Genetics of diabetes.

Diabetes mellitus is a complicated disease characterized by a complex interplay of genetic, epigenetic, and environmental variables. It is one of the world's fastest-growing diseases, with 783 million adults expected to be affected by 2045. Devastating macrovascular consequences (cerebrovascular disease, cardiovascular disease, and peripheral vascular disease) and microvascular complications (like retinopathy, nephropathy, and neuropathy) increase mortality, blindness, kidney failure, and overall quality of life in individuals with diabetes. Clinical risk factors and glycemic management alone cannot predict the development of vascular problems; multiple genetic investigations have revealed a clear hereditary component to both diabetes and its related complications. In the twenty-first century, technological advancements (genome-wide association studies, next-generation sequencing, and exome-sequencing) have led to the identification of genetic variants associated with diabetes, however, these variants can only explain a small proportion of the total heritability of the condition. In this review, we address some of the likely explanations for this "missing heritability", for diabetes such as the significance of uncommon variants, gene-environment interactions, and epigenetics. Current discoveries clinical value, management of diabetes, and future research directions are also discussed.

Association of Endothelial Nitric Oxide Synthase Gene Polymorphisms with Coronary Artery Disease in North Indian Punjabi Population.

Nitric oxide (NO) a potent vasodilator synthesized by endothelial cells has anti-atherosclerotic properties and maintains vascular tone. It has been documented that its reduced bioavailability in vascular endothelium plays an important role in the development and progression of coronary artery disease (CAD). Therefore, we aimed to investigate the association of - 786 T > C and 894 G > T polymorphisms of eNOS with CAD. This study included 211 CAD patients and 260 controls of North Indian Punjabi population. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Logistic regression analysis revealed that the TC and CC genotypes of - 786 T > C were significantly associated with the higher risk of CAD (OR: 2.00, p = 0.001: OR: 4.63, p = 0.001, respectively). Similarly, the GT and TT genotypes of 894 G > T were found to be significantly associated with the higher risk of CAD (OR: 1.96, p = 0.001; OR: 4.54, p = 0.005, respectively). Moreover, the recessive model in  - 786 T > C (OR: 3.58, p = 0.002) and 894 G > T (OR: 3.62, p = 0.009) polymorphisms provided 3.6-fold increased risk for CAD. Furthermore, the CG, TT, and CT haplotypes were also associated with the increased risk of CAD (OR: 2.1, p = 0.001; OR: 2, p = 0.002; OR: 3.1, p = 0.001, respectively). In addition, the CC genotype of - 786 T > C and GT genotype of 894 G > T were significantly associated with higher levels of triglycerides (TG) and very low-density lipoproteins cholesterol (VLDL-C). The present study reported the association of - 786 T > C and 894 G > T polymorphisms of eNOS with CAD and abnormal lipid levels in North Indian Punjabi population.

Comparative Quality Evaluation of Physicochemical, Technological, and Protein Profiling of Wheat, Rye, and Barley Cereals.

Agronomically important cereal crops wheat, barley, and rye of the Triticeace tribe under the genus Triticum were studied with special focus on their physical, proximal, and technological characteristics which are linked to their end product utilization. The physiochemical parameters showed variability among the three cereal grains. Lactic acid-solvent retention capacity (SRC) was found to be higher in wheat (95.86-111.92%) as compared to rye (53.78-67.97%) and barley (50.24-67.12%) cultivars, indicating higher gluten strength. Sucrose-SRC and sodium carbonate-SRC were higher in rye as compared to wheat and barley flours. The essential amino acid proportion in barley and rye cultivars was higher as compared to wheat cultivars. Barley and rye flours exhibited higher biological value (BV) owing to their higher lysine content. SDS-PAGE of wheat cultivars showed a high degree of polymorphism in the low molecular range of 27.03-45.24 kDa as compared to barley and rye cultivars. High molecular weight (HMW) proteins varied from 68.38 to 119.66 kDa (4-5 subunits) in wheat, 82.33 to 117.78 kDa (4 subunits) in rye, and 73.08 to 108.57 kDa (2-4 subunits) in barley. The comparative evaluation of barley and rye with wheat cultivars would help in the development of healthy food products.

Diversity in Grain, Flour, Amino Acid Composition, Protein Profiling, and Proportion of Total Flour Proteins of Different Wheat Cultivars of North India.

