematic review and meta-analysis of randomised controlled trials [RCTs] to quantify placebo rates and identify factors influencing them in perianal CD [pCD]. METHODS: We searched MEDLINE, Embase and CENTRAL from inception to June 2021. Eligible studies were placebo-controlled trials of pharmacological interventions for pCD. Placebo fistula response and remission rates for induction and maintenance trials were extracted and pooled using a random-effects model. Mixed-effects meta-regression was used to evaluate the impact of patient and study-level characteristics on point estimates. RESULTS: In 17 RCTs [13 induction, five maintenance] the pooled placebo fistula response and remission rate for induction trials was 25% (95% confidence interval [CI] 17-36%) and 17% [95% CI 11-25%], respectively. For maintenance trials, the pooled placebo fistula response and remission rate was 23% [95% CI 17-32%] and 19% [95% CI 14-25%], respectively. Trials enrolling patients with less disease activity and a higher proportion with ileal predominant disease were associated with significantly higher placebo response rates. Trials originating in Europe [compared to North America], therapies requiring perianal injection and a longer timepoint to measure remission were associated with higher placebo remission rates. CONCLUSIONS: Placebo response and remission rates in pCD trials are influenced by patient and disease-related factors, as well as the type of intervention being studied. These contemporary rates will inform trial design for novel therapeutics.

How pragmatic are randomized trials of remdesivir and favipiravir for in-hospital treatment of COVID-19: a descriptive methodological review of trial design using the PRECIS-2 framework.

OBJECTIVES: To review the pragmatism of published randomized trials of remdesivir and favipiravir based on the Pragmatic-Explanatory Continuum Indicator Summary (PRECIS-2) framework. STUDY DESIGN AND SETTING: Ten eligible trials were identified from an existing comprehensive living review and were evaluated across the nine PRECIS-2 domains by two independent reviewers. RESULTS: All 10 trials had mostly pragmatic design characteristics. Four of the domains (i.e., recruitment, setting, organization, and primary analysis) were found to be pragmatic with most trials scoring four or five across the two interventions. In comparison scores for four other design domains (i.e., eligibility, follow-up, flexibility of delivery, and primary outcome) varied across the trials with some design choices being more explanatory. CONCLUSION: In our descriptive review of randomized controlled trails for two drugs for patients infected with COVID-19 early in the pandemic, we found that most trials had more pragmatic than explanatory characteristics. Some design choices for some of the trials, however, were not consistent with the urgent goal of informing clinical decision making in an epidemic. PRECIS-2 should be used as a guide by trialists, to help them match their trial design choices to the intended purpose of their trial.

Body mass index trajectories and their predictors in undergraduate students from Canada: Results from the GENEiUS study.

Objective: To explore the patterns and predictors of body mass index (BMI) change among undergraduate students from Ontario (Canada). Participants: 68 undergraduate students were followed longitudinally for 3 years with anthropometric data collected bi-annually. Methods: BMI measurements were plotted to generate individual BMI trajectory curves, which were categorized, based on the observed trajectory pattern. Within and between group comparisons of BMI were conducted via nonparametric paired tests. The association of baseline BMI, sex, and ethnicity with BMI trajectory type was assessed using multinomial logistic regression. Results: Four BMI trajectory types were observed: "stable weight" (n = 15, 22.1%), "weight gain" (n = 30, 44.1%), "weight loss" (n = 12, 17.6%), and "weight cycling" (n = 11, 16.2%) trajectories. Higher baseline BMI was significantly associated with the "weight gain," "weight loss," and the "weight cycling" trajectories as compared to the "stable weight" trajectory type. Conclusions: Our findings demonstrate an association between high baseline BMI and "nonstable" subsequent BMI change patterns among Canadian students.

Micronutrients of the one-carbon metabolism cycle are altered in mothers and neonates by gestational diabetes and are associated with weight, height and head circumference at birth.

