16 research outputs found

    Editorial

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    Improving Mindfulness, Quality of Life, and Controlling Cellular Aging through Meditation

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    Many people suffer from stress and anxiety due to complex lifestyles. Stress is one of the main causes of various diseases. In addition, it causes a lower level of consciousness, quality of life, and a higher rate of cellular aging. Meditation becomes a trending topic to overcome these problems. Key terms including “Meditation,” “Mindfulness,” “Quality of life,” “Telomere,” and “Telomerase” were used to search literature in PubMed, Medline, and Google scholar databases. Meditation is cheap, viable, and simple mental training. Several studies have been conducted on the effects of meditation on well-being, including mindfulness level, quality of life, and cellular aging. Accordingly, many of these studies suggest that meditation practice can improve well-being and may help control cellular aging. Though meditation showed various physiological and psychological benefits, the mechanism behind the meditation and these benefits still remains unclear. However, by reducing a person’s stress level, meditation can improve mindfulness, develop quality of life, and reduce cellular aging

    Association of HLA class I and II genes with cutaneous leishmaniasis: a case control study from Sri Lanka and a systematic review

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    Three dimensional model of HLA-B protein based on PDB entry 1HSA (DOI: 10.2210/pdb1hsa/pdb ). Amino acids at positions 55 and 57 in the alpha1 and alpha2 domains of the molecule which constitute the antigen recognition region are highlighted. (TIF 376 kb

    What information and the extent of information research participants need in informed consent forms: a multi-country survey

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    Background: The use of lengthy, detailed, and complex informed consent forms (ICFs) is of paramount concern in biomedical research as it may not truly promote the rights and interests of research participants. The extent of information in ICFs has been the subject of debates for decades; however, no clear guidance is given. Thus, the objective of this study was to determine the perspectives of research participants about the type and extent of information they need when they are invited to participate in biomedical research. Methods: This multi-center, cross-sectional, descriptive survey was conducted at 54 study sites in seven Asia-Pacific countries. A modified Likert-scale questionnaire was used to determine the importance of each element in the ICF among research participants of a biomedical study, with an anchored rating scale from 1 (not important) to 5 (very important). Results: Of the 2484 questionnaires distributed, 2113 (85.1%) were returned. The majority of respondents considered most elements required in the ICF to be \u27moderately important\u27 to \u27very important\u27 for their decision making (mean score, ranging from 3.58 to 4.47). Major foreseeable risk, direct benefit, and common adverse effects of the intervention were considered to be of most concerned elements in the ICF (mean score = 4.47, 4.47, and 4.45, respectively). Conclusions: Research participants would like to be informed of the ICF elements required by ethical guidelines and regulations; however, the importance of each element varied, e.g., risk and benefit associated with research participants were considered to be more important than the general nature or technical details of research. Using a participant-oriented approach by providing more details of the participant-interested elements while avoiding unnecessarily lengthy details of other less important elements would enhance the quality of the ICF

    Cytokine and phenotypic cell profiles in human cutaneous leishmaniasis caused by Leishmania donovani.

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    BackgroundThe innate immune mediators are likely to influence the clinical phenotype of leishmaniasis by primary responses which limit or facilitate the spread of the parasite, as well as by modulating adaptive immunity. This study investigated the response of key innate immune cells in a focus which regularly reports localised cutaneous leishmaniasis (LCL) caused by Leishmania donovani, a species which typically causes visceral disease.MethodsPeripheral blood mononuclear cell (PBMC) derived macrophages and dendritic cells from patients with LCL and healthy controls from endemic and non-endemic areas, were stimulated with soluble Leishmania antigen (SLA). Inflammatory mediators produced by macrophages (TNF-α/TGF-β/IL-10, ELISA; NO, Griess method) and dendritic cells (IL-12p70, IL-10, flowcytometry) and macrophage expression of surface markers of polarization, activation and maturation (flowcytometry) were determined at 24h, 48h and 72h and compared. Study was conducted prospectively from 2015-2019.ResultsPatient derived macrophages and dendritic cells produced higher levels of both pro and anti-inflammatory mediators compared to controls (pConclusionsThe overall immunophenotypic profile suggests that LCL observed in the country is the result of a balancing immune response between pro-inflammatory and regulatory mediators. The mediators which showed distinct profiles in patients warrant further investigation as potential candidates for immunotherapeutic approaches. A comparison with visceral leishmaniasis caused by the same species, would provide further evidence on the differential role of these mediators in the resulting clinical phenotype

