Targeted sequencing of the DMD locus: A comprehensive diagnostic tool for all mutations

Background & objectives: Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder and is caused mainly by deletion, duplication and point mutations in the DMD gene. Diagnosis of DMD has been a challenge as the mutations in the DMD gene are heterogeneous and require more than one diagnostic strategy for the validation of the mutation. This study was planned to evaluate the targeted next-generation sequencing (NGS) as a single platform to detect all types of mutations in the DMD gene, thereby reducing the time and costs compared to conventional sequential testing and also provide precise genetic information for emerging gene therapies. Methods: The study included 20 unrelated families and 22 patients from an Indian population who were screened for DMD based on phenotypes such as scoliosis, toe walking and loss of ambulation. Peripheral blood DNA was isolated and subjected to multiplex ligation-dependent probe amplification (MLPA) and targeted NGS of the DMD gene to identify the nature of the mutation. Results: In the study patients, 77 per cent of large deletion mutations and 23 per cent single-nucleotide variations (SNVs) were identified. Novel mutations were also identified along with reported deletions, point mutations and partial deletions within the exon of the DMD gene. Interpretation & conclusions: Our findings showed the importance of NGS in the routine diagnostic practice in the identification of DMD mutations over sequential testing. It may be used as a single-point diagnostic strategy irrespective of the mutation type, thereby reducing the turnaround time and cost for multiple diagnostic tests such as MLPA and Sanger sequencing. Though MLPA is a sensitive technique and is the first line of a diagnostic test, the targeted NGS of the DMD gene may have an advantage of having a single diagnostic test. A study on a larger number of patients is needed to highlight NGS as a single, comprehensive platform for the diagnosis of DMD.

Development of Information Skills for Reading Periodicals - A study on Village Library.

Everybody in the world is a reader. A Reader may be an individual or a group of persons who are the end users of any Library. A Reader refers and uses a large number of Books and Periodicals services to satisfy his/her needs and wants. They have much time to read everything by themselves. Hence, this paper attempts to ascertain the development of information skills and the readers’ preference towards Periodicals. For analytical purpose, statistical tools are used. The results reveal the fact that age, education, gender and monthly income do most preferable area of Periodicals in village library. Further there is no significant relationship between monthly time spent and Reader Habits of Periodicals reading.

Synthesis and antimicrobial evaluation of novel 3-(4,6- diphenyl-6H-1,3-thiazin-2-yl)-2-(4-methoxyphenyl) thiazolidin-4-one derivatives.

A novel series of potentially biologically active 3-(4,6-diphenyl-6H-1,3-thiazin-2-yl)-2-(4-methoxyphenyl) thiazolidin-4-one derivatives (5a-5k) have been synthesized by the condensation-cyclization reaction of 4,6- diphenyl-6H-1,3-thiazin-2-amine, aromatic aldehyde and thioglycolic acid in polypropylene glycol at 1100C temperature. The structure of the newly synthesized compounds has been established on the basis of their spectral data and elemental analysis. The antimicrobial activity of the synthesized compounds were tested in vitro against the sensitive organisms Staphylococcus aureus, Bacillus subtilis as a Gram positive bacteria and Escherichia coli, Pseudomonas aeruginosa as a Gram negative bacteria and two pathogenic fungal strains Candida albicans, Aspergillus niger by using the disc diffusion method. The detailed synthesis, spectroscopic data, and antimicrobial screening of synthesized compounds were reported.

Lesion Location in Clinical Significance of Incidental Colorectal FDG Uptake

No abstract available.

Incidence of type 1 diabetes mellitus and associated complications among children and young adults: results from Karnataka Diabetes Registry 1995-2008.

