Non-canonical autophagy functions of ATG16L1 in epithelial cells limit lethal infection by influenza A virus.

Influenza A virus (IAV) and SARS-CoV-2 (COVID-19) cause pandemic infections where cytokine storm syndrome and lung inflammation lead to high mortality. Given the high social and economic cost of respiratory viruses, there is an urgent need to understand how the airways defend against virus infection. Here we use mice lacking the WD and linker domains of ATG16L1 to demonstrate that ATG16L1-dependent targeting of LC3 to single-membrane, non-autophagosome compartments - referred to as non-canonical autophagy - protects mice from lethal IAV infection. Mice with systemic loss of non-canonical autophagy are exquisitely sensitive to low-pathogenicity IAV where extensive viral replication throughout the lungs, coupled with cytokine amplification mediated by plasmacytoid dendritic cells, leads to fulminant pneumonia, lung inflammation and high mortality. IAV was controlled within epithelial barriers where non-canonical autophagy reduced IAV fusion with endosomes and activation of interferon signalling. Conditional mouse models and ex vivo analysis showed that protection against IAV infection of lung was independent of phagocytes and other leucocytes. This establishes non-canonical autophagy in airway epithelial cells as a novel innate defence that restricts IAV infection and lethal inflammation at respiratory surfaces.

FLAgellum Member 8 modulates extravascular distribution of African trypanosomes.

In the mammalian host, the biology of tissue-dwelling Trypanosoma brucei parasites is not completely understood, especially the mechanisms involved in their extravascular colonization. The trypanosome flagellum is an essential organelle in multiple aspects of the parasites' development. The flagellar protein termed FLAgellar Member 8 (FLAM8) acts as a docking platform for a pool of cyclic AMP response protein 3 (CARP3) that is involved in signaling. FLAM8 exhibits a stage-specific distribution suggesting specific functions in the mammalian and vector stages of the parasite. Analyses of knockdown and knockout trypanosomes in their mammalian forms demonstrated that FLAM8 is not essential in vitro for survival, growth, motility and stumpy differentiation. Functional investigations in experimental infections showed that FLAM8-deprived trypanosomes can establish and maintain an infection in the blood circulation and differentiate into insect transmissible forms. However, quantitative bioluminescence imaging and gene expression analysis revealed that FLAM8-null parasites exhibit a significantly impaired dissemination in the extravascular compartment, that is restored by the addition of a single rescue copy of FLAM8. In vitro trans-endothelial migration assays revealed significant defects in trypanosomes lacking FLAM8. FLAM8 is the first flagellar component shown to modulate T. brucei distribution in the host tissues, possibly through sensing functions, contributing to the maintenance of extravascular parasite populations in mammalian anatomical niches, especially in the skin.

GST polymorphism as a predictive biomarker for modulating the susceptibility to chronic obstructive pulmonary disease: A North Indian study.

Chronic obstructive pulmonary disease (COPD) is commonly characterized by shortness of breath, coughing or expectoration. Smoking is the leading cause of COPD development, but only a small percentage of smokers develop symptoms, implying a genetic component. Glutathione S-transferase enzymes are responsible for detoxifying cigarette smoke components. The role of glutathione S-transferase T1 (GSTT1) and glutathione S-transferase M1 (GSTM1) gene polymorphism was assessed with COPD susceptibility and associated clinical parameters in the North Indian population. This was a cross-sectional study involving 200 COPD patients and 200 healthy individuals, with peripheral blood sampling and adequate questionnaires. Multiplex PCR was used for genotyping GSTT1 and GSTM1 gene polymorphism. Logistic regression was used to calculate the odds ratio and 95% confidence intervals to assess the COPD risk and GST polymorphisms. The GSTT1 gene deletion rate was higher in COPD cases (34.5%) than in healthy individuals (20.5%). A statistical relationship between the GSTT1(-) null genotype and COPD risk was observed (odds ratio = 2.04, 95% CI = 1.30-3.20, P = 0.0019). After adjusting for covariates like age, sex and smoking status, a significant association was found for GSTT1(-) null genotype and COPD risk (adjusted odds ratio = 2.90, 95% CI = 1.43-5.87, P = 0.003). The GSTT1(-) genotype was also significantly correlated with clinical parameters for COPD risk. Another primary observation was that females with the GSTT1(-) null genotype were more vulnerable to COPD than males with the same gene deletion. The GSTT1(-) null genotype strongly correlates with COPD development, while no association was observed in the GSTM1(-) null genotype in the North Indian population.

