Effectiveness of respiratory face masks in reducing acute PM2.5 pollution exposure during peak pollution period in Delhi.

The cities of North India, such as Delhi, face a significant public health threat from severe air pollution. Between October 2021 and January 2022, 79 % of Delhi's daily average PM2.5 (Particulate matter with an aerodynamic diameter ≤ 2.5 µm) values exceeded 100 µg/m3 (the permissible level being 60 µg/m3 as per Indian standards). In response to this acute exposure, using Respiratory Face Masks (RFMs) is a cost-effective solution to reduce immediate health risks while policymakers develop long-term emission control plans. Our research focuses on the health and economic benefits of using RFMs to prevent acute exposure to PM2.5 pollution in Delhi for different age groups. Our findings indicate that, among the fifty chosen RFMs, M50 has greatest potential to prevent short-term excess mortality (908 in age ranges 5-44), followed by M49 (745) and M48 (568). These RFMs resulted in estimated economic benefits of 500.6 (46 %), 411.1 (37 %), and 313.4 (29 %) million Indian Rupee (INR), respectively during October-January 2021-22. By wearing RFMs such as M50, M49, and M48 during episodes of bad air quality, it is estimated that 13 % of short-term excess mortality and associated costs could be saved if at least 30 % of Delhi residents followed an alert issued by an operational Air Quality Early Warning System (AQEWS) developed by the Ministry of Earth Sciences. Our research suggests that RFMs can notably decrease health and economic burdens amid peak PM2.5 pollution in post-monsoon and winter seasons until long-term emission reduction strategies are adopted. It is suggested that an advisory may be crafted in collaboration with statutory bodies and should be disseminated to assist the vulnerable population in using RFMs during winter. The analysis presented in this research is purely science based and outcomes of study are in no way to be construed as endorsement of product.

Stubble-burning activities in north-western India in 2021: Contribution to air pollution in Delhi.

Stubble-burning in northern India is an important source of atmospheric particulate matter (PM) and trace gases, which significantly impact local and regional climate, in addition to causing severe health risks. Scientific research on assessing the impact of these burnings on the air quality over Delhi is still relatively sparse. The present study analyzes the satellite-retrieved stubble-burning activities in the year 2021, using the MODIS active fire count data for Punjab and Haryana, and assesses the contribution of CO and PM2.5 from such biomass-burning activities to the pollution load in Delhi. The analysis suggests that the satellite-retrieved fire counts in Punjab and Haryana were the highest among the last five years (2016-2021). Further, we note that the stubble-burning fires in the year 2021 are delayed by ∼1 week compared to that in the year 2016. To quantify the contribution of the fires to the air pollution in Delhi, we use tagged tracers for CO and PM2.5 emissions from fire emissions in the regional air quality forecasting system. The modeling framework suggests a maximum daily mean contribution of the stubble-burning fires to the air pollution in Delhi in the months of October-November 2021 to be around 30-35%. We find that the contribution from stubble burning activities to the air quality in Delhi is maximum (minimum) during the turbulent hours of late morning to afternoon (calmer hours of evening to early morning). The quantification of this contribution is critical from the crop-residue and air-quality management perspective for policymakers in the source and the receptors regions, respectively.

Sensitivity of WRF/Chem simulated PM2.5 to initial/boundary conditions and planetary boundary layer parameterization schemes over the Indo-Gangetic Plain.

