In 1762, Louis-Antoine Marquis de Caraccioli (1719-1803), a prolific writer of the eighteenth century, dedicated a book to a psychological theme that medicine has forgotten: '' in French, which we will translate as 'cheerfulness'. At the beginning of the nineteenth century, this work inspired two doctoral theses in medicine, one defended in Montpellier, the other in Paris. In their texts, Louis Monferran (1785-?) and Vincent Rémi Giganon (1794-1857) explored the therapeutic benefits of the medical prescription of cheerfulness.
View Article and Find Full Text PDFIntroduction: Overlooking the heterogeneity in Alzheimer's disease (AD) may lead to diagnostic delays and failures. Neuroanatomical normative modeling captures individual brain variation and may inform our understanding of individual differences in AD-related atrophy.
Methods: We applied neuroanatomical normative modeling to magnetic resonance imaging from a real-world clinical cohort with confirmed AD ( = 86).
Even in the setting of optimal resuscitation in high-income countries severe sepsis and septic shock have a mortality of 20-40%, with antibiotic resistance dramatically increasing this mortality risk. To develop a reference dataset enabling the identification of common bacterial targets for therapeutic intervention, we applied a standardized genomic, transcriptomic, proteomic and metabolomic technological framework to multiple clinical isolates of four sepsis-causing pathogens: Escherichia coli, Klebsiella pneumoniae species complex, Staphylococcus aureus and Streptococcus pyogenes. Exposure to human serum generated a sepsis molecular signature containing global increases in fatty acid and lipid biosynthesis and metabolism, consistent with cell envelope remodelling and nutrient adaptation for osmoprotection.
View Article and Find Full Text PDFPurpose: Hormonal contraceptives alter hormone levels in women and have been linked to alterations in sleep patterns; however, previous studies yielded inconsistent results and lacked generalizability. This study examines hormonal contraceptive use and its impact on sleep outcomes, including sleep duration and sleep disturbances.
Methods: Women self-reported their sleep patterns and use of contraceptives in the 2017 population-based Behavioral Risk Factor Surveillance System Survey (n=1,970).
Background: Depression has been suggested to be a cause of reversible cognitive impairment but also a risk factor for neurodegenerative disease. Studies suggest that depression prevalence may be high in early onset dementia, particularly Alzheimer's disease, but this has not been systematically assessed in a biomarker-validated clinical dementia cohort to date.
Objective: To examine the prevalence, features, and association with amyloid pathology of lifetime depressive symptoms in a memory clinic cohort meeting appropriate use criteria for amyloid PET imaging.
Resource utilization measures are typically modeled by relying on clinical characteristics. However, in some settings, those clinical markers are not available, and hospitals are unable to explore potential inefficiencies or resource misutilization. We propose a novel approach to exploring misutilization that solely relies on administrative data in the form of patient characteristics and competing resource utilization, with the latter being a novel addition.
View Article and Find Full Text PDFAntimicrob Agents Chemother
October 2020
is an opportunistic fungal pathogen with low susceptibility to current antifungal drugs. Here, we tested the susceptibility of 8 drugs against 42 clinical isolates. All isolates showed high MICs to voriconazole (MIC>16 μg/ml), itraconazole (MIC>16 μg/ml), posaconazole (MIC>16 μg/ml), isavuconazole (MIC>16 μg/ml), amphotericin B (MIC>16 μg/ml), and terbinafine (MIC>64 μg/ml) and high minimum effective concentrations (MECs) to micafungin (MEC>8 μg/ml), with the exception of miltefosine showing an MIC value of 4 μg/ml.
View Article and Find Full Text PDFSustained observations of microbial dynamics are rare, especially in southern hemisphere waters. The Australian Marine Microbial Biodiversity Initiative (AMMBI) provides methodologically standardized, continental scale, temporal phylogenetic amplicon sequencing data describing Bacteria, Archaea and microbial Eukarya assemblages. Sequence data is linked to extensive physical, biological and chemical oceanographic contextual information.
View Article and Find Full Text PDFThe current theoretical framework suggests that tripartite positive feedback relationships between soil biodiversity, fertility and plant productivity are universal. However, empirical evidence for these relationships at the continental scale and across different soil depths is lacking. We investigate the continental-scale relationships between the diversity of microbial and invertebrate-based soil food webs, fertility and above-ground plant productivity at 289 sites and two soil depths, that is 0-10 and 20-30 cm, across Australia.
View Article and Find Full Text PDFMelanoma of the skin is a common cancer only in Europeans, whereas it arises in internal body surfaces (mucosal sites) and on the hands and feet (acral sites) in people throughout the world. Here we report analysis of whole-genome sequences from cutaneous, acral and mucosal subtypes of melanoma. The heavily mutated landscape of coding and non-coding mutations in cutaneous melanoma resolved novel signatures of mutagenesis attributable to ultraviolet radiation.
View Article and Find Full Text PDFBackground: Microbial inhabitants of soils are important to ecosystem and planetary functions, yet there are large gaps in our knowledge of their diversity and ecology. The 'Biomes of Australian Soil Environments' (BASE) project has generated a database of microbial diversity with associated metadata across extensive environmental gradients at continental scale. As the characterisation of microbes rapidly expands, the BASE database provides an evolving platform for interrogating and integrating microbial diversity and function.