Wheat cultivars grown at three different locations in North India were assessed for their variability in kernel and flour characteristics. Protein and the wet and dry gluten contents of the flour varied significantly (p ≤ 0.05) from 9.32 to 12.60%, 23.46 to 43.04%, and from 8.28 to 15.00%, respectively. Wheat varieties exhibited moderate sodium dodecyl sulfate (SDS) sedimentation and solvent retention values. Flour showed a significant (p ≤ 0.05) difference in the amino acid composition. Lysine, having the lowest chemical score, was the first most limiting amino acid in all wheat varieties. The variability of total flour proteins determined by SDS-PAGE showed polymorphism both in the number and intensity of bands, particularly in the molecular weight range of 35.1-42.8 kDa corresponding to the α-, ß-, and γ-gliadin/low-molecular-weight glutenin subunit (LMW-GS) region. Pearson's correlation established between the various grain and flour parameters showed a significant correlation, which can result in better end product use.

Association of TNF-α gene alterations (c.-238G>A, c.-308G>A, c.-857C>T, c.-863C>A) with primary glaucoma in north Indian cohort.

BACKGROUND: Tumor Necrosis Factor-alpha (TNF-α) a pleuripotent pro-inflammatory cytokine, is involved in retinal ganglion cells apoptosis in glaucoma. Thus present study aimed to analyze the association of TNF-α promoter region alterations (c.-238G>A (rs361525), c.-308G>A (rs1800629), c.-857C>T (rs1799724) and c.-863C>A (rs1800630)) with glaucoma in north Indian cohort. METHODS: Present hospital based case control study involved 286 glaucoma patients (Primary Open Angle Glaucoma [POAG], Primary Angle Closure Glaucoma [PACG], Primary Congenital Glaucoma [PCG]) and 300 controls. TNF-α gene alteration (c.-238G>A (also referred as c.-418G>A; NM_000594.3)), c.-308G>A (c.-488G>A; NM_000594.3), c.-857C>T (c.-1037C>T; NM_000594.3) and c.-863C>A (c.-1043C>A; NM_000594.3) harboring regions were PCR amplified and sequenced by Sanger sequencing. Allele frequency and genotype distribution in glaucoma cases and controls were compared using chi-square test and genetic association tested using different genetic models. RESULTS: Statistically significant genotype and allelic association was observed between glaucoma cases and controls for c.-308G>A and c.-863C>A alterations (p = 0.001, p = 0.001; p = 0.001, p = 0.001 respectively). AA genotype of c.-308G>A conferred ~7 fold increased risk towards glaucoma (OR = 6.82, 95% CI = 2.82-16.53, p = 0.001). c.-863C>A alteration under dominant, recessive and co-dominant genetic models conferred ~2 fold increased risk for glaucoma. However, no association for c.-238G>A and c.-857C>T variants with glaucoma was observed. Further, three haplotypes (GGCA, GACC and GACA) (OR = 0.48, 95% CI = 0.35-0.67, p = 0.001; OR = 0.58, 95% CI = 0.36-0.91, p = 0.019 and OR = 0.16, 95% CI = 0.05-0.51, p = 0.002, respectively) conferred protective role towards glaucoma. CONCLUSIONS: Present study is the first to indicate significant association of c.-308G>A and c.-863C>A alterations with glaucoma in cases from north Indian cohort. Also it is the first study from India to analyze the association and interaction of four promoter region alterations (c.-238G>A, c.-308G>A, c.-857C>T and c.-863C>A) in TNF-α resulting in three protective haplotypes.

Popliteal artery pseudoaneurysm due to femur exostosis.

Vascular complications of femur exostoses are rare, with popliteal pseudoaneurysm being the most common. After establishing the diagnosis, surgical treatment is mandatory. A 35-year-old woman presented with a painful pulsatile swelling in the lower medial aspect of the left thigh. Investigations revealed a pseudoaneurysm arising from the left popliteal artery adjacent to femur exostoses. Skeletal survey revealed multiple exostoses involving the upper and lower limbs. Surgical excision of the pseudoaneurysm was followed by ePTFE patch repair of the defect and excision of the exostoses. The patient was discharged after 5 days and followed up for 6 months with excellent results.

Assessment of DNA Damage in Leukocytes of Patients With Coronary Artery Disease by Comet Assay.

