The relationship between subnormal peak-stimulated growth hormone levels and auxological characteristics in obese children

Context: The hypothesis that obese children are overdiagnosed with growth hormone deficiency (GHD) has not been adequately investigated in the context of adiposity-related differences in auxology. Aim: To investigate the differences in auxological parameters between short, prepubertal, obese children, and normal-weight peers who underwent growth hormone stimulation testing (GHST). Hypothesis: Over-weight/obese children with GHD [peak growth hormone (GH) \u3c 10 μg/L] will have higher values for growth velocity (GV) standard deviation score (SDS), bone age minus chronological age (BA − CA), and child height SDS minus mid-parental height (MPTH) SDS when compared to normal-weight GHD peers. Subjects and Methods: A retrospective review of anthropometric and provocative GHST data of 67 prepubertal, GH-naïve children of age 10.21 ± 2.56 years (male n = 45, age 10.8 ± 2.60 years; female n = 22, age 8.94 ± 2.10). Inclusion criteria: GHST using arginine and clonidine. Exclusion criteria: hypopituitarism, abnormal pituitary magnetic resonance imaging scan, syndromic obesity, or syndromic short stature. Data were expressed as mean ± SD. Results: The over-weight/obese children with peak GH of \u3c10 μg/L had significantly lower value for natural log (ln) peak GH (1.45 ± 0.09 vs. 1.83 ± 0.35, p = 0.022), but similar values for GV SDS, insulin-like growth factor-I, insulin-like growth factor binding protein-3, bone age, BA − CA, MPTH, and child height SDS minus MPTH SDS compared to normal-weight peers with GHD. After adjusting for covariates, the over-weight/obese children (BMI ≥ 85th percentile) were \u3e7 times more likely than normal-weight subjects (BMI \u3c 85th percentile) to have a peak GH of \u3c10 μg/L, and 23 times more likely to have a peak GH of \u3c7 μg/L (OR = 23.3, p = 0.021). There was a significant inverse relationships between BMI SDS and the ln of peak GH (β = −0.40, r2 = 0.26, p = 0.001), but not for BMI SDS vs. GV SDS, ln peak GH vs. BA, or ln peak GH vs. GV SDS. Conclusion: Subnormal peak GH levels in obese prepubertal children are not associated with unique pre-GHST auxological characteristics

Adiposity is associated with early reduction in bone mass in pediatric inflammatory bowel disease

Background: The effect of adiposity on bone mass in the early phases of inflammatory bowel disease (IBD) in children and adolescents is unclear. Aims: To determine the role of adiposity on bone mass in the first 3 years of diagnosis of IBD. Hypothesis: Increased adiposity will be associated with increased bone mass in both the controls and IBD subjects. Setting: University tertiary institution. Methods: Height-adjusted bone mineral density (BMD) z-scores of 25 subjects, age 13.97 ± 2.70y, diagnosed with IBD for \u3c 4 years were compared to 24 controls, age 13.65 ± 2.60y. Overweight was defined as BMI of ≥85th but \u3c95th percentile, and obesity as BMI ≥95thpercentile. Severity of IBD was determined by the Pediatric Crohn’s Disease Activity Index and Lichtiger Colitis Activity Index. Results: Prior to stratification by BMI criterion, height-adjusted BMD z-scores were non-significantly lower in IBD subjects vs. controls for both the femoral neck (-0.8 ± 1.1 vs. -0.06 ± 1.1, p=0.070) and lumbar vertebrae (-0.4 ± 1.2 vs. 0.2 ± 1.2, p=0.086). Following stratification, height-adjusted BMD z-scores were significantly lower in the overweight/obese IBD subjects vs. overweight/obese controls for femoral neck (-0.9 ± 0.9 vs. 0.3 ± 1.3, p=0.032); and non-significantly lower for the lumbar spine z-score (-0.4 ± 1.6 vs. 0.5 ± 1.3, p=0.197). BMD z-score had no relationship with the duration of disease, steroid therapy, and the severity of disease. Conclusion: Adiposity was associated with reduced bone mass in the early phases of IBD, but with increased bone mass in the controls

The relationship between adiposity and stature in prepubertal children with celiac disease

Background and Aim: The pathogenesis of short stature in celiac disease (CD) is unknown. Obese children are generally taller than their non-obese peers; however, the role of adiposity on stature in CD is unclear. Our aim was to determine the association between adiposity and stature in CD. Subjects and methods: We compared the anthropometric characteristics of prepubertal children of ages 3-12 years, with biopsy-proven CD (n=40) and who were not on gluten-free diet, to same aged, prepubertal non-CD children (n=50). Body mass index (BMI) was calculated using the formula weight/height2. Sex-adjusted midparental target height (MPTH) standard deviation score (SDS) was calculated using National Children Health Statistics data for 18-year-old adults. Data were expressed as mean±standard deviation. Results: CD subjects had significantly lower BMI SDS than controls (0.61±1.22 vs. 1.28±1.60, p=0.027) but were not significantly shorter than the controls (-0.05±1.21 vs. 0.21±1.71, p=0.41). When the patients were subdivided into the normal-weight and overweight/obese groups, the normal-weight CD patients were of similar height as the normal-weight controls (p=0.76) but were significantly shorter than both the overweight/obese controls (p=0.003). The MPTH SDS did not differ between the groups. Conclusions: Overweight/obese prepubertal children with CD were taller than both their normal-weight CD peers and the normal-weight controls, but were of similar height as the overweight/obese control subjects