A Survey of Xylella fastidiosa in the U.S. State of Virginia Reveals Wide Distribution of Both Subspecies fastidiosa and multiplex in Grapevine.

Global travel and trade in combination with climate change are expanding the geographic distribution of plant pathogens. The bacterium Xylella fastidiosa is a prime example. Native to the Americas, it has spread to Europe, Asia, and the Middle East. To assess the risk that pathogen introductions pose to crops in newly invaded areas, it is key to survey their diversity, host range, and disease incidence in relation to climatic conditions where they are already present. We performed a survey of X. fastidiosa in grapevine in Virginia using a combination of quantitative PCR, multilocus sequencing, and metagenomics. We also analyzed samples from deciduous trees with leaf scorch symptoms. X. fastidiosa subspecies fastidiosa was identified in grapevines in all regions of the state, even in Northern Virginia, where the temperature was below -9°C for 10 days per year on average in the years preceding sampling. Unexpectedly, we also found for the first time grapevine samples infected with X. fastidiosa subspecies multiplex (Xfm). The Xfm lineage found in grapevines had been previously isolated from blueberries in the Southeastern United States and was distinct from that found in deciduous trees in Virginia. The obtained results will be important for risk assessment of X. fastidiosa introductions in other parts of the world.

Impact of ABCB1, ABCC1, ABCC2, and ABCG2 variants in predicting prognosis and clinical outcomes of north Indian lung cancer patients undergoing platinum-based doublet chemotherapy.

BACKGROUND: ABC transporters are membrane proteins expressed in the lungs and are crucial for efflux of various chemotherapeutic agents. Polymorphisms of ABC transporters have a certain impact on the transporter activity because their expression levels may influence the extent and longevity of chemotherapeutic drug outflow, affecting patient outcomes. The present study aimed to assess the impact of ABCB1, ABCC1/2, and ABCG2 gene variants in predicting prognosis and clinical outcomes in lung carcinoma patients. METHODS: In total, 502 lung cancer patients undergoing platinum-based chemotherapy were recruited in this prospective study. Genotyping of ABCB1 (C1236 T, C3435 T, and G2677 T/A), ABCC1 (G3173 A and G2168 A), ABCC2 (G4544 A), and ABCG2 (C421 A) polymorphisms in Northern Indian lung carcinoma patients were evaluated using polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: Poor survival outcomes were noted in patients carrying a heterozygous genotype (CT) for the ABCB1 C1236 T polymorphism compared to the wild-type genotype (CC) (p = 0.04). The mutant genotype (AA) for ABCC1 G3173 A exhibited a lower median survival time compared to the reference genotype (GG) (p = 0.009). Lower survival was observed in individuals carrying a heterozygous genotype (GA) for ABCC2 G4544 A polymorphism compared to the wild-type genotype (GG) (p = 0.017). Small cell lung cancer patients with the ABCB1 G2677 A polymorphism having a heterozygous genotype (GA) showed poor survival compared to the wild-type genotype (GG) (p = 0.03). For ABCC1 G3173 A, adenocarcinoma patients having a mutant genotype (AA) had reduced survival compared to the wild-type (GG) genotype (p = 0.03). For ABCB1 C3435 T, individuals carrying a heterozygous (CT) (p = 0.018) and mutant (TT) genotype (p = 0.007) had poor survival compared to the wild-type (CC) genotype in patients treated with pemetrexed and cisplatin. The patients administered cisplatin and irinotecan and having mutant alleles (AA) for the ABCB1 G2677 A polymorphism showed a lower survival compared to the individuals carrying wild-type alleles (GG) (p = 0.009). CONCLUSIONS: Our findings suggest that ABCB1 C1236 T, ABCB1 C3435 T, ABCB1 G2677 A, ABCC1 G3173 A, and ABCC2 G4544 A are involved in predicting prognosis. Genotyping of the ABC polymorphism is essential for predicting prognosis in lung carcinoma patients.