While several studies have previously described the levels of one-carbon metabolism-related micronutrients in women with gestational diabetes mellitus (GDM) and their neonates, the results in these literature reports have been contradictory. We hypothesized that the concentrations of micronutrients involved in the one-carbon cycle are altered in pregnant women and their neonates by GDM, and that these changes could further modify the neonatal anthropometry. Micronutrient levels were measured in 123 pregnant women with normal glucose levels (M-ND) and their neonates (N-ND), as well as in 54 pregnant women with gestational diabetes (M-GDM) and their neonates (M-GDM). Folate and vitamin B12 levels were measured via competitive ELISA, and betaine, choline, and glycine levels were measured via ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS/MS). Vitamin B12 and Glycine were found to be higher in M-GDM compared to M-ND. N-GDM had higher levels of folic acid and vitamin B12 and lower levels of betaine and choline compared to N-ND. In general, neonates presented with high concentrations of micronutrients compared to their mothers, and the fetus/maternal ratio of micronutrients was higher among the N-ND as compared to the N-GDM. Micronutrients were also variably associated with anthropometric measurements. The association of betaine with neonatal anthropometry in N-GDM is highlighted. In summary, our results implicate a potential role of GDM in altering the levels of one-carbon metabolism-related micronutrients among pregnant women and their neonates. Likewise, our results also elucidate a potential association between the concentrations of micronutrients and the weight, height, and head circumference of neonates.

Early versus late weight bearing & ankle mobilization in the postoperative management of ankle fractures: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: While open reduction and internal fixation is currently considered the optimum treatment option for displaced ankle fractures, the most optimal post-operative rehabilitation strategy in this setting remains unclear. The objective of this investigation was to compare the effect of early vs. late weight bearing and ankle mobilization in the post-operative management of ankle fractures. METHODS: Medline, Embase, CENTRAL, Scopus, CINHAL, and Web of Science were searched to identify randomized controlled trials (RCTs) and quasi-RCTs. Two review authors screened articles, abstracted data, and evaluated risk of bias in duplicate. Outcomes of interest included post-operative ankle function and overall time to return to work. Studies on weight bearing and ankle mobilization were analysed separately and all data were pooled using random-effects models. RESULTS: Eighteen trials were included in the review of which 14 were included in the meta-analysis of at least one outcome of interest. Majority of the studies presented a high overall risk of bias. Early weight bearing demonstrated significantly better short-term postoperative functional scores at 6-9 weeks postoperatively (SMD: 0.39, 95% CI: 0.19, 0.58; p < 0.0001; I2 = 0%). However, the functional effect of early weight bearing compared to late weight bearing gradually became equivalent by the 6 month postoperative time-period. Early weight bearing also demonstrated a significant reduction in the time to return to work/daily activities (MD: -12.29, 95% CI: -17.39, -7.19; p < 0.0001; I2 = 0%). In comparison, no significant differences were found between early ankle mobilization/exercises and immobilization. CONCLUSION: Our findings suggest a potential role of EWB in improving post-operative ankle-function in the short-term and reducing the overall time to return to work/daily activities, but no clinical benefit associated with early ankle mobilization post-surgery.

Low-frequency Coding Variants Associated With Body Mass Index Affect the Success of Bariatric Surgery.

CONTEXT: A recent study identified 14 low-frequency coding variants associated with body mass index (BMI) in 718 734 individuals predominantly of European ancestry. OBJECTIVE: We investigated the association of 2 genetic scores (GS) with i) the risk of severe/morbid obesity, ii) BMI variation before weight-loss intervention, iii) BMI change in response to an 18-month lifestyle/behavioral intervention program, and iv) BMI change up to 24 months after bariatric surgery. METHODS: The 14 low-frequency coding variants were genotyped or sequenced in 342 French adults with severe/morbid obesity and 574 French adult controls from the general population. We built risk and protective GS based on 6 BMI-increasing and 5 BMI-decreasing low-frequency coding variants that were polymorphic in our study. RESULTS: While the risk GS was not associated with severe/morbid obesity status, BMI-decreasing low-frequency coding variants were significantly less frequent in patients with severe/morbid obesity than in French adults from the general population. Neither the risk nor the protective GS was associated with BMI before intervention in patients with severe/morbid obesity, nor did they affect BMI change in response to a lifestyle/behavioral modification program. The protective GS was associated with a greater BMI decrease following bariatric surgery. The risk and protective GS were associated with a higher and lower risk of BMI regain after bariatric surgery. CONCLUSION: Our data indicate that in populations of European descent, low-frequency coding variants associated with BMI in the general population also affect the outcomes of bariatric surgery in patients with severe/morbid obesity.

Causes of early postpartum complications that result in visits to the emergency department.

