Air pollution and its effects on lung health in never-smoker youth of Delhi NCR versus Pauri Garhwal: a comparative cross-sectional study.

Background: Ambient air pollution is a major factor that can affect lung growth and reduce lung capacity. This study aims at drawing parallel between respiratory discomfort and lung function between youth of Delhi-National Capital Region (NCR) where air pollution level is poor and hazardous as compared to that of Pauri Garhwal (Uttarakhand) where air pollution level is low via a comparative cross-sectional study. Methods: A community-based cross-sectional study conducted among 354 never-smoker subjects (177 from NCR and 177 from Pauri) between the ages of 15 and 29 years. Pulmonary Function Test coupled with COPD Assessment Test (CAT)-based questionnaire for respiratory problems helped elicit information regarding lung health of subjects. Results: Mean forced vital capacity (FVC), forced expiratory volume in 1st second (FEV1), forced expiratory flow 25-75%, FEV1/FVC ratio, and peak expiratory flow rate were lower by 12.9%, 17%, 5%, 7.8%, and 7.3%, respectively, in NCR participants as compared to that of Pauri. Upon spirometry, restrictive pattern was present in 40 (22.6%), and obstructive pattern was present in 9 (5.1%) of NCR participants. Out of these, nine (5.1%) having obstructive pattern, five (55.6%) had 50% ≤ FEV1<80%, and four (44.4%) had 30% ≤ FEV1<50% of predicted value. Neither restrictive nor obstructive pattern was found evident in subjects from Pauri. The mean CAT score in subjects from NCR was 5.2 ± 4.9 and .46 ± 1.1 in subjects from Pauri. Conclusion: Subjects belonging to NCR performed poorly in spirometry and reported higher respiratory complaints in comparison to participants from Pauri Garhwal.

Asymmetric Synthesis of Chiral 2-Cyclohexenones with Quaternary Stereocenters via Ene-Reductase Catalyzed Desymmetrization of 2,5-Cyclohexadienones.

Stereoselective synthesis of quaternary stereocenters represents a significant challenge in organic chemistry. Herein, we describe the use of ene-reductases OPR3 and YqjM for the efficient asymmetric synthesis of chiral 4,4-disubstituted 2-cyclohexenones via desymmetrizing hydrogenation of prochiral 4,4-disubstituted 2,5-cyclohexadienones. This transformation breaks the symmetry of the cyclohexadienone substrates, generating valuable quaternary stereocenters with high enantioselectivities (ee, up to >99%). The mechanistic causes for the observed high enantioselectivities were investigated both experimentally (stopped-flow kinetics) as well as theoretically (quantum mechanics/molecular mechanics calculations). The synthetic potential of the resulting chiral enones was demonstrated in several diversification reactions in which the stereochemical integrity of the quaternary stereocenter could be preserved.

Quantitative comparison of cell-cell detachment force in different experimental setups.

We compare three different setups for measuring cell-cell adhesion. We show that the measured strength depends on the type of setup that is used. For identical cells different assays measure different detachment forces. This can be understood from the fact that cell-cell detachment is a global property of the system. We also analyse the role of external force and line tension on contact angle and cell-cell detachment. Comparison with the experiments suggest that viscous forces play an important role in the process. We dedicate this article to Fyl Pincus who for many of us is an example to be followed not only for outstanding science but also for a marvelous human behavior.

Comprehensive antifungal investigation of green synthesized silver nanoformulation against four agriculturally significant fungi and its cytotoxic applications.

The present study reports the green synthesis of silver nanoparticles (AgNPs) in powder form using the leaf extract of Azadirachta indica. The synthesis of AgNPs was confirmed by UV-vis spectroscopy, FTIR, XRD, FESEM, and EDX. The synthesized AgNPs were in a powdered state and dispersed completely in 5% polyethylene glycol (PEG) and demonstrated prolonged shelf life and enhanced bioavailability over a year without any aggregation. The resulting silver nanoformulation demonstrated complete inhibition against Sclerotinia sclerotiorum and Colletotrichum falcatum and 68% to 80% inhibition against Colletotrichum gloeosporioides and Rhizoctonia solani respectively, at 2000 ppm. The EC50 values determined through a statistical analysis were 66.42, 157.7, 19.06, and 33.30 ppm for S. sclerotiorum, C. falcatum, C. gloeosporioides, and R. solani respectively. The silver nanoformulation also established significant cytotoxicity, with a 74.96% inhibition rate against the human glioblastoma cell line U87MG at 250 ppm. The IC50 value for the cancerous cell lines was determined to be 56.87 ppm through statistical analysis. The proposed silver nanoformulation may be used as a next-generation fungicide in crop improvement and may also find application in anticancer investigations. To the best of our knowledge, this is also the first report of silver nanoformulation demonstrating complete inhibition against the economically significant phytopathogen C. falcatum.