Systematic Thiol Decoration in a Redox-Active UiO-66-(SH)2 Metal-Organic Framework: A Case Study under Oxidative and Reductive Conditions.

The practical applicability of thiolated metal-organic frameworks (MOFs) remains challenging due to their low crystallinity and transient stability. Herein, we present a one-pot solvothermal synthesis process using varying ratios of 2,5-dimercaptoterephthalic acid (DMBD) and 1,4-benzene dicarboxylic acid (100/0, 75/25, 50/50, 25/75, and 0/100) to prepare stable mixed-linker UiO-66-(SH)2 MOFs (ML-U66SX). For each variant, the effects of different linker ratios on the crystallinity, defectiveness, porosity, and particle size have been discussed in detail. In addition, the impact of modulator concentration on these features has also been described. The stability of ML-U66SX MOFs was investigated under reductive and oxidative chemical conditions. The mixed-linker MOFs were used as sacrificial catalyst supports to highlight the interplay of template stability on the rate of the gold-catalyzed 4-nitrophenol hydrogenation reaction. The release of catalytically active gold nanoclusters originating from the framework collapse decreased with the controlled DMBD proportion, resulting in a 59% drop in the normalized rate constants (9.11-3.73 s-1 mg-1). In addition, post-synthetic oxidation (PSO) was used to further probe the stability of the mixed-linker thiol MOFs under harsh oxidative conditions. Following oxidation, the UiO-66-(SH)2 MOF underwent immediate structural breakdown, unlike other mixed-linker variants. Along with crystallinity, the microporous surface area of the post-synthetically oxidized UiO-66-(SH)2 MOF could be increased from 0 to 739 m2 g-1. Thus, the present study delineates a mixed-linker strategy to stabilize the UiO-66-(SH)2 MOF under harsh chemical conditions through meticulous thiol decoration.

Genetic variations in ABC transporter genes as a predictive biomarker for toxicity in North Indian lung cancer patients undergoing platinum-based doublet chemotherapy.

ATP-binding cassette (ABC) transporters are expressed in various human tissues and play a vital role in the efflux of various chemotherapeutic drugs. The current study has assessed genetic variants of ABCB1, ABCC1, ABCC2, and ABCG2 genes in 407 lung cancer patients undergoing platinum-based doublet chemotherapy. The association of ABCB1 (C1236 T, C3435 T, and G2677 T/A), ABCC1 (G3173 A and G2168 A),ABCC2 (G4544 A), and ABCG2 (C421 A) polymorphisms with chemotherapy-induced adverse events were assessed, and statistical analysis was conducted. Our data showed that patients harboring heterozygous (GA) genotype for ABCC1 G3173 A had an increased risk of developing leukopenia (odds ratio [OR] = 1.88, p = 0.04) and anemia (adjusted odds ratio [AOR] = 2.70, p = 0.03). For ABCC2 G4544 A polymorphism, patients harboring one copy of the mutant (GA) allele showed an increased risk of developing anemia (OR = 4.24, p = 0.03). After adjusting with various confounding factors, the heterozygous (GA) genotype showed a 5.63-fold increased risk of developing anemia (AOR = 5.63, p = 0.03). The ABCB1 G2677 A (OR = 0.37, p = 0.008) and ABCC1 G3173 A (OR = 0.54, p = 0.04) polymorphism showed a lower incidence of developing nephrotoxicity. In ABCG2 C421 A polymorphism, patients harboring heterozygous (CA) genotype had a lower incidence of having diarrhea (OR = 0.25, p = 0.04). An increased risk of having diarrhea was observed in the heterozygous genotype (GA) for ABCC1 G3173 A polymorphism (AOR = 2.78, p = 0.04). An increased risk of liver injury was found in the patients carrying heterozygous genotype of the ABCC1 G3173 A (OR = 2.06, p = 0.02) and ABCB1 C1236 T (OR = 1.85, p = 0.01). This study demonstrates the role of polymorphic variations in ABCB1, ABCC1, ABCC2, and ABCG2 in predicting hematological, nephrotoxicity, gastrointestinal, and hepatotoxicity.