OBJECTIVE: This study aimed to review the reasons why postpartum women present to the emergency department (ED) over a short term (≤10 days post-delivery) and to identify the risk factors associated with early visits to the ED. METHODS: This retrospective chart review included all women who delivered at a regional health system (William Osler Health System, WOHS) in 2018 and presented to the WOHS ED within 10 days after delivery. Baseline descriptive statistics were used to examine the patient demographics and identify the timing of the postpartum visit. Univariate tests were used to identify significant predictors for admission. A multivariate model was developed based on backward selection from these significant factors to identify admission predictors. RESULTS: There were 381 visits identified, and the average age of the patients was 31.22 years (SD: 4.83), with median gravidity of 2 (IQR: 1-3). Most patients delivered via spontaneous vaginal delivery (53.0%). The median time of presentation to the ED was 5.0 days, with the following most common reasons: abdominal pain (21.5%), wound-related issues (12.6%), and urinary issues (9.7%). Delivery during the weekend (OR 1.91, 95% CI 1.00-3.65, P = 0.05) was predictive of admission while Group B Streptococcus positive patients were less likely to be admitted (OR 0.22, CI 0.05-0.97, P<0.05). CONCLUSIONS: This was the first study in a busy community setting that examined ED visits over a short postpartum period. Patient education on pain management and wound care can reduce the rate of early postpartum ED visits.

The MC4R p.Ile269Asn mutation confers a high risk for type 2 diabetes in the Mexican population via obesity dependent and independent effects.

We investigated the association between the loss-of-function mutation MC4R p.Ile269Asn and T2D risk in the Mexican population. We enrolled 6929 adults [3175 T2D cases and 3754 normal glucose tolerant (NGT) controls] and 994 NGT children in the study. Anthropometric data and T2D-related quantitative traits were studied in 994 NGT children and 3754 NGT adults. The MC4R p.Ile269Asn mutation was genotyped using TaqMan. The MC4R p.Ile269Asn mutation was associated with T2D [OR = 2.00, 95% confidence interval (CI) 1.35-2.97, p = 0.00057] in Mexican adults. Additional adjustment for body-mass index (BMI) attenuated but did not remove the association (OR = 1.70, 95% CI 1.13-2.56, p = 0.011). The MC4R p.Ile269Asn mutation was associated with T2D (OR = 1.88, 95% CI 1.14-3.08, p = 0.013) in a subset of 1269 T2D cases and 1269 NGT controls matched for sex, age, and BMI. A mediation analysis estimated that BMI accounts for 22.7% of the association between MC4R p.Ile269Asn mutation and T2D risk (p = 4.55 × 10-6). An association was observed between the MC4R p.Ile269Asn mutation and BMI in NGT children and adults (children: beta = 3.731 ± 0.958, p = 0.0001; adults: beta = 2.269 ± 0.536, p = 2.3 × 10-5). In contrast, the mutation was not associated with T2D-related quantitative traits. We demonstrate that the MC4R p.Ile269Asn mutation predisposes to T2D via obesity-dependent and independent effects in the Mexican population.

Effect of sex/gender on obesity traits in Canadian first year university students: The GENEiUS study.

BACKGROUND: While weight gain during first year of university has been well documented in North America, literature on sex-specific effects is scarce and inconsistent. The objective of this investigation was to explore sex-specific changes in obesity traits during first year of university at McMaster University (Ontario, Canada). METHODS: 245 first-year students (80.4% females) were followed longitudinally with data collected early in the academic year and towards the end of the year. Obesity parameters including weight, waist and hip circumferences, BMI, and waist to hip ratio were investigated. The Mann-Whitney U test and the Wilcoxon signed-rank test were used for pairwise comparison of traits in the absence of adjustments. Additionally, the repeated-measures ANOVA test was used with covariate adjustments to investigate the interaction between sex and time. RESULTS: Overall sample trends indicated a significant increase in mean weight by 1.55 kg (95% CI: 1.24-1.86) over the school year (p<0.001). This was accompanied by significant gains in BMI, and waist and hip circumferences (p<0.001) in the overall sample. At baseline, males presented with higher body weight, BMI, waist and hip circumferences, and WHR, as compared to their females counterparts (p<0.01). Additionally, sex-stratified analysis indicated significant gains in weight, BMI, and waist and hip circumferences in both males and females (p<0.01). However, a comparison of the magnitude of change over time between the two sex groups revealed no significant difference for any of the investigated traits (p>0.05). CONCLUSION: While our study confirms significant weight gain in both male and female first year university students in Ontario, Canada, it does not show sex specific differences within this context. Our investigation highlights the importance of accounting for sex and gender in health research and supports the need of further studies in this area.

