Effect of Air Pollution on the Occurrences and Death of COVID-19

Air contamination continues to be the leading environmental risk factor for all causes of death, leading to substantial years of lives and economic decline adapted to incapacity increased deaths in air pollution in past pandemics, in 1918, Spanish Flu and in 2003 with SARS-CoV-1. The host susceptibility and respiratory virulence are increased and viral clearance is decreased. Therefore, there is a question about the effect of air contamination on the current 2019 coronavirus pandemic (COVID-19). History and research have until now been concerned with the huge potential consequences of the COVID-19 air pollution pandemic. In order to validate this correlation, more epidemiological and environmental research is necessary. Moreover, countries must leverage air emissions reduction funds to benefit their wellbeing and enhance their possible impact on future pandemics

Proposal for creating a centre for research in solar-terrestrial physics as an interdepartmental activity during IHY at Shivaji University, Kolhapur (16.40°N, 74.15°E)

This note describes teaching and R & D activities presently being carried out in the solar-terrestrial Physics at the Space Science laboratory, Department of Physics, Shivaji University, Kolhapur. A variety of solar and geophysical ground based experiments are available, which can be operated on a regular basis during IHY, with financial help from the government funding agencies in India. The main purpose of this note is to briefly describe our experimental research facilities of relevance to IHY

Human heterochromatin protein 1 isoforms HP1(Hsα) and HP1(Hsβ) interfere with hTERT-telomere interactions and correlate with changes in cell growth and response to ionizing radiation

Telomeres are associated with the nuclear matrix and are thought to be heterochromatic. We show here that in human cells the overexpression of green fluorescent protein-tagged heterochromatin protein 1 (GFP-HP1) or nontagged HP1 isoforms HP1(Hsα) or HP1(Hsβ), but not HP1(Hsγ), results in decreased association of a catalytic unit of telomerase (hTERT) with telomeres. However, reduction of the G overhangs and overall telomere sizes was found in cells overexpressing any of these three proteins. Cells overexpressing HP1(Hsα) or HP1(Hsβ) also display a higher frequency of chromosome end-to-end associations and spontaneous chromosomal damage than the parental cells. None of these effects were observed in cells expressing mutants of GFP-ΔHP1(Hsα), GFP-ΔHP1(Hsβ), or GFP-ΔHP1(Hsγ) that had their chromodomains deleted. An increase in the cell population doubling time and higher sensitivity to cell killing by ionizing radiation (IR) treatment was also observed for cells overexpressing HP1(Hsα) or HP1(Hsβ). In contrast, cells expressing mutant GFP-ΔHP1(Hsα) or GFP-ΔHP1(Hsβ) showed a decrease in population doubling time and decreased sensitivity to IR compared to the parental cells. The effects on cell doubling times were paralleled by effects on tumorigenicity in mice: overexpression of HP1(Hsα) or HP1(Hsβ) suppressed tumorigenicity, whereas expression of mutant HP1(Hsα) or HP1(Hsβ) did not. Collectively, the results show that human cells are exquisitely sensitive to the amount of HP1(Hsα) or HP1(Hsβ) present, as their overexpression influences telomere stability, population doubling time, radioresistance, and tumorigenicity in a mouse xenograft model. In addition, the isoform-specific effects on telomeres reinforce the notion that telomeres are in a heterochromatinized state

Growth factor release from a chemically modified elastomeric poly(1,8‐octanediol‐co‐citrate) thin film promotes angiogenesis in vivo