The purpose of this study was to estimate incidence of type 1 diabetes mellitus (T1DM) among children and young adults aged 0-25 years and to assess growth, glycaemic control, complications, risk factors and mortality associated diabetes mellitus,based on prospective registration of patients in Karnataka Diabetes Registry during the period 1995-2008. Complications were determined in subgroups serving as cohorts by screening tests and based on physicians' report. There were 1040 patients (514 boys and 526 girls) registered during the period 1995-2008. The overall incidence/prevalence of T1 DM (per 100,000 persons) was 3.8(0.32/10(5)/year) [males 3.7(0.3110(5)/year) and females 4(0.33/10(5)/year)]. On cross-sectional analysis of different cohorts, 88% (90/102) were below 50th percentile height, 95% (114/120) were <50th percentile of weight. Thirty-nine patients (10.7%) had poor glycaemic control (A1c>9%), The prevalence of different complications were as follows: Neuropathy 5.2% (12/230), retinopathy 8.4% (14/166), nephropathy 8.6% (20/230), hypertension 2.6% (6/230). Hypercholesterolaemia and hypertriglyceridaemia were found in 20.2% (24/119) and 41.7% (48/115) cases respectively and 18.1% (19/105) had low HDL. The percentage of patient with micro-albuminuria, high sensitive C-reactive protein were 29.6% (n=233) and 44.4% (20/45) respectively. Poor glycaemic control, hypertension and duration were strong consistent predictors of all complications. Twenty patients died during the period of which 10 deaths were related to diabetes. Though the incidence of diabetes in the young is low in our population compared to the western population, the burden of diabetes is high due to large population in our country. In spite of our best efforts there are still a huge gap between the standard of care and practice. Majority of type 1 diabetics are not reaching the ideal glycaemic targets.

Barriers to changing dietary behavior.

Dietary change requires giving up long established patterns of eating behavior and acquiring new habits. 'Non-compliance' to diet advice may be a result of inability to provide diet self-management training and getting the right messages across to change eating behavior. Using a pre-tested questionnaire based interview, we carried out a study amongst 350 adults (> 20 years) with type 2 diabetes from two metro cities in South India, who had previously received diet advice with the objective to understand perceptions, attitudes and practices, as well as study factors that enhance or reduce compliance to diet advice. Ninety six patients (28%) followed diet for the full duration of diabetes (Group1), 131 (38%) followed diet for a partial duration varying between more than a quarter to three quarters of the total diabetes duration (Group 2) and 115 (34%) did not follow diet advice (Group 3) - followed for a duration less than a quarter of their diabetes duration. Study results show that many factors both patient and health care provider related influence outcomes of dietary advice. Factors that have a positive impact on compliance are - older age, shorter duration, nuclear family, good family support, less busy work life, higher health consciousness, advice given by dietician, more frequent visits to dietician, advice that includes elements to promote overall health not merely control of blood sugar, diet counseling that is easy to understand and use and includes healthy food options, cooking methods, practical guidance to deal with lifestyle issues. We conclude that patient barriers related to life circumstance are mostly non-modifiable, most modifiable barriers are related to behavioural aspect and the inability of the health care provider to provide individualized diet advice and self management training. Efforts must be made to improve counseling skills.

Behavioural intervention in the management of compliance in young type-I diabetics.

OBJECTIVES: a) To examine the efficacy of a behavioural intervention programme in the management of compliance in young Type I diabetics, b) To examine the efficacy of a behavioural management programme in enhancing metabolic control in young Type I diabetics, c) To examine the effect of behavioural intervention on level of diabetes knowledge and quality of life in young Type I diabetics. METHODS: A total of 40 patients (Experimental group n = 20, Control group n = 20) was selected from local hospitals' pediatric, endocrinology and diabetology units. The experimental group received 15 individual sessions of behavioural intervention, consisting of behavioural counseling for family and significant others, relaxation, diabetes education and specific behavioural and cognitive strategies such as reinforcement, target-setting and cognitive restructuring. Assessment was carried out on various psychological measures as well as the glycosylated hemoglobin test (HbA1), at pre and post treatment periods. RESULTS: The scores of the two groups were compared at post treatment point. Results indicate that there was significant improvement in the experimental group in compliance and metabolic control. There were also significant changes noted in the level of diabetes knowledge as well as the reported quality of life. These changes in compliance and metabolic control were maintained at a three month follow-up period. CONCLUSIONS: Behavioural intervention can be included as an effective adjunct to routine medical care in the management of young Type I diabetics, especially in the management of compliance and metabolic control, enhancement of knowledge and quality of life.