Folded Pectoralis Major Myocutaneous Flap for Reconstruction of Complex Oral Commissural Defects: A Retrospective Case Series and Technical Report.

Full thickness defects following surgical resection of locally advanced carcinoma buccal mucosa involving oral commissure often require complex microvascular procedures that are technically demanding. We present a novel technique of folded pectoralis major myocutaneous flap for reconstruction of such defects without the need for free flaps or additional sling support.

Self-medication prevalence and associated factors among adult population in Northern India: A community-based cross-sectional study.

Objectives: This study aimed to determine self-medication prevalence and its associated factors. Methods: A community-based cross-sectional study was conducted in the urban and rural catchment areas of Uttar Pradesh, India, among 440 adults using a pretested, semistructured questionnaire. The Chi-square test and logistic regression were used to determine the association of self-medication prevalence with various independent variables. The associations were reported as adjusted odds ratios and 95% confidence intervals. Results: The prevalence of medication use was 66.4%. The majority of participants (45%) took medicine for fever, cough (40.1%), and cold (31.8%). Allopathy (83.2%) was the most common medicine system used for self-medication. More than half reported taking medicine such as paracetamol (52%), followed by cough syrup (21%) and antihistaminic (17%). Convenience (46%) and lack of time (35.3%) were commonly cited reasons for self-medication. Also, 64.4% of the respondents practiced self-medication on the pharmacist's recommendation. Urban participants (adjusted odds ratio: 9.85, 95% confidence interval: 5.32-18.23), females (adjusted odds ratio: 2.32, 95% confidence interval: 1.18-4.57), skilled workers (adjusted odds ratio: 5.62, 95% confidence interval: 1.80-17.5), and those who completed primary school (adjusted odds ratio: 2.48, 95% confidence interval: 1.16-5.25) were more likely to self-medicate than rural, male, unemployed, and illiterate participants, respectively. Also, participants whose income was 30,000 Indian rupees (adjusted odds ratio: 3.21, 95% confidence interval: 1.00-10.21) were more likely to self-medicate than those whose income was less than 4000. Conclusions: A high prevalence of self-medication was found, particularly in urban areas. Convenience and lack of time were commonly cited reasons for self-medication. Allopathy was the most widely used medicine system for self-medication. Antipyretics, cough syrups, and antiallergics were most commonly self-medicated. Gender, education, and income were associated with self-medication. The study highlighted the increased usage among females which could be further explored and role of pharmacists' recommendation as a major driver for self-medication.

Deciphering the Unconventional Reduction of C=N Bonds by Old Yellow Enzymes Using QM/MM.

The reduction of C=X (X = N, O) bonds is a cornerstone in both synthetic organic chemistry and biocatalysis. Conventional reduction mechanisms usually involve a hydride ion targeting the less electronegative carbon atom. In a departure from this paradigm, our investigation into Old Yellow Enzymes (OYEs) reveals a mechanism involving transfer of hydride to the formally more electronegative nitrogen atom within a C=N bond. Beyond their known ability to reduce electronically activated C=C double bonds, e.g., in α, ß-unsaturated ketones, these enzymes have recently been shown to reduce α-oximo-ß-ketoesters to the corresponding amines. It has been proposed that this transformation involves two successive reduction steps and proceeds via imine intermediates formed by the reductive dehydration of the oxime moieties. We employ advanced quantum mechanics/molecular mechanics (QM/MM) simulations, enriched by a two-tiered approach incorporating QM/MM (UB3LYP-6-31G*/OPLS2005) geometry optimization, QM/MM (B3LYP-6-31G*/amberff19sb) steered molecular dynamics simulations, and detailed natural-bond-orbital analyses to decipher the unconventional hydride transfer to nitrogen in both reduction steps and to delineate the role of active site residues as well as of substituents present in the substrates. Our computational results confirm the proposed mechanism and agree well with experimental mutagenesis and enzyme kinetics data. According to our model, the catalysis of OYE involves hydride transfer from the flavin cofactor to the nitrogen atom in oximoketoesters as well as iminoketoesters followed by protonation at the adjacent oxygen or carbon atoms by conserved tyrosine residues and active site water molecules. Two histidine residues play a key role in the polarization and activation of the C=N bond, and conformational changes of the substrate observed along the reaction coordinate underline the crucial importance of dynamic electron delocalization for efficient catalysis.

