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Genetic diversity among 12 cotton bollworm, Helicoverpa armigera (Hubner) populations from different geographic regions of South India was done using mitochondrial DNA-specific markers. Thirteen selected mtDNA universal markers/primers generated a total of 167 PCR amplicons, of which 162 were polymorphic across all 12 populations. An average of 12.85 amplicons per primer was noted. All populations could be differentiated from one another using specific primers; specific band(s) could be potentially used to differentiate individual populations. Genetic relationships between the populations were evaluated by generating a similarity matrix based on Jaccard's index and a phenetic dendrogram was generated by UPGMA method. Principal component analysis separated the 12 populations into different groups based on band-sharing data. Populations showed varied degrees of genetic similarity within a range of 0.04-0.52. Also, the populations appeared to be more dispersed on the principal component plot indicating a wide genetic base. On a larger scale, genetic differences among populations appear to result from low dispersal rates between populations. The level of genetic variation detected between the H. armigera populations with mtDNA-PCR analysis suggests that it is an efficient marker technology for delineating genetic relationships amongst populations and estimating genetic diversity, thereby gaining insight into genetic structure of populations and its further use in formulation of appropriate area wide management strategies for this pest. [ABSTRACT FROM AUTHOR]

Aim: The study was undertaken: 1) To assess salivary glucose (SaG) levels in diabetic and nondiabetic subjects and to determine if saliva could be used as a noninvasive tool to diagnose and monitor Type II diabetes mellitus. 2) Correlation of SaG levels with serum glucose (SeG) levels in nondiabetic and diabetic patients. 3) To correlate the oral manifestations of diabetes mellitus with serum and SaG levels. Material and Methods: Both fasting and postprandial serum and SaG levels were analyzed from 70 Type II diabetic and 70 nondiabetic subjects. The detailed examination of oral cavity in relation to periodontal and dental status and subjective oral complaints were recorded. The obtained values were subjected to statistical analysis. Results: The mean fasting salivary glucose (FSaG) was 5.469 + 2.347 mg/dL and 7.634 + 4.468 mg/dL in nondiabetic and diabetics, respectively (P = 0.000) and postprandial salivary glucose (PSaG) was 6.434 + 2.111 mg/dL and 8.736 + 4.962 mg/dL in nondiabetic and diabetics, respectively (P = 0.000). The positive correlation was found between SeG levels and SaG in diabetics (P = 0.000). Strong positive correlation was observed between SeG and SaG with oral manifestations in Type II diabetic patients (P < 0.05). Conclusion: Saliva can be a useful tool in regular monitoring of “already diagnosed Type II diabetics” (by their SeG levels) rather than diagnosing subjects with “unknown status of diabetes mellitus.” Strong positive correlation exists between SeG level and SaG level with oral manifestations in Type II diabetic patients.

Background Although coffee consumption is often reported as a trigger for atrial fibrillation (AF) among patients with paroxysmal AF, prospective studies on the relation of coffee consumption with AF risk have been inconsistent. Hence, we sought to assess the association between coffee consumption and risk of AF in men. Methods and Results We prospectively studied men who participated in the Physicians’ Health Study (N=18 960). Coffee consumption was assessed through self‐reported food frequency questionnaires. The incidence of AF was assessed through annual questionnaires and validated through review of medical records in a subsample. Cox proportional hazard models were used to calculate hazard ratios and 95% CIs of AF. The average age was 66.1 years. A total of 2098 new cases of AF occurred during a mean follow‐up of 9 years. Hazard ratios (95% CI) of AF were 1.0 (reference), 0.85 (0.71‐1.02), 1.07 (0.88‐1.30), 0.93 (0.74‐1.17), 0.85 (0.74‐0.98), 0.86 (0.76‐0.97), and 0.96 (0.80‐1.14) for coffee consumption of rarely/never, ≤1 cup/week, 2 to 4 cups/week, 5 to 6 cups/week, 1 cup/day, 2 to 3 cups/day, and 4+ cups/day, respectively; adjusting for age, smoking, alcohol intake, and exercise (P for nonlinear trend=0.01). In a secondary analysis the multivariable adjusted hazard ratio (95% CI) of AF per standard deviation (149‐mg) change in caffeine intake was 0.97 (0.92‐1.02). Conclusions Our data suggest a lower risk of AF among men who reported coffee consumption of 1 to 3 cups/day.

Background: Most newborns in NICU would be on respiratory support either on invasive or non-invasive ventilation and it is difficult to measure anthropometries like weight, length and head circumference in these sick newborns. This study was aimed to determine the correlation of foot length of a newborn with occipitofrontal head circumference (OFC), crown-heel length (CHL) and weight of the newborn. Methods: A cross-sectional study was conducted in the NICU of Shri B M Patil Medical College Hospital and Research center, Vijayapura. The foot length, occipitofrontal head circumference (OFC) and crown-heel length (CHL) of neonates of gestational ages 28-42 weeks were measured between 12 hours and 7 days of life. Results: Among 350 neonates enrolled, 61% of babies were preterm and 39% were term babies. In premature babies, the correlation between foot length and birth weight (r=0.90) and foot length and length (r=0.89) was pronounced. A positive linear correlation was observed between foot length and weight in babies of all gestational ages. For the identification of LBW babies (

