Diagnostic salivary biomarkers in oral cancer and oral potentially malignant disorders and their relationships to risk factors ? : A systematic review

Acknowledgements NP was financially supported by University of Aberdeen (Elphinstone scholarship) and University grants commission of Sri Lanka. Authors would like to thank the library staff at Medical library and Sri Duncan Rice library for their support in the literature search and recovery of research articles.Peer reviewedPublisher PD

Salivary Interleukin Levels in Oral Squamous Cell Carcinoma and Oral Epithelial Dysplasia : Findings from a Sri Lankan Study

Acknowledgments The authors would like to thank the laboratory staff at the Department of Microbiology, Faculty of Medical Sciences, University of Sri Jayewardenepura, Gangodawila, Nugegoda, Sri Lanka. The authors would like to thank Thilini Nisansala and Chamikara Liyanage for their help in the laboratory analysis. Funding N.S.P. was financially supported by the Elphinstone Scholarship, University of Aberdeen, UK and the University Grants Commission, Sri Lanka.Peer reviewedPublisher PD

Gene expression profiling in treatment-naive schizophrenia patients identifies abnormalities in biological pathways involving AKT1 that are corrected by antipsychotic medication

Distinct gene expression profiles can be detected in peripheral blood mononuclear cells (PBMCs) in patients with schizophrenia; however, little is known about the effects of antipsychotic medication. This study compared gene expression profiles in PMBCs from treatment-naive patients with schizophrenia before and after antipsychotic drug treatment. PBMCs were obtained from 10 treatment-naive schizophrenia patients before and 6 wk after initiating antipsychotic drug treatment and compared to PMBCs collected from 11 healthy community volunteers. Genome-wide expression profiling was conducted using Illumina HumanHT-12 expression bead arrays and analysed using significance analysis of microarrays. This analysis identified 624 genes with altered expression (208 up-regulated, 416 down-regulated) prior to antipsychotic treatment (p < 0.05) including schizophrenia-associated genes AKT1, DISC1 and DGCR6. After 6–8 wk treatment of patients with risperidone or risperidone in combination with haloperidol, only 106 genes were altered, suggesting that the treatment corrected the expression of a large proportion of genes back to control levels. However, 67 genes continued to show the same directional change in expression after treatment. Ingenuity® pathway analysis and gene set enrichment analysis implicated dysregulation of biological functions and pathways related to inflammation and immunity in patients with schizophrenia. A number of the top canonical pathways dysregulated in treatment-naive patients signal through AKT1 that was up-regulated. After treatment, AKT1 returned to control levels and less dysregulation of these canonical pathways was observed. This study supports immune dysfunction and pathways involving AKT1 in the aetiopathophysiology of schizophrenia and their response to antipsychotic medication

Diagnosing human cutaneous leishmaniasis using fluorescence in situ hybridization

Cutaneous leishmaniasis (CL) is endemic in Sri Lanka. Giemsa-stained slit-skin-smears (SSS-Giemsa) and histology are routinely used in diagnosis with a sensitivity of 40–70%. PCR currently has limited accessibility. Therefore, we assessed the sensitivity and specificity of a previously described fluorescence in situ hybridization assay, on skin smears and biopsy samples to overcome the limitations encountered with routine diagnostic methods. Samples from a total of 123 suspected CL patients were collected and subjected to SSS-Giemsa, fluorescence in situ hybridization (FISH) on slit skin smears (SSS-FISH), formalin-fixed-paraffin-embedded-tissues stained with Hematoxylin & Eosin staining (FFPE-H&E) and FISH on formalin-fixed-paraffin-embedded-tissues (FFPE-FISH). Negative controls of 61 patient samples were collected from a CL non-endemic area and subjected to the same procedures. The gold standard PCR was used as a comparator. For FISH, two previously described cyanine 3 tagged Leihsmania genus-specific probes were used. Compared to PCR, SSS-Giemsa, SSS-FISH, FFPE-H&E, and FFPE-FISH had sensitivities of 76.5%, 79.1%, 50.4% and 80.9%, respectively. Routine diagnostic tests (SSS-Giemsa and FFPE-H&E) had a specificity of 100%. SSS-FISH and FFPE-FISH had specificities of 96.7% and 93.4%, respectively. FFPE-FISH had a statistically significant higher diagnostic performance than FFPE-H&E (p  0.05 for all comparisons). We conclude that FFPE-FISH is a more accurate diagnostic tool than FFPE–H&E. SSS-FISH did not have an additional advantage over SSS-Giemsa in diagnosis. However, SSS-FISH could be recommended as a minimally invasive method in studies assessing wound healing where immunological probes are used

Transcriptome-wide mega-analyses reveal joint dysregulation of immunologic genes and transcription regulators in brain and blood in schizophrenia

