Health effects of selected environmental Exposomes Across the Life courSe in Indian populations using longitudinal cohort studies: GEOHealth HEALS Study protocol.

INTRODUCTION: Air pollution presents a major public health threat to India, affecting more than three quarters of the country's population. In the current project, GEOHealth Health Effects of Selected Environmental Exposomes Across the Life CourSe-India, we aim to study the effect of environmental exposomes-fine particulate matter (PM2.5), nitrogen dioxide (NO2), ozone (O3) and extremes of temperature-on multiple health outcomes using a modified life course approach. The associated training grant aims to build capacity in India to address the unique environmental health problems. METHODS AND ANALYSIS: The project aims to (A) Develop exposure assessments in seven cities, namely Delhi, Chennai, Sonipat, Vizag, Pune, Hyderabad and Bikaner, for: (1) A fine-scale spatiotemporal model for multiple pollutants (PM2.5, NO2, O3, temperature); (2) Combined ground monitoring and modelling for major chemical species of ambient PM2.5 at seven cities; and (3) Personal exposure assessment in a subsample from the six cities, except Pune, and (B) Conduct health association studies covering a range of chronic non-communicable diseases and their risk factors leveraging a unique approach using interdigitating cohorts. We have assembled existing pregnancy, child, adolescent, adult and older adult cohorts across India to explore health effects of exposomes using causal analyses. We propose to use Bayesian kernel machine regression to assess the effects of mixtures of all pollutants including species of PM2.5 on health while accounting for potential non-linearities and interactions between exposures. This builds on earlier work that constructed a fine spatiotemporal model for PM2.5 exposure to study health outcomes in two Indian cities. ETHICS AND DISSEMINATION: Ethical clearance for conduct of the study was obtained from the Institutional Ethics Committee (IEC) of the Centre for Chronic Disease Control, and all the participating institutes and organisations. National-level permission was provided by the Indian Council of Medical Research. The research findings will be disseminated through peer-reviewed publications, policy briefs, print and social media, and communicating with the participating communities and stakeholders. Training of Indian scientists will build the capacity to undertake research on selected adverse environmental exposures on population health in India.

Highly Permeable Mixed Matrix Membranes for Gas Separation via Dual Defect-Engineered Zeolitic Imidazolate Framework-8.

Defect engineering of metal-organic frameworks (MOFs) is a promising strategy for tailoring the interfacial characteristics between MOFs and polymers, aiming to create high-performance mixed matrix membranes (MMMs). This study introduces a new approach using dual defective alkylamine (AA)-modulated zeolitic imidazolate framework-8 (DAZIF-8), to develop high-flux MMMs. Tributylamine (TBA) and triethylamine (TEA) monodentate ligands coordinate with zinc ions in varying compositions. A mixture of Zn(CH3COO)2·2H2O:2-methylimidazole (Mim):AA in a 1:1.75:5 molar ratio facilitates high-yield coordination between Zn and multiple organic ligands, including Zn-Mim, Zn-TEA, and Zn-TBA (>80%). Remarkably, DAZIF-8 containing 3 mol% TBA and 2 mol% TEA exhibits exceptional characteristics, such as a Brunauer-Emmett-Teller surface area of 1745 m2 g-1 and enhanced framework rigidity. Furthermore, dual Zn-AA coordination sites on the framework's outer surface enhance compatibility with the polyimide (PI) matrix through electron donor-acceptor interactions, enabling the fabrication of high-loading MMMs with excellent mechanical durability. Importantly, the PI/DAZIF-8 (60/40 w/w) MMM demonstrates an unprecedented 759% enhancement in ethylene (C2H4) permeability (281 Barrer) with a moderate ethylene/ethane (C2H4/C2H6) selectivity of 2.95 compared to the PI, surpassing the polymeric upper limit for C2H4/C2H6 separation.

Spontaneous α-C-H Carboxylation of Ketones by Gaseous CO2 at the Air-water Interface of Aqueous Microdroplets.

