The Antibacterial Properties of Brookite Phase Titanium Dioxide Nanoparticles Against Methicillin-Resistant Staphylococcus aureus

Staphylococcus aureus (S. aureus), a major human pathogen, is a common cause of infections worldwide due to its high virulence intensity. By adapting to rapidly changing and uniformly hostile environments, strains of S. aureus acquire resistance to antimicrobial agents shortly after their exposure. For example, within a year of its introduction, S. aureus developed resistance to methicillin which triggered the development of other antimicrobial treatments. In spite of the various antibiotics currently used to treat methicillin-resistant S. aureus (MRSA) infections, antimicrobial resistance is an unavoidable consequence due to the selective pressure of antibiotic exposure. Thus, other prevention modalities are warranted to prevent MRSA transmission. Titanium dioxide (TiO2) nanoparticles decompose organic compounds by the formation and constant release of hydroxyl radicals and superoxide ions when exposed to non-lethal ultraviolet (UV) light of 365nm at 370µw/cm2. Commercially available anatase phase TiO2 nanoparticles can serve as antimicrobial agents via UV light activation. However, brookite phase nanoparticles, due to their smaller particle size, may increase the efficiency of TiO2 nanoparticles to inhibit bacterial growth by promoting a greater surface area contact ratio which subsequently causes cell death in less time than anatase phase nanoparticles. Both the TiO2-free suspension and drop-coated slide bioassays were conducted to determine the effects of UV light activated TiO2 nanoparticles on gram-negative, Escherichia coli, and gram-positive, S. aureus, cells and the results revealed non-selective killing properties of the nanoparticles. Furthermore, UV light activated brookite nanoparticles (1mg/mL) caused a 100% reduction in MRSA cell growth within 30 minutes while anatase nanoparticles, under the same conditions, required approximately 75 minutes for such complete cell death. Additionally, physical damage to the cells by UV light activated TiO2 nanoparticles was confirmed by scanning electron microscopy images. Due to MRSA\u27s ability to acquire resistance to antibiotics, these agents remain a temporary solution for the treatment of such pathogenic infections. In contrast, brookite phase TiO2 nanoparticles offer promise for the prevention of MRSA due to their physical, non-selective inhibitory effects on cells. Additionally, the utilization of TiO2 nanoparticles, as a means to prevent transmission could further reduce the emergence of multiple drug-resistant bacteria. The long term goal of this research is to develop visible light activated surface coatings of TiO2 nanoparticles that could be used in clinical settings to reduce the transmission of bacterial infections. Therefore, visible light activation of brookite nanoparticles for practical usage was also evaluated

Discovery of genetic determinants for refractive error

Refractive errors such as myopia are the leading cause of reversible visual impairment worldwide with their prevalence rapidly increasing, resulting in greater burden on public health services. The aim of this series of investigations was to leverage the latest statistical methods and large-scale cohorts available in order to develop our understanding of the genetic determinants for the refractive error traits of spherical equivalent, corneal astigmatism and refractive astigmatism. Investigation of genetic variants on the X-chromosome, a region often neglected in genome-wide association studies (GWAS), identified four genes demonstrating association in a gene-based analysis of spherical equivalent for a cohort of teenagers. Meta-analysis of GWAS results for corneal astigmatism including European and Asian ancestry cohorts performed on behalf of the CREAM consortium successfully replicated the previously identified association near the PDGFRA gene (lead variant: rs7673984, odds ratio = 1.12, P = 5.55 × 10−9). The availability of data from the UK Biobank facilitated the largest GWAS for corneal and refractive astigmatism performed to date (N = 86,335 and 88,005 respectively). Here, GWAS for these traits identified four and two novel loci associated with corneal and refractive astigmatism respectively. Each of these loci had previously been associated with other ocular traits including myopia. Phenotypic variance explained by common genetic variants was relatively low for corneal and refractive astigmatism at ~6% and ~5% respectively, thus proposing a greater role for rare variants in explaining astigmatism variance due to genetics. Lastly, in order to link identified variants and genes functionally influenced in myopia development, several candidate myopia genes identified from a primate myopia model demonstrated enrichment with refractive error associated variants in human samples. Overall, the findings from these investigations are a starting point in guiding further research into the complex biological mechanisms underlying refractive error development