Poly(d,l-lactide-co-glycolide) Surface-Anchored Biotin-Loaded Irinotecan Nanoparticles for Active Targeting of Colon Cancer.

A poly(d,l-lactide-co-glycolide) (PLGA) copolymer was synthesized using the ring-opening polymerization of d,l-lactide and glycolide monomers in the presence of zinc proline complex in bulk through the green route and was well characterized using attenuated total reflectance-Fourier transform infrared, 1H and 13C nuclear magnetic resonance, gel permeation chromatography, differential scanning calorimetry, X-ray diffraction, matrix-assisted laser desorption/ionization time-of-flight, etc. Furthermore, PLGA-conjugated biotin (PLGA-B) was synthesized using the synthesized PLGA and was employed to fabricate nanoparticles for irinotecan (Ir) delivery. These nanoparticles (PLGA-NP-Ir and PLGA-B-NP-Ir) were tested for physicochemical and biological characteristics. PLGA-B-NP-Ir exhibited a stronger cellular uptake and anticancer activity as compared to PLGA-NP-Ir in CT-26 cancer cells (log p < 0.05). The accumulation and retention of fluorescence-labeled nanoparticles were observed to be better in CT-26-inoculated solid tumors in Balb/c mice. The PLGA-B-NP-Ir-treated group inhibited tumor growth significantly more (log p < 0.001) than the untreated control, PLGA-NP-Ir, and Ir-treated groups. Furthermore, no body weight loss, hematological, and blood biochemical tests demonstrated the nanocarriers' nontoxic nature. This work presents the use of safe PLGA and the demonstration of a proof-of-concept of biotin surface attached PLGA nanoparticle-mediated active targeted Ir administration to combat colon cancer. To treat colon cancer, PLGA-B-NP-Ir performed better due to specific active tumor targeting and greater cellular uptake due to biotin.

Unconventional Reactivity of a Grubbs Catalyst: Hydroalkylation Overriding Metathesis.

Unprecedented reactivity of a Grubbs catalyst has been disclosed in a reaction between vinyl azaarenes and alkenylnitriles under standard metathesis conditions. No metathesis was observed; only hydroalkylation products were obtained in high yields. The practical utility of this method has been demonstrated by the application of the products in useful transformations, e.g., the formation of cyclic iminoesters and highly challenging medium-sized carbocycles.

In situ assembly of bioresorbable organic bioelectronics in the brain.

Bioelectronics can potentially complement classical therapies in nonchronic treatments, such as immunotherapy and cancer. In addition to functionality, minimally invasive implantation methods and bioresorbable materials are central to nonchronic treatments. The latter avoids the need for surgical removal after disease relief. Self-organizing substrate-free organic electrodes meet these criteria and integrate seamlessly into dynamic biological systems in ways difficult for classical rigid solid-state electronics. Here we place bioresorbable electrodes with a brain-matched shear modulus-made from water-dispersed nanoparticles in the brain-in the targeted area using a capillary thinner than a human hair. Thereafter, we show that an optional auxiliary module grows dendrites from the installed conductive structure to seamlessly embed neurons and modify the electrode's volume properties. We demonstrate that these soft electrodes set off a controlled cellular response in the brain when relaying external stimuli and that the biocompatible materials show no tissue damage after bioresorption. These findings encourage further investigation of temporary organic bioelectronics for nonchronic treatments assembled in vivo.

Volume regulation in adhered cells: Roles of surface tension and cell swelling.