DNA damage in the peripheral blood leukocytes (PBL) of patients with coronary artery disease (CAD) was investigated using the sensitive alkaline single cell gel electrophoresis (SCGE)/comet assay.This case-control study consisted of CAD patients (n = 200; mean age, 59.04 ± 0.75 years) undergoing treatment at local hospitals and age-, sex-, and ethnicity-matched healthy controls (n = 200; mean age, 57.88 ± 0.96 years) from the general population.CAD patients had significantly (P < 0.001) increased DNA damage (tail DNA percent (T-DNA %) 22.45 ± 0.50 versus 5.81 ± 0.28; tail moment (TM) 89.35 ± 3.16 versus 9.98 ± 0.69; Olive tail moment (OTM) 60.50 ± 1.79 versus 10.94 ± 0.63; damage frequency (DF) 91.12 ± 0.93 versus 41.78 ± 2.04, damage index (DI) 173.68 ± 3.36 versus 48.53 ± 2.59) compared to controls. Patients with acute myocardial infarction (AMI) showed significantly higher DNA damage than patients with unstable angina (UA) (T-DNA % 24.05 ± 0.87 versus 21.06 ± 0.90; TM 100.02 ± 6.19 versus 81.61 ± 5.84; OTM 66.19 ± 3.20 versus 56.47 ± 3.33; DF 94.02 ± 0.84 versus 91.10 ± 1.16, DI 184.13 ± 5.33 versus 166.42 ± 5.89). Moreover, DNA damage was found to be significantly (P < 0.05) elevated in patients receiving ecosprin, ramipril, and metoprolol therapy compared to aspirin and nitrocontin.The increased DNA damage in CAD patients may be the consequence of disease and/or drug therapy. These observations are of concern because unrepaired DNA can lead to malignancy, and the likelihood of increasing mortality and morbidity rates in CAD patients.

Association of GSTT1 and GSTM1 gene polymorphisms with coronary artery disease in North Indian Punjabi population: a case-control study.

BACKGROUND: Glutathione S-transferases are metabolic enzymes which are responsible for detoxification of endogenous (products of oxidative stress) as well as exogenous (drugs, pesticides, herbicides, environmental pollutants and carcinogens) products. Dysfunctional detoxification enzymes are responsible for the production of oxidative stress; a major contributor to the development of coronary artery disease (CAD). OBJECTIVES: The present case-control study aimed to investigate the association of GSTT1 and GSTM1 gene polymorphisms with CAD. METHODS: In the present study, 200 patients diagnosed with CAD and 200 age, sex and population subgroup matched healthy controls were enrolled. The GSTT1 and GSTM1 gene polymorphisms were examined using multiplex PCR. RESULTS: The frequency of GSTT1 null genotype was significantly (p=0.038) lower in patients with CAD (6.00%) than in controls (12.50%). The GSTT1 null genotype showed protection against CAD (OR=0.45, 95% CI 0.22 to 0.92, p=0.028). The frequency of GSTM1 null genotype was significantly (p=0.004) higher in patients (31%) compared with controls (18%). The GSTM1 null genotype conferred twofold increased risk of developing CAD (OR=2.05, 95% CI 1.28 to 3.27, p=0.003). CONCLUSIONS: The results concluded that the GSTT1 null genotype showed protection against CAD while the GSTM1 null genotype might be involved in the pathogenesis and development of CAD.

Outcome of trans-axillary approach for surgical decompression of thoracic outlet: a retrospective study in a tertiary care hospital.

OBJECTIVE: The aim of this study was to evaluate the trans-axillary surgical approach in patients with thoracic outlet syndrome. METHODS: This retrospective study is comprised of data acquired from January 1998 until Oct 2008. Case histories of all the patients were reviewed from the Medical Records Department of Sher-i-Kashmir Institute. Relevant information and follow-up of the patients was carried out by examining the relevant clinical notes available by telephone interviews and personal contact whenever possible. All data was compiled and analyzed statistically. RESULTS: There were a total of 139 patients. The female: male ratio was about 6:1. Pain was the most common presenting symptom followed by weakness and parasthesia. Nerve conduction velocity was abnormal in 111 patients. Twenty-eight patients had abnormal Doppler study of subclavian vessels. Preoperative symptoms persisted in 13 patients. Overall, 126 patients showed improvement in symptoms and no recurrence or persistence of symptoms on follow-up examination. CONCLUSION: Trans-axillary approach provides a good exposure and cosmesis in patients with thoracic outlet syndrome. It should be considered as the gold standard in the management of thoracic outlet syndrome.

Efficacy and safety of beating heart mitral valve replacement.