The ability of a chemical transport model to simulate accurate meteorological and chemical processes depends upon the physical parametrizations and quality of meteorological input data such as initial/boundary conditions. In this study, weather research and forecasting model coupled with chemistry (WRF-Chem) is used to test the sensitivity of PM2.5 predictions to planetary boundary layer (PBL) parameterization schemes (YSU, MYJ, MYNN, ACM2, and Boulac) and meteorological initial/boundary conditions (FNL, ERA-Interim, GDAS, and NCMRWF) over Indo-Gangetic Plain (Delhi, Punjab, Haryana, Uttar Pradesh, and Rajasthan) during the winter period (December 2017 to January 2018). The aim is to select the model configuration for simulating PM2.5 which shows the lowest errors and best agreement with the observed data. The best results were achieved with initial/boundary conditions from ERA and GDAS datasets and local PBL parameterization (MYJ and MYNN). It was also found that PM2.5 concentrations are relatively less sensitive to changes in initial/boundary conditions but in contrast show a stronger sensitivity to changes in the PBL scheme. Moreover, the sensitivity of the simulated PM2.5 to the choice of PBL scheme is more during the polluted hours of the day (evening to early morning), while that to the choice of the meteorological input data is more uniform and subdued over the day. This work indicates the optimal model setup in terms of choice of initial/boundary conditions datasets and PBL parameterization schemes for future air quality simulations. It also highlights the importance of the choice of PBL scheme over the choice of meteorological data set to the simulated PM2.5 by a chemical transport model.

Orally Bioavailable Enzymatic Inhibitor of CD38, MK-0159, Protects against Ischemia/Reperfusion Injury in the Murine Heart.

CD38 is one of the major nicotinamide adenine dinucleotide (NAD+)- and nicotinamide adenine dinucleotide phosphate (NADP+)-consuming enzymes in mammals. NAD+, NADP+, and their reduced counterparts are essential coenzymes for numerous enzymatic reactions, including the maintenance of cellular and mitochondrial redox balance. CD38 expression is upregulated in age-associated inflammation as well as numerous metabolic diseases, resulting in cellular and mitochondrial dysfunction. Recent literature studies demonstrate that CD38 is activated upon ischemia/reperfusion (I/R), leading to a depletion of NADP+, which results in endothelial damage and myocardial infarction in the heart. Despite increasing evidence of CD38 involvement in various disease states, relatively few CD38 enzymatic inhibitors have been reported to date. Herein, we describe a CD38 enzymatic inhibitor (MK-0159, IC50 = 3 nM against murine CD38) that inhibits CD38 in in vitro assay. Mice treated with MK-0159 show strong protection from myocardial damage upon cardiac I/R injury compared to those treated with NAD+ precursors (nicotinamide riboside) or the known CD38 inhibitor, 78c.

Performance of high resolution (400 m) PM2.5 forecast over Delhi.

This study reports a very high-resolution (400 m grid-spacing) operational air quality forecasting system developed to alert residents of Delhi and the National Capital Region (NCR) about forthcoming acute air pollution episodes. Such a high-resolution system has been developed for the first time and is evaluated during October 2019-February 2020. The system assimilates near real-time aerosol observations from in situ and space-borne platform in the Weather Research and Forecasting model coupled with Chemistry (WRF-Chem) to produce a 72-h forecast daily in a dynamical downscaling framework. The assimilation of aerosol optical depth and surface PM2.5 observations improves the initial condition for surface PM2.5 by about 45 µg/m3 (about 50%).The accuracy of the forecast degrades slightly with lead time as mean bias increase from + 2.5 µg/m3 on the first day to - 17 µg/m3 on the third day of forecast. Our forecast is found to be very skillful both for PM2.5 concentration and unhealthy/ very unhealthy air quality index categories, and has been helping the decision-makers in Delhi make informed decisions.

How Much Does Large-Scale Crop Residue Burning Affect the Air Quality in Delhi?

Elevated PM2.5 concentrations frequently cause severe air pollution events in Delhi. Till recently, the effect of crop residue burning on the air quality in Delhi has not been fully quantified and the approaches to control the impact of fire emissions have not been effective. In this study, for the first time, we quantified the statewise contribution of post-monsoon crop residue burning in the northwestern states of India to surface PM2.5 concentrations in Delhi using several sensitivity experiments with the Weather Research and Forecasting model coupled with Chemistry (WRF-Chem) and FINNv1.5 fire emission inventory. Results were evaluated with ground-based observations in Delhi (21 stations), Punjab, and Haryana (14 stations). On average, ∼20% of PM2.5 concentration in Delhi during the post-monsoon season (October-November) was found to be contributed by nonlocal fire emissions. However, on typical air pollution events, fire emissions contributed as high as 50-75% (80-120 µg/m3) to PM2.5 in Delhi, highlighting the importance of both external transport and local emissions to PM2.5 pollution in Delhi.