Aims and Objectives: Certain strains of human papillomavirus (HPV) have been shown to be etiologically related to the development of uterine, cervical, and other genital cancers, but their role in the development of malignancies at other sites is less well established. Previous studies have shown HPV in tumors of the head and neck, but its prevalence has varied depending on the detection methods and the types of tumor and/or tissue examined. This study was undertaken for the detection of high-risk HPV types 16 and 18 and human immunodeficiency virus (HIV) in oral squamous cell carcinoma. Materials and Methods: Twenty-five patients histologically diagnosed with oral squamous cell carcinoma and 10 apparently normal persons as controls were selected for the present study. Two biopsy specimens were removed surgically by incision biopsy for histopathological examination and polymerized chain reaction (PCR) study. Results: Out of 25 oral squamous cell carcinoma subjects, 8 were found to be HPV positive in PCR. Out of these eight subjects, four had HPV 16 and the other four had other genotypes, and one subject was HIV positive. Conclusion: The conclusion drawn from the present study was that well-defined risk factors like HPV may play a prominent role in the development of oral squamous cell carcinomas, in addition to other risk factors. Further studies with a larger sample size are necessary to arrive at conclusions and to explore the relationship of HPV and HIV in oral squamous cell carcinoma.

Loperamide is over-the-counter antidiarrheal agent acting on peripherally located μ opioid receptors. It is gaining popularity among drug abusers as opioid substitute. We report a case of a 46-year-old male that was presented after cardiac arrest. After ruling out ischemia, cardiomyopathy, pulmonary embolism, central nervous system pathology, sepsis, and other drug toxicity, we found out that patient was using around 100 mg of Loperamide to control his chronic diarrhea presumably because of irritable bowel syndrome for last five years and consumed up to 200 mg of Loperamide daily for last two days before the cardiac arrest. We hypothesize that the patient’s QTc prolongation and subsequent cardiac arrest are due to Loperamide toxicity. Patient experienced gradual resolution of tachyarrhythmia and gradual decrease in QTc interval during hospitalization which supports the evidence of causal relationship between Loperamide overdose and potentially fatal arrhythmias. It also provided the clue that patient may have congenital long QT syndrome which was unmasked by Loperamide causing ventricular arrhythmias. This case adds one more pearl in the literature to support that Loperamide overdose related cardiac toxicity does exist and it raises concerns over Loperamide abuse in the community.

The article offers chemical structure for the article "A Concise Li/liq. NH3 Mediated Synthesis of (4E,10Z)-Tetradeca-4,10-dienyl Acetate (I): The Major Sex Pheromone of Apple Leafminer Moth, Phyllonorycter ringoniella" by Y.-S. Xie and others in "Bulletin of the Korean Chemical Society" in 2014.

The study provides simple protocol for identifying unknown genes (DNA and RNA) and proteins present in the plants. The exact mechanism of nanoparticle synthesis from plant extracts is still unclear. Although functionalization of nanoparticle has been achieved by binding biomolecules and stabilizing through exchange of ligands and electrostatic interactions. This study will help in case of difficulty in extraction of proteins and DNA from nanoparticles due to less sample collection or degradation of active biomolecules. Plant extracts holds various biomolecules and can be used to presume the basic formulae of plant proteins by using software. The presence of DNA traces on silver nanoparticles confirmed and DNA sequence was extracted from NCBI gene bank. Homology modeling is an alternative method to predict 3D structure of proteins in the absence of experimental results. DNA gel electrophoresis and quantification of biomolecules and 3D protein structures have built from known sequences of conforming family members of protein using SWISS-MODEL. A major advantage of automated homology modeling is creating protein models that are easy to design the structure. Protein sequencing is continuously evolving nowadays. Experts are improving SWISS-MODEL to enhance the efficient transition. The study will help in easy and rapid identification of genes and proteins present on the surface of biological nanoparticles. Structural analysis of protein (proteomics) helps to identify novel functions that could facilitate designing of efficient biosensors.

Objective: The Cancer Genome Atlas (TCGA) project identified favorable prognosis regarding the ultra-mutated endometrial cancer (EC) subtype linked to polymerase epsilon gene (POLE) mutations. This study investigated POLE mutations in EC of Indian patients., Methods: This retrospective analytical study was conducted between January 2016 and January 2023 at the Government Medical College, Kozhikode, and the MVR Cancer Center, Kozhikode, Kerala. Sanger sequencing of POLE gene exons 9 and 13 in 151 EC patients was carried out to analyze the relationship between mutations and epidemiological factors, clinicopathologic features, and treatment outcomes., Results: Among 151 cases enrolled, 39 were unique POLE-mutated cases. Significant associations were high-grade tumors, myometrial invasion >50%, and Lymph-vascular space invasion (LVSI). The median follow-up was 40 months (95% confidence interval [CI], 34-46). A lower mean disease-specific survival (DSS) of 51.7 months (95% CI, 43.7-59.6) was noted in the POLE-mutated group compared with 72.11 months (95% CI, 67.60-76.62) for the POLE wild-type. A statistically significant hazard ratio (HR) of 2.683 for DSS in the POLE-mutated group was noted. In advanced stages (FIGO stages II-IV), a nine-fold HR for DSS and overall survival (OS) compared with POLE wild-type was identified. After controlling for treatment effects using Cox proportional HR, advanced-stage POLE-mutated tumors had a significantly higher HR of 8.67 for DSS compared with POLE-wild-type tumors of the same stage., Conclusion: This study identified a unique set of POLE mutations in Indian EC patients associated with poor prognosis, which were particularly pronounced in advanced stages. Advanced stage of presentation, type of POLE mutations, and possibly ethnicity are predictors of adverse outcomes in POLE-mutated EC. The present study highlights ethnicity as a determinant of phenotypic expression of genetic change., (© 2024 International Federation of Gynecology and Obstetrics.)

