A prospective longitudinal study to evaluate bone health, implication of FRAX tool and impact on quality of life (FACT-P) in advanced prostate cancer patients.

BACKGROUND: Androgen-deprivation therapy (ADT) as a treatment modality in advanced prostate cancer has deleterious effect on bone mineral density (BMD) and quality of life (QOL). Using FRAX (Fracture Risk Assessment) model, candidates at high risk of fractures can be predicted and appropriate treatment can be initiated at early step to prevent skeletal-related events. Objectives of the present study were to evaluate bone health, implication of FRAX tool in advanced prostate cancer and to see the impact of ADT and Bone-directed therapy (BDT) on FRAX and FACT-P QOL scores. MATERIAL & METHOD: We conducted a prospective longitudinal study of 83 localized and metastatic prostate cancer patients from March 2017 to Dec 2020. FRAX tool using BMD femoral neck (GE-Lunar) was used to compute the probability of 10-year Major osteoporotic fracture (MOF) and hip fracture risk %. Patients who received monthly Zolendronic acid with or without Vitamin-D/calcium supplementation were classified as BDT group. FRAX and FACT-P were measured at baseline and 12 months follow-up and compared between different therapeutic modalities to see the impact on clinical outcomes. RESULTS: Majority of patients had skeletal metastasis (78.3%) and high-grade disease at presentation. Secondary osteoporosis was the most commonly (82.05%) observed clinical risk factor (CRF) followed by smoking (19.23%). Hip fracture risk ≥3% accounted for larger proportion of patients than did MOF risk ≥20% (21.2% and 2.5%, respectively). Statistically significant reduction was observed in both MOF and hip fracture risk in BDT group, while worsening on ADT. ADT duration correlated positively with both MOF and hip fracture risk (R2=0.148, P<0.001 and R2=0.164, P<0.001, respectively). FRAX score accurately predict future fracture events in majority (80%) of high-risk patients. Statistically and clinically significant worsening in PWB, EWB, PCS, FACT-P Total, FACT-P TOI and FAPSI scores were observed in patients on ADT. Statistically and clinically significant improvement was noted in physical well-being in BDT group. However, other QOL domains and FACT-P total scores remained stable. CONCLUSIONS: ADT caused duration depended worsening of FRAX and FACT-P score in these patients while improvements of FRAX were seen on BDT. FRAX tool is advantageous in identifying the patients who require early intervention or therapy to decrease skeletal-related events.

Protective role of Convolvulus pluricaulis on lipid abnormalities in high-fat diet with low dose streptozotocin-induced experimental rat model.

BACKGROUND: The methanolic extract of Convolvulus pluricaulis had earlier shown lipid lowering activity in Triton induced reversible hyperlipidemia model, but, the hypolipidemic activity in irreversible models and hypoglycaemic activity are not investigated so far. OBJECTIVE: This study was designed to validate the lipid and glucose-lowering actions of C. pluricaulis methanolic extract (CPME) by using ingredients from the Indian diet for induction of hyperlipidemia and diabetes on experimental rats. MATERIALS AND METHODS: Experimental animals were divided into four groups having six animals in each group (n = 6). Animals of Group I II, III and IV received - no treatment, 0.9% NaCl, Glipizide (GPZ) 5 mg/kg and CPME 400 mg/kg once daily for two weeks respectively. Animals of all groups except group I were fed a high fat-based Indian diet for 21 days followed by a single STZ (35 mg/kg) i.p. administration in model induction phase. Afterwards, animals were sacrificed, and the pancreas was dissected for histological changes, and blood was collected for measuring lipid parameters, FBS, insulin levels, and HOMA scores. RESULTS: CPME significantly ameliorate the lipid abnormalities in HFD-STZ-treated experimental model (p < 0.001) but fails to reverse the hyperglycaemia developed in diabetic rats with no protective effect on islet architecture (p > 0.05) as compared to experimental group while, GPZ showed protective effect on both lipid abnormalities and hyperglycemia by modulating the levels of lipid parameters and insulin respectively. CONCLUSION: In conclusion, the study confirm that CPME possesses significant hypolipidemic activity but fails to reverse the hyperglycaemia developed in diabetic rats.