Suicide in European Hodgkin Lymphoma Patients

The purpose of this study was to determine whether there is an increased risk of suicide in European Hodgkin Lymphoma (HL) patients compared to the general European population. European HL patients enrolled in the German Hodgkin Study Group (GHSG) HD7 through HD15 studies were analyzed and standardized mortality ratio (SMR) was calculated using suicide mortality rates for the general European population. Case-control analysis was performed to identify characteristics associated with risk of death by suicide. Among 12,202 European HL patients observed for 94,972 person-years, 19 suicides (17 males and 2 females) were identified resulting in a SMR 1.63 (95% CI: 1.01-2.50, p = 0.046). The only characteristic associated with a statistically significant increased risk of suicide was male sex with an odds ratio (OR) 8.42 (95% CI = 1.04-67.85; p = 0.046) on multivariate analysis. These findings were confirmed in an independently analyzed Surveillance, Epidemiology, and End Results Program (SEER) validation dataset. European HL patients have a significantly increased incidence of suicide compared to the general European population. Male HL patients have a greater than 8-fold increased risk of suicide compared to female HL patients. Further study of social risk factors associated with an increased risk of suicide in HL patients is needed

Partial clinical remission in type 1 diabetes: a comparison of the accuracy of total daily dose of insulin of \u3c0.3 units/kg/day to the gold standard insulin-dose adjusted hemoglobin A1c of ≤9 for the detection of partial clinical remission

BACKGROUND: It is unclear whether the gold standard test for the detection of partial clinical remission (PCR) in new-onset type 1 diabetes (T1D), the insulin-dose adjusted Hemoglobin A1c (IDAA1c) of ≤9, is superior to a new tool, total daily dose of insulin (TDD) of METHODS: A retrospective analysis of 204 subjects of ages 2-14 years, mean age 7.9±3.2 years, (male 7.8±3.4 years, [n=98]; female 7.9±3.0 years, [n=106], p=0.816) with new-onset T1D. Anthropometric and biochemical data were collected for the first 36 months of disease. PCR was defined by both IDAA1c≤9 and TDD RESULTS: There were 86 (42.2%) (age 9.1±3.0 years; male 57%) remitters by IDAA1c≤9 criterion, and 82 (40.2%) remitters (age 7.3±2.8 years) by TDD of CONCLUSIONS: There were no significant differences in the number of remitters, duration of PCR, or the time of peak remission defined by IDAA1c of ≤9 or TDD o

Cervical Cancer in Cameroon: A Three Pronged Approach to Increase Awareness, Vaccination, Screening and Treatment

Problem: Cameroon has a disproportionately high burden of cervical cancer due to low awareness that the disease is preventable with prophylactic vaccines, lack of screening and treatment of pre-cancerous lesions, and high prevalence of human immunodeficiency virus (HIV). Between 2007-2013, the Cameroon Baptist Convention Health Services (CBCHS) devised three programs to: (1) increase awareness about cervical cancer; (2) immunize girls aged 9-13 years against human papilloma virus (HPV); and (3) conduct cervical cancer screening and treatment. Approaches: In collaboration with clinicians and researchers at University of Massachusetts and Northeastern University, CBCHS conducted education programs about HPV vaccine and cervical cancer for parents, adolescents, health care workers, and community members. The HPV vaccination demonstration project was implemented in three settings: schools, healthcare facilities, and in communities. CBCHS conducted cervical cancer screening in six sites using a “see and treat approach”. Findings: Following approval by the Ministry of Health, CBCHS nurses educated girls, parents, and communities about HPV, cervical cancer, and HPV vaccine through multimedia coverage. A total of 6,851, 6,517 and 5,876 girls were immunized with first, second and third doses, respectively. Achieving an 84.6% 3-dose completion rate. Since 2007, 30,617 women have been screened with visual inspection with acetic acid and digital cervicography. Women with precancerous lesions were treated with cryotherapy or loop electrical excision procedure. Lesions suspicious for cancer were biopsied for histology. Of those screened, 3,015 (10%) self reported HIV-positivity, 19,837 (64%) were HIV-negative, and the HIV status of the remaining women was unreported (25%). The percentage of HIV infected women diagnosed with cancer was consistently higher than the percentage of HIV uninfected women diagnosed with cancer. Lessons Learned: The project demonstrated that, with adequate education of stakeholders, HPV vaccination and cervical cancer screening programs are acceptable and feasible methods to improve cervical cancer outcomes in Cameroon

