Inference on the dynamics of COVID-19 in the United States.

The evolution of the COVID-19 pandemic is described through a time-dependent stochastic dynamic model in discrete time. The proposed multi-compartment model is expressed through a system of difference equations. Information on the social distancing measures and diagnostic testing rates are incorporated to characterize the dynamics of the various compartments of the model. In contrast with conventional epidemiological models, the proposed model involves interpretable temporally static and dynamic epidemiological rate parameters. A model fitting strategy built upon nonparametric smoothing is employed for estimating the time-varying parameters, while profiling over the time-independent parameters. Confidence bands of the parameters are obtained through a residual bootstrap procedure. A key feature of the methodology is its ability to estimate latent unobservable compartments such as the number of asymptomatic but infected individuals who are known to be the key vectors of COVID-19 spread. The nature of the disease dynamics is further quantified by relevant epidemiological markers that make use of the estimates of latent compartments. The methodology is applied to understand the true extent and dynamics of the pandemic in various states within the United States (US)

Hydroxyl radical is the major causative factor in stress-induced gastric ulceration

The role of the metal-catalyzed production of hydroxyl radicals (OH.) on gastric ulceration caused by restraint-cold stress in rat was studied. Stress causes a 50% increase in the thiobarbituric acid reactive species (TBARS) as a measure of the lipid peroxidation, nearly 70% increase in protein oxidation as measured by its carbonyl content and about 40% decrease in the glutathione content of the fundic stomach, suggesting oxidative damage by stress. Stress also causes a time-dependent increase in the mitochondrial superoxide dismutase activity and a decrease in the peroxidase activity, both of which correlate well with the increase in the severity of ulceration as measured by the ulcer index. Specific OH scavengers such as benzoate or dimethylsulfoxide (DMSO) and the free radical trap such as α-phenyl N-tert-butyl nitrone (PBN) significantly inhibit gastric ulceration suggesting the role of OH in this oxidative damage. Desferrioxamine (DFO), a nontoxic transition metal ion chelator, protects the mucosa against stress-ulceration dose dependently. Increased level of TBARS and the inactivation of gastric peroxidase are also prevented by DFO or by antioxidants such as glutathione or vitamin E, suggesting the critical role of metal ion and OH in the oxidative damage. A metal-catalyzed OH generating system constituted by Cu2+, H2O2 and ascorbate (reducing equivalent of O2-) causes inactivation of the purified gastric peroxidase in vitro, which can be effectively prevented by DFO. The stress-induced activation of the superoxide dismutase is completely blocked by pretreatment with a-amanitin indicating an increased synthesis of the enzyme by increased transcription of its m-RNA. Quantitative measurement indicates that stress causes a fivefold increase in the generation of OH, which correlates well with the increase in ulcer index with the progress of stress. The results indicate that the stress-induced gastric ulceration is a consequence of the oxidative damage of the gastric mucosa. This is caused by the OH generated through the metal-catalyzed Haber-Weiss reaction between O2- and H2O2, the latter being formed by the stimulation of the superoxide dismutase and inactivation of the gastric peroxidase

Role of reactive oxygen species in mercaptomethylimidazole-induced gastric acid secretion and stress-induced gastric ulceration