Comparison of acceptability & efficacy of thermal ablation (thermocoagulation) & cryotherapy in VIA positive cervical lesions: A pilot study.

BACKGROUND OBJECTIVES: The World Health Organization (WHO) has endorsed thermal ablation (thermocoagulation) as an efficient and safe modality for treatment of cervical pre-cancer lesions. More evidence is being looked up by WHO through rigorous studies for health delivery models using screen-and-treat strategies incorporating thermal ablation and studies comparing it against the conventional standard modality cryotherapy. The objective of this study was to assess the acceptability of thermal ablation both among the providers and clients and compare the same with cryotherapy. METHODS: A randomized control trial was conducted for one year from September 2019 to October 2020 after obtaining ethics approval. Computer-generated random number table was used for randomization, and eligible candidates were divided into two groups following informed consent. Women with visual inspection with acetic acid (VIA) positive cervical lesions in Group A received cryotherapy and Group B received thermal ablation. After the procedure, the acceptability of the provider and the client were assessed using the International Agency for Research on Cancer-validated questionnaire for both the procedures. Immediate side effects and problems at six weeks and at six months were assessed as well. Efficacy was decided by the absence of VIA positivity at six months. RESULTS: The overall VIA positivity in this study was 11.8 per cent. Thermal ablation (thermocoagulation) had better provision and client acceptability than cryotherapy (significant difference). The efficacy of thermal ablation was 97.6 per cent, while, it was 92 per cent for cryotherapy (not significant). INTERPRETATION CONCLUSIONS: In the context of screen-and-treat programme in settings such as India, thermal ablation appears to be a better method of treatment than cryotherapy for cervical pre-cancerous lesions particularly in terms of better provision and client acceptability.

Exploring genetic diversity and ascertaining genetic loci associated with important fruit quality traits in apple (Malus × domestica Borkh.).

Genetic diversity is the primary source of variability in any crop improvement program, and the diverse germplasm of any crop species represents an important genetic resource for gene or allele mining to meet future needs. Huge genetic and phenotypic diversity is present in the apple gene pool, even though, breeding programs have been mainly focused on a few traits of interests, which have resulted in the reduction of the diversity in the cultivated lines of apple. Therefore, the present study was carried out on 70 diverse apple genotypes with the objective of analyzing the genetic diversity and to identify the genetic loci associated with important fruit quality traits. A total of 140 SSR primers were used to characterize the 70 genotypes of apples, out of which only 88 SSRs were found to be polymorphic. The PIC values varied from 0.03 to 0.75. The value of MI, EMR, and RP varied from 0.03 to 3.5, 0.5 to 5.0, and 1.89 to 6.74, respectively. The dendrogram and structure analysis divided all the genotypes into two main groups. In addition to this, large phenotypic variability was observed for the fruit quality traits under study indicated the suitability of the genotypes for association studies. Altogether 71 novel MTAs were identified for 10 fruit quality traits, of which 15 for fruit length, 15 for fruit diameter, 12 for fruit weight, 2 for total sugar, 2 for TSS, 4 for reducing sugar, 5 for non-reducing sugar, 5 for fruit firmness, 5 for fruit acidity and 6 for anthocyanin, respectively. Consistent with the physicochemical evaluation of traits, there was a significant correlation coefficient among different fruit quality characters, and many common markers were found to be associated with these traits (fruit diameter, length, TSS, total sugar, acidity and anthocyanin, respectively) by using the different modeling techniques (GLM, MLM). The inferred genetic structure, diversity pattern and the identified MTAs will be serving as resourceful grounds for better predictions and understanding of apple genome towards efficient conservation and utilization of apple germplasm for facilitating genetic improvement of fruit quality traits. Furthermore, these findings also suggested that association mapping could be a viable alternative to the conventional QTL mapping approach in apple. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01382-w.

Polymorphism in Thymidylate Synthase Gene Predicts Survival and Toxicity in North Indian Lung Cancer Patients Undergoing Platinum-Based Doublet Chemotherapy.