The ultimate success of in vivo organ formation utilizing ex vivo expanded “starter” tissues relies heavily upon the level of vascularization provided by either endogenous or artificial induction of angiogenic or vasculogenic events. To facilitate proangiogenic outcomes and promote tissue growth, an elastomeric scaffold previously shown to be instrumental in the urinary bladder regenerative process was modified to release proangiogenic growth factors. Carboxylic acid groups on poly(1,8‐octanediol‐co‐citrate) films (POCfs) were modified with heparan sulfate creating a heparan binding POCf (HBPOCf). Release of proangiogenic growth factors vascular endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF2), and insulin‐like growth factor 1 (IGF‐1) from HBPOCfs demonstrated an approximate threefold increase over controls during a 30‐day time course in vitro . Atomic force microscopy demonstrated significant topological differences between films. Subcutaneous implantation of POCf alone, HBPOCf, POCf‐VEGF, and HBPOCf‐VEGF within the dorsa of nude rats yielded increased vascular growth in HBPOCf‐VEGF constructs. Vessel quantification studies revealed that POCfs alone contained 41.1 ± 4.1 vessels/mm 2 , while HBPOCf, POCf‐VEGF, and HBPOCF‐VEGF contained 41.7 ± 2.6, 76.3 ± 9.4, and 167.72 ± 15.3 vessels/mm 2 , respectively. Presence of increased vessel growth was demonstrated by CD31 and vWF immunostaining in HBPOCf‐VEGF implanted areas. Data demonstrate that elastomeric POCfs can be chemically modified and possess the ability to promote angiogenesis in vivo . © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90248/1/33306_ftp.pd

Plant breeding increases spring wheat yield potential in Afghanistan

Wheat (Triticum aestivum L.) is an essential food security crop in Afghanistan. To determine the contribution of wheat breeding to increasing productivity, we analyzed data obtained from 192 trials conducted over 11 locations from 2002–2003 to 2015–2016. Using this data, we estimated annual genetic gains for grain yield, days to heading and plant height over the 14-yr period. We used best linear unbiased estimates to measure genetic gains across CIMMYT Elite Spring Wheat Yield Trials per se and for the top 5 and top 10% performing genotypes relative to checks. Mean realized genetic gain for grain yield was 115 kg ha–1 yr−1, whereas the top 10 genotypes achieved annual yield gains of 123 kg ha–1. The continually replaced local check. s also contributed an annual genetic gain for yield of 107 kg ha–1. The associated adaptive traits days to heading and plant height varied in their response over time with the top 10 yielding genotypes having a 1.82 d annual reduction in heading date while plant height increased by 0.77 cm yr−1 for the same set of genotypes. Results show that continual breeding improvements confer yield gains, contributing to increasing Afghan wheat productivity. This has wider relevance for demonstrating the value of continued investment in public sector plant breeding supporting wheat production and food security in Central Asia

Unmet Diagnostic and Therapeutic Opportunities for COPD in Low- and Middle-Income Countries

RATIONALE: Chronic obstructive pulmonary disease (COPD) is a prevalent and burdensome condition in low- and middle-income countries (LMICs). Challenges to better care include more effective diagnosis, and access to affordable interventions. There are no previous reports describing therapeutic needs in LMIC populations with COPD identified through screening. OBJECTIVE: To describe unmet therapeutic need in screening-detected COPD in LMIC settings. METHODS: We compared interventions recommended by the international 'GOLD' COPD strategy document, with that received, in 1000 people with COPD identified by population screening at three LMIC sites in Nepal, Peru and Uganda. We calculated costs using data on the availability and affordability of medicines. MEASUREMENT AND MAIN RESULTS: The greatest unmet need for non-pharmacological interventions was for education and vaccinations (applicable to all), pulmonary rehabilitation (49%), smoking cessation (30%) and advice on biomass smoke exposure (26%). 95% of cases were previously undiagnosed and few were receiving therapy (4.5% had short-acting beta-agonists). Only three of 47 people (6%) with a previous COPD diagnosis had access to drugs consistent with recommendations. None of those with more severe COPD were accessing appropriate maintenance inhalers. Even when available, maintenance treatments were unaffordable with 30 days of treatment more than a low-skilled workers' daily average wage. CONCLUSION: We found significant missed opportunity to reduce the burden of COPD in LMIC settings, with most cases undiagnosed. Whilst there is unmet need in developing novel therapies, in LMICs where the burden is greatest, better diagnosis together with access to affordable interventions could translate to immediate benefit. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/)

Novel seleno-aspirinyl compound AS-10 induces apoptosis, G1 arrest of pancreatic ductal adenocarcinoma cells, inhibits their NF-kappa B signaling and synergizes with gemcitabine cytotoxicity