The response to type I IFNs involves the rapid induction of prototypical IFN signature genes (ISGs). It is not known whether the tightly controlled ISG expression observed at the cell population level correctly represents the coherent responses of individual cells or whether it masks some heterogeneity in gene modules and/or responding cells. We performed a time-resolved single-cell analysis of the first 3 h after in vivo IFN stimulation in macrophages and CD4+ T and B lymphocytes from mice. All ISGs were generally induced in concert, with no clear cluster of faster- or slower-responding ISGs. Response kinetics differed between cell types: mostly homogeneous for macrophages, but with far more kinetic diversity among B and T lymphocytes, which included a distinct subset of nonresponsive cells. Velocity analysis confirmed the differences between macrophages in which the response progressed throughout the full 3 h, versus B and T lymphocytes in which it was rapidly curtailed by negative feedback and revealed differences in transcription rates between the lineages. In all cell types, female cells responded faster than their male counterparts. The ISG response thus seems to proceed as a homogeneous gene block, but with kinetics that vary between immune cell types and with sex differences that might underlie differential outcomes of viral infections., (Copyright © 2024 by The American Association of Immunologists, Inc.)

Background: High-risk human papillomavirus (HPV) is a primary cause of an increasing number of oropharyngeal squamous cell carcinomas (OPSCCs). The viral etiology of these cancers provides the opportunity for antigen-directed therapies that are restricted in scope compared with cancers without viral components. However, specific virally-encoded epitopes and their corresponding immune responses are not fully defined., Methods: To understand the OPSCC immune landscape, we conducted a comprehensive single-cell analysis of HPV16+ and HPV33+ primary tumors and metastatic lymph nodes. We used single-cell analysis with encoded peptide-human leukocyte antigen (HLA) tetramers to analyze HPV16+ and HPV33+ OPSCC tumors, characterizing the ex vivo cellular responses to HPV-derived antigens presented in major Class I and Class II HLA alleles., Results: We identified robust cytotoxic T-cell responses to HPV16 proteins E1 and E2 that were shared across multiple patients, particularly in HLA-A*01:01 and HLA-B*08:01. Responses to E2 were associated with loss of E2 expression in at least one tumor, indicating the functional capacity of these E2-recognizing T cells and many of these interactions validated in a functional assay. Conversely, cellular responses to E6 and E7 were limited in quantity and cytotoxic capacity, and tumor E6 and E7 expression persisted., Conclusions: These data highlight antigenicity beyond HPV16 E6 and E7 and nominate candidates for antigen-directed therapies., Competing Interests: Competing interests: CM, BV, QT, DL-E, DCP and AJC are employees and/or stockholders of Repertoire Immune Medicine. GJH reports grants and institutional support from ASCO CCF, Bicara, BMS, Gateway for Cancer Research, GSK, Kite, KSQ, Kura Oncology, ImmunityBio, Regeneron. Consulting/honoraria from Bicara, BMS, Coherus, Exicure, Kura, Maverick, Merck, Naveris, Regeneron, and SIRPant. AME reports support from NIH/NIDCR U0 DE029188. RU serves on a Merck advisory board., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) provokes a potentially fatal pneumonia with multiorgan failure, and high systemic inflammation. To gain mechanistic insight and ferret out the root of this immune dysregulation, we modeled, by in vitro coculture, the interactions between infected epithelial cells and immunocytes. A strong response was induced in monocytes and B cells, with a SARS-CoV-2-specific inflammatory gene cluster distinct from that seen in influenza A or Ebola virus-infected cocultures, and which reproduced deviations reported in blood or lung myeloid cells from COVID-19 patients. A substantial fraction of the effect could be reproduced after individual transfection of several SARS-CoV-2 proteins (Spike and some nonstructural proteins), mediated by soluble factors, but not via transcriptional induction. This response was greatly muted in monocytes from healthy children, perhaps a clue to the age dependency of COVID-19. These results suggest that the inflammatory malfunction in COVID-19 is rooted in the earliest perturbations that SARS-CoV-2 induces in epithelia., (Copyright © 2021 the Author(s). Published by PNAS.)