Pharmacological evaluation of Convolvulus pluricaulis as hypolipidaemic agent in Triton WR-1339-induced hyperlipidaemia in rats.

OBJECTIVE: The aim of the study was to evaluate the effect of Convolvulus pluricaulis (CP; C. pluricaulis) methanolic extract on Triton WR-1339-induced hyperlipidaemia in rats. METHODS: The study comprised of six groups namely normal control, experimental control and treatment groups (100, 200 and 400 mg/kg of C. pluricaulis, and 65 mg/kg of Fenofibrate). Hyperlipidaemia was induced by a single intraperitoneal injection of Triton WR-1339 400 mg/kg in rats. Parameters such as lipid profile, oxidative stress, histological analysis and atherogenic index were evaluated. The plant extract was further studied by HPLC and LCMS, for analyses of active phytochemicals. KEY FINDINGS: The result of the study showed that C. pluricaulis significantly decreased total cholesterol, triglycerides, LDL-c, MDA levels and atherogenic index while the levels of HDL-c and GSH were found to be raised. Plant extract at the dose of 400 mg had a consistent effect on all lipid profile parameters. Lower doses (100 and 200 mg) did not produce a statistically significant reduction in LDL-c. In addition, the protective effect of C. pluricaulis was confirmed by histological analysis. Further, the findings of the study were found to be comparable with fenofibrate. CONCLUSIONS: Therefore, the present study suggests that C. pluricaulis has the potential for the treatment of hyperlipidaemia.

Folic acid, dietary habits, and homocysteine levels in relation to neural tube defects: A case-control study in North India.

PURPOSE: The present study attempts to understand the complex contribution of biochemical (plasma homocysteine) and nutritional parameters (dietary pattern and folate supplementation) to the neural tube defects (NTDs) affected pregnancies and controls in North Indian population. METHODS: Case-control study design was adopted to assess the role of folic acid, dietary habits, and homocysteine in relation to NTD births. The subjects comprised of 130 mothers of affected children (cases) and 233 mothers of healthy children (controls), who were either carrying NTD fetus or gave birth to NTD child. RESULTS: The mean homocysteine levels were elevated in cases (15.71 ± 8.35 µmol/L) as compared to controls (12.87 ± 5.95 µmol/L) but were lower among the non-vergetarians (13.55 ± 6.64 µmol/L) than the vegetarians (14.78 ± 7.93 µmol/L). Vegetarian dietary habit increased the NTD risk by 1.6 fold (95% CI = 1.0-2.7) while folic acid supplementation demonstrated a protective effect for conceptions (OR = 0.59; 95% CI = 0.3-0.9). Consumption of folic acid with non-vegetarian diet witnessed lowering of homocysteine in cases (12.88 ± 6.81 µmol/L) and in controls (11.85 ± 5.54 µmol/L), with an odds ratio depicting a 3.1 fold risk for consuming vegetarian diet without folic acid supplementation during the peri-conceptional period. CONCLUSION: It is suggested that plasma hyperhomocysteinemia bears negative impact on child-bearing women group, of north Indian ancestry, in modulating the risk of NTDs. Efforts should be made to enhance awareness regarding folic acid and vitamin B12 (non-vegetarian diet) supplementations alongwith proper nutritional intake among women, especially those consuming vegetarian diet to control homocysteine levels in order to reduce the risk of NTDs.

Heart beats in the cloud: distributed analysis of electrophysiological 'Big Data' using cloud computing for epilepsy clinical research.