Current available therapies for pancreatic ductal adenocarcinoma (PDAC) provide minimal overall survival benefits and cause severe adverse effects. We have identified a novel molecule AS-10, a selenazolidine-bis-aspirinyl derivative, that was two to three orders of magnitude more potent than aspirin and at least one to two orders of magnitude more potent than gemcitabine in inhibiting PDAC cancer cell growth/viability against three PDAC cell lines while sparing mouse embryonic fibroblasts in the same exposure range. In Panc-1 cells, AS-10 induced apoptosis without necrosis, principally through caspase-3/7 cascade and reactive oxygen species, in addition to an induction of G1 cell cycle block. Transcriptomic profiling with RNA-seq indicated the top responses to AS-10 exposure as CDKN1A (P21Cip1), CCND1, and nuclear transcription factor-kappa B (NF-B) complex and the top functions as cell cycle, cell death, and survival without inducing the DNA damage gene signature. AS-10 pretreatment (6 h) decreased cytokine tumor necrosis factor-alpha (TNF-)-stimulated NF-B nuclear translocation, DNA binding activity, and degradation of cytosolic inhibitor of B (IB) protein. As NF-B activation in PDAC cells confers resistance to gemcitabine, the AS-10 combination with gemcitabine increased the in vitro cytotoxicity more than the additivity of both compounds. Overall, our results suggest AS-10 may be a promising drug lead for PDAC, both as a single agent and in combination therapy

Preliminary physiologically based pharmacokinetic models for benzo[a]pyrene and dibenzo[def,p]chrysene in rodents

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants generated as byproducts of natural and anthropogenic combustion processes. Despite significant public health concern, physiologically based pharmacokinetic (PBPK) modeling efforts for PAHs have so far been limited to naphthalene, plus simpler PK models for pyrene, nitropyrene, and benzo[a]pyrene (B[a]P). The dearth of published models is due in part to the high lipophilicity, low volatility, and myriad metabolic pathways for PAHs, all of which present analytical and experimental challenges. Our research efforts have focused upon experimental approaches and initial development of PBPK models for the prototypic PAH, B[a]P, and the more potent, albeit less studied transplacental carcinogen, dibenzo[def,p]chrysene (DBC). For both compounds, model compartments included arterial and venous blood, flow limited lung, liver, richly perfused and poorly perfused tissues, diffusion limited fat, and a two compartment theoretical gut (for oral exposures). Hepatic and pulmonary metabolism was described for both compounds, as were fractional binding in blood and fecal clearance. Partition coefficients for parent PAH along with their diol and tetraol metabolites were estimated using published algorithms and verified experimentally for the hydroxylated metabolites. The preliminary PBPK models were able to describe many, but not all, of the available data sets, comprising multiple routes of exposure (oral, intravenous) and nominal doses spanning several orders of magnitude. Supported by Award Number P42 ES016465 from the National Institute of Environmental Health Sciences. Published by Elsevier Inc.Keywords: Metabolic activation, Gastrointestinal absorption, Cytochrome P450, Mouse skin, Benzo[a]Pyrene, Rat mammary gland, Ultimate carcinogens, Aromatic hydrocarbons, Tumor initiating activity, Partition coefficient

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: Update 2013

The Canadian Network for Mood and Anxiety Treatments published guidelines for the management of bipolar disorder in 2005, with updates in 2007 and 2009. This third update, in conjunction with the International Society for Bipolar Disorders, reviews new evidence and is designed to be used in conjunction with the previous publications.The recommendations for the management of acute mania remain largely unchanged. Lithium, valproate, and several atypical antipsychotic agents continue to be first-line treatments for acute mania. Monotherapy with asenapine, paliperidone extended release (ER), and divalproex ER, as well as adjunctive asenapine, have been added as first-line options.For the management of bipolar depression, lithium, lamotrigine, and quetiapine monotherapy, as well as olanzapine plus selective serotonin reuptake inhibitor (SSRI), and lithium or divalproex plus SSRI/bupropion remain first-line options. Lurasidone monotherapy and the combination of lurasidone or lamotrigine plus lithium or divalproex have been added as a second-line options. Ziprasidone alone or as adjunctive therapy, and adjunctive levetiracetam have been added as not-recommended options for the treatment of bipolar depression. Lithium, lamotrigine, valproate, olanzapine, quetiapine, aripiprazole, risperidone long-acting injection, and adjunctive ziprasidone continue to be first-line options for maintenance treatment of bipolar disorder. Asenapine alone or as adjunctive therapy have been added as third-line options. © 2012 John Wiley and Sons A/S