AGT rs4762 is associated with diastolic blood pressure in Mexicans with diabetic nephropathy.

AIMS: Since angiotensinogen has a pivotal role in the renin-angiotensin-aldosterone system, the analysis of polymorphisms of the angiotensinogen (AGT) gene could help explain its potential involvement in hypertension and diabetic nephropathy (DN) pathogenesis. For that reason, we investigated 1) the association of AGT rs4762 with blood pressure (BP) and kidney function-related traits and 2) the interaction effect of AGT rs4762 with DN on BP and kidney function-related traits in 546 Mexican adults with type 2 diabetes (T2D). METHODS: We enrolled 546 unrelated Mexican patients with T2D (350 cases with DN and 196 controls without DN). AGT rs4762 was genotyped in all participants using TaqMan technology (effect allele: A). BP and kidney function-related traits, including serum urea and creatinine, urinary albumin, urine albumin to urine creatinine ratio (ACR), and glomerular filtration rate, were studied. DN was defined as having a previous diagnosis of T2D and an ACR ≥ 30 mg/g. The association between these parameters was investigated using logistic regression with adjustment for covariates. RESULTS: AGT rs4762 A allele was significantly associated with diastolic blood pressure (N = 546, ß = 1.243 ± 0.918, p = 0.029). A significant interaction between DN and AGT rs4762 was also observed in relation to diastolic blood pressure (DBP) (N = 546, ß = 0.930 ± 0.433, p=0.032). A follow-up analysis of simple effects particularly revealed a positive association between AGT rs4762 A allele and DBP only in patients with diabetic nephropathy (N = 350, ß = 2.837 ±â€¯1.267, p = 0.026). CONCLUSION: Our results evidence that, although AGT rs4762 is not associated with DN, the AGT rs4762 A allele is positively associated with DBP in the Mexican population with DN.

Sex/Gender Modifies the Association Between the MC4R p.Ile269Asn Mutation and Type 2 Diabetes in the Mexican Population.

CONTEXT: Studies in mice and humans suggest that melanocortin-4 receptor (MC4R) deficiency affects body weight in a sex-/gender-dependent manner. However, similar evidence for type 2 diabetes (T2D) is scarce. OBJECTIVE AND DESIGN: We investigated whether sex/gender modifies the association between the loss-of-function MC4R p.Ile269Asn mutation and T2D in 6929 Mexican adults (3175 T2D cases and 3754 normal glucose tolerance [NGT] controls). The 2003 American Diabetes Association criteria were used to define NGT and T2D. The MC4R p.Ile269Asn mutation was genotyped in all participants using TaqMan technology. RESULTS: The MC4R p.Ile269Asn mutation was associated with T2D in 6929 Mexican adults (Ncontrols = 3754, Ncases = 3175, odds ratio [OR] = 2.00, 95% confidence interval [CI], 1.35-2.97; P = 5.7 × 10-4). The MC4R p.Ile269Asn mutation had a frequency of 0.86 and 1.05% in women with NGT and T2D, and 0.78 and 1.32% in men with NGT and T2D, respectively. We identified a significant interaction between the MC4R p.Ile269Asn mutation and sex/gender on T2D risk (P = 0.049). Although a strong association between the mutation and T2D was observed in men (Ncontrols = 2418, Ncases = 1807, OR = 2.63, 95% CI, 1.62-4.28, P = 9.3 × 10-5), results were not significant in women (Ncontrols = 1336, Ncases = 1368, OR = 1.16, 95% CI, 0.60-2.26, P = 0.65). Further adjustment for body mass index in the logistic regression model did not alter the sex-/gender-specific pattern of association (men: OR = 2.22, 95% CI, 1.34-3.67, P = 0.0019; women: OR = 1.02, 95% CI, 0.51-2.02, P = 0.95). CONCLUSION: This is the first report of a male-specific association between the MC4R p.Ile269Asn loss-of-function mutation and T2D in the Mexican population.

Effect of living arrangement on anthropometric traits in first-year university students from Canada: The GENEiUS study.