    Diagnostic Tools for Cutaneous Leishmaniasis Caused by <i>Leishmania donovani</i>: A Narrative Review

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    Leishmaniasis, a neglected tropical disease, encompasses a spectrum of clinical conditions and poses a significant risk of infection to over one billion people worldwide. Visceral leishmaniasis (VL) in the Indian sub-continent (ISC), where the causative parasite is Leishmania donovani, is targeted for elimination by 2025, with some countries already reaching such targets. Other clinical phenotypes due to the same species could act as a reservoir of parasites and thus pose a challenge to successful control and elimination. Sri Lanka has consistently reported cutaneous leishmaniasis (CL) due to L. donovani as the primary disease presentation over several decades. Similar findings of atypical phenotypes of L. donovani have also been reported from several other countries/regions in the Old World. In this review, we discuss the applicability of different methods in diagnosing CL due to L. donovani and a comprehensive assessment of diagnostic methods spanning clinical, microscopic, molecular, and immunological approaches. By incorporating evidence from Sri Lanka and other regions on L. donovani-related CL, we thoroughly evaluate the accuracy, feasibility, and relevance of these diagnostic tools. We also discuss the challenges and complexities linked to diagnosing CL and review novel approaches and their applicability for detecting CL

    Relative normalized luciferase activity for the recombinant vector constructs carrying the ancestral and variant alleles for XRCC2:rs3218550 and PHB:rs6917

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    Abstract Objective The data presented herein represents the preliminary results of the functional assays of a recently conducted larger study in which two single nucleotide polymorphisms (SNPs) [XRCC2:rs3218550 and PHB:rs6917] were significantly associated with risk of breast cancer among Sri Lankan postmenopausal women. The rs3218550 T allele and rs6917 A allele were found to increase breast cancer risk by 1.5-fold and 1.4-fold, respectively. Both SNPs are located in the 3′untranslated region (3′UTR) of the respective genes. It was hypothesized that these non-coding SNPs may be exerting some transcriptional regulatory effects on gene expression. Their putative functional effects were further investigated by generating bioluminescent recombinant experimental reporter gene constructs carrying the ancestral and variant alleles of these 2 SNPs, transiently transfecting them in MCF-7 breast cancer cell lines and performing dual-luciferase reporter gene assays to measure the luminescent signals. Data description The normalized relative luciferase activity for the recombinant vector constructs carrying the ancestral and variant alleles for XRCC2:rs3218550 and PHB:rs6917 are presented herein. This data might be of relevance to other researchers involved in delineating the functional mechanisms of SNPs located in the 3′UTR of the XRCC2 and PHB breast cancer related genes

    Relative normalized luciferase activity for the recombinant vector constructs carrying the ancestral and variant alleles for XRCC2:rs3218550 and PHB:rs6917

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    <p><br></p><p>This dataset consists of two Excel <b>.xlsx</b> spreadsheets, each containing relative luciferase activity for the recombinant vector constructs.</p><p><b>Dataset_1.xlsx </b>is the relative luciferase activity for the recombinant vector constructs carrying C and T alleles for rs3218550. <br><b>Dataset_2.xlsx </b>is the relative luciferase activity for the recombinant vector constructs carrying G and A alleles for rs6917.</p><p>There is also one <b>.docx </b>file containing sequences of 3′UTR inserts, primer sequences, partial electropherograms of final experimental vectors and vector diagrams.</p><p>The columns of each spreadsheet capture luciferase activity for firefly luciferase, renilla luciferase, and the ratio of firefly/renilla (relative luciferase activity). The rows of each spreadsheet capture the recombinant vector constructs carrying the ancestral and variant alleles for XRCC2:rs3218550 and PHB:rs6917 SNPs, along with the pGL3P vector (lacking the insert) and the pGL3C vector (containing the SV40 promoter and enhancer). The results are expressed as relative luminescence units (RLU). The triplicate results given for each vector represent the data obtained from three independent transfections. </p><p>The associated study investigates the link between two common SNPs in the XRCC2 and PHB genes and increased risk of sporadic breast cancer among Sri Lankan postmenopausal women. The putative functional effects of these two SNPs was further investigated by transfecting the recombinant vector constructs carrying the ancestral and variant alleles of these two SNPs in MCF-7 breast cancer cell lines and performing the dual-luciferase reporter gene assays to measure their bioluminescence.<br></p

