Management of congenital talipes equino varus using Ponseti method: 3 year follow up in 166 club feet

Background: Our aim was to study the effectiveness of Ponseti method using Pirani score in children with club foot treated over the past three years at our hospital.Methods: We studied 111 children with 166 idiopathic club feet who were treated at our teaching hospital between period of January 2012 and January 2017.The foot deformities were assessed using Pirani score at the time of first visit and the scores were recorded with each subsequent visit, with each casting and manipulation until correction of deformity. Tenotomy was performed on all the idiopathic club feet and continued with Steenbeek foot abduction brace (FAB) and the scores were recorded with every follow up and the progress was noted. All the relevant data in terms of treatment and demographics were recorded with dates and maintained.Results: Total of 166 feet of 111 children was treated out of which 72 were males and 39 were females. 55 children had bilateral involvement remaining were unilateral. Mean Pirani score was 5.5 (range 4-6) when the treatment was started. On an average 5.7 casts (range 3-9) were required before preforming a tenotomy. Tenotomy was performed on all the feet (100%) with idiopathic club foot. Foot abduction orthosis was given to all the patients and 108 patients (97.3%) were compliant. Mean Pirani score after three years of treatment was 0.26. Skin complications like blister formation were seen in three children during the course of the treatment. Four patients did not follow up and defaulted. Three patients had relapse or worsening of Pirani score. The recurrence or worsening of scores is thought to be due to poor compliance while using the foot abduction brace.Conclusions: Ponseti method of treatment for CTEV is very effective, simple, non-invasive and convenient with excellent outcomes over long term with no significant complications

A Phase IV Study of Thromboembolic and Bleeding Events Following Hip and Knee Arthroplasty Using Oral Factor Xa Inhibitor

AbstractBackgroundMultiple randomized controlled trials have documented the effectiveness of rivaroxaban in the prevention of venous thromboembolism up to 1-month following total joint arthroplasty. However, the effectiveness and safety of rivaroxaban in the real-world setting, outside of the strict protocols used by randomized clinical trials, are unknown.MethodsThis was a prospective, observational, noninterventional, phase IV study of 3914 consecutive patients who underwent total joint arthroplasty from June 2010 to December 2012. Patients were treated with rivaroxaban 10 mg by mouth daily starting postoperative day 1 and continued for 15 days. Participants were followed up in clinic at 6 weeks and contacted by telephone at 12 weeks. The primary outcome of interest was symptomatic venous thromboembolism; secondary outcomes included bleeding events, transfusion requirements, and death.ResultsThe incidence of symptomatic deep venous thrombosis at 3 months was 0.5% (n = 18). Only 1 deep venous thrombosis event occurred within 7 days of surgery. The incidence of symptomatic pulmonary embolism (PE) at 3 months was 0.7% (n = 28). Thirteen PEs (46%) occurred within 7 days of surgery. The rate of major bleeding while on prophylaxis was 0.1%. Only 5% of patients received a blood transfusion. No deaths were attributed to thromboembolic events.ConclusionThis prospective, observational, phase IV study demonstrates that rivaroxaban appears to protect patients against symptomatic PE and is not associated with major bleeding events when used in a real-world setting as described

A Covering Method for Detecting Genetic Associations between Rare Variants and Common Phenotypes

Genome wide association (GWA) studies, which test for association between common genetic markers and a disease phenotype, have shown varying degrees of success. While many factors could potentially confound GWA studies, we focus on the possibility that multiple, rare variants (RVs) may act in concert to influence disease etiology. Here, we describe an algorithm for RV analysis, RARECOVER. The algorithm combines a disparate collection of RVs with low effect and modest penetrance. Further, it does not require the rare variants be adjacent in location. Extensive simulations over a range of assumed penetrance and population attributable risk (PAR) values illustrate the power of our approach over other published methods, including the collapsing and weighted-collapsing strategies. To showcase the method, we apply RARECOVER to re-sequencing data from a cohort of 289 individuals at the extremes of Body Mass Index distribution (NCT00263042). Individual samples were re-sequenced at two genes, FAAH and MGLL, known to be involved in endocannabinoid metabolism (187Kbp for 148 obese and 150 controls). The RARECOVER analysis identifies exactly one significantly associated region in each gene, each about 5 Kbp in the upstream regulatory regions. The data suggests that the RVs help disrupt the expression of the two genes, leading to lowered metabolism of the corresponding cannabinoids. Overall, our results point to the power of including RVs in measuring genetic associations.National Science Foundation (U.S.) (grant (IIS-0810905)National Institutes of Health (U.S.) (U19 AG023122-05)National Institutes of Health (U.S.) (R01 MH078151-03)Louis & Harold Price FoundationNational Institutes of Health (U.S.) (N01 MH22005)National Institutes of Health (U.S.) (U01-DA024417-01)National Institutes of Health (U.S.) (P50 MH081755-01)National Institutes of Health (U.S.) (R01 AG030474-02)National Institutes of Health (U.S.) (N01 MH022005)National Institutes of Health (U.S.) (R01 HL089655-02)National Institutes of Health (U.S.) (R01 MH080134-03)National Institutes of Health (U.S.) (U54 CA143906-01)National Institutes of Health (U.S.) (UL1 RR025774-03)Scripps Genomic Medicine ProgramNational Human Genome Research Institute (U.S.) (Grant Number T32 HG002295