BACKGROUND: With an estimated 1.8 million deaths, lung cancer is one of the widely reported malignancies, with substantial morbidity and mortality rates. Thymidylate synthase (TS) is an important drug target for platinum-based doublet chemotherapy as it is the only de novo source of thymidylate production in the cell. TS polymorphisms in the 5'UTR of Thymidylate synthase enhancer region (TSER) 2R/3R and 3'- UTR 1494del6 are investigated in this study. METHODS: A total of 700 lung cancer patients with platinum-based doublet chemotherapy were recruited in this study. TSER (2R/3R) and TS 1494del6 polymorphisms in North Indian lung cancer patients were examined, and statistical analysis was performed. RESULTS: According to our findings, patients with the wild genotype (2R/2R) for the TSER polymorphism had a longer median survival time as compared to patients harboring the mutant type genotype (3R/3R) [MST=9.77 vs. 7.57 months; p=0.04]. On the contrary, patients with the mutant 14946del6 polymorphism (-6/-6) had a longer survival time than patients with the wild-type genotype (+6/+6) [MST=7.23 vs. 9 months]. Further, our findings elucidated that the patients with heterozygous genotype (2R3R) for TSER polymorphism had a 2.30-fold increased risk of developing leukopenia (AOR=2.30, 95% CI=0.96-5.52; p=0.05). A substantial risk of 5.14-fold constipation was found in heterozygous genotype (2R3R) when intermediate grade 2 toxicity was compared with low toxicity (grade 1) (p=0.007).An increased risk of nausea/vomiting was observed in patients with mutant genotype (-6/-6bp) for 1494 ins/del6 polymorphism compared to patients with wild-type genotype (+6/+6bp) (AOR= 2.77; 95%CI=1.10-6.96, p=0.03). CONCLUSION: According to our findings, TSER and the 1494del6 polymorphism may operate as a prognostic marker in lung cancer patients receiving platinum-based chemotherapy. Furthermore, TS polymorphisms may influence the onset of platinum-related toxicity, such as hematological and gastrointestinal toxicity. These findings might facilitate therapeutic decisions for individualized therapy in lung cancer patients.

Immunotherapy in Small Cell Lung Cancer Treatment: a Promising Headway for Future Perspective.

OPINION STATEMENT: Despite advancements in clinical research, both prognosis and treatment for SCLC patients are still in the nascent stage. SCLC is a fatal disease with high tumor mutational burden and is strongly associated with exposure to tobacco. This leads to the development of potential neo-antigens, inhibition of immune responses, and development of paraneoplastic disorders. Surgery, radiation, and chemotherapy are widely accepted treatments for cancer globally, and most recently, immunotherapy has now become the "fourth pillar" of SCLC treatment. Various immune checkpoint pathways regulate the activation of T cells at multiple stages during an immune response. T cell checkpoint inhibitors such as anti-PD1 (pembrolizumab, nivolumab), anti-PDL1, and anti-CTLA-4 (tremelimumab, ipilimumab) have potential to show anti-cancer activity along with the promise to prolong survival in patients with SCLC. Treatment with the CTLA-4-specific antibodies can restore the immune response by increasing the accumulation and survival of T-cells whereas monoclonal antibodies block either PD-1 or its ligands that prevent downregulation of effector T-cell, which enables the T-cells to mediate the death of tumor cells. Furthermore, monoclonal antibody in combination with chemotherapy has attained quite a focus to enhance the survival of SCLC patients. Apart from this, various immunotherapeutic approaches have been evaluated in the clinical trials for SCLC patients such as TLR9 agonist, anti-CD47, anti-ganglioside therapy, and anti-Notch signaling. The current review focuses on the rationale as well as on the clinical studies of immunotherapy in SCLC along with the clinical end results of certain immunotherapeutic agents and novel therapeutic combinations in SCLC patients.

Predictive role of polymorphic variants of phase II drug metabolising enzyme in modulating toxicity in North Indian lung cancer patients undergoing chemotherapy.