OBJECTIVE: The rapidly growing volume of multimodal electrophysiological signal data is playing a critical role in patient care and clinical research across multiple disease domains, such as epilepsy and sleep medicine. To facilitate secondary use of these data, there is an urgent need to develop novel algorithms and informatics approaches using new cloud computing technologies as well as ontologies for collaborative multicenter studies. MATERIALS AND METHODS: We present the Cloudwave platform, which (a) defines parallelized algorithms for computing cardiac measures using the MapReduce parallel programming framework, (b) supports real-time interaction with large volumes of electrophysiological signals, and (c) features signal visualization and querying functionalities using an ontology-driven web-based interface. Cloudwave is currently used in the multicenter National Institute of Neurological Diseases and Stroke (NINDS)-funded Prevention and Risk Identification of SUDEP (sudden unexplained death in epilepsy) Mortality (PRISM) project to identify risk factors for sudden death in epilepsy. RESULTS: Comparative evaluations of Cloudwave with traditional desktop approaches to compute cardiac measures (eg, QRS complexes, RR intervals, and instantaneous heart rate) on epilepsy patient data show one order of magnitude improvement for single-channel ECG data and 20 times improvement for four-channel ECG data. This enables Cloudwave to support real-time user interaction with signal data, which is semantically annotated with a novel epilepsy and seizure ontology. DISCUSSION: Data privacy is a critical issue in using cloud infrastructure, and cloud platforms, such as Amazon Web Services, offer features to support Health Insurance Portability and Accountability Act standards. CONCLUSION: The Cloudwave platform is a new approach to leverage of large-scale electrophysiological data for advancing multicenter clinical research.

Ichthyosis associated with rickets in two Indian children.

We wish to report two cases of rickets due to vitamin D deficiency secondary to underlying ichthyotic skin disorder. The first case is of an 8-year-old male with history of multiple fluid-filled lesions over the body that would rupture to heal with thickening and scaling of skin, suggestive of epidermolytic hyperkeratosis, and the second is of a 14-year-old female with thick, large, quadrilateral scales over the extremities and back clinically consistent with lamellar ichthyosis. Both showed improvement with parenteral vitamin D3 and oral calcium supplements in addition to topical emollients.

Whole genome expression and biochemical correlates of extreme constitutional types defined in Ayurveda.

BACKGROUND: Ayurveda is an ancient system of personalized medicine documented and practiced in India since 1500 B.C. According to this system an individual's basic constitution to a large extent determines predisposition and prognosis to diseases as well as therapy and life-style regime. Ayurveda describes seven broad constitution types (Prakritis) each with a varying degree of predisposition to different diseases. Amongst these, three most contrasting types, Vata, Pitta, Kapha, are the most vulnerable to diseases. In the realm of modern predictive medicine, efforts are being directed towards capturing disease phenotypes with greater precision for successful identification of markers for prospective disease conditions. In this study, we explore whether the different constitution types as described in Ayurveda has molecular correlates. METHODS: Normal individuals of the three most contrasting constitutional types were identified following phenotyping criteria described in Ayurveda in Indian population of Indo-European origin. The peripheral blood samples of these individuals were analysed for genome wide expression levels, biochemical and hematological parameters. Gene Ontology (GO) and pathway based analysis was carried out on differentially expressed genes to explore if there were significant enrichments of functional categories among Prakriti types. RESULTS: Individuals from the three most contrasting constitutional types exhibit striking differences with respect to biochemical and hematological parameters and at genome wide expression levels. Biochemical profiles like liver function tests, lipid profiles, and hematological parameters like haemoglobin exhibited differences between Prakriti types. Functional categories of genes showing differential expression among Prakriti types were significantly enriched in core biological processes like transport, regulation of cyclin dependent protein kinase activity, immune response and regulation of blood coagulation. A significant enrichment of housekeeping, disease related and hub genes were observed in these extreme constitution types. CONCLUSION: Ayurveda based method of phenotypic classification of extreme constitutional types allows us to uncover genes that may contribute to system level differences in normal individuals which could lead to differential disease predisposition. This is a first attempt towards unraveling the clinical phenotyping principle of a traditional system of medicine in terms of modern biology. An integration of Ayurveda with genomics holds potential and promise for future predictive medicine.