The hallmark of severe COVID-19 is an uncontrolled inflammatory response, resulting from poorly understood immunological dysfunction. We hypothesized that perturbations in FoxP3 + T regulatory cells (Treg), key enforcers of immune homeostasis, contribute to COVID-19 pathology. Cytometric and transcriptomic profiling revealed a distinct Treg phenotype in severe COVID-19 patients, with an increase in Treg proportions and intracellular levels of the lineage-defining transcription factor FoxP3, correlating with poor outcomes. These Tregs showed a distinct transcriptional signature, with overexpression of several suppressive effectors, but also proinflammatory molecules like interleukin (IL)-32, and a striking similarity to tumor-infiltrating Tregs that suppress antitumor responses. Most marked during acute severe disease, these traits persisted somewhat in convalescent patients. A screen for candidate agents revealed that IL-6 and IL-18 may individually contribute different facets of these COVID-19-linked perturbations. These results suggest that Tregs may play nefarious roles in COVID-19, by suppressing antiviral T cell responses during the severe phase of the disease, and by a direct proinflammatory role., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Immune responses to cancer are highly variable, with mismatch repair-deficient (MMRd) tumors exhibiting more anti-tumor immunity than mismatch repair-proficient (MMRp) tumors. To understand the rules governing these varied responses, we transcriptionally profiled 371,223 cells from colorectal tumors and adjacent normal tissues of 28 MMRp and 34 MMRd individuals. Analysis of 88 cell subsets and their 204 associated gene expression programs revealed extensive transcriptional and spatial remodeling across tumors. To discover hubs of interacting malignant and immune cells, we identified expression programs in different cell types that co-varied across tumors from affected individuals and used spatial profiling to localize coordinated programs. We discovered a myeloid cell-attracting hub at the tumor-luminal interface associated with tissue damage and an MMRd-enriched immune hub within the tumor, with activated T cells together with malignant and myeloid cells expressing T cell-attracting chemokines. By identifying interacting cellular programs, we reveal the logic underlying spatially organized immune-malignant cell networks., Competing Interests: Declaration of interests K.P., M.H., J.H.C., V.K.K., A.J.A., O.R.-R., A. Regev., and N.H. are co-inventors on US Patent Application No. 16/995,425 relating to methods for predicting outcomes and treating colorectal cancer as described in the manuscript. A.J.A. is a Consultant for Oncorus, Arrakis Therapeutics, and Merck and receives research funding from Mirati Therapeutics, Deerfield, and Novo Ventures. R.B.C. receives consulting/speaking fees from Abbvie, Amgen, Array Biopharma/Pfizer, Asana Biosciences, Astex Pharmaceuticals, AstraZeneca, Avidity Biosciences, BMS, C4 Therapeutics, Chugai, Elicio, Fog Pharma, Fount Therapeutics/Kinnate Biopharma, Genentech, Guardant Health, Ipsen, LOXO, Merrimack, Mirati Therapeutics, Natera, N-of-one/QIAGEN, Novartis, nRichDx, Revolution Medicines, Roche, Roivant, Shionogi, Shire, Spectrum Pharmaceuticals, Symphogen, Tango Therapeutics, Taiho, Warp Drive Bio, and Zikani Therapeutics; holds equity in Avidity Biosciences, C4 Therapeutics, Fount Therapeutics/Kinnate Biopharma, nRichDx, and Revolution Medicines; and has received research funding from Asana, AstraZeneca, Lilly, and Sanofi. V.K.K. consults for Pfizer, GSK, Tizona Therapeutics, Celsius Therapeutics, Bicara Therapeutics, Compass Therapeutics, Biocon, and Syngene. G.M.B. has sponsored research agreements with Palleon Pharmaceuticals, Olink Proteomics, and Takeda Oncology; served on SABs for Novartis and Nektar Therapeutics; and received honoraria from Novartis. A.C.A. is a paid consultant for iTeos Therapeutics, and is an SAB member for Tizona Therapeutics, Compass Therapeutics, Zumutor Biologics, and ImmuneOncia, which have interests in cancer immunotherapy. A.C.A.’s interests were reviewed and managed by the BWH and Partners Healthcare in accordance with their conflict of interest policies. M.G. receives research funding from BMS, Merck, and Servier. J.W.R., C.A.F., and M.L.H. are employees of and stockholders for NanoString Technologies Inc. D.R.Z. is a former employee of NanoString Technologies Inc. B.I. is a consultant for Merck and Volastra Therapeutic. R.B. is an UptoDate Author. A. Rotem is an equity holder in Celsius Therapeutics and NucleAI. K.N. has research funding from Janssen, Revolution Medicines, Evergrande Group, Pharmavite; advisory board: Seattle Genetics, BiomX; consulting: X-Biotix Therapeutics; research funding: BMS, Merck, and Servier. B.E.J. is on the SAB for Checkpoint Therapeutics. O.R.-R. is a named inventor on patents and patent applications filed by the Broad Institute in single-cell genomics. From October 2020, O.R.-R. is an employee of Genentech. A. Regev. is a founder of and equity holder in Celsius Therapeutics, an equity holder in Immunitas Therapeutics, and was an SAB member for Thermo Fisher Scientific, Syros Pharmaceuticals, and Neogene Therapeutics until August 1, 2020. From August 1, 2020, A. Regev. is an employee of Genentech. A. Regev. is a named inventor on several patents and patent applications filed by the Broad Institute in single-cell and spatial genomics. N.H. holds equity in BioNTech and is an advisor for Related Sciences/Danger Bio., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Neutrophils are implicated in multiple homeostatic and pathological processes, but whether functional diversity requires discrete neutrophil subsets is not known. Here, we apply single-cell RNA sequencing to neutrophils from normal and inflamed mouse tissues. Whereas conventional clustering yields multiple alternative organizational structures, diffusion mapping plus RNA velocity discloses a single developmental spectrum, ordered chronologically. Termed here neutrotime, this spectrum extends from immature pre-neutrophils, largely in bone marrow, to mature neutrophils predominantly in blood and spleen. The sharpest increments in neutrotime occur during the transitions from pre-neutrophils to immature neutrophils and from mature marrow neutrophils to those in blood. Human neutrophils exhibit a similar transcriptomic pattern. Neutrophils migrating into inflamed mouse lung, peritoneum and joint maintain the core mature neutrotime signature together with new transcriptional activity that varies with site and stimulus. Together, these data identify a single developmental spectrum as the dominant organizational theme of neutrophil heterogeneity.