The volume of adhered cells has been shown experimentally to decrease during spreading. This effect can be understood from the pump-leak model, which we have extended to include mechano-sensitive ion transporters. We identify a novel effect that has important consequences on cellular volume loss: cells that are swollen due to a modulation of ion transport rates are more susceptible to volume loss in response to a tension increase. This effect explains in a plausible manner the discrepancies between three recent, independent experiments on adhered cells, between which both the magnitude of the volume change and its dynamics varied substantially. We suggest that starved and synchronized cells in two of the experiments were in a swollen state and, consequently, exhibited a large volume loss at steady state. Nonswollen cells, for which there is a very small steady-state volume decrease, are still predicted to transiently lose volume during spreading due to a relaxing viscoelastic tension that is large compared with the steady-state tension. We elucidate the roles of cell swelling and surface tension in cellular volume regulation and discuss their possible microscopic origins.

Palladium-Catalyzed Dearomative [4 + 2]-Cycloaddition toward Hydrocarbazoles.

An efficient method for the construction of hydrocarbazoles bearing three continuous sterically hindered stereocenters, two quaternary and one tertiary, via a highly diastereoselective palladium-catalyzed [4 + 2]-cycloaddition/dearomatization of 3-nitroindoles has been developed. The cycloaddition of 3-nitroindoles occurs at ambient conditions with a 1,4-zwitterionic intermediate, in situ generated from γ-methylidene-δ-valerolactones. The further synthetic utility of this method is demonstrated by the multifaceted transformations possible from the products. The catalytic asymmetric aspect of this transformation has also been explored.

Immunohistochemical Analysis of the Expression of Cytokeratins in Acquired Cholesteatoma and Its Clinico-Radiological Correlation

Background and Objectives@#Cholesteatomatous chronic otitis media acquires epithelial proliferation and differentiation characteristics, which render it able to erode the underlying bone and cause complications. We attempt to characterize the cholesteatoma epithelium by observing the expression of cytokeratins (such as 34ße12, CK17, and CK13) and Ki67 among patients with cholesteatoma with different aggressiveness as compared to disease-free controls. @*Subjects and Methods@#In this prospective study (2017-2021), we enrolled all consenting consecutive patients with cholesteatomatous chronic otitis media. They were staged in accordance with the staging guidelines of the European Academy of Otology and Neurotology and the Japanese Otological Society. Bony external auditory canal (EAC) skin specimens of the patients undergoing tympanoplasty were chosen as controls. We did an immunohistochemical analysis of the cholesteatoma specimens and normal bony EAC controls by observing the expression of 34ße12, CK17, CK13, and Ki67 across the layers of the epithelium. Fisher’s exact test and chi-square test were used to evaluate any statistical significance between the cases and the controls, and the subgroups were made based on the clinical stage. @*Results@#An increased expression of CK17 (p<0.001), CK13 (p<0.03), and Ki67 (p<0.001) was observed in cholesteatoma specimens when compared to normal bony EAC controls. Also, there was a loss of expression of 34ße12 in a subset of cholesteatoma specimens, all of which showed full-thickness expression of CK13. There was no difference in the expression of cytokeratin among specimens from patients belonging to different subgroups based on clinical stage, age, sex, duration of ear symptoms, or type of hearing loss (conductive vs. sensorineural). @*Conclusions@#The majority of cholesteatoma specimens significantly overexpressed CK17, CK13, and Ki67 when compared to normal bony EAC skin controls, while a subset showed loss of expression of 34ße12, which provides some insight into its pathogenesis.

Serum Survivin in Oral Submucosal Fibrosis and Squamous Cell Carcinoma.

Survivin, an inhibitor of apoptosis protein is a biomarker of significance in prognostication of many malignancies. In the current study we investigated the serum survivin levels in patients with oral submucosal fibrosis (OSMF) and squamous cell carcinoma (OSCC). Serum was isolated from, peripheral blood collected of clinically and histopathologically confirmed OSMF and OSCC patients. Circulating level of survivin was measured in patients and control subjects by ELISA and analyzed further using Kruskal-Wallis test and two-sample Wilcoxon rank-sum (Mann-Whitney) test. Serum Survivin levels were significantly reduced in the OSCC group as compared to the control group. No significant correlation was noted between the serum survivin level and various clinicopathological characteristics of OSCC and OSMF patients. Our study suggests that free, wild form of circulating survivin probably has no role in predicting the prognosis of oral cancer or the malignant transformation potential of oral submucosal fibrosis.