The objective of the present study is to delineate the role of reactive oxygen species in drug-induced gastric hyperacidity and stress-induced gastric ulceration. We reported earlier that mercaptomethylimidazole (MMI), an antithyroid drug, induces gastric acid (HCl) secretion partially through H2 receptor activation of the parietal cell by histamine release and partially through an intracellular mechanism. While studying the latter, MMI-induced acid secretion was found to correlate well with the inactivation of the peroxidase, an important H2O2 metabolizing enzyme of the mucosa. MMI activates the isolated parietal cell for acid secretion, which is sensitive to omeprazole. Peroxidase and catalase activity of the isolated cell is also irreversibly inactivated by MMI. It thus creates a favourable condition for endogenous accumulation of H2O2. Acid secretion by gastric gland preparation or isolated gastric mucosa is stimulated by exogenous H2O2, which is inhibited by omeprazole. Studies indicate that H2O2 inactivates the prostaglandin synthetase and removes the inhibitory influence of prostaglandin on acid secretion. MMI thus stimulates acid secretion not only through H2, receptor activation but also through the stimulation of the parietal cell by intracellular generation of H2O2 following inactivation of the peroxidase-catalase system. Among the various factors responsible for gastric ulceration, stress was found to cause severe haemorrhagic lesions mainly through oxidative damage of the mucosa as indicated by increased lipid peroxidation, increased protein carbonyl content, and decreased glutathione level. The severity of ulcer correlates well with the time-dependent induction of superoxide dismutase and inactivation of peroxidase, a condition favourable for accumulation of endogenous H2O2. Desferrioxamine prevents stress ulcer, indicating involvement of transition metal ion in the process. Studies indicate that severity of stress ulcer is dependent on the concurrent generation of hydroxyl radical (•OH) formed through metal-catalysed Haber-Weiss reaction between O2- and H2O2

Incidence and risk factors of cognitive impairment: A 6-year follow-up study from North India

Background: More than 55 million people globally suffer from cognitive impairment (CI), and over 60% of them reside in low- and middle-income countries. Longitudinal studies provide a more robust understanding of incidence and risk factors. The present study aimed to estimate the incidence and socio-demographic, anthropometric, and biochemical risk factors of CI in the Jat community of North India. Methods: The present longitudinal study recruited 223 adult individuals of both sexes from the Jat community residing in the Palwal district of Haryana, North India. Data on socio-demographic variables were collected through a pretested interview schedule. Assessment of cognition in both baseline and end-line was done through RUDAS. Data on anthropometric and biochemical variables were collected through standardized methods. Results: The overall incidence rate of CI in the studied population was found to be 28.4 per 1000 individuals-years. Further, among all the socio-demographic, anthropometric, and biochemical variables considered, illiteracy (2.5-fold), high waist-hip ratio (WHR) (5.1-fold), and high percentage body fat (PBF) (2.9-fold) in the baseline were significantly associated with increased risk for incidence-CI. However, none of the biochemical variables posed any significantly increased risk for the incidence of CI. Conclusion: The present study is the first of its kind follow-up study on CI in India, which evaluated the incidence rate and associated risk factors for the incidence of CI in the population. The study revealed a substantial incidence rate of CI in the studied population and found illiteracy, high WHR, and high PBF to be associated with the incidence of CI

Metal alkoxides as versatile precursors for group 4 phosphonates: synthesis and X-ray structure of a novel organosoluble zirconium phosphonate

Reactions of Ph<SUB>2</SUB>P(O)(OH) and t-BuP(O)(OSiMe<SUB>3</SUB>)(OH) with Ti(O-i-Pr)<SUB>4</SUB> in equimolar ratios gave titanium phosphonates of the type [(O-i-Pr)<SUB>3</SUB>Ti(&#956; -O)<SUB>2</SUB>PR<SUP>1</SUP>R<SUP>2</SUP>]<SUB>2</SUB> (1, R<SUP>1</SUP> = R<SUP>2</SUP> = Ph; 2, R<SUP>1</SUP> = t-Bu, R<SUP>2</SUP> = OSiMe<SUB>3</SUB>) as colorless crystalline solids in moderate yields. Reactions of Ph<SUB>2</SUB>P(O)(OH) and the isopropoxides of zirconium and hafnium resulted in products of the composition [(O-i-Pr)<SUB>3</SUB>M(&#956; -O-i-Pr)<SUB>2</SUB>(&#956; -OPOPh<SUB>2</SUB>)M(O-i-Pr)<SUB>2</SUB>]Ph<SUB>2</SUB>P(O)(OH) (M = Zr (3), Hf (4)) in high yields. The compounds were characterized by <SUP>1</SUP>H, <SUP>31</SUP>P, and <SUP>29</SUP>Si NMR, infrared (IR), and mass spectroscopic (MS) techniques. The molecular structures of 2 and 3 were confirmed by X-ray crystallography