BACKGROUND: The transition to university often involves a change in living arrangement for many first-year students. While weight gain during first year of university has been well documented, Canadian literature on the impact of living arrangement within this context is limited. The objective of this investigation was to explore the effect of living arrangement on anthropometric traits in first-year university students from Ontario, Canada. METHODS: 244 first-year undergraduate students were followed longitudinally with data collected early in the academic year and towards the end of the year. Anthropometric parameters including weight, waist and hip circumference, body mass index (BMI), and waist-to-hip ratio (WHR) were examined. The Wilcoxon signed-rank test was used for pairwise comparison of traits from the beginning to end the year in the absence of adjustments. Additionally, linear regression models with covariate adjustments were used to investigate effect of the type of living arrangement (i.e. on-campus, off-campus, or family home) on the aforementioned traits. RESULTS: In the overall sample, a significant weight increase of 1.55kg (95% CI: 1.24-1.86) was observed over the school year (p<0.001), which was also accompanied by significant gains in BMI, and waist and hip circumferences (p<0.001). At baseline, no significant differences were found between people living on-campus, off-campus, and at home with family. Stratified analysis of change by type of living arrangement indicated significant gains across all traits among students living on-campus (p<0.05), and significant gains in weight and BMI among students living at home with family. Additionally, a comparison between living arrangements revealed that students living on campus experienced significantly larger gains in weight and BMI compared to students living off-campus (p<0.05). CONCLUSION: Our findings indicate that living arrangement is associated with different weight gain trajectories in first-year university students.

The effect of race/ethnicity on obesity traits in first year university students from Canada: The GENEiUS study.

BACKGROUND: Little is known about the impact of race/ethnicity on weight change at university. The objective of this study is to determine if ethnicity has an impact on obesity traits in a multiethnic cohort of first-year students at McMaster University in Ontario, Canada. METHODS: 183 first year students from the three most represented ethnic groups (South Asian, East Asian, and white-Caucasian) in our study sample were followed longitudinally with data collected early in the academic year and towards the end of the year. Obesity parameters including body weight, body mass index (BMI), waist and hip circumference, and waist hip ratio (WHR) were analyzed. The Wilcoxon signed-rank test was used for pairwise comparison of traits from the beginning to the end of the year in the absence of adjustments. Linear regression was used with covariate adjustments to investigate the effect of ethnicity on obesity traits. RESULTS: A significant increase in weight by 1.49 kg (95%CI: 1.13-1.85) was observed over the academic year in the overall analyzed sample. This was accompanied by significant gains in BMI, waist and hip circumferences, and WHR. Ethnicity stratified analysis indicated significant increase in all investigated obesity traits in East Asians and all traits, but WHR, in South Asians. White-Caucasians only displayed significant increases in weight and BMI. Body weight and hip circumference were significantly lower in East Asians compared to white-Caucasians at baseline. However, East Asians displayed a significantly larger increase in mean BMI and weight compared to white-Caucasians after first-year. South Asians displayed larger waist circumference at baseline compared to East Asians and larger WHR compared to white-Caucasians. CONCLUSION: Our findings demonstrate that ethnicity has an impact on obesity traits in first-year university students. Universities should take ethnicity into account while implementing effective obesity prevention programs to promote healthy and active lifestyles for students.

Circulating levels of CTRP3 in patients with type 2 diabetes mellitus compared to controls: A systematic review and meta-analysis.

Growing evidence suggests that adipokines may be therapeutic targets for cardiometabolic diseases such as type 2 diabetes mellitus (T2DM). C1q TNF Related Protein 3 (CTRP3) is a newly discovered adipokine which shares properties with adiponectin. The literature about the association between circulating levels of CTRP3 and T2DM has been conflicting. The present study reassessed the data on circulating CTRP3 levels in T2DM patients compared to controls through a systematic review and meta-analysis. A literature search was performed in Medline, Embase, Scopus, and Web of science to identify studies that measured circulating CTRP3 levels in T2DM patients and controls. The search identified 124 studies of which 59 were screened for title and abstract and 13 were subsequently screened at the full text stage and 12 studies included into the meta-analysis. Subgroup analyses, depending on the presence of T2DM complications, matching for BMI, age, and cut off value of fasting blood sugar and HOMA-IR, were performed. The results show that circulating CTRP3 levels are negatively associated with T2DM status (SMD: -0.837; 95% CI: (-1.656 to -0.017); p = 0.045). No publication bias was identified using the Begg's rank correlation and Egger's linear regression tests (P = 1 and P = 0.44, respectively). Meta-regression demonstrated significant association between CRTP3 levels with BMI (slope: 0.11; 95% CI: 0.04-0.19; p = 0.001) and sex (slope: -0.07; 95% CI: -0.12 to -0.01; p = 0.008). The present systematic review and meta-analysis evidences a negative association between circulating level of CTRP3 and T2DM status. BMI and sex may modify this association.

