Fragment based drug design

Rational approaches towards drug development have emerged as one of the most promising ways among the tedious conventional procedures with the aim of redefining the drug discovery process. The need of current medical system is demanding a much precise, faster and reliable approaches in parallel to faster growing technology for development of drugs with more intrinsic action and fewer side effects. Systematic and well-defined diagnostic studies have revealed the specific causes of disease and related targets for drug development. Designing a drug as per the specific target, studying it in-silico prior to its development has been proved as an added benefit to the studies. Many approaches like structure based drug design, fragment based drug design and ligand based drug design are been in practice for the drug discovery and development with the similar fundamental theory. Fragment based drug design utilizes a library of fragments designed specifically for the concerned target and these fragments are studied further before screening with virtual methods as well as with biophysical methods. The process follows a well-defined pathway which moulds a fragment into a perfect drug candidate. In this chapter we have tried to cover all the basic aspects of fragment based drug design and related technologies.

Operationalizing the Exposome Using Passive Silicone Samplers

The exposome, which is defined as the cumulative effect of environmental exposures and corresponding biological responses, aims to provide a comprehensive measure for evaluating non-genetic causes of disease. Operationalization of the exposome for environmental health and precision medicine has been limited by the lack of a universal approach for characterizing complex exposures, particularly as they vary temporally and geographically. To overcome these challenges, passive sampling devices (PSDs) provide a key measurement strategy for deep exposome phenotyping, which aims to provide comprehensive chemical assessment using untargeted high-resolution mass spectrometry for exposome-wide association studies. To highlight the advantages of silicone PSDs, we review their use in population studies and evaluate the broad range of applications and chemical classes characterized using these samplers. We assess key aspects of incorporating PSDs within observational studies, including the need to preclean samplers prior to use to remove impurities that interfere with compound detection, analytical considerations, and cost. We close with strategies on how to incorporate measures of the external exposome using PSDs, and their advantages for reducing variability in exposure measures and providing a more thorough accounting of the exposome. Continued development and application of silicone PSDs will facilitate greater understanding of how environmental exposures drive disease risk, while providing a feasible strategy for incorporating untargeted, high-resolution characterization of the external exposome in human studies.

Relationship between Housewife Behavior in Using Clean Water and Diarrhea in Toddlers (0-59 Months) at Sukamulya Public Health Center, Singkup District, Ketapang Regency

Diarrhea is one of the leading causes of morbidity and mortality, especially in children under five. Some of the causes of disease are clean water and disposal of feces, both of which are influenced by human behavior. This research is research using the observational method with a case-control study design. The samples taken in this study were toddlers (0-59 months) who suffered from diarrhea and the houses around the patients who did not have diarrhea. The data used in this study is secondary data from related agencies and primary data obtained from interviews and observations. From the survey results, 31.1% suffer from diarrhea, and 68.9% are not sick. Then from the bivariate results with X2 5% analysis received four variables that are not related to diarrheal disease in toddlers, namely the variable of using clean water sources (0.297), behavior variable choosing clean water (0.227), behavior variable transporting clean water (1,000), behavioral variable using clean water (0.073) and one related variable, namely the variable protecting clean water (0.021).

250 years after Morgagni (1682-1771), author of the masterpiece De Sedibus et Causis Morborum, and his contributions to neurology development / 250 anos depois de Morgagni (1682-1771), autor da obra-prima De Sedibus et Causis Morborum, e de suas contribuições para o desenvolvimento da neurologia

Giovanni Battista Morgagni (1682-1771) is recognized as the father of modern anatomical pathology1. Ten years before his death, 250 years ago, he published his monumental five-volume book De Sedibus et Causis Morborum per Anatomen Indagatis (On the Seats and Causes of Disease)2, which contributed to the current experience in neuroscience. He was one of the pioneers of anatomoclinical method, based on the correlation between the clinic and anatomic lesions, that was essential for neurology development.

Use of the genus Satureja as food supplement: possible modulation of the immune system via intestinal microbiota during SARS-CoV-2 infection?

