Cascade Radical Pathway-Enabled Nitrogen-Sulfur Coupling: Access to Isothiazolo[3,4-b]-meso-tetraarylporphyrins.

A catalyst-free radical-mediated domino strategy for the construction of isothiazolo[3,4-b]-meso-tetraarylporphyrins was developed. During the course of the reaction, 2-benzothioylamino-3-thioformyl-meso-tetraarylporphyrins generated in situ after the addition of Lawesson's reagent to a solution of 2-benzoylamino-3-formyl-meso-tetraarylporphyrins in refluxing toluene underwent a homolytic cleavage to produce nitrogen-sulfur radicals. Subsequently, the formation of a new N-S bond through an intramolecular cascade radical coupling provided direct access to novel ß-isothiazole-fused porphyrins.

A divergent one-pot thiol-Michael strategy to create ß-thiophene-fused porphyrins.

A divergent one-pot domino strategy for the synthesis of nickel(II) and copper(II) ß-thiophene-fused 5,10,15,20-tetraarylporphyrins was developed through a thiol-Michael addition of thioglycolic/thiolactic acid to the corresponding 2-iminoporphyrins, formed in situ after the reaction of nickel(II) and copper(II) 2-formyl-5,10,15,20-tetraarylporphyrins with sterically hindered tert-butylamine in 1,2-dichloroethane at 80 °C. Interestingly, the reaction of 2-formylporphyrins with comparatively less sterically hindered primary amines and thioglycolic acid afforded a mixture of ß-substituted porphyrinic thiazolidinones and ß-thiophene-fused porphyrins. A similar one-pot thiol-Michael protocol was applied to construct a novel free-base thieno[2,3-b]-meso-tetrakis(4-methoxyphenyl)porphyrin, which underwent zinc insertion by using zinc acetate in a CHCl3-MeOH mixture and afforded zinc(II) ß-thiophene-fused meso-tetrakis(4-methoxyphenyl)porphyrin in an appreciable isolated yield. On photophysical evaluation, these new porphyrins displayed a modest bathochromically shifted electronic absorption in contrast to meso-tetraarylporphyrin building blocks.

Prognostic value of late-gadolinium enhancement on cardiac magnetic resonance in patients with cardiac sarcoidosis.

BACKGROUND: Late-gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is a predictor of adverse events in patients with cardiac sarcoidosis (CS), but available studies had small sample sizes and did not consider all relevant endpoints. OBJECTIVE: To evaluate the association between LGE on CMR in patients with CS and mortality, ventricular arrhythmias (VA) and sudden cardiac death (SCD), and heart failure (HF) hospitalization. METHODS: A literature search was conducted for studies reporting the association between LGE in CS and the study endpoints. The endpoints were mortality, VA and SCD, and HF hospitalization. The search included the following databases: Ovid MEDLINE, EMBASE, Web of Science, and Google Scholar. The search was not restricted to time or publication status. The minimum follow-up duration was 1 year. RESULTS: A total of 17 studies and 1915 CS patients (595 with LGE vs. 1320 without LGE) were included; mean follow-up was 3.3 years (ranging between 17 and 84 months). LGE was associated with increased all-cause mortality (OR 6.05, 95% CI 3.16-11.58; p < .01), cardiovascular mortality (OR 5.83, 95% CI 2.89-11.77; p < .01), and VA and SCD (OR 16.48, 95% CI 8.29-32.73; p < .01). Biventricular LGE was associated with increased VA and SCD (OR 6.11, 95% CI 1.14-32.68; p = .035). LGE was associated with an increased HF hospitalization (OR 17.47, 95% CI 5.54-55.03; p < .01). Heterogeneity was low: df = 7 (p = .43), I2 = 0%. CONCLUSIONS: LGE in CS patients is associated with increased mortality, VA and SCD, and HF hospitalization. Biventricular LGE is associated with an increased risk of VA and SCD.