The Diploid Genome Sequence of an Individual Human

Presented here is a genome sequence of an individual human. It was produced from ∼32 million random DNA fragments, sequenced by Sanger dideoxy technology and assembled into 4,528 scaffolds, comprising 2,810 million bases (Mb) of contiguous sequence with approximately 7.5-fold coverage for any given region. We developed a modified version of the Celera assembler to facilitate the identification and comparison of alternate alleles within this individual diploid genome. Comparison of this genome and the National Center for Biotechnology Information human reference assembly revealed more than 4.1 million DNA variants, encompassing 12.3 Mb. These variants (of which 1,288,319 were novel) included 3,213,401 single nucleotide polymorphisms (SNPs), 53,823 block substitutions (2–206 bp), 292,102 heterozygous insertion/deletion events (indels)(1–571 bp), 559,473 homozygous indels (1–82,711 bp), 90 inversions, as well as numerous segmental duplications and copy number variation regions. Non-SNP DNA variation accounts for 22% of all events identified in the donor, however they involve 74% of all variant bases. This suggests an important role for non-SNP genetic alterations in defining the diploid genome structure. Moreover, 44% of genes were heterozygous for one or more variants. Using a novel haplotype assembly strategy, we were able to span 1.5 Gb of genome sequence in segments >200 kb, providing further precision to the diploid nature of the genome. These data depict a definitive molecular portrait of a diploid human genome that provides a starting point for future genome comparisons and enables an era of individualized genomic information

Violent aggression predicted by multiple pre-adult environmental hits

Early exposure to negative environmental impact shapes individual behavior and potentially contributes to any mental disease. We reported previously that accumulated environmental risk markedly decreases age at schizophrenia onset. Follow-up of matched extreme group individuals (≤1 vs. ≥3 risks) unexpectedly revealed that high-risk subjects had >5 times greater probability of forensic hospitalization. In line with longstanding sociological theories, we hypothesized that risk accumulation before adulthood induces violent aggression and criminal conduct, independent of mental illness. We determined in 6 independent cohorts (4 schizophrenia and 2 general population samples) pre-adult risk exposure, comprising urbanicity, migration, physical and sexual abuse as primary, and cannabis or alcohol as secondary hits. All single hits by themselves were marginally associated with higher violent aggression. Most strikingly, however, their accumulation strongly predicted violent aggression (odds ratio 10.5). An epigenome-wide association scan to detect differential methylation of blood-derived DNA of selected extreme group individuals yielded overall negative results. Conversely, determination in peripheral blood mononuclear cells of histone-deacetylase1 mRNA as 'umbrella mediator' of epigenetic processes revealed an increase in the high-risk group, suggesting lasting epigenetic alterations. Together, we provide sound evidence of a disease-independent unfortunate relationship between well-defined pre-adult environmental hits and violent aggression, calling for more efficient prevention

Pharmacological Potential of Polyherbal Formulation, Sudarshan Churna – A Review

The Sudarshan Churna is a valuable Ayurvedic preparation, which was usedtraditionally as antimalarial, antipyretic, antiviral and antidiabetic agent. It has been givenfrom ancient time by Vaidyas to cure all types of fever including bone fever, fever due tocommon cold, viral fever etc. In Sudarshan Churna, Swertia Chirata is present in 50% oftotal quantity, remaining other ingredients is in equal proportion in remaining 50% of totalchurna. The pharmacological activities are proven on Sudarshan Churna by differentresearcher are antipyretic activity, antimicrobial activity. This review helps the researcher toexplode this formulation for more pharmacological activity and its safely use