A prospective randomised study comparing intermittent intramuscular regimen and intravenous infusion regimen of magnesium sulfate in the treatment of severe preclampsia and eclampsia

Background: Eclampsia and preeclampsia are important causes of mortality during childbirth and puerperium. Commonly used regimens of magnesium sulfate are i.m. Pritchard regimen and i.v. zuspan regimen. This study was done with aim to compare the efficacy of i.m. regimen with i.v. regimen for prevention and recurrence of seizures.Methods: This study was carried out in the department of obstetrics and gynaecology, in a medical college in north India. 88 patients presenting with pre-eclampsia and eclampsia were included. Duration of the study was 18 months (from 1st October 2017-31st March 2019). The patients enrolled were classified randomly into two groups, group A and group B. Our target was to include 50 patients in both groups but few patients left against medical advice and not all patients met inclusion criteria group A was given the following regimen- loading dose of magnesium sulfate 4 gm MgSO4 in 12 ml normal saline slow intravenous infusion in 10-15 minutes and 5 gm MgSO4 deep intramuscular route each buttock, then maintenance dose of magnesium sulfate 5 gm alternate buttock group B was given- loading dose of magnesium sulfate 4 gm MgSO4 in 12 ml normal saline slow i.v. infusion in 10-15 minutes then maintainence dose of magnesium sulfate i.v infusion 1 gm/hr.Results: There was no significant difference between serum Mg2+ levels measure at 0 hours (baseline), 2 hours, 4 hours, 6 hours and 8 hours after administration of loading dose in both groups.Conclusions: The intermittent i.m. regimen and i.v. infusion regimen are comparable in terms of recurrence and prevention of seizure, maternal and neonatal outcome

Drug Trafficking Routes and Hepatitis B in Injection Drug Users, Manipur, India

Prevalence of hepatitis B genotype C in injection drug users in the northeastern Indian state of Manipur, neighboring the "Golden Triangle," correlates well with overland drug-trafficking routes, the injection drug use epidemic, and the spread of HIV. Further spread to other regions of India through mobile populations is possible

Quantum Deep Hedging

Quantum machine learning has the potential for a transformative impact across industry sectors and in particular in finance. In our work we look at the problem of hedging where deep reinforcement learning offers a powerful framework for real markets. We develop quantum reinforcement learning methods based on policy-search and distributional actor-critic algorithms that use quantum neural network architectures with orthogonal and compound layers for the policy and value functions. We prove that the quantum neural networks we use are trainable, and we perform extensive simulations that show that quantum models can reduce the number of trainable parameters while achieving comparable performance and that the distributional approach obtains better performance than other standard approaches, both classical and quantum. We successfully implement the proposed models on a trapped-ion quantum processor, utilizing circuits with up to $16$ qubits, and observe performance that agrees well with noiseless simulation. Our quantum techniques are general and can be applied to other reinforcement learning problems beyond hedging

Autism community priorities in diverse low-resource settings: a country-wide scoping exercise in India

While studies to map the priorities of the autistic community have been undertaken in some high-income countries, there has been little or no such systematic assessment in the global south. India alone is home to an estimated >5 million autistic individuals. To address this gap in the literature, this study conducted a survey of the Indian autism community on their priorities for three areas: skills training, intervention and research. Individuals with a clinical diagnosis of autism spectrum disorders and parents/guardians of autistic individuals were invited to take part in the study. Data from 280 respondents were collected online and followed up with interviews on a subset (n = 40) chosen through stratified random selection. Results highlighted a unanimous prioritisation for self-help skills as the most important area in skills training, as it was considered the foundation for acquiring all other skills. Speech and language therapy was identified as the most important intervention for autistic individuals. Within research, identifying the most effective ways for the community to support autistic people was given the topmost priority. Researchers, clinicians and policymakers may use these insights to develop services and shape future research that is more in accord with the community’s needs

Fifteen-year incidence rate and risk factors of pterygium in the Southern Indian state of Andhra Pradesh.