Radiological tumor thickness as a clinical predictor of pathological depth of invasion in oral squamous cell carcinoma: a retrospective analysis.

PURPOSE: Inclusion of depth of invasion (DOI) in the recent AJCC/UICC TNM staging for oral cancer has incorporated the concept of tumor third dimension and its prognostic importance. However, there is no uniform consensus about measuring DOI at clinical setting at present. For more practical reasons, radiological tumor thickness (rTT) is a simple and practical measurement which can be used as a clinical predictor of pDOI. METHODS: We compared rTT and pathological DOI (pDOI) of 179 patients with OSCC who underwent curative surgery from April 2018 to April 2020 at AIIMS Rishikesh, India. Spearman correlation was used to determine correlation between rTT and pDOI. ROC curve was used to determine inter-group cutoff values. RESULTS: Overall, rTT showed a strong correlation with pDOI (rho = 0.74; 95% CI 0.667-0.8; p < 0.001). The inter-group cutoff value for rTT were 8 mm (Sn 89.1%; Sp 53.2%) between Group A (pDOI ≤ 5 mm) and B (pDOI > 5 mm, ≤ 10 mm), and 14 mm (Sn 89.5%; Sp 78.3%) between Group B and C (pDOI > 10 mm), respectively. CONCLUSIONS: rTT is a clinical predictor of pDOI in OSCC, and may be considered as a surrogate of DOI in the clinical setting.

Influence of stubble burning on air quality of Northern India: a case study of Indo-Gangetic plains of India.

Stubble burning is an emerging environmental issue in Northern India, which has severe implications for the air quality of the region. Although stubble burning occurs twice during a year, first during April-May and again in October-November due to paddy burning, the effects are severe during October-November months. This is exacerbated by the role of meteorological parameters and presence of inversion conditions in the atmosphere. The deterioration in the atmospheric quality can be attributed to the emissions from stubble burning which can be perceived from the changes observed in land use land cover (LULC) pattern, fire events, and sources of aerosol and gaseous pollutants. In addition, wind speed and wind direction also play a role in changing the concentration of pollutants and particulate matter over a specified area. The present study has been carried out for the states of Punjab, Haryana, Delhi, and western Uttar Pradesh to study the influence of stubble burning on the aerosol load of this region of Indo-Gangetic Plains (IGP). In this study, the aerosol level, smoke plume characteristics, long-range transport of pollutants, and affected areas during October-November from year 2016 to 2020 were examined over the Indo-Gangetic Plains (Northern India) region by the satellite observations. By MODIS-FIRMS (Moderate Resolution Imaging Spectroradiometer-Fire Information for Resource Management System) observations, it was revealed that there was an increase in stubble burning events with the highest number of events being observed during the year 2016 and then a decrease in the number of events in subsequent years from 2017 to 2020. MODIS observations revealed a strong AOD gradient from west to east. The prevailing north-westerly winds assist the spread of smoke plumes over Northern India during the peak burning season of October to November. The findings of this study might be used to expand on the atmospheric processes that occur over northern India during the post-monsoon season. The pollutant, smoke plume features, and impacted regions of biomass-burning aerosols in this region are critical for weather and climate research, especially given the rising trend in agricultural burning over the previous two decades.

Miniphocaeibacter halophilus sp. nov., an ammonium-tolerant acetate-producing bacterium isolated from a biogas system.