An audit of clinician compliance with best practice recommendations to repair severe obstetric anal sphincter injuries.

CONTEXT: Obstetric anal sphincter injuries occur uncommonly in Caribbean practice but are accompanied by substantial morbidity. OBJECTIVE: To evaluate clinicians' compliance with management guidelines at a national referral hospital in Jamaica. DESIGN: Retrospective review of the records of all consecutive obstetric patients with anal sphincter injuries between November 1, 2007, and December 30, 2012. MAIN OUTCOME MEASURES: The primary end point was the completion of each of 8 tasks from existing management guidelines: 1) interdisciplinary consultation, 2) perineal examination with the patient under anesthesia, 3) injury repair in the operating room, 4) prophylactic antibiotics at induction, 5) repair by an experienced clinician, 6) repair method appropriate for injury grade, 7) slowly absorbable suture chosen for sphincter repair, and 8) rapidly absorbable suture for mucosal repair. We quantified clinician compliance with the guidelines by assigning a score of 1 for each task completed and 0 for an incomplete task. Individual task scores were summed. Clinicians were considered compliant when their overall score was above 6. RESULTS: Twenty-six women (mean age = 27 years; standard deviation = 5.78 years) had obstetric anal sphincter injuries. Nine cases (34.6%) earned clinician compliance scores above 6, and 17 (65.4%) had scores of 6 or below. Experienced clinicians repaired all the injuries in this study-the only task for which compliance was 100%. CONCLUSION: Despite attempts at improving therapeutic outcomes by creating tailored guidelines for repair of obstetric anal sphincter injuries, there is a serious barrier to success because 65% of senior clinicians were noncompliant.

Enantioselective synthesis and physicochemical properties of libraries of 3-amino- and 3-amidofluoropiperidines.

The enantioselective syntheses of 3-amino-5-fluoropiperidines and 3-amino-5,5-difluoropiperidines were developed using the ring enlargement of prolinols to access libraries of 3-amino- and 3-amidofluoropiperidines. The study of the physicochemical properties revealed that fluorine atom(s) decrease(s) the pKa and modulate(s) the lipophilicity of 3-aminopiperidines. The relative stereochemistry of the fluorine atoms with the amino groups at C3 on the piperidine core has a small effect on the pKa due to conformationnal modifications induced by fluorine atom(s). In the protonated forms, the C-F bond is in an axial position due to a dipole-dipole interaction between the N-H(+) and C-F bonds. Predictions of the physicochemical properties using common software appeared to be limited to determine correct values of pKa and/or differences of pKa between cis- and trans-3-amino-5-fluoropiperidines.

Severe Perineal Lacerations in Obstetric Practice: The Effect of Institutional Practice Guidelines on Repair Failures in a Single Centre.

Background. There is a high incidence of failure after repair of severe perineal lacerations (SPLs). A tertiary referral hospital in the Caribbean introduced guidelines in an attempt to improve outcomes. We performed an audit of SPL repairs at this centre in an attempt to determine the effect on repair failure. Methods. All patients with SPL repairs between November 1, 2007, and December 30, 2012, were identified. The primary aim was to determine the incidence of failed repairs (wound dehiscence, anal sphincter disruption, rectovaginal fistula, and/or faecal incontinence). The Cleveland Clinic Incontinence Score (CCIS) was used to assess continence at discharge and 24 weeks after repair. Data were analyzed with SPSS version 12. Results. There were 8108 vaginal deliveries, 23 third-degree injuries, and 3 fourth-degree injuries. Three patients experienced a repair failure. Notably, 69% of surgeons chose an inappropriate suture for sphincter repair. Conclusions. Experienced operators are performing repairs, but there is a high prevalence of inappropriate suture choice for repairs. A targeted educational campaign may be necessary to remind clinicians of the best practice in repair techniques.

More with LESS: a novel report of nerve sparing radical hysterectomy performed using LESS.