The application of microarray technology in schizophrenia research was heralded as paradigm-shifting, as it allowed for high-throughput assessment of cell and tissue function. This technology was widely adopted, initially in studies of postmortem brain tissue, and later in studies of peripheral blood. The collective body of schizophrenia microarray literature contains apparent inconsistencies between studies, with failures to replicate top hits, in part due to small sample sizes, cohort-specific effects, differences in array types, and other confounders. In an attempt to summarize existing studies of schizophrenia cases and non-related comparison subjects, we performed two mega-analyses of a combined set of microarray data from postmortem prefrontal cortices (n = 315) and from ex-vivo blood tissues (n = 578). We adjusted regression models per gene to remove non-significant covariates, providing best-estimates of transcripts dysregulated in schizophrenia. We also examined dysregulation of functionally related gene sets and gene co-expression modules, and assessed enrichment of cell types and genetic risk factors. The identities of the most significantly dysregulated genes were largely distinct for each tissue, but the findings indicated common emergent biological functions (e.g. immunity) and regulatory factors (e.g., predicted targets of transcription factors and miRNA species across tissues). Our network-based analyses converged upon similar patterns of heightened innate immune gene expression in both brain and blood in schizophrenia. We also constructed generalizable machine-learning classifiers using the blood-based microarray data. Our study provides an informative atlas for future pathophysiologic and biomarker studies of schizophrenia

Transcriptomic abnormalities in peripheral blood in bipolar disorder, and discrimination of the major psychoses

We performed a transcriptome-wide meta-analysis and gene co-expression network analysis to identify genes and gene networks dysregulated in the peripheral blood of bipolar disorder (BD) cases relative to unaffected comparison subjects, and determined the specificity of the transcriptomic signatures of BD and schizophrenia (SZ). Nineteen genes and 4 gene modules were significantly differentially expressed in BD cases. Thirteen gene modules were shown to be differentially expressed in a combined case-group of BD and SZ subjects called "major psychosis", including genes biologically linked to apoptosis, reactive oxygen, chromatin remodeling, and immune signaling. No modules were differentially expressed between BD and SZ cases. Machine-learning classifiers trained to separate diagnostic classes based solely on gene expression profiles could distinguish BD cases from unaffected comparison subjects with an area under the curve (AUC) of 0.724, as well as BD cases from SZ cases with AUC = 0.677 in withheld test samples. We introduced a novel and straightforward method called "polytranscript risk scoring" that could distinguish BD cases from unaffected subjects (AUC = 0.672) and SZ cases (AUC = 0.607) significantly better than expected by chance. Taken together, our results highlighted gene expression alterations common to BD and SZ that involve biological processes of inflammation, oxidative stress, apoptosis, and chromatin regulation, and highlight disorder-specific changes in gene expression that discriminate the major psychoses