The immune and enteric nervous (ENS) systems monitor the frontier with commensal and pathogenic microbes in the colon. We investigated whether FoxP3 + regulatory T (Treg) cells functionally interact with the ENS. Indeed, microbe-responsive RORγ + and Helios + subsets localized in close apposition to nitrergic and peptidergic nerve fibers in the colon lamina propria (LP). Enteric neurons inhibited in vitro Treg (iTreg) differentiation in a cell-contact-independent manner. A screen of neuron-secreted factors revealed a role for interleukin-6 (IL-6) in modulating iTreg formation and their RORγ + proportion. Colonization of germfree mice with commensals, especially RORγ + Treg inducers, broadly diminished colon neuronal density. Closing the triangle, conditional ablation of IL-6 in neurons increased total Treg cells but decreased the RORγ + subset, as did depletion of two ENS neurotransmitters. Our findings suggest a regulatory circuit wherein microbial signals condition neuronal density and activation, thus tuning Treg cell generation and immunological tolerance in the gut., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

CD4 + effector lymphocytes (T eff ) are traditionally classified by the cytokines they produce. To determine the states that T eff cells actually adopt in frontline tissues in vivo, we applied single-cell transcriptome and chromatin analyses to colonic T eff cells in germ-free or conventional mice or in mice after challenge with a range of phenotypically biasing microbes. Unexpected subsets were marked by the expression of the interferon (IFN) signature or myeloid-specific transcripts, but transcriptome or chromatin structure could not resolve discrete clusters fitting classic helper T cell (T H ) subsets. At baseline or at different times of infection, transcripts encoding cytokines or proteins commonly used as T H markers were distributed in a polarized continuum, which was functionally validated. Clones derived from single progenitors gave rise to both IFN-γ- and interleukin (IL)-17-producing cells. Most of the transcriptional variance was tied to the infecting agent, independent of the cytokines produced, and chromatin variance primarily reflected activities of activator protein (AP)-1 and IFN-regulatory factor (IRF) transcription factor (TF) families, not the canonical subset master regulators T-bet, GATA3 or RORγ.

Objectives: To assess the efficacy of self-collected vaginal samples compared with physician-collected cervical samples for the detection of HPVDNA., Methods: A hospital-based cross-sectional study was carried out among patients with newly diagnosed cervical cancer attending the Gynecologic Oncology Division, Department of Obstetrics and Gynecology and Radiation Oncology Department at Government Medical College, Kozhikode, Kerala between March 2017 and April 2019. Consenting patients collected their vaginal samples, followed by cervical sample collection by the clinician. The paired samples were transported at 4-8 °C to the laboratory. Amplification of LCR/E6/E7 regions of the HPV genome was done by polymerase chain reaction (PCR). The agreement level between paired samples was assessed by the Kappa index., Results: Among the 114 cervical cancer patients enrolled in the present cross-sectional study, the prevalence of HPV DNA was 78.1% (95% confidence interval [CI] 69.2%-85%) in cervical samples and 77.2% in vaginal samples (95% CI 68.7%-83.9%). The overall agreement between the two sampling methods was 93.9% and the kappa value was 0.82 (P<0.001). The sensitivity of HPV detection using vaginal samples was 98.9% (95% CI 93.9%-99.8%) and the specificity was 100% (95% CI 86.7%-100%) with cervical sampling as the gold standard. By Kappa index, an almost perfect agreement for HPV DNA detection between self-collected and physician-collected samples was observed., Conclusion: Self-collection of vaginal samples ensures equity of cervical cancer screening in low-income countries such as India., (© 2020 International Federation of Gynecology and Obstetrics.)

A full account on the first total synthesis of a chroman meroterpenoid, (-)-phomoarcherin C, has been described. Key synthetic transformations include phenyl boronic acid-mediated 6π-electrocyclization reaction, a stereospecific hydrogenation driven by thermodynamic conformational stability of the product, and regioselective formylation. The strategy employed is considerably short, is atom-economical, and can open the doors to provide access to various other natural products of the same kind.

Background: WHO has recommended Visual Inspection with Acetic acid (VIA) or Human Papillomavirus (HPV) DNA testing if feasible, for cervical cancer screening in low income countries. However, the number of women undergoing screening is very low as a result of limited information, inadequate infrastructure and invasive nature of sampling. Methods: A cross sectional study was carried out comparing HPV DNA detection by Polymerase Chain Reaction (PCR) in paired cervical and urine samples procured from histologically confirmed cervical cancer cases. Results: Amongst the samples collected from 114 cervical cancer cases, HPV DNA was tested positive in cervical samples of 89 (78.1%) and urine samples of 55 (48.2%) patients. The agreement between the two sampling methods was 66.7% and the kappa value was 0.35 indicating a fair agreement. The sensitivity of HPV detection using urine samples was 59.6% (95% confidence interval 49.16%-69.15%) and the specificity was 92% (95% confidence interval 75.0%-97.8%). Conclusion: Even though not acceptable as an HPV DNA screening tool due to low sensitivity, the urine sampling method is inexpensive and more socially acceptable for large epidemiological surveys in developing countries to estimate the burden.

