The Association Between Body Mass Index and Parental History of Hypertension Among Young Indian Adults.

BACKGROUND: Hypertension is a disease of multifactorial etiology. Individuals with parental history of hypertension (PHH) have also been observed to be at an increased risk of developing hypertension in their adult life. However, there is a dearth of studies among youth. Obesity is one of the risk factors, and studies conducted among adults of all age groups have observed that there is a highly significant correlation between hypertension and body mass index (BMI). Hence, the association between the two factors, viz., parental history of hypertension and BMI, among the young Indian male and female population was analyzed in this study. METHOD: This cross-sectional study conducted in Central India comprised 100 young adults between 18 and 25 years of age. On the basis of parental history of hypertension, the subjects were divided into two groups: group 1 comprised youth with parental history of hypertension and group 2 comprised youth without parental history of hypertension, involving 32 and 68 subjects in each of these groups, respectively. Anthropometric measurements were done using standard methods, and BMI was calculated. Statistical analysis was done using Epi Info software. RESULTS: The study subjects in both groups were comparable in age. The mean age of the study participants was 19.32 years and 19.45 years in group 1 and group 2, respectively. The study did not find any association between BMI and parental history of hypertension. CONCLUSION: The association between parental history of hypertension and BMI, the non-modifiable and modifiable independent risk factors, respectively, needs to be further explored in light of the iceberg phenomenon, multifactorial causation, and natural history of disease. It is worth mentioning that parental history of hypertension and other risk factors should be considered even if the BMI is normal as per Asian Indian cutoff levels.

Body composition predicts mortality and decompensation in compensated cirrhosis patients: A prospective cohort study.

BACKGROUND & AIMS: Body composition, particularly sarcopenia, is associated with mortality in patients with decompensated cirrhosis undergoing transplant evaluation. Similar data are limited for non-transplant eligible or compensated patients. METHODS: A total of 274 patients with cirrhosis were followed prospectively for ≤5 years after a CT scan. We utilized Analytic Morphomics® to measure body composition (fat, muscle, and bone) which was rendered into relative values (percentiles) in relation to a reference population. The model for end-stage liver disease (MELD) score was used as a reference model for survival prediction. We validated our models in a separate cohort. RESULTS: Our cohort had a mean Child-Pugh score of 7.0 and a mean MELD of 11.3. The median follow-up time was 5.05 years. The proportion of patients alive at 1, 3 and 5 years was 86.5%, 68.0%, and 54.3%; 13 (4.6%) underwent liver transplantation. Child-Pugh B/C (vs. A) cirrhosis was associated with decreased muscle, subcutaneous, and visceral fat area but increased subcutaneous/visceral fat density. Decreased normal density muscle mass was associated with mortality (hazard ratio [HR] 0.984, p <0.001) as well as visceral and subcutaneous fat density (HR 1.013 and 1.014, respectively, p <0.001). Models utilizing these features outperformed MELD alone for mortality discrimination in both the derivation and validation cohort, particularly for those with compensated cirrhosis (C-statistics of 0.74 vs. 0.58). Using competing risk analysis, we found that subcutaneous fat density was most predictive of decompensation (subdistribution HR 1.018, p = 0.0001). CONCLUSION: The addition of body composition features to predictive models improves the prospective determination of prognosis in patients with cirrhosis, particularly those with compensated disease. Fat density, a novel feature, is associated with the risk of decompensation. LAY SUMMARY: Am I at high risk of getting sicker and dying? This is the key question on the mind of patients with cirrhosis. The problem is that we have very few tools to help guide our patients, particularly if they have early cirrhosis (without symptoms like confusion or fluid in the belly). We found that how much muscle and fat the patient has and what that muscle or fat looks like on a CT scan provide helpful information. This is important because many patients have CT scans and this information is hiding in plain sight.

Functional classification of protein structures by local structure matching in graph representation.

As a result of high-throughput protein structure initiatives, over 14,400 protein structures have been solved by Structural Genomics (SG) centers and participating research groups. While the totality of SG data represents a tremendous contribution to genomics and structural biology, reliable functional information for these proteins is generally lacking. Better functional predictions for SG proteins will add substantial value to the structural information already obtained. Our method described herein, Graph Representation of Active Sites for Prediction of Function (GRASP-Func), predicts quickly and accurately the biochemical function of proteins by representing residues at the predicted local active site as graphs rather than in Cartesian coordinates. We compare the GRASP-Func method to our previously reported method, Structurally Aligned Local Sites of Activity (SALSA), using the Ribulose Phosphate Binding Barrel (RPBB), 6-Hairpin Glycosidase (6-HG), and Concanavalin A-like Lectins/Glucanase (CAL/G) superfamilies as test cases. In each of the superfamilies, SALSA and the much faster method GRASP-Func yield similar correct classification of previously characterized proteins, providing a validated benchmark for the new method. In addition, we analyzed SG proteins using our SALSA and GRASP-Func methods to predict function. Forty-one SG proteins in the RPBB superfamily, nine SG proteins in the 6-HG superfamily, and one SG protein in the CAL/G superfamily were successfully classified into one of the functional families in their respective superfamily by both methods. This improved, faster, validated computational method can yield more reliable predictions of function that can be used for a wide variety of applications by the community.

The Groucho-associated phosphatase PPM1B displaces Pax transactivation domain interacting protein (PTIP) to switch the transcription factor Pax2 from a transcriptional activator to a repressor.

Pax genes encode developmental regulatory proteins that specify cell lineages and tissues in metazoans. Upon binding to DNA through the conserved paired domain, Pax proteins can recruit both activating and repressing complexes that imprint distinct patterns of histone methylation associated with either gene activation or silencing. How the switch from Pax-mediated activation to repression is regulated remains poorly understood. In this report, we identify the phosphatase PPM1B as an essential component of the Groucho4 repressor complex that is recruited by Pax2 to chromatin. PPM1B can dephosphorylate the Pax2 activation domain and displace the adaptor protein PTIP, thus inhibiting H3K4 methylation and gene activation. Loss of PPM1B prevents Groucho-mediated gene repression. Thus, PPM1B helps switch Pax2 from a transcriptional activator to a repressor protein. This can have profound implications for developmental regulation by Pax proteins and suggests a model for imprinting specific epigenetic marks depending on the availability of co-factors.