Genetic polymorphism of drug-metabolising enzymes such as NQO1, SULT1A1, EPHX1, and NAT2 alters its activity which hampers the detoxification and disposal of chemotherapeutic compounds. Thus, in the present study, we have comprehensively investigated the associations between SNPs of the Phase II detoxifying genes and its relationship towards platinum-induced toxicity of lung cancer patients.NQO1 (609 C > T), SULT1A1 (Arg213 His), EPHX1 (Tyr113His, His139Arg), and NAT2 (481 C > T, 803 A > G, 590 G > A, 857 G > A) were evaluated in our study for their associated adverse events caused due to the administration of platinum-based chemotherapy to the lung cancer patients.For NQO1 609 C > T polymorphism, the TT genotype showed reduced risk of constipation (OR = 0.10, p = 0.04) and anorexia (OR = 0.15, p = 0.03). For SULT1A1 Arg213His, heterozygous genotype (Arg/His) (AOR = 0.38, p = 0.006) and combined genotype (Arg/His + His/His) were not associated with increased risk of nephrotoxicity (AOR = 0.38, p = 0.004). For NAT2, heterozygous (NAT2*4/*6) and combined genotypes (NAT2*4/*4+*4/*6) for NAT2*6 polymorphism exhibit 2.4 folds (p = 0.005), and two-folds (p = 0.01) increased risk of hematological toxicity. The heterozygous (AOR = 0.45, p = 0.004) and variant genotype (AOR = 0.39, p = 0.02) for NAT2*5C had decreased risk for hematological toxicity. The heterozygous genotype for NAT2*7 polymorphism showed two-fold increased risk for developing thrombocytopenia.This study provides association of NAT2 polymorphic variants in predicting haematological toxicity.

Polymorphisms in solute carrier genes (SLC19A1, SLCO1B1, and SLCO1B3) predicts survival and toxicity in North Indian lung cancer patients undergoing platinum-based doublet chemotherapy.

WHAT IS KNOWN AND OBJECTIVE: Solute Carrier (SLC) transporters are known mediators of drug disposition that facilitate the influx of substrates and various chemotherapeutic agents into cells. Polymorphisms in the SLC19A1, SLCO1B1, and SLCO1B3 gene influence the prognosis in the cancer patients, but little is known about their role in lung cancer in Asians. So, the current study aims to investigate the polymorphisms in SLC19A1, SLCO1B1, and SLCO1B3 genes in Northern Indian lung cancer patients. METHODS: Patients with lung cancer who had a confirmed histology and cytology diagnosis were enrolled in the study. SLC polymorphisms were assessed by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) for variations in SLC19A1 (G80 A), SLCO1B1 (A388 G, T521 C), and SLCO1B3 (A1683-5676 G). RESULTS AND DISCUSSION: Our results showed that mutant genotype for SLC19A1 G80 A polymorphism had higher median survival time (MST) compared to wild genotype. ADCC patients with mutant genotype showed better survival compared to wild genotype for SLC19A1 G80 A. SCLC patients G80 A polymorphism showed increased survival in patients with mutant genotype (p = 0.04). In SLCO1B3, A1683-5676 G patients carrying heterozygous alleles and administered with platinum and docetaxel showed inferior survival (p = 0.006). In T521 C variant, patients with carrier genotype had reduced chances of developing anaemia (p = 0.04). Patients with SLC19A1 and SLCO1B3 variants showed lower incidence of thrombocytopenia and nephrotoxicity. WHAT IS NEW AND CONCLUSION: Our findings imply that Solute Carrier gene polymorphisms modulate the overall survival in lung cancer patients undergoing platin-based doublet chemotherapy, also these polymorphisms have a modifying impact on the associated adverse events/toxicity.

Synergistic polymorphic interactions of phase II metabolizing genes and their association toward lung cancer susceptibility in North Indians.

Lung cancer is a multifactorial carcinoma with diverse heterogeneity. Genetic variations in drug-metabolizing enzymes may lead to defective detoxification and clearance of carcinogenic compounds. The high-order gene-gene interaction has been carried out between different genotypes of Phase II detoxification genes (NQO1, SULT1A1, NAT2, and EPHX1). Our results depict the genetic combination of SULT1A1 R213H with NAT2 × 5B L161L, SULT1A1 R213H with NAT2 × 5C K268R, EPHX1 H139R and NAT2 × 5B L161L exhibit a protective effect towards lung cancer risk. Further, the triple combinations of NQO1 P187S, EPHX1 Y113H, and EPHX1 H139R; NQO1 P187S, EPHX1 Y113H, and NAT2 × 6 R197Q; NQO1 P187S, EPHX1 Y113H, and NAT2 × 7 G286E; SULT1A1 R213H, EPHX1 H139R, and NAT2 × 7 G286E suggested a two-fold increased risk of lung cancer for subjects. Genetic polymorphisms of phase II detoxifying genes (NAT2, NQO1, EPHX1, SULT1A1) are prognostic markers for lung cancer.