An anaerobic bacterial strain, designated AMB_01T, recovered from mesophilic propionate enrichment of a high-ammonia biogas digester, was characterised using phenotypic and molecular taxonomic methods. Cells of AMB_01T are coccus-shaped and often occur arranged as diplococci or sarcina. Growth occurred at 20-45 °C, initial pH 5.5-8.5 and with up to 0.7 M NH4Cl, with optimum growth at 37-42 °C and pH 8.0. AMB_01T achieved high cell density and highest acetate production when grown on carbohydrates, including monomers, disaccharides and polysaccharides, such as glucose, maltose, cellobiose and starch. The strain was also able to use amino acids and some organic acids and alcoholic compounds for growth. Acetate was formed as the main product and yeast was not required for growth. The major cellular fatty acids were summed feature 4 (iso-C17 : 1I and/or anteiso-C17 : 1B), C18 : 1ω7, C14 : 0, C16 : 0 and summed feature 3 (C16 : 1ω7 and/or iso-C15 : 0 2OH). The highest 16S rRNA gene sequence similarity found was with Miniphocaeibacter massiliensis (96.6 %), within the family Peptoniphilaceae, phylum Bacillota (Firmicutes). The genomic DNA G+C content was 29.0 mol%. An almost complete set of genes for the acetyl-CoA pathway was found. Genome comparisons between AMB_01T and close relatives showed highest digital DNA-DNA hybridisation to Finegoldia magna (23 %), highest average nucleotide identity with genome nucleotide and amino acid sequences to M. massiliensis (72 and 73 %, respectively) and highest average nucleotide identity (87 %) with Schnuerera ultunensis, indicating that AMB_01T represents a novel species. Analysis of genomic, chemotaxonomic, biochemical and physiological data confirmed that strain AMB_01T represents a novel species, for which the name Miniphocaeibacter halophilus sp. nov. is proposed. The type strain is AMB_01T (=DSM 110247T=JCM 39107 T).

Enrichment and description of novel bacteria performing syntrophic propionate oxidation at high ammonia level.

Inefficient syntrophic propionate degradation causes severe operating disturbances and reduces biogas productivity in many high-ammonia anaerobic digesters, but propionate-degrading microorganisms in these systems remain unknown. Here, we identified candidate ammonia-tolerant syntrophic propionate-oxidising bacteria using propionate enrichment at high ammonia levels (0.7-0.8 g NH3 L-1 ) in continuously-fed reactors. We reconstructed 30 high-quality metagenome-assembled genomes (MAGs) from the propionate-fed reactors, which revealed two novel species from the families Peptococcaceae and Desulfobulbaceae as syntrophic propionate-oxidising candidates. Both MAGs possess genomic potential for the propionate oxidation and electron transfer required for syntrophic energy conservation and, similar to ammonia-tolerant acetate degrading syntrophs, both MAGs contain genes predicted to link to ammonia and pH tolerance. Based on relative abundance, a Peptococcaceae sp. appeared to be the main propionate degrader and has been given the provisional name "Candidatus Syntrophopropionicum ammoniitolerans". This bacterium was also found in high-ammonia biogas digesters, using quantitative PCR. Acetate was degraded by syntrophic acetate-oxidising bacteria and the hydrogenotrophic methanogenic community consisted of Methanoculleus bourgensis and a yet to be characterised Methanoculleus sp. This work provides knowledge of cooperating syntrophic species in high-ammonia systems and reveals that ammonia-tolerant syntrophic propionate-degrading populations share common features, but diverge genomically and taxonomically from known species.

Robust expression of LINE-1 retrotransposon encoded proteins in oral squamous cell carcinoma.

