Role of Chronobiology in Determining the Distribution of Non-Communicable Diseases across Geographies-Thinking beyond Diet

Background: Over the last few years, it is being realised that the increasing burden of non-communicable diseases ( NCDs) may be linked to some macro-level determinants. Material and Methods: The present systematic review uses data distributed across geographies to explore the role played by chronobiology. Results: The paper is based on the role of these factors in affecting the prevalence of diabetes, hypertension and dementia. The paper uses extensive empirical scrutiny, covering areas across a state and applying the outcome of these to generate a hypothesis. Conclusion: Our results though initial indicate that change in chronotype appears to contribute to an increase in NCDs

Role of chronobiology in determining the distribution of non-communicable diseases across geographies-thinking beyond diet

Background: Over the last few years, it is being realised that the increasing burden of non-communicable diseases (NCDs) may be linked to some macro-level determinants. Material and Methods: The present systematic review uses data distributed across geographies to explore the role played by chronobiology. Results: The paper is based on the role of these factors in affecting the prevalence of diabetes, hypertension and dementia. The paper uses extensive empirical scrutiny, covering areas across a state and applying the outcome of these to generate a hypothesis. Conclusion: Our results though initial indicate that change in chronotype appears to contribute to an increase in NCDs

Trend of Neuropsychiatric Morbidity in Sub-Himalayan Region: An Audit of Retrospective Data Mining

Background: There is a paradigm shift in health loss due to premature mortality and disability from neuropsychiatric disorders with major burden in low- and middle-income countries. Objective: To study the trend of admissions with neuropsychiatric and substance-use disorders in 3 years in psychiatry and medicine wards of tertiary care hospital in rural Himachal Pradesh. Methodology: A retrospective data mining was done from records of Inpatient wards of Dr. R. P. Government Medical College, Tanda, Himachal Pradesh, for the year 2013–2015. Demographic details and diagnosis of neuropsychiatric disorders, licit and illicit drug use, and their consequences in the form of hanging and poisoning were analyzed. Results: Majority of admissions were attributed to alcohol abuse which increased in 3 years significantly in the months of July–September (P = 0.02) and October–December (P = 0.00). Almost all cases of neuropsychiatric disorders and majority of poisoning (58.2%) were observed among females. The productive young and middle age group (21–40 years) was mostly affected by all cause neuropsychiatric disorders (80.9%) and presented with poisoning (66.2%). Illicit drug abuse was on increasing drift among females. Conclusion: Indoor admissions were attributed to alcohol use and poisoning while neuropsychiatric disorders and substance abuse were probably dealt with at outpatient level. Treatment pertaining to mental illnesses was sought in severe cases only. Data demonstrating population burden are needed urgently to address the barriers to treatment to reduce burden

Chemical approaches to targeted protein degradation through modulation of the ubiquitin–proteasome pathway

Manipulation of the ubiquitin-proteasome system to achieve targeted degradation of proteins within cells using chemical tools and drugs has the potential to transform pharmacological and therapeutic approaches in cancer and other diseases. An increased understanding of the molecular mechanism of thalidomide and its analogues following their clinical use has unlocked small-molecule modulation of the substrate specificity of the E3 ligase cereblon (CRBN), which in turn has resulted in the advancement of new immunomodulatory drugs (IMiDs) into the clinic. The degradation of multiple context-specific proteins by these pleiotropic small molecules provides a means to uncover new cell biology and to generate future drug molecules against currently undruggable targets. In parallel, the development of larger bifunctional molecules that bring together highly specific protein targets in complexes with CRBN, von Hippel-Lindau, or other E3 ligases to promote ubiquitin-dependent degradation has progressed to generate selective chemical compounds with potent effects in cells and in vivo models, providing valuable tools for biological target validation and with future potential for therapeutic use. In this review, we survey recent breakthroughs achieved in these two complementary methods and the discovery of new modes of direct and indirect engagement of target proteins with the proteasome. We discuss the experimental characterisation that validates the use of molecules that promote protein degradation as chemical tools, the preclinical and clinical examples disclosed to date, and the future prospects for this exciting area of chemical biology