Evaluation of the effects of 0.05% sodium hypochlorite and 0.12% chlorhexidine gluconate twice daily rinse on periodontal parameters and gingival crevicular fluid HSV1 and CMV levels in patients with chronic periodontitis: a multicentric study.

Background: Mechanical debridement of periodontal pockets remains the mainstay of therapy in all forms of periodontitis. There is 47% greater reduction in plaque amount when sodium hypochlorite (NaOCl) is used as an adjunct when compared with water rinsing. The aim of this study was to evaluate the effects of 0.05% NaOCl and 0.12% chlorhexidine gluconate twice daily rinse on periodontal parameters and gingival crevicular fluid (GCF) HSV1 and CMV levels in chronic periodontitis. Methods: Patients assigned to group A were prescribed 0.05% NaOCl mouthwash for twice daily rinse. Patients in group B were prescribed 0.12% chlorhexidine gluconate mouthwash to be used twice daily. Evaluation of periodontal parameters was done at baseline and after six months following therapy. GCF HSV1 and CMV levels were evaluated using a polymerase chain reaction. Results: A statistically significant difference was noted in the improvement in periodontal parameters between both groups, when evaluated six months following therapy with greater reduction in group A vis-a-vis group B. Conclusion: NaOCl when prescribed as a twice daily mouthwash can be recommended as a part of the home care regime in patients with chronic periodontitis. It is more cost-effective, easily available and can be beneficial to the troops in difficult terrains and extremes of climates, where oral healthcare facilities are not easily accessible.

Genome Resource: Ralstonia solanacearum Phylotype II Sequevar 1 (Race 3 Biovar 2) Strain UW848 From the 2020 U.S. Geranium Introduction.

Ralstonia solanacearum phylotype II sequevar 1 (RsII-1, formerly race 3 biovar 2) causes tomato bacterial wilt, potato brown rot, and Southern wilt of geranium. Strains in RsII-1 cause wilting in potato and tomato at cooler temperatures than tropical lowland R. solanacearum strains. Although periodically introduced, RsII-1 has not established in the United States. This pathogen is of quarantine concern and listed as a Federal Select Agent. We report a rapidly sequenced (<2 days) draft genome of UW848, a RsII-1 isolate introduced to the United States in geranium cuttings in spring 2020. UW848 belongs to the near-clonal cluster of RsII-1 global pandemic strains.

Strain-Level Identification of Bacterial Tomato Pathogens Directly from Metagenomic Sequences.

Routine strain-level identification of plant pathogens directly from symptomatic tissue could significantly improve plant disease control and prevention. Here we tested the Oxford Nanopore Technologies (ONT) MinION sequencer for metagenomic sequencing of tomato plants either artificially inoculated with a known strain of the bacterial speck pathogen Pseudomonas syringae pv. tomato or collected in the field and showing bacterial spot symptoms caused by one of four Xanthomonas species. After species-level identification via ONT's WIMP software and the third-party tools Sourmash and MetaMaps, we used Sourmash and MetaMaps with a custom database of representative genomes of bacterial tomato pathogens to attempt strain-level identification. In parallel, each metagenome was assembled and the longest contigs were used as query with the genome-based microbial identification Web service LINbase. Both the read-based and assembly-based approaches correctly identified P. syringae pv. tomato strain T1 in the artificially inoculated samples. The pathogen strain in most field samples was identified as a member of Xanthomonas perforans group 2. This result was confirmed by whole genome sequencing of colonies isolated from one of the samples. Although in our case metagenome-based pathogen identification at the strain level was achieved, caution still must be exercised in interpreting strain-level results because of the challenges inherent to assigning reads to specific strains and the error rate of nanopore sequencing.