BACKGROUND: Oral Squamous Cell Carcinoma (OSCC) results from a series of genetic alteration in squamous cells. This particular type of cancer considers one of the most aggressive malignancies to control because of its frequent local invasions to the regional lymph node. Although several biomarkers have been reported, the key marker used to predict the behavior of the disease is largely unknown. Here we report Long INterpersed Element-1 (LINE1 or L1) retrotransposon activity in post-operative oral cancer samples. L1 is the only active retrotransposon occupying around 17% of the human genome with an estimated 500,000 copies. An active L1 encodes two proteins (L1ORF1p and L1ORF2p); both of which are critical in the process of retrotransposition. Several studies report that the L1 retrotransposon is highly active in many cancers. L1 activity is generally determined by assaying L1ORF1p because of its high expression and availability of the antibody. However, due to its lower expression and unavailability of a robust antibody, detection of L1ORF2p has been limited. L1ORF2p is the crucial protein in the process of retrotransposition as it provides endonuclease and reverse transcriptase (RT) activity. METHODS: Immunohistochemistry and Western blotting were performed on the post-operative oral cancer samples and murine tissues. RESULTS: Using in house novel antibodies against both the L1 proteins (L1ORF1p and L1ORF2p), we found L1 retrotransposon is extremely active in post-operative oral cancer tissues. Here, we report a novel human L1ORF2p antibody generated using an 80-amino-acid stretch from the RT domain, which is highly conserved among different species. The antibody detects significant L1ORF2p expression in human oral squamous cell carcinoma (OSCC) samples and murine germ tissues. CONCLUSIONS: We report exceptionally high L1ORF1p and L1ORF2p expression in post-operative oral cancer samples. The novel L1ORF2p antibody reported in this study will serve as a useful tool to understand why L1 activity is deregulated in OSCC and how it contributes to the progression of this particular cancer. Cross-species reactivity of L1ORF2p antibody due to the conserved epitope will be useful to study the retrotransposon biology in mice and rat germ tissues.

Cytomorphology of Warthin-like variant of papillary thyroid carcinoma: A diagnosis not to be missed.

The authors have elaborated the cytological features of Warthin-like variant of papillary thyroid carcinoma (WLPTC) presenting unusually with nodal metastasis in a 43-year-old lady, and which was reported on cytology as papillary thyroid carcinoma (PTC) with lymphocytic thyroiditis.

Biochemical, functional and molecular characterization of pigeon pea rhizobia isolated from semi-arid regions of India.

Pigeon pea (Cajanus cajan (L.) Millspaugh) is among the top ten legumes grown globally not only having high tolerance to environmental stresses along, but also has the high biomass and productivity with optimal nutritional profiles. In the present study, 55 isolates of rhizobia were identified from 22 nodule samples of pigeon pea collected from semi-arid regions of India on the basis of morphological, biochemical, plant growth promoting activities and their ability to tolerate the stress conditions viz. pH, salt, temperature and drought stress. Amongst all the 55 isolates, 37 isolates showed effective nodulation under in vitro conditions in pigeon pea. Further, five isolates having multiple PGP activities and high in vitro symbiotic efficiency were subjected to 16S rRNA sequencing and confirmed their identities as Rhizobium, Mesorhizobium, Sinorhizobium sp. Further these 37 isolates were characterized at molecular level using ARDRA and revealed significant molecular diversity. Based on UPGMA clustering analysis, these isolates showed significant molecular diversity. The high degree of molecular diversity is due to mixed cropping of legumes in the region. The assessment of genetic diversity and molecular characterization of novel strains is a very important tool for the replacement of ineffective rhizobial strains with the efficient strains for the improvement in the nodulation and pigeon pea quality. The pigeon pea isolates with multiple PGPR activities could be further used for commercial production.

Molecular Diversity Analysis of Plant Growth Promoting Rhizobium Isolated from Groundnut and Evaluation of Their Field Efficacy.

Rhizobium are nitrogen-fixing bacteria which possess the nif gene that codes for the nitrogenase enzyme involved in the reduction of atmospheric dinitrogen (N2) to ammonia. Thirty rhizobial strains were identified from ten groundnut plant root nodules collected from semi-arid regions of Rajasthan, India. The isolates were initially identified on the basis of morphological, biochemical, and molecular characteristics. These rhizobium strains were further screened for plant growth promoting activities. Twenty-eight strains were able to produce indole acetic acid, nine strains could solubilize phosphate, and twenty-nine strains exhibited positive results for siderophore and ammonia production. All the bacterial strains were able to efficiently nodulate the groundnut under pot conditions and based on multiple PGP activities six strains were selected for field evaluation. Field experiments confirmed the effectiveness of these selected rhizobium strains resulted in significantly higher nodule number, nodule dry weight, grain yield, and yield components of inoculated plants. Inoculation of the rhizobium strain GN223 followed by GN221 resulted in high yield and field efficiency. Isolation of effective microbial strains is the prerequisite to increase the yield which is evident from the field data of the present study. Hence, these strains might serve as proficient inoculants.