PURPOSE: To report 15-year incidence rate and associated risk factors of pterygium among people aged 30 years and above at baseline in the rural clusters of longitudinal Andhra Pradesh Eye Disease Study (APEDS III). METHODS: The baseline APEDS I included 7771 participants of which 6447 (83%) were traced and 5395 (83.7%) were re-examined in APEDS III. To estimate the incidence of pterygium, we selected participants who were 30 years and above at baseline (4188), of which 2976 were traced and 2627 (88.3%) were examined, and based on inclusion criteria, 2290 participants were included in the study. The incidence rate of pterygium was defined as the proportion of people free of pterygium at baseline who had developed the condition at 15-year follow-up (range 13-17 years). Univariate and multivariable analyses for risk factors were undertaken. RESULTS: The sex-adjusted incidence rate of pterygium was 25.2 per 100 person-years (95% CI 24.8 to 25.7) which was significantly higher for men than women (26.3 per 100 person-years (95% CI 25.6 to 27.0) and 24.7 (95% CI 24.1 to 25.3) respectively). At the multivariable analysis, male gender (RR: 1.35, 95% CI 1.0 to 1.83), no formal education (RR: 2.46, 95% CI 1.22 to 4.93), outdoor occupation (RR: 1.47, 95% CI 1.14 to 1.9) and lower body mass index (BMI) (<18.5) (RR: 1.25, 95% CI 1.02 to 1.55) were associated with increased risk of pterygium. CONCLUSIONS: The overall incidence rate of pterygium was high in this rural population, especially in men and those engaged in outdoor activities, lack of formal education and with lower BMI. It is likely that greater exposure to ultraviolet light is a major contributing factor, thus warranting preventive strategies

Incidence, Incident Causes, and Risk Factors of Visual Impairment and Blindness in a Rural Population in India: 15-Year Follow-up of the Andhra Pradesh Eye Disease Study.

PURPOSE: To report 15-year incidence rate of visual loss (blindness and visual impairment [VI]), causes, and risk factors for participants in Andhra Pradesh Eye Disease Study III (APEDS III). DESIGN: Population-based cohort study. METHODS: From 2012 to 2016, all rural participants were interviewed and underwent a comprehensive eye examination, including dilated fundus examination and imaging. Presenting visual acuity (PVA) and best-corrected visual acuity (BCVA) were measured using a standard logarithm of Minimum Angle of Resolution chart at 3 meters. World Health Organization (WHO) and United States of America (USA) categories of VI and blindness were used. Incident visual loss was defined as the development of or worsening of visual loss of one or more categories. RESULTS: In APEDS I, 7,771 rural participants were examined using stratified, random-cluster systematic sampling; in APEDS III, 5,395 participants (69.4% of rural or 52.4% of total participants) were re-examined. Using WHO categories, the crude incidence rate of any visual loss based on PVA and BCVA were 14.6 (95% confidence interval [CI]:13.6-15.7) and 6.3 (95% CI: 6.1-6.4) per 100 person-years, respectively. Using USA criteria, the values were 22.6 (95% CI: 22.3-23.0) and 10.6 (95% CI: 10.3-10.8) per 100 person-years, respectively. More than 90% of visual loss was attributable to cataract and uncorrected refractive error. Using WHO categories, significant independent risk factors for the incident visual loss were increasing age, female gender, illiteracy, past or current smoker, and current use of alcohol. Using the USA definition, an additional risk factor was lower level of education. CONCLUSIONS: The high incidence likely reflects poor access to eye care in this population, which needs to be taken into account when planning eye care programs

Fifteen-Year Incidence Rate of Primary Angle Closure Disease in the Andhra Pradesh Eye Disease Study.

