Cardiovascular risk factors and determinants of clinical outcomes in type 2 diabetic patients at a tertiary-care centre

Background: The prevalence of type 2 diabetes mellitus (T2DM) is growing rapidly worldwide. The global burden of T2DM in 2013 was 382 million and projected to 592 million by 2035, accounting for 7.8% of the adult population. The objective of this study was to record treatments, risk factor control, determinants of glycaemic control and cardiovascular outcomes in type 2 diabetes (T2DM).Methods: We included adult T2DM patients and followed up for 6 months. Patients were categorised into good (HbA1c 8.5%). We used multiple logistic regression to identify determinants of glycaemic control and outcomes.Results: We recruited 785 patients with a mean age of 55.43 (±11.1) years, and 43.8% were women. At baseline, patients with poor control (45%) were younger and from lower socioeconomic strata (73.5%). At 6 months, the American Diabetes Association (ADA) targets of HbA1c was met only in 27.52%, systolic blood pressure (SBP) in 81.47% and low density lipoprotein (LDL) cholesterol in 48.86% patients. Patients with sedentary or low physical activity (Odds ratio 11.51, 95% confidence interval 3.48, 37.98; p<0.001) and with diabetes for a longer duration (OR 1.14 [1.07-1.22], p<0.001) were more likely to be in poor glucose control. Patients having sedentary or low physical activity (OR 6.66 [1.730-25.63] p = 0.006) and higher LDL cholesterol (OR 1.04 [1.01-1.07], p = 0.008) were more likely to get microvascular complications.Conclusions: Management of modifiable risk factors and early control of hyperglycaemia should be given more importance

Biotechnological interventions in food waste treatment for obtaining valuea‘added compounds to combat pollution

Over the last few decades, the globe is facing tremendous effects due to the unnecessary piling of municipal solid waste among which food waste holds a greater portion. This practice not only affects the environment in terms of generating greenhouse gas emissions but when left dumped in landfills will also trigger poverty and malnutrition. This review focuses on the global trend in food waste management strategies involved in the effective utilization of food waste to produce various value-added products in a microbiology aspect, thereby diminishing the negative impacts caused by the unnecessary side effects of non-renewable energy sources. The review also detailed the efficiency of microorganisms in the production of various bio-energies as well. Further, recent attempts to the exploitation of genetically modified microorganisms in producing value-added products were enlisted. This also attempted to address food waste valorization techniques, the combined applications of various processes for an enhanced yield of different compounds, and addressed various challenges. Further, the current challenges involved in various processes and the effective measures to tackle them in the future have been addressed. Thus, the present review has successfully addressed the circular bio-economy in food waste valorization

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

Luminal breast cancer metastasis is dependent on estrogen signaling

Luminal breast cancer is the most frequently encountered type of human breast cancer and accounts for half of all breast cancer deaths due to metastatic disease. We have developed new in vivo models of disseminated human luminal breast cancer that closely mimic the human disease. From initial lesions in the tibia, locoregional metastases develop predictably along the iliac and retroperitoneal lymph node chains. Tumors cells retain their epithelioid phenotype throughout the process of dissemination. In addition, systemically injected metastatic MCF-7 cells consistently give rise to metastases in the skeleton, floor of mouth, adrenal glands, as well as in the lungs, liver, brain and mammary fat pad. We show that growth of luminal breast cancer metastases is highly dependent on estrogen in a dose-dependent manner and that estrogen withdrawal induces rapid growth arrest of metastatic disease. On the other hand, even though micrometastases at secondary sites remain viable in the absence of estrogen, they are dormant and do not progress to macrometastases. Thus, homing to and seeding of secondary sites do not require estrogen. Moreover, in sharp contrast to basal-like breast cancer metastasis in which transforming growth factor-beta signaling plays a key role, luminal breast cancer metastasis is independent of this cytokine. These findings have important implications for the development of targeted anti-metastatic therapy for luminal breast cancer

Identification of Novel Mutations in ABCA4 Gene: Clinical and Genetic Analysis of Indian Patients with Stargardt Disease