We present a catalyst-free route for the reduction of carbon dioxide integrated with the formation of a carbon-carbon bond at the air/water interface of negatively charged aqueous microdroplets, at ambient temperature. The reactions proceed through carbanion generation at the α-carbon of a ketone followed by nucleophilic addition to CO2. Online mass spectrometry reveals that the product is an α-ketoacid. Several factors, such as the concentration of the reagents, pressure of CO2 gas, and distance traveled by the droplets, control the kinetics of the reaction. Theoretical calculations suggest that water in the microdroplets facilitates this unusual chemistry. Furthermore, such a microdroplet strategy has been extended to seven different ketones. This work demonstrates a green pathway for the reduction of CO2 to useful carboxylated organic products.

Induced Migration of CO2 from Hydrate Cages to Amorphous Solid Water under Ultrahigh Vacuum and Cryogenic Conditions.

Restricted migration of reactive species limits chemical transformations within interstellar and cometary ices. We report the migration of CO2 from clathrate hydrate (CH) cages to amorphous solid water (ASW) in the presence of tetrahydrofuran (THF) under ultrahigh vacuum (UHV) and cryogenic conditions. Thermal annealing of sequentially deposited CO2 and H2O ice, CO2@H2O, to 90 K resulted in the partitioning of CO2 in 512 and 51262 CH cages (CO2@512, CO2@51262). However, upon preparing a composite ice film composed of CO2@512, CO2@51262 and THF distributed in the water matrix at 90 K, and annealing the mixture for 6 h at 130 K produced mixed CO2-THF CH, where THF occupied the 51264 cages (THF@51264) exclusively while CO2 in 51262 cages (CO2@51262) got transferred to the ASW matrix and CO2 in the 512 cages (CO2@512) remained as is. This cage-matrix exchange may create a more conducive environment for chemical transformations in interstellar environments.

Enzyme-substrate interactions in orotate-mimetic OPRT inhibitor complexes: a QM/MM analysis.

Orotate phosphoribosyltransferase (OPRT) catalyses the reversible phosphoribosyl transfer from α-D-5-phosphoribosyl-1-pyrophosphate (PRPP) to orotic acid (OA) to yield orotidine 5'-monophosphate (OMP) during the de novo synthesis of nucleotides. Numerous studies have reported the inhibition of this reaction as a strategy to check diseases like tuberculosis, malaria and cancer. Insight into the inhibition of this reaction is, therefore, of urgent interest. In this study, we implemented a QM/MM framework on OPRT derived from Saccharomyces cerevisiae to obtain insights into the competitive binding of OA and OA-mimetic inhibitors by quantifying their interactions with OPRT. 4-Hydroxy-6-methylpyridin-2(1H) one showed the best inhibiting activity among the structurally similar OA-mimetic inhibitors, as quantified from the binding energetics. Our analysis of protein-ligand interactions unveiled the association of this inhibitory ligand with a strong network of hydrogen bonds, a large contribution of hydrophobic contacts, and bridging water molecules in the binding site. The ortho-substituted CH3 group in the compound resulted in a large population of π-electrons in the aromatic ring of this inhibitor, supporting the ligand binding further.

Epidemiology and transmission dynamics of COVID-19 in two Indian states.

Although most cases of coronavirus disease 2019 (COVID-19) have occurred in low-resource countries, little is known about the epidemiology of the disease in such contexts. Data from the Indian states of Tamil Nadu and Andhra Pradesh provide a detailed view into severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission pathways and mortality in a high-incidence setting. Reported cases and deaths have been concentrated in younger cohorts than would be expected from observations in higher-income countries, even after accounting for demographic differences across settings. Among 575,071 individuals exposed to 84,965 confirmed cases, infection probabilities ranged from 4.7 to 10.7% for low-risk and high-risk contact types, respectively. Same-age contacts were associated with the greatest infection risk. Case fatality ratios spanned 0.05% at ages of 5 to 17 years to 16.6% at ages of 85 years or more. Primary data from low-resource countries are urgently needed to guide control measures.

On the ligand-free palladium cluster catalysed Suzuki-Miyaura reaction.