PURPOSE: To report on the 15-year incidence of primary angle closure disease (PACD) among participants aged ≥40 years in rural southern India DESIGN: Population-based longitudinal incidence rate study METHODS: Setting: 3 rural study centres. STUDY POPULATION: Phakic participants aged ≥40 years who participated in both examination time points. OBSERVATION PROCEDURES: All participants at the baseline and at the mean 15-year follow-up visit underwent a detailed interview, anthropometry, blood pressure measurement, and comprehensive eye examination. Automated perimetry was attempted based on predefined criteria. Main outcome measures included development of any form of PACD, as defined by the International Society for Geographical and Epidemiological Ophthalmology (ISGEO), during the follow-up period in phakic participants, who did not have the disease at baseline. RESULTS: We analyzed data obtained from 1,197 (81.4% out of available 1,470) participants to calculate the incidence of the disease. The mean age (standard deviation) of the study participants at the baseline was 50.2 (8.1) years, with 670 male (45.5%) and 800 female (54.4%) participants. The incidence rate per 100 person-years (95% confidence interval) for primary angle closure suspect, primary angle closure, and primary angle closure glaucoma was 8.8 (8.4, 9.2), 6.2 (5.9, 6.6), and 1.6 (1.4, 1.8), respectively. Thus, the incidence of all forms of PACD was 16.4 (15.9, 17) per 100 person-years. On logistic regression analysis, female gender was a significant risk factor whereas presence of myopia was protective. CONCLUSIONS: This study reports long-term incidence of PACD from rural India. It has implications for eye health care policies, strategies, and planning

Molecular association of glucose-6- phosphate isomerase and pyruvate kinase M2 with glyceraldehyde-3-phosphate dehydrogenase in cancer cells

Background: For a long time cancer cells are known for increased uptake of glucose and its metabolization through glycolysis. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a key regulatory enzyme of this pathway and can produce ATP through oxidative level of phosphorylation. Previously, we reported that GAPDH purified from a variety of malignant tissues, but not from normal tissues, was strongly inactivated by a normal metabolite, methylglyoxal (MG).Molecular mechanism behind MG mediated GAPDH inhibition in cancer cells is not well understood. Methods: GAPDH was purified from Ehrlich ascites carcinoma (EAC) cells based on its enzymatic activity. GAPDH associated proteins in EAC cells and 3-methylcholanthrene (3MC) induced mouse tumor tissue were detected by mass spectrometry analysis and immunoprecipitation (IP) experiment, respectively. Interacting domains of GAPDH and its associated proteins were assessed by in silico molecular docking analysis. Mechanism of MG mediated GAPDH inactivation in cancer cells was evaluated by measuring enzyme activity, Circular dichroism (CD) spectroscopy, IP and mass spectrometry analyses. Result: Here, we report that GAPDH is associated with glucose-6-phosphate isomerase (GPI) and pyruvate kinase M2 (PKM2) in Ehrlich ascites carcinoma (EAC) cells and also in 3-methylcholanthrene (3MC) induced mouse tumor tissue. Molecular docking analyses suggest C-terminal domain preference for the interaction between GAPDH and GPI. However, both C and N termini of PKM2 might be interacting with the C terminal domain of GAPDH. Expression of both PKM2 and GPI is increased in 3MC induced tumor compared with the normal tissue. In presence of 1 mM MG,association of GAPDH with PKM2 or GPI is not perturbed, but the enzymatic activity of GAPDH is reduced to 26.8 ± 5 % in 3MC induced tumor and 57.8 ± 2.3 % in EAC cells. Treatment of MG to purified GAPDH complex leads to glycation at R399 residue of PKM2 only, and changes the secondary structure of the protein complex. Conclusion: PKM2 may regulate the enzymatic activity of GAPDH. Increased enzymatic activity of GAPDH in tumor cells may be attributed to its association with PKM2 and GPI. Association of GAPDH with PKM2 and GPI could be a signature for cancer cells. Glycation at R399 of PKM2 and changes in the secondary structure of GAPDH complex could be one of the mechanisms by which GAPDH activity is inhibited in tumor cells by MG

Sitting at the edge: How biomolecules use hydrophobicity to tune their interactions and function

Water near hydrophobic surfaces is like that at a liquid-vapor interface, where fluctuations in water density are substantially enhanced compared to that in bulk water. Here we use molecular simulations with specialized sampling techniques to show that water density fluctuations are similarly enhanced, even near hydrophobic surfaces of complex biomolecules, situating them at the edge of a dewetting transition. Consequently, water near these surfaces is sensitive to subtle changes in surface conformation, topology, and chemistry, any of which can tip the balance towards or away from the wet state, and thus significantly alter biomolecular interactions and function. Our work also resolves the long-standing puzzle of why some biological surfaces dewet and other seemingly similar surfaces do not.Comment: 12 pages, 4 figure