View Article and Find Full Text PDFThe mass spectrometry technique of multiple reaction monitoring (MRM) was used to quantify and compare the expression level of lactoferrin in tear films among control, prostate cancer (CaP), and benign prostate hyperplasia (BPH) groups. Tear samples from 14 men with CaP, 15 men with BPH, and 14 controls were analyzed in the study. Collected tears (2 μl) of each sample were digested with trypsin overnight at 37 °C without any pretreatment, and tear lactoferrin was quantified using a lactoferrin-specific peptide, VPSHAVVAR, both using natural/light and isotopic-labeled/heavy peptides with MRM.
View Article and Find Full Text PDFWhole genome sequencing (WGS) of cancer patients' tumours offers the most comprehensive method of identifying both novel and known clinically-actionable genomic targets. However, the practicalities of performing WGS on clinical samples are poorly defined.This study was designed to test sample preparation, sequencing specifications and bioinformatic algorithms for their effect on accuracy and cost-efficiency in a large WGS analysis of human melanoma samples.
View Article and Find Full Text PDFPeople with addictive disorders commonly do not receive efficacious medications. Chronic care management (CCM) is designed to facilitate delivery of effective therapies. Using data from the CCM group in a trial testing its effectiveness for addiction (N=282), we examined factors associated with the prescription of addiction medications.
View Article and Find Full Text PDFThe large and complex genome of wheat makes genetic and genomic analysis in this important species both expensive and resource intensive. The application of next-generation sequencing technologies is particularly resource intensive, with at least 17 Gbp of sequence data required to obtain minimal (1×) coverage of the genome. A similar volume of data would represent almost 40× coverage of the rice genome.
View Article and Find Full Text PDFThe depth of proteome analysis is severely limited in complex samples with a wide dynamic range of protein abundance such as plasma. Removal of high-abundance proteins should reveal the signal of lower abundance plasma proteins. However, smaller proteins may be part of larger protein complexes and hence the removal of proteins involved in complexes with high-abundance proteins such as albumin may inhibit the search for disease biomarkers.
View Article and Find Full Text PDFThis is the first 2-DE study using sequential dyes to analyse phospho-, glyco- and total tear protein profiles (Pro-Q Diamond for phosphoprotein, Pro-Q Emerald for glycoprotein and Sypro Ruby for total protein). This method minimised the gel-gel variations, allowing better comparisons among the three profiles and generated a whole map of PTM profiles of tear protein. A novel tear protein, dermcidin, was identified for the first time in this study.
View Article and Find Full Text PDFWith antigenically novel epidemic and pandemic influenza strains persistently on the horizon it is of fundamental importance that we understand whether heterosubtypic antibodies gained from exposures to circulating human influenzas exist and can protect against emerging novel strains. Our studies of IVIG obtained from an infection-naive population (Australian) enabled us to reveal heterosubtypic influenza antibodies that cross react with H5N1. We now expand those findings for an Australian donor population to include IVIG formulations from a variety of northern hemisphere populations.
View Article and Find Full Text PDFThe hemi-biotrophic fungus Venturia inaequalis infects members of the Maloideae, causing the economically important apple disease, scab. The plant-pathogen interaction of Malus and V. inaequalis follows the gene-for-gene model.
View Article and Find Full Text PDFBladder cancer (BLCa) is a severe urological cancer of both men and women that commonly recurs and once invasive, is difficult to treat. MINA-05 (CK Life Sciences Int'l, Hong Kong) is a derivative of complex botanical extracts, shown to reduce cellular proliferation of bladder and prostate carcinomas. We tested the effects of MINA-05 against human BLCa cell sublines, B8, B8-RSP-GCK, B8-RSP-LN and C3, from a transitional cell carcinoma, grade IV, to determine the molecular targets of treatment by observing the cellular protein profile.
View Article and Find Full Text PDFMany low-molecular weight proteins and peptides in human tears are potentially bioactive proteins but the range and number of these is yet to be fully characterized. A number of different sample preparation techniques were used to maximize the visualization of peptides from reflex tears. Samples were pretreated using precipitation and filtration techniques prior to analyses using MALDI-TOF MS.
View Article and Find Full Text PDFThe success of proteomics relies heavily in the ability to characterize very diverse species of proteins. This diversity stems from a proteins physicochemical properties, its copy number and abundance and its association with other proteins. Prefractionation and simplification of biological samples prior to downstream MS analysis is showing some virtue in obtaining greater depth of protein analysis.
View Article and Find Full Text PDFRNA-mediated gene silencing has been demonstrated in plants, animals, and more recently in filamentous fungi. Here, we report high frequency, RNA-mediated gene silencing in the apple scab fungus, Venturia inaequalis. The green fluorescent protein (GFP) transgene was silenced in a GFP-expressing transformant.
View Article and Find Full Text PDFWe report the development of two new transformation systems, polyethylene glycol (PEG)-mediated transformation of protoplasts and Agrobacterium tumefaciens-mediated transformation of mycelium, for the filamentous ascomycete Venturia inaequalis. New binary vectors have been created for the latter. Although transformation was initially achieved using a PEG-mediated method, this was superseded by the A.
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