C-C cross coupling reactions have been widely used for developing synthesis protocols for pharmaceuticals and agricultural products in the past few decades. Of all the reported C-C cross coupling reactions, the Suzuki-Miyaura reaction is preferred because of its mild reaction conditions, the commercial availability of associated reagents and the ease of removal of boron containing by-products. Recently, Corma and co-workers [Leyva-Perez et al., Angew. Chem., 2013, 125, 11768] reported water-stabilized three- and four-atom Pd clusters as highly active catalytic species for C-C coupling reactions. The present work focuses on developing detailed mechanistic insights into the Suzuki-Miyaura reaction with Pd3 and Pd4 clusters utilizing density functional theory calculations. The role of the base in the reaction was analysed in this study, which was found to lower the activation barriers of transmetalation over both Pd3 and Pd4. Free energy landscapes for Suzuki-Miyaura coupling of bromobenzene and phenylboronic acid over Pd3 and Pd4 clusters were developed. The highest free energy barriers of 34.7 and 30.4 kcal mol-1 were observed for the oxidative addition over Pd3 and Pd4, respectively, indicating the oxidative addition as the rate limiting step. Detailed energetics conclusively proved the active nature of small-atom Pd clusters for catalyzing the Suzuki-Miyaura reaction.

COVID-19: Impact analysis and recommendations for power sector operation.

The demand of electricity has been reduced significantly due to the recent COVID-19 pandemic. Governments around the world were compelled to reduce the business activity in response to minimize the threat of coronavirus. This on-going situation due to COVID-19 has changed the lifestyle globally as people are mostly staying home and working from home if possible. Hence, there is a significant increase in residential load demand while there is a substantial decrease in commercial and industrial loads. This devastating situation creates new challenges in the technical and financial activities of the power sector and hence most of the utilities around the world initiated a disaster management plan to tackle this ongoing challenges/threats. Therefore, this study aims to investigate the global scenarios of power systems during COVID-19 along with the socio-economic and technical issues faced by the utilities. Then, this study further scrutinized the Indian power system as a case study and explored scenarios, issues and challenges currently being faced to manage the consumer load demand, including the actions taken by the utilities/power sector for the smooth operation of the power system. Finally, a set of recommendations are presented to support the government/policymakers/utilities around the world not only to overcome the current crisis but also to overcome future unforeseeable pandemic alike scenario.

Modelling photovoltaic soiling losses through optical characterization.

The accumulation of soiling on photovoltaic (PV) modules affects PV systems worldwide. Soiling consists of mineral dust, soot particles, aerosols, pollen, fungi and/or other contaminants that deposit on the surface of PV modules. Soiling absorbs, scatters, and reflects a fraction of the incoming sunlight, reducing the intensity that reaches the active part of the solar cell. Here, we report on the comparison of naturally accumulated soiling on coupons of PV glass soiled at seven locations worldwide. The spectral hemispherical transmittance was measured. It was found that natural soiling disproportionately impacts the blue and ultraviolet (UV) portions of the spectrum compared to the visible and infrared (IR). Also, the general shape of the transmittance spectra was similar at all the studied sites and could adequately be described by a modified form of the Ångström turbidity equation. In addition, the distribution of particles sizes was found to follow the IEST-STD-CC 1246E cleanliness standard. The fractional coverage of the glass surface by particles could be determined directly or indirectly and, as expected, has a linear correlation with the transmittance. It thus becomes feasible to estimate the optical consequences of the soiling of PV modules from the particle size distribution and the cleanliness value.

Association of trans fatty acids with lipids and other cardiovascular risk factors in an Indian industrial population.