A new bioactive proline-rich cyclohexapeptide - diandrine C ( 6 ), previously isolated from whole plant of Drymaria diandra (Caryophyllaceae), was synthesized through coupling reactions of tetrapeptide unit Boc-Gly--Pro--Tyr--Trp-OH with dipeptide unit -Pro-Gly-OMe using N,N -diisopropylcarbodiimide (DIPC) as the coupling agent, followed by cyclization of linear hexapeptide unit under alkaline condition. Structure of cyclohexapeptide was confirmed by means of chemical, and spectroscopic analyses and also was screened for its antimicrobial and anthelmintic properties. Bioevaluation results indicated that the newly synthesized hexacyclopeptide exhibited potent antimicrobial activity against Gram-negative bacteria Pseudomonas aeruginosa , Klebsiella pneumoniae and pathogenic Candida albicans at 6 μg/mL. Moderate to good level of antihelmintic activity against three earthworm species Megascoplex konkanensis , Pontoscotex corethruses and Eudrilus eugeniae was also observed at concentration of 2 mg/mL.

An N -methylated analog of a marine bacteria-derived natural proline-rich tetracyclopeptide was synthesized by coupling the deprotected dipeptide fragments Boc-l-prolyl-l- N -methylleucine-OH and l-prolyl-l- N -methylphenylalanine-OMe. A coupling reaction was accomplished utilizing N , N '-Dicyclohexylcarbodidimde (DCC) and 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC·HCl) as coupling agents and Triethylamine (TEA) or N -methylmorpholine (NMM) as the base in the presence of the racemization suppressing agent. This was followed by the cyclization of the linear tetrapeptide fragment under alkaline conditions. The structure of the synthesized cyclooligopeptide was confirmed using quantitative elemental analysis, FTIR (Fourier-transform infrared spectroscopy), ¹H NMR (Nuclear magnetic resonance spectroscopy), 13 C NMR, and mass spectrometry. From the bioactivity results, it was clear that the newly synthesized proline-rich tetracyclopeptide exhibited better anthelmintic potential against Megascoplex konkanensis , Pontoscotex corethruses , and Eudrilus eugeniae at a concentration of 2 mg/mL as well as improved antifungal activity against pathogenic dermatophytes Trichophyton mentagrophytes and Microsporum audouinii at a concentration of 6 μg/mL, as compared to non-methylated tetracyclopeptide. Moreover, N -methylated tetracyclopeptide displayed significant activity against pathogenic Candida albicans .

Toxoplasma gondii (T.gondii) infection can be devastating in the immunodeficient causing high morbidity and mortality. Due to limited availability of both diagnostic facilities and Highly Active Antiretroviral Therapy (HAART), toxoplasmosis continues to be a significant problem amongst Acquired Immuno Deficiency Syndrome (AIDS) patients in India. While scanty literature is available on T. gondii isolates in animals in India, little is known about the genetic diversity of the parasite in humans. Therefore, the present study investigated the genetic diversity of T. gondii in 25 confirmed cases of cerebral toxoplasmosis developing on the background of human immunodeficiency virus (HIV) infection/AIDS. PCR DNA sequencing was performed at four important genetic loci of T. gondii: BTUB, GRA6, alternative SAG2 (alt SAG2) and SAG3 on DNA from tissues obtained at postmortem. The amplified products from all the cases were successfully sequenced except at one locus for one case. Results of the present study suggest that majority of the patients (22/25; 88%) in South India are infected with strains that are recombinants of type II/III and/or strains representing T. gondii different from the archetypal lineages I, II, and III. In addition, clonal types III, MAS, and MAS variant genotypes were encountered. No clonal type I or II was seen in the present study. In addition, variants were observed at alt SAG2 and SAG3 but BTUB and GRA6 were highly conserved. Single nucleotide polymorphisms were observed mainly at two loci which are coding for surface antigens at alt SAG2 and SAG3. In conclusion, the present study reveals genetic diversity in India amongst strains of T. gondii from clinical cases of toxoplasmosis which is in accordance with other recent studies showing a high rate of genetic diversity in this parasite across the globe. There is a need to genotype T. gondii from different forms of toxoplasmosis in humans in India., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Febrile neutropenia (FN) is a common but serious complication of chemotherapy in patients with solid tumors (ST) and hematological malignancies (HM). The epidemiology of FN keeps changing., Objective: The objective was to study the epidemiology of FN in adult patients with ST and HM at Kidwai Memorial Institute of Oncology, Bangalore - A tertiary cancer care center., Materials and Methods: Data of all episodes of FN that occurred during the period July 2011 to December 2011 were collected prospectively and analyzed., Results: A total of 75 episodes of FN was observed during study period involving 55 patients. Febrile neutropenic episodes were more frequent in HM than in ST (57% vs. 43%). The rate of bloodstream infection was 14.7%. Gram-negative organisms were the predominant isolates (56.25%). Overall mortality rate was 13.3%. Presence of medical co-morbidity and positive culture predicted high mortality. Mortality rate did not differ significantly between HM and ST (14% vs. 12.5%; P = 1.0). Gram-positive bacteremia was associated with greater mortality than Gram-negative bacteremia (P = 0.02)., Conclusion: Empiric antibiotic treatment for FN should be tailored to the locally prevalent pathogens and their susceptibility patterns.