Stargardt disease (STGD) is the leading cause of juvenile macular degeneration associated with progressive central vision loss, photophobia, and colour vision abnormalities. In this study, we have described the clinical and genetic features of Stargardt patients from an Indian cohort. The next generation sequencing was carried out in five clinically confirmed unrelated patients and their family members using a gene panel comprising 184 retinal specific genes. Sequencing results were analyzed by read mapping and variant calling in genes of interest, followed by their verification and interpretation. Genetic analysis revealed ABCA4 mutations in all of the five unrelated patients. Among these, four patients were found with compound heterozygous mutations and another one had homozygous mutation. All the affected individuals showed signs and symptoms consistent with the disease phenotype. We report two novel ABCA4 mutations in Indian patients with STGD disease, which expands the existing spectrum of disease-causing variants and the understanding of phenotypic and genotypic correlations. Screening for causative mutations in patients with STGD using panel of targeted gene sequencing by NGS would be a cost effective tool, might be helpful in confirming the precise diagnosis, and contributes towards the genetic counselling of asymptomatic carriers and isolated patients

Functional consequences of novel connexin 26 mutations associated with hereditary hearing loss

In a study of 530 individuals with non-syndromic, sensorineural hearing loss, we identified 18 mutations at connexin 26 (Cx26), four of which are novel (-23G>T, I33T, 377_383dupTCCGCAT, W172R) and the remaining 14 (ivs1+1G>A, M1V, 35delG, W24X, I35S, V37I, R75W, W77X, 312del14, E120del, Q124X, Y136X, R143W, R184P) being mutations previously described. To gain insight into functional consequences of these mutations, cellular localization of the mutant proteins and their ability to permit lucifer yellow transfer between cells was studied in seven of them (W24X, I33T, I35S, R75W, E120del, W172R and R184P). I35S and R184P showed impaired trafficking of the protein to the plasma membrane. I33T, R75W, E120del and W172R showed predominantly membrane localization but did not form functional gap junction channels. Surprisingly, W24X, a protein-truncating mutation, apparently permits formation of a full-length protein, perhaps due to a stop codon read-through mechanism. These results provide further evidence that Cx26 mutations affect gap junction activity by mis-regulation at multiple levels

Non-Syndromic Hearing Impairment in India: High Allelic Heterogeneity among Mutations in TMPRSS3, TMC1, USHIC, CDH23 and TMIE

Mutations in the autosomal genes TMPRSS3, TMC1, USHIC, CDH23 and TMIE are known to cause hereditary hearing loss. To study the contribution of these genes to autosomal recessive, non-syndromic hearing loss (ARNSHL) in India, we examined 374 families with the disorder to identify potential mutations. We found four mutations in TMPRSS3, eight in TMC1, ten in USHIC, eight in CDH23 and three in TMIE. Of the 33 potentially pathogenic variants identified in these genes, 23 were new and the remaining have been previously reported. Collectively, mutations in these five genes contribute to about one-tenth of ARNSHL among the families examined. New mutations detected in this study extend the allelic heterogeneity of the genes and provide several additional variants for structure-function correlation studies. These findings have implications for early DNA-based detection of deafness and genetic counseling of affected families in the Indian subcontinent

Genetic studies in a patient with X-linked retinoschisis coexisting with developmental delay and sensorineural hearing loss

<p><i>Background</i>: In this study, we present a juvenile retinoschisis patient with developmental delay, sensorineural hearing loss, and reduced axial tone. X-linked juvenile retinoschisis (XLRS) is a retinal dystrophy, most often not associated with systemic anomalies and also not showing any locus heterogeneity. Therefore it was of interest to understand the genetic basis of the condition in this patient.</p> <p><i>Materials and methods: RS1</i> gene screening for XLRS was performed by Sanger sequencing. Whole genome SNP 6.0 array analysis was carried out to investigate gross chromosomal aberrations that could result in systemic phenotype. In addition, targeted next generation sequencing (NGS) was employed to determine any possible involvement of X-linked syndromic and non-syndromic mental retardation genes. This NGS panel consisted of 550 genes implicated in several other rare inherited diseases.</p> <p><i>Results: RS1</i> gene screening revealed a pathogenic hemizygous splice site mutation (c.78+1G>T), inherited from the mother. SNP 6.0 array analysis did not indicate any significant chromosomal aberrations that could be disease-associated. Targeted resequencing did not identify any mutations in the X-linked mental retardation genes. However, variations in three other genes (<i>NSD1, LARGE</i>, and <i>POLG</i>) were detected, which were all inherited from the patient’s unaffected father.</p> <p><i>Conclusions</i>: Taken together, <i>RS1</i> mutation was found to segregate with retinoschisis phenotype while none of the other identified variations were co-segregating with the systemic defects. Hereby, we infer that the multisystemic defects harbored by the patient are a rare coexistence of XLRS, developmental delay, sensorineural hearing loss, and reduced axial tone reported for the first time in the literature.</p