OBJECTIVE: Trans-fat, an invariable component of industrial fat is considered as one of the major dietary factors associated with CVD. Although the use of trans-fat is completely banned in some of the high-income countries where the CVD epidemic is declining, it is widely used in LMIC. We aimed to investigate the association of trans fatty acid in serum with risk markers of CVD in an industrial population in India. Participants were randomly selected from a study conducted in an industrial setting among employees and their family members. Information related to their demographic profile, anthropometric measurements, oil intake were recorded. Fasting samples were collected and stored at - 80 °C for analysis. Their lipid profile and hs CRP were measured and fatty acids analyzed using gas chromatography (GC) with flame ionization detector (FID). RESULTS: Complete data was available for 176 participants. Among trans fatty acids, mono trans fatty acid was significant predictor of serum triglycerides [Unadjusted ß (95% CI) 22.9 (2.6, 43.2); Adjusted ß (95% CI) 20.4 (3.5, 37.3)]. None of the other trans fatty acids either individually or in group correlated with any of the biochemical markers studied.

Clinical outcomes of hepatitis C treatment before and after kidney transplantation and its impact on time to transplant: A multicenter study.

Waitlist time for kidney transplantation is long but may be shortened with the utilization of hepatitis C positive allografts. We retrospectively reviewed the course of 36 hepatitis C positive patients awaiting kidney transplantation at 2 large centers within the same health system, with near-identical care delivery models with the exception of timing of hepatitis C treatment, to determine the impact of timing of hepatitis C treatment on access to transplant, waitlist time, and treatment efficacy and tolerability. The majority of patients had hepatitis C genotype 1a or 1b, and all received direct acting antiviral therapy with 100% treatment response. One patient underwent transplantation in the pretransplant treatment group. The 1-year transplantation rate was 12.5% vs 67.9% (P = .0013) in those treated posttransplantation. The median waitlist time in the posttransplant group was 122 (interquartile range [IQR] 21.5, 531.0) days, which was significantly shorter than the center's regional and national wait time. Pathologic review revealed no difference in allograft quality. Overall treatment related adverse events were not different between the 2 groups. A strategy of posttransplant hepatitis C treatment increased access to transplant and reduced waitlist time. Delaying treatment until after transplant did not appear to adversely affect recipients' kidney allograft or overall survival.

Abnormal Nuclear Variations in Response to Radiotherapy- As a Tool in Treatment Planning and Assessment of Prognosis.

INTRODUCTION: The treatment approaches for oral squamous cell carcinoma (OSCC) include single management with surgery, radiotherapy, along with chemotherapy or various combinations of these modalities. The estimation of radio sensitivity of individual tumours is essential for planning the optimum radiation schedule for each patient. Assessment of radiation induced histo morphological changes in the nucleus is a known marker of radiosensitivity. AIM: The aim of this study was to establish the relationship between nuclear changes with radiation dose and to investigate the prospect of utilizing them as an assay to predict tumour response to radiotherapy in oral cancers. MATERIALS AND METHODS: The present study included 50 patients (age range of 30-65yrs) with histopathologically confirmed squamous cell carcinoma of oral mucosa and being treated by radiotherapy alone with a radiation dose schedule of 4, 14, 24 and 60 Gy respectively at 2(nd), 7(th), 12(th) and 30(th) day. From the included patients, smear of the buccal mucosa was collected and was air dried and fixed with methanol. The Nuclear changes of Micronucleus (MN), Nuclear Budding (NB) and Multinucleation (MNU) were evaluated under the bright field microscopy after staining with Giemsa and May-Grunwald's stain. RESULTS: Out of the 50, 37(74%) were males and 13(26%) were females (Ratio 3:1). The mean percentage increase of MN and MNU were found to be statistically significant (p=0.001) when compared with pre-treatment day. Similar findings were seen with NB, except between pretreatment and after 14 Gy (p-0.110). In the present study the measurement of relative increment index done in respect to all nuclear abnormalities show a sustained increase with increasing dosage of radiation. CONCLUSION: The present study, was undertaken to explore the possibility of establishing a relationship between the frequencies of nuclear abnormalities in patients with oral cancer with applied dosage and duration of radiotherapy. The progressive increase in Micronucleus and Multinucleation indices with increasing dose of radiation proves that these parameters can be used as indicators for assessing the response of tumour for radiotherapy. These parameters can be used as prognostic indicator in oral carcinoma cases undergoing radiotherapy.

Do Patient Assessments of Hospital Quality Correlate With Kidney Transplantation Surgical Outcomes?