Hazardous giant pharyngoesophageal liposarcoma.

A man in his early 80s presented to the otorhinolaryngology department with progressively worsening dysphagia to solids and a recent episode of difficulty breathing accompanied by a very brief expulsion of a solid mass from the mouth. Based on the endoscopic appearance of a fatty lesion of an elongated mass with a thick stalk on the posterior pharyngeal wall, a diagnosis of the benign fibrovascular polyp was given after clinical and radiological correlation. The pharyngeal polyp was resected at the base of its pedicle by transoral endoscopy with a thunder beat vessel sealing device. Histopathological examination of the mass revealed a well-differentiated liposarcoma composed of mature adipocytes. Following surgical excision, the patient made a full recovery. This case signifies the integrated role of preoperative biopsy, new surgical technologies and targeted therapies in managing pharyngoesophageal polyps.

Correlation of fraction of exhaled nitric oxide with asthma control test and asthma severity in diagnosed cases of asthma.

Background: Fraction of NO in exhaled air (FENO) has emerged as a simple, non-invasive, sensitive marker of airway inflammation in asthma diagnosis and management. Correlation studies of FENO with clinical grades of asthma and symptom burden are sparse, more so in Indian population. Hence, this study was carried out in Indian subjects to evaluate FENO correlation with asthma severity. Methods: The study was performed on 52 proven cases of asthma in the age group of 17-90 years in period of December 2016 to May 2018. All the subjects had assessment in the form of Asthma Control Test (ACT)questionnaire, FENO parts per billion measurement with a portable NO analyzer (NIOX MINO Airway Inflammation Monitor; Aerocrine) and spirometry. Statistical analysis was presented in the form of percentage (%) and mean. Results: Of a total of 52 asthma cases, 27 (51.9%) were male cases while 25 (48.1%) were female cases. Study population ranged from 17 to 82 years. Subjects categorized into 03 categories of asthma severity based on their treatment step. ACT score of ranged between 11 and 25 with a mean value of 20.27 and standard deviation of 3.73. No significant correlation was found between FENO and ACT (r) = -0.177, P-value = 0.210 (>0.05). Significant correlation between FENO and different grades of asthma severity was found with p-value 0.032 (<0.05). Conclusion: Asthma severity as assessed by the step of treatment is correlated well with FENO value in an asthmatic individual to maintain the controlled asthma status. FENO and ACT were found to have no correlation.

Iridium-Catalyzed Enantioselective Ring Opening of Alkenyl Oxiranes by Unactivated Carboxylic Acids.

An iridium-catalyzed enantioselective ring-opening of alkenyl oxiranes by unactivated carboxylic acids has been developed. The reaction undergoes at ambient conditions between an in-situ-generated chiral iridium-π-allyl complex and carboxylic acids to provide rapid access to valuable alkenyl diols in high yields. The synthetic utility of this method is demonstrated by the elaboration of the products into various medium and large ring-sized compounds that are part of biologically relevant molecules.

Delayed mechanical thrombectomy after systemic thrombolysis in massive unilateral pulmonary thromboembolism.

Pulmonary thromboembolism (PTE) remains the third leading cause of cardiovascular death, after a heart attack and stroke. Haemodynamically unstable PTE (previously called high-risk or massive) is one of the dreaded conditions commonly found in people working in high-altitude areas. Due to the individual variations in clot characteristics and the haemodynamics, these patients offer unique therapeutic challenges by delay in access to tertiary care, being recalcitrant to the systemic thrombolysis as well as complete recanalisation by endovascular thrombectomy. We present a rare case of haemodynamically unstable right pulmonary trunk occlusion with delayed presentation and sustained right ventricular strain despite systemic thrombolysis, managed successfully by catheter-directed thrombectomy. Despite the partial recanalisation of only the right inferior pulmonary artery branches and persistent superior branch occlusion, there was an immediate clinical benefit and no recurrence of symptoms with maintenance therapy of newer oral anticoagulants.

Applicability of Adults 2015 American Thyroid Association Differentiated Thyroid Cancer Guidelines for Postoperative Risk Stratification and Postradioiodine Treatment Dynamic Risk Stratification in Pediatric Population.