Ethics of DNA research on human remains: Five globally applicable guidelines

We are a group of archaeologists, anthropologists, curators and geneticists representing diverse global communities and 31 countries. All of us met in a virtual workshop dedicated to ethics in ancient DNA research held in November 2020. There was widespread agreement that globally applicable ethical guidelines are needed, but that recent recommendations grounded in discussion about research on human remains from North America are not always generalizable worldwide. Here we propose the following globally applicable guidelines, taking into consideration diverse contexts. These hold that: (1) researchers must ensure that all regulations were followed in the places where they work and from which the human remains derived; (2) researchers must prepare a detailed plan prior to beginning any study; (3) researchers must minimize damage to human remains; (4) researchers must ensure that data are made available following publication to allow critical re-examination of scientific findings; and (5) researchers must engage with other stakeholders from the beginning of a study and ensure respect and sensitivity to stakeholder perspectives. We commit to adhering to these guidelines and expect they will promote a high ethical standard in DNA research on human remains going forward.Fil: Alpaslan Roodenberg, Songül. Harvard Medical School; Estados Unidos. Universidad de Viena; AustriaFil: Anthony, David. Harvard University; Estados UnidosFil: Babiker, Hiba. Max Planck Institute For The Science Of Human History; Estados UnidosFil: Bánffy, Eszter. No especifíca;Fil: Booth, Thomas. No especifíca;Fil: Capone, Patricia. Harvard University; Estados UnidosFil: Deshpande Mukherjee, Arati. No especifíca;Fil: Eisenmann, Stefanie. Institut Max Planck for Evolutionary Anthropology; AlemaniaFil: Fehren Schmitz, Lars. University of California; Estados UnidosFil: Frachetti, Michael. Washington University in St. Louis; Estados UnidosFil: Fujita, Ricardo. Universidad de San Martín de Porres; PerúFil: Frieman, Catherine J.. The Australian National University; AustraliaFil: Fu, Qiaomei. No especifíca;Fil: Gibbon, Victoria. University of Cape Town; SudáfricaFil: Haak, Wolfgang. Max Planck Institute For The Science Of Human History; AlemaniaFil: Hajdinjak, Mateja. The Francis Crick Institute; Reino UnidoFil: Hofmann, Kerstin P.. Deutsches Archäologisches Institut; AlemaniaFil: Holguin, Brian. University of California; Estados UnidosFil: Inomata, Takeshi. University of Arizona; Estados UnidosFil: Kanzawa Kiriyama, Hideaki. National Museum Of Nature And Science; JapónFil: Keegan, William. University Of Florida. Florida Museum Of History; Estados UnidosFil: Kelso, Janet. Institut Max Planck for Evolutionary Anthropology; AlemaniaFil: Krause, Johannes. Institut Max Planck for Evolutionary Anthropology; AlemaniaFil: Kumaresan, Ganesan. Madurai Kamaraj University; IndiaFil: Kusimba, Chapurukha. University of Florida; Estados UnidosFil: Kusimba, Sibel. University of Florida; Estados UnidosFil: Lalueza Fox, Carles. Consejo Superior de Investigaciones Científicas; EspañaFil: Llamas, Bastien. University of Adelaide; AustraliaFil: MacEachern, Scott. University of Duke; Estados UnidosFil: Mallick, Swapan. Harvard Medical School; Estados UnidosFil: Matsumura, Hirofumi. Sapporo Medical University; JapónFil: Morales Arce, Ana Y.. University of Bern; SuizaFil: Motuzaite Matuzeviciute, Giedre. Vilniaus Universitetas; LituaniaFil: Mushrif Tripathy, Veena. Deccan College Post Graduate and Research Institute; IndiaFil: Nakatsuka, Nathan. Harvard Medical School; Estados UnidosFil: Nores, Rodrigo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Antropología de Córdoba. Universidad Nacional de Córdoba. Facultad de Filosofía y Humanidades. Instituto de Antropología de Córdoba; ArgentinaFil: Ogola, Christine. National Museums Of Kenya; KeniaFil: Okumura, Mercedes. Universidade de Sao Paulo; BrasilFil: Patterson, Nick. Harvard University; Estados UnidosFil: Pinhasi, Ron. Universidad de Viena; AustriaFil: Prasad, Samayamantri P. R.. No especifíca;Fil: Prendergast, Mary E.. Rice University; Estados UnidosFil: Punzo, Jose Luis. No especifíca;Fil: Reich, David. Harvard University; Estados Unidos. Harvard Medical School; Estados UnidosFil: Sawafuji, Rikai. The Graduate University For Advanced Studies; JapónFil: Sawchuk, Elizabeth. University of Alberta; CanadáFil: Schiffels, Stephan. Institut Max Planck for Evolutionary Anthropology; AlemaniaFil: Sedig, Jakob. Harvard University; Estados Unidos. Harvard Medical School; Estados UnidosFil: Shnaider, Svetlana. Centre National de la Recherche Scientifique; FranciaFil: Sirak, Kendra. Harvard University; Estados Unidos. Harvard Medical School; Estados UnidosFil: Skoglund, Pontus. The Francis Crick Institute; Reino UnidoFil: Slon, Viviane. Universitat Tel Aviv; IsraelFil: Snow, Meradeth. University Of Montana Missoula; Estados UnidosFil: Soressi, Marie. Leiden University; Países BajosFil: Spriggs, Matthew. The Australian National University; AustraliaFil: Stockhammer, Philipp W.. Ludwig Maximilians Universitat; Alemania. Institut Max Planck for Evolutionary Anthropology; AlemaniaFil: Szécsényi Nagy, Anna. No especifíca;Fil: Thangaraj, Kumarasamy. Centre for Cellular and Molecular Biology; IndiaFil: Tiesler, Vera. Universidad Autónoma de Yucatán; MéxicoFil: Tobler, Ray. University of Adelaide; AustraliaFil: Wang, Chuan Chao. Xiamen University; ChinaFil: Warinner, Christina. Institut Max Planck for Evolutionary Anthropology; Alemania. Harvard University; Estados UnidosFil: Yasawardene, Surangi. No especifíca;Fil: Zahir, Muhammad. Hazara University; Pakistá

Ethics of DNA research on human remains: five globally applicable guidelines.

We are a group of archaeologists, anthropologists, curators and geneticists representing diverse global communities and 31 countries. All of us met in a virtual workshop dedicated to ethics in ancient DNA research held in November 2020. There was widespread agreement that globally applicable ethical guidelines are needed, but that recent recommendations grounded in discussion about research on human remains from North America are not always generalizable worldwide. Here we propose the following globally applicable guidelines, taking into consideration diverse contexts. These hold that: (1) researchers must ensure that all regulations were followed in the places where they work and from which the human remains derived; (2) researchers must prepare a detailed plan prior to beginning any study; (3) researchers must minimize damage to human remains; (4) researchers must ensure that data are made available following publication to allow critical re-examination of scientific findings; and (5) researchers must engage with other stakeholders from the beginning of a study and ensure respect and sensitivity to stakeholder perspectives. We commit to adhering to these guidelines and expect they will promote a high ethical standard in DNA research on human remains going forward