Association of AMY1A/AMY2A copy numbers and AMY1/AMY2 serum enzymatic activity with obesity in Mexican children.

BACKGROUND: Mexican children are characterized by a high-starch intake diet and high prevalence of obesity. OBJECTIVES: To investigate the association of AMY1A/AMY2A copy numbers (CNs) and AMY1/AMY2 serum enzymatic activity with childhood obesity in up to 427 and 337 Mexican cases and controls. METHODS: Anthropometric and dietary starch intake data were collected. CN of AMY1A/AMY2A and AMY1/AMY2 serum enzymatic activity were determined using droplet digital PCR (ddPCR) and enzymatic colorimetry, respectively. An individual participant level data meta-analysis of association between AMY1A CNVs and obesity was also performed. RESULTS: A positive association between AMY1A/AMY2A CNs and their corresponding AMY1/AMY2 serum enzyme activity was observed in children with normal weight and obesity. The serum enzyme activity of AMY1 and AMY2 was negatively associated with childhood obesity risk, and the association was restricted to kids eating medium/high amount of starch (Pinteraction = .004). While no association between AMY1A and AMY2A CNs and childhood obesity was observed in our sample, we confirmed a significant association between AMY1A CN and obesity in a meta-analysis of 3100 Mexican children. CONCLUSIONS: Our data suggest that genetically determined salivary and pancreatic amylase activity can increase/decrease the risk of obesity in Mexican children, this effect being blunted by a low-starch diet.

Contribution of rare coding mutations in CD36 to type 2 diabetes and cardio-metabolic complications.

We sequenced coding regions of the cluster of differentiation 36 (CD36) gene in 184 French individuals of European ancestry presenting simultaneously with type 2 diabetes (T2D), arterial hypertension, dyslipidemia, and coronary heart disease. We identified rare missense mutations (p.Pro191Leu/rs143150225 and p.Ala252Val/rs147624636) in two heterozygous cases. The two CD36 mutation carriers had no family history of T2D and no clustering of cardio-metabolic complications. While the p.Pro191Leu mutation was found in 84 heterozygous carriers from five ethnic groups from the genome aggregation database (global frequency: 0.0297%, N = 141,321), only one European carrier of the p.Ala252Val mutation was identified (global frequency: 0.00040%, N = 125,523). The Pro191 and Ala252 amino acids were not conserved (74.8% and 68.9% across 131 animal species, respectively). In vitro experiments showed that the two CD36 mutant proteins are expressed and trafficked to the plasma membrane where they bind modified low-density-lipoprotein (LDL) cholesterol as normal. However, molecular modelling of the recent CD36 crystal structure showed that Pro191 was located at the exit/entrance gate of the lipid binding chamber and Ala252 was in line with the chamber. Overall, our data do not support a major contribution of CD36 rare coding mutations to T2D and its cardio-metabolic complications in the French population.

Changes in the morphology of the labial alveolar bone of protruded permanent maxillary incisors secondary to orthodontic alignment.

AIM: Treatment of protruded maxillary incisors involves retraction. Lingual positioning of protruded incisors improves the width of the attached gingiva. This study was conducted to document changes in the buccal alveolar bone upon retraction of protruded permanent maxillary central incisors. METHODS: Cephalometric radiographs of 13 patients, ages 12 to 18 years, whose orthodontic treatment involved lingual positioning of protruded permanent maxillary central incisors were selected. RESULTS: Comparison of tracings from radiographs taken before and after treatment indicated that the alveolar bone height increased in 76.9% of cases. In addition, a significant positive correlation (r = 0.95) was found between the changes in the distance from the M point to the incisal edge and alveolar bone height. CONCLUSION: The present study indicated that an increase in the amount of buccal alveolar bone was a result of orthodontic treatment that involved lingual positioning of protruded maxillary permanent central incisors.