    Genomic insights into virulence mechanisms of Leishmania donovani: evidence from an atypical strain

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    Abstract Background Leishmaniasis is a neglected tropical disease with diverse clinical phenotypes, determined by parasite, host and vector interactions. Despite the advances in molecular biology and the availability of more Leishmania genome references in recent years, the association between parasite species and distinct clinical phenotypes remains poorly understood. We present a genomic comparison of an atypical variant of Leishmania donovani from a South Asian focus, where it mostly causes cutaneous form of leishmaniasis. Results Clinical isolates from six cutaneous leishmaniasis patients (CL-SL); 2 of whom were poor responders to antimony (CL-PR), and two visceral leishmaniasis patients (VL-SL) were sequenced on an Illumina MiSeq platform. Chromosome aneuploidy was observed in both groups but was more frequent in CL-SL. 248 genes differed by 2 fold or more in copy number among the two groups. Genes involved in amino acid use (LdBPK_271940) and energy metabolism (LdBPK_271950), predominated the VL-SL group with the same distribution pattern reflected in gene tandem arrays. Genes encoding amastins were present in higher copy numbers in VL-SL and CL-PR as well as being among predicted pseudogenes in CL-SL. Both chromosome and SNP profiles showed CL-SL and VL-SL to form two distinct groups. While expected heterozygosity was much higher in VL-SL, SNP allele frequency patterns did not suggest potential recent recombination breakpoints. The SNP/indel profile obtained using the more recently generated PacBio sequence did not vary markedly from that based on the standard LdBPK282A1 reference. Several genes previously associated with resistance to antimonials were observed in higher copy numbers in the analysis of CL-PR. H-locus amplification was seen in one cutaneous isolate which however did not belong to the CL-PR group. Conclusions The data presented suggests that intra species variations at chromosome and gene level are more likely to influence differences in tropism as well as response to treatment, and contributes to greater understanding of parasite molecular mechanisms underpinning these differences. These findings should be substantiated with a larger sample number and expression/functional studies

    Genetic determinants of sporadic breast cancer in Sri Lankan women

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    Abstract Background While a range of common genetic variants have been identified to be associated with risk of sporadic breast cancer in several Western studies, little is known about their role in South Asian populations. Our objective was to examine the association between common genetic variants in breast cancer related genes and risk of breast cancer in a cohort of Sri Lankan women. Methods A case-control study of 350 postmenopausal women with breast cancer and 350 healthy postmenopausal women was conducted. Genotyping using the iPLEX GOLD assay was done for 56 haplotype-tagging single nucleotide polymorphisms (SNPs) in 36 breast cancer related genes. Testing for association was done using an additive genetic model. Odds ratios and 95% confidence intervals were calculated using adjusted logistic regression models. Results Four SNPs [rs3218550 (XRCC2), rs6917 (PHB), rs1801516 (ATM), and rs13689 (CDH1)] were significantly associated with risk of breast cancer. The rs3218550 T allele and rs6917 A allele increased breast cancer risk by 1.5-fold and 1.4-fold, respectively. The CTC haplotype defined by the SNPs rs3218552|rs3218550|rs3218536 on chromosome 7 (P = 0.0088) and the CA haplotype defined by the SNPs rs1049620|rs6917 on chromosome 17 (P = 0.0067) were significantly associated with increased risk of breast cancer. The rs1801516 A allele and the rs13689 C allele decreased breast cancer risk by 0.6-fold and 0.7-fold, respectively. Conclusions These findings suggest that common genetic polymorphisms in the XRCC2, PHB, CDH1 and ATM genes are associated with risk of breast cancer among Sri Lankan postmenopausal women. The exact biological mechanisms of how these variants regulate overall breast cancer risk need further evaluation using functional studies
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