Laparoendoscopic single-site surgery (LESS) and natural orifice translumenal endoscopic surgery are now being used in gynecologic oncologic procedures. We used our expertise with LESS to perform nerve-sparing laparoscopic radical hysterectomy. A 45-year-old woman with stage IA2 cervical cancer was referred to us. The biopsy specimen showed grade II invasive keratinizing squamous cell carcinoma. We duplicated the steps of our laparoscopic nerve-sparing radical hysterectomy procedure to perform a nerve-sparing radical hysterectomy via LESS using conventional ports and instruments. Oncologic clearance was comparable to that in conventional laparoscopic radical hysterectomy. Bladder function recovered completely after removal of the Foley catheter. Nerve-sparing laparoscopic radical hysterectomy using fewer ports is technically feasible. The oncologic clearance and functional results are comparable to those in the multiport variant.

Fragment-based discovery of new highly substituted 1H-pyrrolo[2,3-b]- and 3H-imidazolo[4,5-b]-pyridines as focal adhesion kinase inhibitors.

Focal adhesion kinase (FAK) is considered as an attractive target for oncology, and small-molecule inhibitors are reported to be in clinical testing. In a surface plasmon resonance (SPR)-mediated fragment screening campaign, we discovered bicyclic scaffolds like 1H-pyrazolo[3,4-d]pyrimidines binding to the hinge region of FAK. By an accelerated knowledge-based fragment growing approach, essential pharmacophores were added. The establishment of highly substituted unprecedented 1H-pyrrolo[2,3-b]pyridine derivatizations provided compounds with submicromolar cellular FAK inhibition potential. The combination of substituents on the bicyclic templates and the nature of the core structure itself have a significant impact on the compounds FAK selectivity. Structural analysis revealed that the appropriately substituted pyrrolo[2,3-b]pyridine induced a rare helical DFG-loop conformation. The discovered synthetic route to introduce three different substituents independently paves the way for versatile applications of the 7-azaindole core.

Tuberculosis of larynx revisited: a report on clinical characteristics in 10 cases.

Tuberculosis is the most frequent granulomatous disease involving larynx. In most cases it is secondary to pulmonary tuberculosis. Incidence of tuberculosis is now on a rise due to increase in incidence of immune deficiency states. Here we present a report of clinical characteristic of laryngeal tuberculosis based on our experience of 10 cases. A detailed retrospective analysis of 10 patients of laryngeal tuberculosis was done at our tertiary care laryngology centre. Majority of patients had change of voice and dry cough. All the patients had hyperemia and edema of vocal cords. 80% patients had involvement of the arytenoids and ary-epiglottic folds. Frank granulomatous growth was seen in 70% of patients. In all patients histopathological report was consistent with tubercular granuloma. Two patients had associated pulmonary tuberculosis. Eight patients did not reveal any feature suggestive of previous or co-existent pulmonary tuberculosis. All patients responded to chemotherapy with complete resolution. Primary laryngeal tuberculosis is not as rare as generally considered. This series provides an insight towards clinical feature, growth pattern and management of tuberculosis of larynx.

Unexpected opioid activity profiles of analogues of the novel peptide kappa opioid receptor ligand CJ-15,208.

An alanine scan was performed on the novel κ opioid receptor (KOR) peptide ligand CJ-15,208 to determine which residues contribute to the potent in vivo agonist activity observed for the parent peptide. These cyclic tetrapeptides were synthesized by a combination of solid-phase peptide synthesis of the linear precursors, followed by cyclization in solution. Like the parent peptide, each of the analogues exhibited agonist activity and KOR antagonist activity in an antinociceptive assay in vivo. Unlike the parent peptide, the agonist activity of the potent analogues was mediated predominantly, if not exclusively, by µâ€…opioid receptors (MOR). Thus analogues 2 and 4, in which one of the phenylalanine residues was replaced by alanine, exhibited both potent MOR agonist activity and KOR antagonist activity in vivo. These peptides represent novel lead compounds for the development of peptide-based opioid analgesics.

Anomalous low tropospheric column ozone over eastern India during the severe drought event of monsoon 2002: a case study.