BACKGROUND: The interest in beating heart surgery is growing since better results can be obtained with this procedure compared to conventional myocardial protection techniques using cardioplegic solutions. This led us to consider mitral valve replacement with beating heart. OBJECTIVES: This study aimed to determine the safety and efficacy of beating heart mitral valve replacement without cross clamp. METHODS: This prospective study was conducted on the patients with isolated mitral valve disease requiring mitral valve replacement according to ACC / AHA guidelines. In this study, 15 patients underwent mitral valve replacement using beating heart technique (Group A) and 15 ones underwent mitral valve replacement using arrested heart technique (Group B). The patients were randomized using block randomization. The data were analyzed using the SPSS statistical software. RESULTS: Preoperative parameters were comparable in the two groups. Most of the patients in both study groups were in NYHA class III or IV. Postoperatively, however, most of the patients in the two groups were either in NYHA class I or II. No mortality occurred in the beating heart group, while one mortality occurred in the arrested heart group. The results showed a significant difference between the two groups regarding the mean bypass time, mean operating time, mean ICU stay, and mean length of hospital stay. CONCLUSIONS: Beating heart mitral valve replacement is equally safe as the arrested heart technique. Thus, it is recommended as an appropriate alternative to the arrested heart technique for mitral valve replacement.

Pattern, presentation and management of vascular injuries due to pellets and rubber bullets in a conflict zone.

BACKGROUND: Rubber bullets and pellet guns are considered non-lethal low-velocity weapons. They are used to disperse a mob during street protests. The present study was undertaken to analyze the pattern, presentation and management of vascular injuries caused by these weapons. PATIENTS AND METHODS: This was a prospective study of patients with features of vascular injuries due to pellets and rubber bullets from June 2010 to November 2010. All patients with features of vascular injuries due to these non-lethal weapons were included in the study. Vascular injuries caused by other causes were excluded from the study. RESULTS: A total of 35 patients who presented with features of vascular injury during this period were studied. All of them were males. The mean age was 22 years. Fifteen patients were revascularized primarily, 19 patients needed reverse saphenous vein graft and, in one, patient lateral repair was done. There were two mortalities in our series. Wound infection was the most common complication. The amputation rate was around 6%. CONCLUSION: Pellet and rubber bullets can cause serious life-threatening injuries. Vascular injury caused by these weapons need no different approach than other vascular injuries. Early revascularization and prompt resuscitation prevents the loss of limb or life.

DNA and chromosomal damage in coronary artery disease patients.

DNA and chromosomal damage in peripheral blood leukocytes of patients with coronary artery disease (CAD) were investigated by using the single cell gel electrophoresis assay /comet and cytokinesis- block micronucleus (CBMN) assays, respectively. The case-control study comprised patients with CAD (n = 46; average age 53.0 ± 1.27 y) undergoing treatment at local hospitals, and healthy age-and sex-matched controls (n = 19; average age 54.21 ± 0.91 y) from the general population. The results of the comet assay revealed that the mean values of DNA damage were significantly (p < 0.001) higher in CAD patients than in controls (Tail DNA% 11.55 ± 0.38 vs. 5.31 ± 0.44; Tail moment 6.17 ± 0.31 vs. 2.93 ± 0.21 AU; Olive tail moment 3.52 ± 0.23 vs. 1.25 ± 0.11 AU). The mean values of chromosomal damage were also significantly higher (p < 0.001) in CAD patients than in controls (Binucleated cells with MN- 28.15 ± 1.18 vs. 18.16 ± 2.59; micronuclei 29.52 ± 1.21 vs. 18.68 ± 2.64, respectively) while nuclear division index (1.48 ± 0.01 vs. 1.63 ± 0.01) was significantly higher (p < 0.001) in controls. The results of the present study indicate that coronary artery disease patients had increased levels of both, unrepaired (DNA) and repaired (chromosomal) genetic damage which may be a pathological consequence of the disease and/or the drug-treatment. This accumulation of DNA/chromosomal damage is of concern as it can lead to the development of cancer with increased chances of morbidity and mortality in the CAD patients.

Profile of missile-induced cardiovascular injuries in Kashmir, India.

BACKGROUND: Missile cardiovascular injuries have taken an epidemic proportion in Kashmir valley since the eruption of militancy in 1990. Present study was undertaken to analyse the pattern, presentation and management of missile cardiovascular injuries. PATIENTS AND METHODS: Three hundred and eighty-six patients with missile cardiovascular injuries since Jan 1996 to Oct 2008 were studied retrospectively. All patients of cardiovascular injuries due to causes other than missiles were excluded from the study. RESULTS: All patients of missile cardiac injuries were treated by primary cardiorrhaphy. Right ventricle was the most commonly affected chamber. Left anterior thoracotomy was most common approach used. Most of the patients of missile vascular group were treated by reverse saphenous vein graft or end-to-end anastomosis. Most common complication was wound infection (20.83%) followed by graft occlusion (1.94%) in missile vascular group. Amputation rate was 4.66%. Amputation rate was higher in patients with delay of >6 hours and associated fractures. CONCLUSION: Missile cardiac injuries should be operated early without wasting time for investigations. Clinical status at arrival, time interval till management, nature of injury and associated injuries, tell upon the mortality. Missile vascular injury needs prompt resuscitation and revascularization at the earliest. Time interval till revascularization and associated fractures has a bearing on mortality and morbidity.