Comprehensive Identification of Host Modulators of HIV-1 Replication using Multiple Orthologous RNAi Reagents

SummaryRNAi screens have implicated hundreds of host proteins as HIV-1 dependency factors (HDFs). While informative, these early studies overlap poorly due to false positives and false negatives. To ameliorate these issues, we combined information from the existing HDF screens together with new screens performed with multiple orthologous RNAi reagents (MORR). In addition to being traditionally validated, the MORR screens and the historical HDF screens were quantitatively integrated by the adaptation of an established analysis program, RIGER, for the collective interpretation of each gene’s phenotypic significance. False positives were addressed by the removal of poorly expressed candidates through gene expression filtering, as well as with GESS, which identifies off-target effects. This workflow produced a quantitatively integrated network of genes that modulate HIV-1 replication. We further investigated the roles of GOLGI49, SEC13, and COG in HIV-1 replication. Collectively, the MORR-RIGER method minimized the caveats of RNAi screening and improved our understanding of HIV-1–host cell interactions

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Data from: The Effects of Vitamin D Supplementation on Hepatic Dysfunction, Vitamin D Status, and Glycemic Control in Children and Adolescents with Vitamin D Deficiency and Either Type 1 or Type 2 Diabetes Mellitus

Background: The effects of vitamin D supplementation on mild hepatic dysfunction and glycemic control are unclear in children and adolescents with either type 1 (T1D) or type 2 diabetes (T2D). Hypothesis: Vitamin D supplementation will improve hepatic dysfunction and glycemic control. Aim: To determine the effect of vitamin D supplementation on alanine transaminase (ALT), hemoglobin A1c (HbA1c), and serum 25-hydroxyvitamin D [25(OH)D] concentration. Subjects and Methods: A retrospective study of 131 subjects with either T1D (n=88: 46 females, 42 males), or T2D ( n=43: 26 females, 17 males) of ages 3-18 years between 2007-2013. All subjects had (1) a diagnosis of diabetes for \u3e12 mo, (2) received vitamin D supplementation for the management of vitamin D deficiency (3) had baseline and subsequent simultaneous measurements of HbA1c, ALT, and 25(OH)D. Vitamin D deficiency was defined as 25(OH)D concentration of \u3c50nmol/L (20 ng/mL). Results: At baseline, vitamin D deficiency occurred in 72.1% of patients with T2D and in 37.5% of T1D patients (p Conclusions: Vitamin D supplementation in subjects with T2D was associated with statistically significant decreases in BMI SDS, ALT, and a clinically-significant decrease in HbA1c

The nondietary determinants of vitamin D status in pediatric inflammatory bowel disease

OBJECTIVES: The aim of this study was to investigate the relationships between 25-hydroxy vitamin D (25[OH]D) and markers of vitamin D status in inflammatory bowel disease (IBD). METHODS: We conducted a retrospective case-control study of 59 pediatric patients with IBD (age 16.4 ± 2.2 y) and 116 controls (age 14.6 ± 4.4 y), to investigate the association between 25(OH)D and albuminemia for protein-losing enteropathy (PLE) and hepatic dysfunction; alanine transaminase (ALT) for hepatic inflammation; erythrocyte sedimentation rate (ESR) for intestinal inflammation; body mass index (BMI) for adiposity; seasons and skin pigmentation for insolation. Vitamin D deficiency was defined as 25(OH)D \u3c 50 nmol/L; abnormal liver enzyme by ALT \u3e40 U/L; overweight status by BMI of ≥85th but \u3c95th \u3epercentile, and obesity by BMI ≥95th percentile. Seasons were categorized as summer, winter, spring, and fall. RESULTS: Patients with IBD had a higher prevalence of vitamin D deficiency (42.4% versus 26.7%; P = 0.04), elevated ALT (16.9% versus 2.6%; P \u3c 0.001), and lower albumin (41.1 ± 4.8 versus 45.1 ± 3.8; P \u3c 0.001) than controls. In both the IBD cohort and controls, 25(OH)D was highest in summer and lowest in winter, and significantly higher in white than in non-white patients. ESR varied significantly with 25(OH)D (R(2) = 0.24; β = -0.32; P = 0.010), and only patients with IBD with elevated ESR had lower 25(OH)D than controls (49.5 ± 25.2 versus 65.3 ± 28.0 nmol/L; P = 0.045). CONCLUSION: Intestinal inflammation, not the loss of albumin-bound vitamin D in the gut, is the primary intestinal determinant of vitamin D status in IBD. The extraintestinal determinants are seasons and skin pigmentation, but not adiposity and hepatic inflammation