NMNAT1 Mutations Cause Leber Congenital Amaurosis

Leber congenital amaurosis (LCA) is an infantile-onset form of inherited retinal degeneration characterized by severe vision loss. Two-thirds of LCA cases are caused by mutations in 17 known disease genes (RetNet Retinal Information Network). Using exome sequencing, we identified a homozygous missense mutation (c.25G>A, p.Val9Met) in NMNAT1 as likely disease-causing in two siblings of a consanguineous Pakistani kindred affected by LCA. This mutation segregated with disease in their kindred, including in three other children with LCA. NMNAT1 resides in the previously identified LCA9 locus and encodes the nuclear isoform of nicotinamide mononucleotide adenylyltransferase, a rate-limiting enzyme in nicotinamide adenine dinucleotide $(NAD^+)$ biosynthesis. Functional studies showed the p.Val9Met mutation decreased NMNAT1 enzyme activity. Sequencing NMNAT1 in 284 unrelated LCA families identified 14 rare mutations in 13 additional affected individuals. These results are the first to link an NMNAT isoform to disease and indicate that NMNAT1 mutations cause LCA

Emotional Stress Consequences in the Development of Type 2 Diabetes Mellitus and Solutions

India is recognized as diabetic capital of the world now and among all chronic diseases increased prevalence of Type 2 Diabetes mellitus has been recognized globally. Though various modifiable risk factors are identified for the development of type 2 diabetes mellitus such as prediabetes, overweight, obesity, poor diet, smoking, physical inactivity and given importance in the management of disease. But among all stress and anxiety has not been getting proper importance in development and management of Type 2 diabetes. Though number of studies have been identified stress as risk factor for type 2 diabetes. Thus, the present write up is aimed to review the effect of different emotional stressor as risk in the development and uncontrolled hyperglycemia in type 2 diabetes mellitus patients with effective solutions. Material and Methods: This review is based on data collected from classical Ayurvedic literature, and published research works in various journals. Observations and Results: cited based on research reviews to find out risk odds of different emotional stressor and type 2 diabetes with solutions based on Ayurveda and Yoga principles such as role of Raga therapy, Yogasan, Pranayama (breathing technique), Panchakarma procedures and use of Medhya Rasayana (nootropic) drugs. Conclusion: Counselling would be one of the best strategy to create awareness among healthy individual and type 2 diabetic to opt healthy behaviour to manage emotional stress and for the prevention and better control of type 2 diabetes mellitus. Thus, Present write up is an effort to provide attention on various emotional stressor as risk factor and also discuss the various healthy behavioural techniques to control emotional stress

A Critical Review on Clinical Manifestations of Obesity in Type 2 Diabetes Mellitus and Solution through Physical Activity

Diabesity term recently coined in medical field because of the very close epidemiological and pathogenic associations between central obesity and Type 2DM. Material and Methods: This review is based on data collected from published research works in various journals. Observations and Results: cited based on research reviews to find out risk odds of obesity and physical inactivity and initiation of type 2 diabetes with solutions based on improve physical activity. Conclusion: Counseling would be one of the best strategies to opt physical exercise with moderate and vigorous intensity recommended as world health organization as healthy behaviour to prevent and control of type 2 diabetes. Thus, Present write up is an effort to critically evaluate and assess the published research data on obesity and its association with development of type 2 diabetes and role of Physical exercises for prevention and control of type 2 DM as its solution with research evidences

Studies on Coordination Polymers: Part I-Polymeric Complexes of ɑ-Dipyridyl Disulphide with Nickel(II)

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Role and Recent Advancements of Ionic Liquids in Drug Delivery Systems

Advancements in the fields of ionic liquids (ILs) broaden its applications not only in traditional use but also in different pharmaceutical and biomedical fields. Ionic liquids “Solutions for Your Success” have received a lot of interest from scientists due to a myriad of applications in the pharmaceutical industry for drug delivery systems as well as targeting different diseases. Solubility is a critical physicochemical property that determines the drug’s fate at the target site. Many promising drug candidates fail in various phases of drug research due to poor solubility. In this context, ionic liquids are regarded as effective drug delivery systems for poorly soluble medicines. ILs are also able to combine different anions/cations with other cations/anions to produce salts that satisfy the concept behind the ILs. The important characteristics of ionic liquids are the modularity of their physicochemical properties depending on the application. The review highlights the recent advancement and further applications of ionic liquids to deliver drugs in the pharmaceutical and biomedical fields

Precision Radiotherapy: Reduction in Radiation for Oropharyngeal Cancer in the 30 ROC Trial

BackgroundPatients with human papillomavirus-related oropharyngeal cancers have excellent outcomes but experience clinically significant toxicities when treated with standard chemoradiotherapy (70 Gy). We hypothesized that functional imaging could identify patients who could be safely deescalated to 30 Gy of radiotherapy.MethodsIn 19 patients, pre- and intratreatment dynamic fluorine-18-labeled fluoromisonidazole positron emission tomography (PET) was used to assess tumor hypoxia. Patients without hypoxia at baseline or intratreatment received 30 Gy; patients with persistent hypoxia received 70 Gy. Neck dissection was performed at 4 months in deescalated patients to assess pathologic response. Magnetic resonance imaging (weekly), circulating plasma cell-free DNA, RNA-sequencing, and whole-genome sequencing (WGS) were performed to identify potential molecular determinants of response. Samples from an independent prospective study were obtained to reproduce molecular findings. All statistical tests were 2-sided.ResultsFifteen of 19 patients had no hypoxia on baseline PET or resolution on intratreatment PET and were deescalated to 30 Gy. Of these 15 patients, 11 had a pathologic complete response. Two-year locoregional control and overall survival were 94.4% (95% confidence interval = 84.4% to 100%) and 94.7% (95% confidence interval = 85.2% to 100%), respectively. No acute grade 3 radiation-related toxicities were observed. Microenvironmental features on serial imaging correlated better with pathologic response than tumor burden metrics or circulating plasma cell-free DNA. A WGS-based DNA repair defect was associated with response (P = .02) and was reproduced in an independent cohort (P = .03).ConclusionsDeescalation of radiotherapy to 30 Gy on the basis of intratreatment hypoxia imaging was feasible, safe, and associated with minimal toxicity. A DNA repair defect identified by WGS was predictive of response. Intratherapy personalization of chemoradiotherapy may facilitate marked deescalation of radiotherapy

Book of Abstracts of the 2nd International Conference on Applied Mathematics and Computational Sciences (ICAMCS-2022)

It is a great privilege for us to present the abstract book of ICAMCS-2022 to the authors and the delegates of the event. We hope that you will find it useful, valuable, aspiring, and inspiring. This book is a record of abstracts of the keynote talks, invited talks, and papers presented by the participants, which indicates the progress and state of development in research at the time of writing the research article. It is an invaluable asset to all researchers. The book provides a permanent record of this asset. Conference Title: 2nd International Conference on Applied Mathematics and Computational SciencesConference Acronym: ICAMCS-2022Conference Date: 12-14 October 2022Conference Organizers: DIT University, Dehradun, IndiaConference Mode: Online (Virtual