Vascular injuries caused by tear gas shells: surgical challenge and outcome.

BACKGROUND: Tear gas shells are used to disperse the mob during any type of street protests. Vascular injuries due to tear gas shells have not been reported. The present study was undertaken to analyse the pattern, presentation, management and outcome of vascular injury due to tear gas shells. METHODS: Eighteen patients with vascular injury caused by tear gas shells from 1(st) Jan. 2008 to 31(st) Dec 2009 were studied. Patients with vascular injuries caused by causes other than tear gas shells were excluded from the study. RESULTS: All patients were treated with reverse saphenous vein graft as segmental loss was less than 2.5 cm. Wound infection was the most common complication, followed by graft occlusion. Amputation rate was 16.66%. Associated nerve injury occurred in 44.44% of the patients. CONCLUSION: Tear gas shell injuries should not be taken lightly. They can cause injuries as serious as vascular injuries. Vascular injuries cased by tear gas shells require prompt revascularisation to improve limb salvage. Despite proper revascularisation, patients have significant morbidity and need proper rehabilitation in the follow ups.

Feeding jejunostomy: does the benefit overweight the risk (a retrospective study from a single centre).

BACKGROUND: The purpose of this study was to review the efficacy and safety of feeding jejunostomy in terms of achieving the nutritional goals in patients undergoing esophagectomy for carcinoma of oesophagus and complications associated hence with. METHODS: A total of 463 patients underwent esophagogastrectomy for carcinoma oesophagus during this period. All these patients underwent Witzel feeding jejunostomy for post-operative enteral nutrition. Enteral feeding was started after 24 h of surgery and increased gradually till target caloric and protein value was achieved. Nutritional goals achieved were reviewed. All complications related to jejunostomy were recorded. RESULTS: The study comprised of 463 patients who underwent elective esophagogastrectomy. Mean age was 58 +/- 8.4 in male patients and 55 +/- 4.2 years in female patients. Patients spend a mean of 19 +/- 8.4 (range 10-49) days on jejunostomy feed. The targeted calorie requirement was achieved by post-operative day 3 in 408 (88.12%) patients. The catheter blockage was one of the main complications during the course of feeding. Seven patients required relaparotomy for catheter blockage. CONCLUSION: Feeding jejunostomy is an effective, safe, economic and well tolerated method of providing nutrition to the patients of esophagogastrectomy. Feeding jejunostomy should be done in every patient undergoing esophagectomy at the time of laparotomy.

Traumatic diaphragmatic rupture, a diagnostic dilemma in the presence of eventration: a case report.

Eventration of the diaphragm is the condition where the muscle is permanently elevated, but retains its continuity and attachments to the costal margins. Traumatic diaphragmatic rupture is a recognized consequence of high velocity blunt trauma to the abdomen usually a result of motor vehicle accident. Multi-slice CT and Magnetic Resonance Imaging in the pre-operative evaluation of trauma patients, diaphragmatic rupture can be still overlooked if not evaluated with the fair degree of clinical suspicion, more so if it is associated with an eventration of diaphragm - as was in our case.

Missile cardiac injuries: review of 16 years' experience.

BACKGROUND: Penetrating cardiac trauma represents an increasingly important form of trauma due to the frequent use of firearms and bombs in civilian violence. We report our experience over the past 16 years with missile-induced cardiac injuries. METHODS: A retrospective study reviewing 40 cases (30 males, 10 females) of missile cardiac injuries was conducted. The nature of injuries, management and outcomes were analyzed. RESULTS: The ages ranged from 14-68 years. The mean time in which patients reached the hospital was 4.1 hours. Forty percent of the patients had firearm injuries and the remaining 60% had pellet or splinter injuries to the heart. Survival was noted in 37.5% in the gunshot group and in 66.6% in the splinter/pellet group. The survival in patients with isolated cardiac injury was 60%, while it was only 40% in those with associated injuries. Single-chamber injury was noted in 87.5% of the patients and the survival in these was 62.8%. Fourteen complications were noted in the patients who were resuscitated. One patient was re-explored for excessive bleeding and a missed right ventricular perforation was repaired. CONCLUSION: In missile cardiac injuries, results are best if operated early, and outcome depends upon multiple factors including clinical status at arrival, time interval till management, nature of injury, and associated injuries.