BACKGROUND, AIM, AND SCOPE: The present study is an attempt to examine some of the probable causes of the unusually low tropospheric column ozone observed over eastern India during the exceptional drought event in July 2002. METHOD: We examined horizontal wind and omega (vertical velocity) anomalies over the Indian region to understand the large-scale dynamical processes which prevailed in July 2002. We also examined anomalies in tropospheric carbon monoxide (CO), an important ozone precursor, and observed low CO mixing ratio in the free troposphere in 2002 over eastern India. RESULTS AND DISCUSSION: It was found that instead of a normal large-scale ascent, the air was descending in the middle and lower troposphere over a vast part of India. This configuration was apparently responsible for the less convective upwelling of precursors and likely caused less photochemical ozone formation in the free troposphere over eastern India in July 2002. CONCLUSION: The insight gained from this case study will hopefully provide a better understanding of the process controlling the distribution of the tropospheric ozone over the Indian region.

Synthesis of CJ-15,208, a novel κ-opioid receptor antagonist.

The tryptophan isomers of the cyclic tetrapeptide CJ-15,208, reported to be a kappa opioid receptor (KOR) antagonist [Saito, T.; Hirai, H.; Kim, Y. J.; Kojima, Y.; Matsunaga, Y.; Nishida, H.; Sakakibara, T.; Suga, O.; Sujaku, T.; Kojima, N. J. Antibiot. (Tokyo)2002, 55, 847-854.], were synthesized to determine the tryptophan stereochemistry in the natural product. A strategy was developed to select linear precursor peptides that favor cyclization using molecular modeling, and optimized cyclization conditions are reported. The optical rotation of the l-Trp isomer is consistent with that of the natural product. Unexpectedly both isomers exhibit similar nanomolar affinity for KOR.

Structure-activity relationships comparing N-(6-methylpyridin-yl)-substituted aryl amides to 2-methyl-6-(substituted-arylethynyl)pyridines or 2-methyl-4-(substituted-arylethynyl)thiazoles as novel metabotropic glutamate receptor subtype 5 antagonists.

The metabotropic glutamate receptor subtype 5 (mGluR5) has been implicated in anxiety, depression, pain, mental retardation, and addiction. The potent and selective noncompetitive mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP, 1) has been a critically important tool used to further elucidate the role of mGluR5 in these CNS disorders. In an effort to provide novel and structurally diverse selective mGluR5 antagonists, we previously described a set of analogues with moderate activity wherein the alkyne bond was replaced with an amide group. In the present report, extended series of both amide and alkyne-based ligands were synthesized. MGluR5 binding and functional data were obtained that identified (1) several novel alkynes with comparable affinities to 1 at mGluR5 (e.g., 10 and 20-23), but (2) most structural variations to the amide template were not well tolerated, although a few potent amides were discovered (e.g., 55 and 56). Several of these novel analogues show drug-like physical properties (e.g., cLogP range = 2-5) that support their use for in vivo investigation into the role of mGluR5 in CNS disorders.

The efficiency of the human observer for lesion detection and localization in emission tomography.

For the medically relevant task of joint detection and localization of a signal (lesion) in an emission computed tomographic (ECT) image, it is of interest to measure the efficiency, defined as the relative task performance of a human observer versus that of an ideal observer. Efficiency studies can be used in system optimization, improving postprocessing (e.g., reconstruction) algorithms, deriving human-emulating model observers and computer-aided detection methods. Calculation of ideal observer performance for ECT is highly computationally complex. We can, however, compute ideal observer performance exactly using a simplified 'filtered-noise' model of ECT. This model results in images whose correlation structure, due to quantum noise, background variability and regularization, is similar to that of real ECT reconstructed images. A two-alternative forced choice test is used to obtain the performance of the human observers. We compare the efficiency of our joint detection-localization task with that of a corresponding signal-known-exactly (SKE) detection task. For the joint task, efficiency is low when the search tolerance is stringent. Efficiency for the joint task rises with signal intensity but is flat for the SKE task. For both tasks, efficiency peaks at a mid-range level of regularization corresponding to a particular noise-resolution tradeoff.