Satureja genus belongs to the Lamiaceae family, they are used in food products and by pharmaceutical and cosmetic industries. The chemical composition of Satureja are responsible for its pharmacological and phytochemical properties. Among the various biological activities, notably antioxidant, antibacterial and antifungal, Satureja also has a potential antiviral activity. The existence of a microbiota modulation potential by Satureja in farming animals has also been reported. Viral pathologies are one of the main causes of disease in the world. It is commonly known that gut microbiota plays a crucial role in the fight and progression of viral infection. Previous studies conducted on coronavirus disease 2019 (COVID-19) pandemic have prouved an imbalance in the intestinal and pulmonary microbiota via gut-lung axis. Knowing the properties of Satureja and its traditional use, one can suggest the possibility of using it as dietary supplement to modulate immune system in order to prevent and fight viral infections. The objective of this review is to reveal the potential impact of medicinal plants such as Satureja genus as food supplement, on immune enhancing during SARS-CoV-2 infection and their relationships with the intestinal microbiota.

How a Nutritional Deficiency Became Treated with Fluoride

Ignoring evidence on causes of disease such as smoking can harm public health. This report explores how public health experts started to ignore evidence that pediatric vitamin D deficiencies are associated with dental caries. Historical analyses show that an organization of clinical specialists, the American Dental Association (ADA), initiated this view. The ADA was a world-leading organization and its governing bodies worked through political channels to make fluoride a global standard of care for a disease which at the time was viewed as an indicator of vitamin D deficiencies. The ADA scientific council was enlisted in this endeavor and authorized the statement saying that “claims for vitamin D as a factor in tooth decay are not acceptable”. This statement was ghost-written, the opposite of what the ADA scientific council had endorsed for 15 years, and the opposite of what the National Academy of Sciences concluded. Internal ADA documents are informative on the origin of this scientific conundrum; the ADA scientific council had ignored their scientific rules and was assisting ADA governing bodies in conflicts with the medical profession on advertising policies. The evidence presented here suggests that professional organizations of clinical specialists have the power to create standards of care which ignore key evidence and consequently can harm public health.

Environmental health methods

Both host and environmental factors are involved in the development of human diseases. Environmental causes of disease include physical, chemical, biological, behavioural, and social factors. Consistent findings in both observational and interventional studies at aggregate and individual levels provide strong evidence of causation between human diseases and environmental agents. They are illustrated by the elucidation of the pleiotropic health effects of arsenic in drinking water and the multifactorial aetiology of hepatocellular carcinoma caused by viral hepatitis. Molecular and genomic biomarkers are used to explore the time-dependent host–environment interaction in the natural history of human diseases. They include dosimetry of exposure to environmental agents; the health outcomes at molecular, cellular, and histological levels; and the genetic and acquired susceptibility. Risk calculators combining multiple biomarkers are developed for the prediction of long-term disease risk. Global partnerships need to be strengthened to achieve interrelated goals of human health, environmental sustainability, and socioeconomic development.

Drug Reprofiling: In Silico Modelling of Haemophilus Influenzae Disease, Staphylococcus aureus Related Pneumonia and Urinary Tract Infections