Purpose This retrospective study aimed to study the applicability of 2015 adult American Thyroid Association (ATA) differentiated thyroid cancer (DTC) postoperative risk stratification and guidelines in the pediatric population for evaluating the number of metastatic lymph nodes in the postoperative risk stratification and postradioactive iodine (RAI) treatment dynamic risk stratification (DRS) using response to treatment (RTT) reclassification. In addition, the effect of pubertal status and gender was assessed on disease presentation and prognosis. Methods Data of 63 DTC patients aged 20 years or less, stratified into prepubertal, pubertal, and postpubertal age groups, was divided into low, intermediate, and high-risk groups using pediatric ATA recurrence risk stratification. Forty-seven patients were classified as responders (excellent and indeterminate responses) and incomplete responders (biochemical and structurally incomplete responses) by assessing the RTT at 1.5 years follow-up similar to recommendation of 2015 adult DTC ATA guidelines. Results Female-to-male ratio showed a trend of gradual increase with increasing age. Significantly more responders were observed in low- and intermediate-risk groups than in high-risk group ( p = 0.0013; p = 0.017, respectively), while prepubertal group had more extensive (N1b) disease. Using DRS at follow-up of 1.5 year, pubertal and postpubertal groups showed significantly better response to RAI. More female than male patients showed response and took significantly less time to respond to RAI ( p = 0.003). Conclusion RAI response in pediatric DTC depends on pubertal status, gender, and number of malignant nodes. DRS using RTT classification may be applicable early at 1.5 years after initial therapy in different pubertal age and risk groups.

Imaging CXCR4 receptors expression for staging multiple myeloma by using 68Ga-Pentixafor PET/CT: comparison with 18F-FDG PET/CT.

OBJECTIVES: 68Ga-Pentixafor positron emission tomography (PET) imaging targets CXCR4 expression which is overexpressed in multiple myeloma (MM). In this study, we evaluated the diagnostic utility of 68Ga-Pentixafor PET/CT for imaging CXCR4 expression in MM and compared results with 18F-fluorodeoxyglucose (18F-FDG) PET/CT. METHODS: 34 (21M; 13F; median age = 57.5 years) treatment naive multiple myeloma patients were recruited. All the patients underwent 18F-FDG PET/CT and 68Ga-Pentixafor PET/CT imaging. Freshly prepared 68Ga-Pentixafor (148-185 MBq) was injected intravenously and whole-body PET/CT (low-dose CT) was acquired at 1 h post-injection. The pattern of uptake (diffuse, focal or mixed) and the mean SUVmax value of all the lesions (when lesions were ≤5) or of the five most tracer avid lesions (when lesions was >5) were evaluated. Tumor to background ratio (TBRmax) was calculated for both the tracers. Durie Salmon plus staging (DSPS) was used for disease staging on PET and the results were compared with International staging system (ISS). RESULTS: 68Ga-Pentixafor PET/CT showed higher disease extent than seen on 18F-FDG PET/CT in 23/34 patients (68.0%), lesser disease extent in 2/34 (6%) and similar disease extent in 9/34 (26%) patients. Significantly (p < 0.001) higher TBRmax values (5.7; IQR 8.8) were observed on 68Ga-Pentixafor PET/CT as compared to 18F-FDG PET/CT values (2.9; IQR = 4.0). Both the techniques detected extramedullary lesions in six patients. On the other hand, 68Ga-Pentixafor detected medullary lesions in five, whereas, 18F-FDG PET in three patients. Further, only 68Ga-Pentixafor TBRmax correlated significantly (ρ = 0.421; 0.013) with bone marrow plasma cell percentage. 68Ga-Pentixafor PET upstaged more number (9/29) of patients as compared to (4/29) 18F-FDG PET imaging. On the other hand, 18F-FDG PET down-staged 9/29, whereas 68Ga-Pentixafor PET downstaged only 3/29 patients. CONCLUSION: 68Ga-Pentixafor PET/CT evaluated the whole-body disease burden of CXCR4 receptors non-invasively which is not possible by tissue sampling methods. This novel PET tracer has also implication for disease staging. Dual 68Ga-Pentixafor/18F-FDG PET/CT imaging may help in determining the tumor heterogeneity in MM. ADVANCES IN KNOWLEDGE: This CXCR4 targeting PET tracer has a promising role in the development of CXCR4 targeting theranostics and also for response assessment to these therapies including the conventional treatment.