Micro-metastasis and isolated tumour cells: the span between elective neck dissection versus neck observation in early oral cancer.

Early oral squamous cell carcinoma (SCC) has a propensity for lymph-node metastasis. To address or not to address the neck electively during the ablative surgery has been an ongoing debate. In recent years, some practice-changing trial and systematic reviews have emerged and put to rest the discussion of elective neck dissection versus neck observation. Today elective neck is not a mere staging procedure. It has a definitive survival advantage, but the pathological basis of this advantage has not been elaborated. Understanding this could help answer some of the critical aspects of tumour spread.

Severe acute respiratory syndrome coronavirus-2 and pulmonary tuberculosis: convergence can be fatal.

Disease associated with SARS-CoV-2 also termed as Coronavirus disease 2019 or COVID-19, has become a potential threat to public health by spreading across more than 200 countries worldwide within a short span of time. Tuberculosis (TB) is already existing as unprecedented pandemic worldwide over several years. Both diseases have many overlapping features but there are striking differences too. There is usually chronicity of symptoms in TB as compared to acute or rapid progression in COVID-19. Little evidence exists regarding TB and COVID-19 coinfection. It is anticipated that person with TB either in active, previously treated or latent forms are more at risk of poor outcomes with COVID-19. The relationship between the two diseases is still unclear at present, and more studies are needed to enable analyses of interactions and determinants of outcomes in patients affected by both the diseases. Most of the countries across the world imposed nationwide lockdown to promote social distancing, which is one important preventive measure to mitigate the spread of COVID-19 pandemic. However, it becomes quite challenging to ensure smooth functioning of programmatic services, leading to disruption of routine TB care, leading to transmission of infection. Health authorities should frame polices that can support TB patients by providing diagnostic, management and prevention services without any interruption during this era of ongoing COVID-19 pandemic. Effort should be made to control both the diseases simultaneously and avoid unfavourable outcome in near future.

Effect of Start-Up Strategies and Electrode Materials on Carbon Dioxide Reduction on Biocathodes.

The enrichment of CO2-reducing microbial biocathodes is challenging. Previous research has shown that a promising approach could be to first enrich bioanodes and then lower the potential so the electrodes are converted into biocathodes. However, the effect of such a transition on the microbial community on the electrode has not been studied. The goal of this study was thus to compare the start-up of biocathodes from preenriched anodes with direct start-up from bare electrodes and to investigate changes in microbial community composition. The effect of three electrode materials on the long-term performance of the biocathodes was also investigated. In this study, preenrichment of acetate-oxidizing bioanodes did not facilitate the start-up of biocathodes. It took about 170 days for the preenriched electrodes to generate substantial cathodic current, compared to 83 days for the bare electrodes. Graphite foil and carbon felt cathodes produced higher current at the beginning of the experiment than did graphite rods. However, all electrodes produced similar current densities at the end of the over 1-year-long study (2.5 A/m2). Methane was the only product detected during operation of the biocathodes. Acetate was the only product detected after inhibition of the methanogens. Microbial community analysis showed that Geobacter sp. dominated the bioanodes. On the biocathodes, the Geobacter sp. was succeeded by Methanobacterium spp., which made up more than 80% of the population. After inhibition of the methanogens, Acetobacterium sp. became dominant on the electrodes (40% relative abundance). The results suggested that bioelectrochemically generated H2 acted as an electron donor for CO2 reduction.IMPORTANCE In microbial electrochemical systems, living microorganisms function as catalysts for reactions on the anode and/or the cathode. There is a variety of potential applications, ranging from wastewater treatment and biogas generation to production of chemicals. Systems with biocathodes could be used to reduce CO2 to methane, acetate, or other high-value chemicals. The technique can be used to convert solar energy to chemicals. However, enriching biocathodes that are capable of CO2 reduction is more difficult and less studied than enriching bioanodes. The effect of different start-up strategies and electrode materials on the microbial communities that are enriched on biocathodes has not been studied. The purpose of this study was to investigate two different start-up strategies and three different electrode materials for start-up and long-term operation of biocathodes capable of reducing CO2 to valuable biochemicals.