According to reports of ReAct forum, every year more than 750,000 patients die due to bacterial infections, making bacterial infection one of the leading causes of disease infestation in an individual. Haemophilus influenzae disease, pneumonia and urinary tract infections make the top of this list. Haemophilus influenzae is a gram-negative, commensal, facultative bacterium, which can mostly cause pneumonia along with other diseases including bloodstream infections and arthritis. Though vaccine exists for Hib infections, during infections of Hib and NThi the patients are administered antibiotics to treat the disease. Staphylococcus aureus is a grampositive versatile bacterium of the micrococcaceae family and one of the most dangerous pathogen-affecting humans as it can cause pneumonia. Pneumonia is an acute pulmonary infection, which is associated with high mortality having a more pronounced effect on young children. Urinary Tract Infection is a prevalent public health problem that is more common in women than in men. Though it can be treated by appropriate antibiotics, due to recurrent infections, they lead to a gain of resistance. Thousands of research are going on around the world to come up with a potential drug that can cure the Hi disease, Staphylococcus aureus related pneumonia and UTIs entirely with the least drawbacks. In this study, we present a docking-based screening using a quantum mechanical scoring of a library built from approved drugs and compounds, Amoxicillin and Cefuroxime with proteins with PDB ids 3CKM, 3EMF, 3ZU0, 4MV9, 5KCN, 5VBG, and 6XXY for Hi disease, 4RBR, 4MVN, 3KOR and 2RKZ for Staphylococcus aureus related pneumonia and 6QVX, 2F00, 6AYI and 2ID0 for UTIs could display antibacterial activity against the respective bacterial infections. This study needs to be evaluated and further confirmed through experimental assays and clinical trials to validate the predicted results. This finding aims to provide a better understanding and contribute

Estimating the direct Covid-19 disability-adjusted life years impact on the Malta population for the first full year

Background Disability-adjusted life years (DALYs) combine the impact of morbidity and mortality, allowing for comprehensive comparisons of the population. The aim was to estimate the DALYs due to Covid-19 in Malta (March 2020–21) and investigate its impact in relation to other causes of disease at a population level. Methods Mortality and weekly hospital admission data were used to calculate DALYs, based on the European Burden of Disease Network consensus Covid-19 model. Covid-19 infection duration of 14 days was considered. Sensitivity analyses for different morbidity scenarios, including post-acute consequences were presented. Results An estimated 70,421 people were infected (with and without symptoms) by Covid-19 in Malta (March 2020–1), out of which 1636 required hospitalisation and 331 deaths, contributing to 5478 DALYs. These DALYs positioned Covid-19 as the fourth leading cause of disease in Malta. Mortality contributed to 95% of DALYs, while post-acute consequences contributed to 60% of morbidity. Conclusions Covid-19 over 1 year has impacted substantially the population health in Malta. Post-acute consequences are the leading morbidity factors that require urgent targeted action to ensure timely multidisciplinary care. It is recommended that DALY estimations in 2021 and beyond are calculated to assess the impact of vaccine roll-out and emergence of new variants.

Monitoring the incidence and causes of disease potentially transmitted by food in Australia: Annual report of the OzFoodNet network, 2016

In 2016, a total of 44,455 notifications of enteric diseases potentially related to food were received by state and territory health departments in Australia. Consistent with previous years, campylobacteriosis (n = 24,171) and salmonellosis (n = 18,060) were the most frequently-notified infections. Notable increases in incidence were observed for shiga toxin-producing Escherichia coli (n = 343; 166% increase), shigellosis (n = 1,408; 93% increase), campylobacteriosis (33% increase) and salmonellosis (30% increase) when compared with the historical five-year mean. The extent to which the introduction of culture-independent testing as a method of diagnosis has contributed to these increases remains unclear. In total, 188 gastrointestinal outbreaks, including 177 foodborne outbreaks, were reported in 2016. The 11 non-foodborne outbreaks were due to environmental or probable environmental transmission (nine outbreaks) and animal-to-person or probable animal-to-person transmission (two outbreaks). No outbreaks of waterborne or probable waterborne transmission were reported in 2016. Foodborne outbreaks affected 3,639 people, resulting in at least 348 hospital admissions and four deaths. Eggs continue to be a source of Salmonella Typhimurium infection across the country: 35 egg-related outbreaks, affecting approximately 510 people, were reported across six jurisdictions in 2016. Three large multi-jurisdictional Salmonella outbreaks associated with mung bean sprouts (n = 419 cases); bagged salad products (n = 311 cases); and rockmelons (n = 144 cases) were investigated in 2016. These outbreaks highlight the risks associated with fresh raw produce and the ongoing need for producers, retailers and consumers to implement strategies to reduce potential Salmonella contamination.