BACKGROUND: Currently, transplant patients have limited metrics available to understand transplant center quality. Graft and patient survival do not capture the patient experience, and patients may use more general consumer assessments of hospital care to help select transplant centers. We evaluated whether consumer assessments of hospital quality correlate with short- and long-term kidney transplant center performance. MATERIALS AND METHODS: CMS uses the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) to publicly report patients' perspectives on hospital care. We merged 2012 SRTR kidney transplant (n = 200 centers), HCAHPS and American Hospital Association survey data. Center performance was determined by variation in observed-to-expected (O/E) ratios for 1-month and 1-year graft failure. We used multivariate regression to determine whether HCAHPS measures correlate with center performance, after risk-adjusting for structural characteristics and volume. RESULTS: Center-specific graft failure varied significantly (30 day O/E range: 0-4.1). At 30 days, compared to average centers, cleanliness (OR = 1.26, P = .001), patient recommendation (OR = 1.18, P = .005), and high overall ratings (OR = 1.11, P = .036) predicted high performance. Poor nursing-patient communication (OR = 0.70, P = .030), lower cleanliness (OR = 0.67, P < .001), poor overall ratings (OR = 0.79, P = .038), and no recommendation (OR = 0.68, P = .019) correlated with average/low performance. There was no significant correlation between HCAHPS measures and 1-year outcomes. CONCLUSIONS: The association between hospital consumer assessments of hospital care and center performance after kidney transplantation is limited. More specific metrics oriented to capturing transplant patient perspectives may be valuable in further defining transplant quality.

Change in the Quality of Life in Oropharyngeal, Laryngeal and Hypopharyngeal Cancer Patients treated with Volumetric Modulated Arc-Based Concomitant Boost Radiotherapy.

OBJECTIVE: To assess the change in the quality of life (QOL) in Oropharyngeal, Laryngeal and Hypopharyngeal cancer patients treated with concomitant boost radiotherapy by Volumetric Intensity Modulated Arc Therapy (VMAT) technique. METHODS: Thirty patients with oropharynx, larynx or hypopharynx cancers of stage II to IVA were treated with an Accelerated fractionation schedule using Concomitant boost. The dose given was 1.8Gy/fraction daily, 5 days a week to the large field for 28 fractions and a daily concomitant boost of 1.5Gy/fraction to the boost field over the last 12 treatment days for a total dose of 68.4Gy/40 fractions/5½weeks by VMAT technique with concurrent chemotherapy (in stage III and IV patients) using Cisplatin 100mg/m2 IV three weekly during week 1 and week 4 of irradiation. QOL was assessed using the European Organization of Research and Treatment of Cancer Quality of Life Core Questionnaire, version 3.0 (EORTC QLQC30) and EORTC head and neck module (EORTC QLQ-HN35) before treatment, at the end of treatment, 1 month, 3 months and 6 months post treatment. The QOL scores and their evolution over the five measurements were calculated. RESULTS: The change in the QOL scores was acceptable in general. There was a significant reduction in quality of life scores at the end of treatment. The QOL improved in the followup period; and by 3 months post irradiation, there was a return of QOL scores to the baseline value. CONCLUSION: The QOL scores indicate that concomitant boost radiotherapy by VMAT is well tolerated and helps in rapid return to baseline quality of life scores. We believe that this is one of the first papers which have combined concomitant boost radiotherapy with VMAT technique in head and neck cancers. VMAT based concomitant boost radiotherapy helps in rapid return to baseline quality of life.

Increasing the Use of Kidneys From Unconventional and High-Risk Deceased Donors.