Extensively drug-resistant tuberculosis in India: Current evidence on diagnosis & management.

Emergence of extensively drug-resistant tuberculosis (XDR-TB) has significantly threatened to jeopardize global efforts to control TB, especially in HIV endemic regions. XDR-TB is mainly an iatrogenically created issue, and understanding the epidemiological and risk factors associated with it is of paramount importance in curbing this menace. Emergence of this deadly phenomenon can be prevented by prompt diagnosis and effective treatment with second-line drugs in rifampicin-resistant TB (RR-TB) as well as multidrug-resistant TB (MDR-TB) patients. Optimal treatment of RR-TB, MDR-TB and XDR-TB cases alone will not suffice to reduce the global burden. The TB control programmes need to prioritize on policies focusing on the effective as well as rational use of first-line drugs in every newly diagnosed drug susceptible TB patients so as to prevent the emergence of drug resistance.

A study to estimate prevalence and risk factors of Obstructive Sleep Apnoea Syndrome in a semi-urban Indian population.

Obstructive Sleep Apnea Syndrome (OSAS) has been recognised as a major cause of morbidity and mortality in developing countries like India. There is still a paucity of Indian studies regarding the prevalence of OSAS. The current single centre prospective cross-sectional study was undertaken to know prevalence estimates for key symptoms and features that can indicate the presence of OSAS in an Indian population. A survey was conducted on subjects with age groups ≥ 25 years at King George's Medical University, Lucknow, Uttar Pradesh, India from August 2009 to July 2011. Data was recorded during the interview on the basis of Berlin Questionnaire (BQ). Risk factors for OSAS were also evaluated. Risk group categorization for OSAS was done with the help of a questionnaire and overnight polysomnography was performed in each group to measure apnea and hypopnea index (AHI). Out of 1816 subjects, 1512 (response rate 83.3%) finally participated in the survey with mean age 42.6±11.2 years, males 67.9% and females 32.1%. Of them 6.2% were found to be at high-risk OSAS; 12.2% were obese (Body Mass Index ≥30 kg/m2) and 33.5% of the obese population were at high-risk OSAS. Among high-risk patients with OSAS, 62.4% had hypertension. Statistically significant and independent risk factors found for OSAS were obesity, large neck size, alcoholism and use of sedatives/tranquillizers. High-risk category predicted an AHI ≥5 with a sensitivity of 86.3% (95% CI 73.1-93.8), specificity of 93.1% (95% CI 89.1-95.7), positive and negative predictive values of 70.9% (95% CI 57.9-81.4) and 97.2% (95% CI 94.1-98.8) respectively. It can be concluded that BQ questionnaire can still be used as a pre-assessment tool for predicting persons at risk for OSAS in clinical practice. Further studies on estimation of prevalence of OSAS by applying BQ are warranted in near future from other regions of India.

Co-existence of Bronchiectasis and Chronic Obstructive Pulmonary Disease.

We present the case of a 56-year-old male who presented with cough and breathlessness. Chest radiograph (postero-anterior view) showed bulla and signs of hyperinflation in the right upper zone with cystic shadows in the left lower zone. Spirometry showed severe irreversible airflow obstruction with restriction and decreased diffusion capacity for carbon monoxide. On high resolution computed tomography (HRCT), right upper lobe bulla with emphysematous changes and left lower lobe cystic bronchiectasis were seen. Considering its rarity of occurrence and paucity of data in literature regarding co-existence of bronchiectasis with emphysema, this case is being reported.