Background: The prevalence of hepatitis B virus (HBV) infection is high in Asian countries. Little is known about outcome of leukemia in HBV infected patients in these regions. Hence, we conducted this study in two cohorts of patients., Procedure: We retrospectively evaluated mortality, reduction in dose intensity and duration of therapy (intensive phase and maintenance phase) in children with acute lymphoblastic leukemia (ALL) who developed HBV infection. Sixty-three patients with ALL were included in the retrospective cohort of the study. These were followed up for a minimum of 5 years. We prospectively investigated the prevalence of anti-HBc antibodies in 105 treatment naïve pediatric patients with ALL and negative for HbsAg., Results: Twenty of the 63 patients developed hepatitis, of which 10 were attributed to HBV. All the 10 patients with HBV hepatitis had significantly reduced dose intensity during maintenance therapy with an average delay in completion of therapy of 140 ± 83 days and also a high mortality (40%). In the prospective cohort of the study, 39% of treatment naive patients who were HBsAg negative were anti-HBc positive at presentation, possibly reflecting occult HBV infection., Conclusions: HBV infection poses a serious problem in patients with ALL. Hence we propose that in India, in addition to screening for HBsAg, patients with leukemia should also be screened for anti-HBc. Improved hepatitis B vaccine coverage in the community under the universal immunization programme and introduction of HBV nucleic acid test (NAT) for blood donations should also help in addressing the problem., (© 2014 Wiley Periodicals, Inc.)

Cilostazol is a promising drug for antiplatelet combination therapy that is very important for treatment for various cardiovascular disorders. However, oral delivery of this drug is greatly impeded by the poor solubility in aqueous solutions. The aim of this study was to develop microemulsion (ME) delivery system capable of improving the drug bioavailability. In this study, Capmul MCM C8 (glycerol monocaprylate) based MEs containing Tween 20(polysorbate 20) and/or Labrafil M 1944(poly oxyglycerides) as surfactant(S) and Transcutol P(diethyl glycol monoethyl ether) as cosurfactant(CoS) were studied as potential delivery systems of cilostazol. A number of such systems were prepared containing different S:CoS ratios(1:1, 2:1 and 3:1) based on phase diagrams. Loading of cilostazol was selected as per solubilization capacity and was characterized for pH, viscosity, conductivity, particle size, zeta potential and % transmittance. The MEs systems were further investigated for chemical stability, diffusion and bioavailability. Cilostazol displayed high solubility in microemulsions with particle size up to 70 nm. It was also stable at ambient temperature up to 6 months without significant change in particle size, zeta potential, and % transmittance. Dilution up to 100 fold with aqueous medium observed a visible cloudiness having a particle size up to 104 nm. The in vitro release, and ex vivo intraduodenal diffusion, and in vivo study indicated the capacity of developed ME to improve the bioavailability (1.43 fold) via oral route administration when compared with commercially available tablets (Pletoz-50).

Methylene blue (MB) has been shown to slow down the progression of the Alzheimer's disease (AD) and other tauopathies; however distribution of MB into the brain is limited due its high hydrophilicity. In this study, we aimed to prepare novel hydrophobic glutathione coated PLGA nanoparticles to improve bioavailability of MB in the brain. Glutathione coated poly-(lactide-co-glycolide) (PLGA-b-PEG) nanoparticles (NPs) were prepared and tested in two different cell culture models of AD expressing microtubule associated protein tau (tau). The NPs showed a particle size averaging 136.5±4.4nm, which is suitable for the blood brain barrier (BBB) permeation. The in vitro release profile of the NPs exhibited no initial burst release and showed sustained drug release for up to 144 hours. Interestingly, treatment of newly formulated MB-NPs showed a potent reduction in both endogenous and over expressed tau protein levels in human neuroblastoma SHSY-5Y cells expressing endogenous tau and transfected HeLa cells over-expressing tau protein, respectively. Furthermore, in vitro BBB Transwell™ study showed significantly higher permeation of MB-NP compared to the MB solution through the co culture of rat brain endothelial 4 (RBE4) and C6 astrocytoma cells (p<0.05). The proposed MB loaded nanoparticles could provide a more effective treatment option for AD and many other related disorders.