In this paper, we have reviewed the literature and report on kidney donors that are currently used at relatively low rates. Kidneys from donors with acute kidney injury (AKI) seem to have outcomes equivalent to those from donors without AKI, provided one can rule out significant cortical necrosis. Kidneys from donors with preexisting diabetes or hypertension may have marginally lower aggregate survival but still provide patients with a significant benefit over remaining on the wait list. The Kidney Donor Profile Index derives only an aggregate association with survival with a very modest C statistic; therefore, the data indicated that this index should not be the sole reason to discard a kidney, except perhaps in patients with extremely low estimated posttransplant survival scores. It is important to note that the Scientific Registry of Transplant Recipients models of risk adjustment should allay concerns regarding regulatory issues for observed outcomes falling below expectations. The successful utilization of kidneys from donation after cardiac death over the past decade shows how expanding our thinking can translate into more patients benefiting from transplantation. Given the growing number of patients on the wait list, broadening our approach to kidney acceptance could have an important impact on the population with end-stage renal disease. Many lives could be prolonged by carefully considering use of kidneys that are often discarded.

Understanding tenderness variability and ageing changes in buffalo meat: biochemical, ultrastructural and proteome characterization.

Understanding of biological impact of proteome profile on meat quality is vital for developing different approaches to improve meat quality. Present study was conducted to unravel the differences in biochemical, ultrastructural and proteome profile of longissimus dorsi muscle between buffaloes (Bubalus bubalis) of different age groups (young v. old). Higher (P<0.05) myofibrillar and total protein extractability, muscle fibre diameter, and Warner-Bratzler shear force (WBSF) values was observed in old buffalo meat relative to meat from young buffaloes. Scanning electron microscopy photographs revealed reduced fibre size with increased inter-myofibrillar space in young compared with old buffalo meat. Transmission electron microscopy results revealed longer sarcomeres in young buffalo meat relative to meat from old buffaloes. Proteomic characterization using two-dimensional gel electrophoresis (2DE) found 93 differentially expressed proteins between old and young buffalo meat. Proteome analysis using 2DE revealed 191 and 95 differentially expressed protein spots after 6 days of ageing in young and old buffalo meat, respectively. The matrix assisted laser desorption ionization time-of flight/time-of flight mass spectrometry (MALDI-TOF/TOF MS) analysis of selected gel spots helped in identifying molecular markers of tenderness mainly consisting of structural proteins. Protein biomarkers identified in the present study have the potential to differentiate meat from young and old buffaloes and pave the way for optimizing strategies for improved buffalo meat quality.

Rapid Resolution of Donor-Derived Glomerular Fibrin Thrombi After Deceased Donor Kidney Transplantation.

The aim of this study was to determine the clinical and histologic outcomes related to transplanting kidneys from deceased donors with glomerular fibrin thrombi (GFT). We included all cases transplanted between October 2003 and October 2014 that had either a preimplantation biopsy or an immediate postreperfusion biopsy showing GFT. The study cohort included 61 recipients (9.9%) with GFT and 557 in the control group without GFT. Delayed graft function occurred in 49% of the GFT group and 39% in the control group (p = 0.14). Serum creatinine at 1, 4, and 12 months and estimated GFR at 12 months were similar in the two groups. Estimated 1-year graft survival was 93.2% in the GFT group and 95.1% in the control group (p = 0.22 by log-rank). Fifty-two of the 61 patients in the GFT group (85%) had a 1-month protocol biopsy, and only two biopsies (4%) showed residual focal glomerular thrombi. At the 1-year protocol biopsy, the prevalence of moderate to severe interstitial fibrosis and tubular atrophy was 24% in the GFT group and 30% in the control group (p = 0.42). We concluded that GFT resolves rapidly after transplantation and that transplanting selected kidneys from deceased donors with GFT is a safe practice.

Global health governance - the next political revolution.

The recent Ebola crisis has re-opened the debate on global health governance and the role of the World Health Organization. In order to analyze what is at stake, we apply two conceptual approaches from the social sciences - the work on gridlock and the concept of cosmopolitan moments - to assess the ability of the multilateral governance system to reform. We find that gridlock can be broken open by a health crisis which in turn generates a political drive for change. We show that a set of cosmopolitan moments have led to the introduction of the imperative of health in a range of policy arenas and moved health into 'high politics' - this has been called a political revolution. We contend that this revolution has entered a second phase with increasing interest of heads of state in global health issues. Here lies the window of opportunity to reform global health governance.