Epigenetics and oxidative stress: A twin-edged sword in spermatogenesis.

Spermatogenesis is a series of complex events involving a delicate balance between cell proliferation and cell differentiation. Aggregation of chromatins and epigenetic modifications play a vital role in spermatogenesis via regulation of molecular pathways to maintain testicular homeostasis. These epigenetic mechanisms consist of histone modification, chromatin remodelling, DNA methylation and miRNA, etc., which reportedly are critical players in spermatogenesis. One such mechanism involves regulation of oxidative stress in the male reproductive system. The fact that testicular cells contain plenty of unsaturated fatty acids and undergo division at a high rate makes spermatogenic cells highly susceptible to oxidative insult leading to deleterious effect on spermatozoa, which may culminate in infertility in men. Although the correlation between ROS-mediated oxidative stress and epigenetic alterations has been indicated, research in this regard is still in infancy. Further, the fact that environmental and life style factors are critical determinants of spermatogenic potential indicates the importance of epigenetic regulation of key molecular events in spermatogenesis. Therefore, the current review aims to discuss the ROS-induced epigenetic deregulation of the molecular mechanism(s) involved in spermatogenesis.

Indomethacin Exacerbates Oleic Acid-Induced Acute Respiratory Distress Syndrome in Adult Rats.

Acute respiratory distress syndrome (ARDS) is an acute fulminant condition associated with acute lung injury and inflammation leading to hypoxemia, pulmonary edema and respiratory failure. Even though prostaglandins are inflammatory mediators, the role of prostaglandins in ARDS is still not clear. Therefore, we examined the involvement of prostaglandin in experimentally induced ARDS by using prostaglandin synthesis inhibitor, indomethacin. Experiments were conducted on anesthetized adult rats (total n=15). Cannulation of trachea, jugular vein and carotid artery was done in these rats. Recording of respiratory excursions (for respiratory frequency; RF), ECG (for heart rate; HR) and blood pressure, before and after lethal dose of oleic acid (75 µL i.v.) was done for 120 min or till death of the animals. Arterial blood sample was collected 15 min after oleic acid injection to determine PaO2/FiO2 ratio. Lungs were excised at the end of experiment for estimation of pulmonary water content. Administration of oleic acid produced progressive increase in the RF up to 45 min followed by decrease. Subsequently, the respiration stopped and all the animals died by 75 min (mean survival time = 64±8.2 min). HR and mean arterial pressure (MAP) exhibited an immediate decrease followed by an increase up to 45 min. Thereafter, the HR and MAP progressively decreased. PaO2/FiO2 ratio in this group was 182±2.6 mm Hg and pulmonary water content was significantly greater than saline control group. However in indomethacin pretreated rats, injection of oleic acid produced instantaneous decrease in RF and all the animals died within 10 min (mean survival time = 6.6±1.07 min). HR and MAP followed the same pattern as seen with RF. Pulmonary water content in indomethacin pretreated animals was also significantly greater than control group. These observations indicate that indomethacin exacerbates the OA-induced ARDS. Thus, prostaglandins play an important role in the pathophysiology of OA-induced ARDS.

Sphygmomanometric Blood Pressure Drop on Consecutive Measurements: The Search for a Cause.

This study was inspired by our oft-noted observation that the first sphygmomanometric reading of blood pressure (BP) is invariably higher than the subsequent ones recorded immediately thereafter. The objectives of this study were to establish the statistical validity of this observation and further, to probe the possible causes of the same. The sphygmomanometric BP was recorded in 30 non-obese young adults using two different protocols. In protocol-1, BP in the left arm was repeated thrice in quick succession, both in standing and supine postures. In protocol-2, BP was recorded in the supine position six times in quick succession, thrice in the left arm and immediately thereafter, thrice in the right arm. Data was compiled and analysed using appropriate statistical tests. In protocol-1, a statistically-significant drop in the blood pressure was consistently noted between quickly consecutive measurements in both standing and supine postures. Importantly, this pressure drop was not significantly affected by posture. In protocol-2, significant pressure drop was recordable from both arms. These findings rule out baroreflex as a cause of the pressure-drop on consecutive measurements and suggest a likely role of tissue compaction in the same.