Background: Infectious disease and malnutrition are common in children. Primary health care came into being to decrease the morbidity. Quality assessment is neither clinical research nor technology assessment. It is primarily an administrative device used to monitor performance to determine whether it continues to remain within acceptable bounds., Aims and Objectives: To assess the quality of service in the delivery of child health care in a primary health care setting. To evaluate client satisfaction. To assess utilization of facilities by the community., Study Type: Cross-sectional community-based study. Quality assessment was done by taking 30-50%, of the service provider. Client satisfaction was determined with 1 Immunization and child examination-90 clients each. Utilization of services was assessed among 478 households., Statistical Analysis: Proportions, Likert's scale to grade the services and Chi-square., Results: IMMUNIZATION SERVICE: Identification of needed vaccine, preparation and care was average. Vaccination technique, documentation, EPI education, maintenance of cold chain and supplies were excellent. Client satisfaction was good. Growth monitoring: It was excellent except for mother's education andoutreach educational session. Acute respiratory tract infection care: History, physical examination, ARI education were poor. Classification, treatment and referral were excellent. Client satisfaction was good. Diarrheal disease care: History taking was excellent. But examination, classification, treatment, ORT education were poor., Conclusion: Mothers education was not stressed by service providers. Service providers' knowledge do not go with the quality of service rendered. Physical examination of the child was not good. Except for immunization other services were average.

Aim: To evaluate the antifertility activity of various extracts of Crotalaria juncea seeds in male mice., Methods: Adult male mice were gavaged the petroleum ether, benzene and ethanol extracts of C. juncea seeds, 25 mg x (100g)(-1) x day(-1) for 30 days. On day 31 the animals were sacrificed by cervical dislocation and the testes, epididymis, vas deferens, seminal vesicles, prostate gland, bulbourethral gland and levator ani were dissected out and weighed. The organs were processed for biochemical and histological examination., Results: In petroleum ether, benzene and ethanol extracts treated rats, there was a decrease in the weights of testis and accessory reproductive organs. The diameters of the testis and seminiferous tubules were decreased. Spermatogonia, spermatocytes and spermatids in the testis and the sperm count in cauda epididymis were also decreased. There was a significant reduction in the protein and glycogen contents and an increase in the cholesterol content in the testis, epididymis and vas deferens. Of the 3 extracts, the ethanol extract appeared to be the most potent in antispermatogenic activity. When the ethanol extract was tested in immature male mice, there was an antiandrogenic effect as the weights of accessory organs were reduced., Conclusion: The various extracts of C. juncea seeds arrest spermatogenesis and are likely to have an antiandrogenic activity.

Histological and biochemical studies carried out on the male reproductive organs of the Indian garden lizard, Calotes versicolor after the treatment with pituitary gonadotrophins (FSH and LH), showed a significant increase in the weight, protein content and diameter of testis, but decrease in its cholesterol. The spermatogonia, spermatocytes and spermatids increased significantly in the germinal epithelium of seminiferous tubule, and spermatozoa appeared in its lumen. The Leydig and Sertoli cells were hypertrophied with increase in their nuclear diameter. The epidymal weight, diameter and protein content also increased after gonadotrophins treatment. There was a significant decrease in the testicular cholesterol indicating the utilization of cholesterol for steroid hormone synthesis. The combined gonadotrophin (FSH + LH) treatment was more effective than the individual gonadotrophin treatment.

A patient with ALL on anticancer chemotherapy developed fever which was later attributed to be due to Fusarium fungemia. The details of the case & a review of literature follows.

During mammalian preimplantation development, a substantial numbers of embryos are believed to be lost for reasons that are unclear. Using female rats, we investigated whether the developmental status of embryos is influenced by bacterial infection and endotoxin in the reproductive tract. From the vagina of cycling rats (n = 11), 21 bacterial isolates were identified; they were Streptococcus faecalis (S. faecalis; 38%), Escherichia coli (E. coli; 19%), Acinetobactor calcoaceticus (A. calcoaceticus; 14%), and coagulase negative staphylococcus (14%), Micrococcus sp. (5%), Bacillus subtilis (B. subtilis; 5%) and Proteus vulgaris (P. vulgaris; 5%). From the vagina of day 4 pregnant rats (n = 12), 26 isolates were identified; they were S. faecalis (23%), A. calcoaceticus (23%), E. coli (15%), Micrococcus sp. (15%), B. subtilis (8%), P. vulgaris (4%), Staphylococcus aureus (4%), beta-hemolytic streptococcus (4%) and Pseudomonas aeruginosa (4%). Gram negative bacteria found in the vagina of cycling and day 4 pregnant rats were 38% and 46%, respectively. In both, bacterial load was 10(3)-10(5) colony forming units and there was no association with the abnormality of the recovered embryos. However, in two day 4 pregnant animals, pathogenic bacteria (Staphylococcus aureus and beta-hemolytic streptococcus) were isolated and embryos recovered from them were degenerated and deformed. The vagina of day 9 pregnant animals (n = 7) were, however, sterile. Consistently, in all animals, the upper reproductive tract (uterus and oviduct) was devoid of any bacteria and no anaerobic bacteria were isolated from any part of the tract. The levels of endotoxin in the vagina of cycling and day 4 pregnant rats were 1.35 +/- 0.1 and 1.17 +/- 0.1 endotoxin units (EU), respectively. It was undetectable in the oviduct and uterus of all animals (n = 5) except one which showed high levels of endotoxin in uterus (4.5 EU) and oviduct (2.2 EU) and the animal also produced degenerated and deformed embryos. These results indicate that common bacterial flora of vagina may not affect embryo development and the presence of pathogenic bacteria in the vagina and/or endotoxin in reproductive tract could be detrimental to viability of gametes and preimplantation embryos in rats.