Support matrix machine: A review

Support vector machine (SVM) is one of the most studied paradigms in the realm of machine learning for classification and regression problems. It relies on vectorized input data. However, a significant portion of the real-world data exists in matrix format, which is given as input to SVM by reshaping the matrices into vectors. The process of reshaping disrupts the spatial correlations inherent in the matrix data. Also, converting matrices into vectors results in input data with a high dimensionality, which introduces significant computational complexity. To overcome these issues in classifying matrix input data, support matrix machine (SMM) is proposed. It represents one of the emerging methodologies tailored for handling matrix input data. The SMM method preserves the structural information of the matrix data by using the spectral elastic net property which is a combination of the nuclear norm and Frobenius norm. This article provides the first in-depth analysis of the development of the SMM model, which can be used as a thorough summary by both novices and experts. We discuss numerous SMM variants, such as robust, sparse, class imbalance, and multi-class classification models. We also analyze the applications of the SMM model and conclude the article by outlining potential future research avenues and possibilities that may motivate academics to advance the SMM algorithm

Pantoea agglomerans bacteremia: A rare case of spontaneous human infection by a plant pathogen in an immunocompromised host.

Introduction: Pantoea agglomerans is a Gram negative ubiquitous bacteria commonly isolated from plant surfaces, seeds, fruits and animal/human feces usually introduced to human by ingestion of infected fruits/vegetables, thorn pricks and gastrointestinal translocation in lack of stomach acidity. However, the pathogen can also cause opportunistic human infection especially when the immune system is impaired. The aim of this case report is to investigate clinical features in a patient with P. agglomerans bacteremia and bring attention the opportunistic infection by this rare bacteria. Case presentation: We present a case of 57 year old caucasian lady with past medical history of Chronic Obstructive Pulmonary Disease, Atrial fibrillation, Immunoglobulin (IgG) deficiency, recurrent pneumonia, urine infection, oral/vaginal candidiasis, Gastro-esophageal reflux disease who presents with one week history of increased shortness of breath, chest tightness and productive cough without fever/chills. She also had high INR of 4.7 (target 2-3) despite taking normal dose of warfarin. She denies plant exposure. Her vitals were stable, saturation maintained with oxygen supplementation. Chest exam revealed very poor air entry bilaterally suggesting exacerbation of COPD. Oral thrush was present. Recent IgG level within last 6 months was low. Blood culture grew Pantoea agglomerans, pan-sensitive to most of the antibiotics. Chest X ray, CT scan abdomen and urine studies could not localize the source of infection. She was treated with Ceftriaxone, INR normalized to therapeutic range and she improved to baseline after 10 days of treatment. Discussion and conclusion: P. agglomerans is a rare cause of bacteremia which usually presents as fever, chills and general toxicity, however could also present as a cause of exacerbation of chronic diseases. Spontaneous infection can occur in a immunocompromised host, however the pathogen is of low virulence. The link between upper GI symptoms along with antacid receipt and spontaneous P. agglomerans infection could be possible, however needs further study. Hence, P. agglomerans should be considered one of the possible cause of spontaneous bacteremia in a immunocompromised host

Analysis of genetic networks regulating refractive eye development in collaborative cross progenitor strain mice reveals new genes and pathways underlying human myopia

Abstract: Background: Population studies suggest that genetic factors play an important role in refractive error development; however, the precise role of genetic background and the composition of the signaling pathways underlying refractive eye development remain poorly understood. Methods: Here, we analyzed normal refractive development and susceptibility to form-deprivation myopia in the eight progenitor mouse strains of the Collaborative Cross (CC). We used RNA-seq to analyze gene expression in the retinae of these mice and reconstruct genetic networks and signaling pathways underlying refractive eye development. We also utilized genome-wide gene-based association analysis to identify mouse genes and pathways associated with myopia in humans. Results: Genetic background strongly influenced both baseline refractive development and susceptibility to environmentally-induced myopia. Baseline refractive errors ranged from − 21.2 diopters (D) in 129S1/svlmj mice to + 22.0 D in CAST/EiJ mice and represented a continuous distribution typical of a quantitative genetic trait. The extent of induced form-deprivation myopia ranged from − 5.6 D in NZO/HILtJ mice to − 20.0 D in CAST/EiJ mice and also followed a continuous distribution. Whole-genome (RNA-seq) gene expression profiling in retinae from CC progenitor strains identified genes whose expression level correlated with either baseline refractive error or susceptibility to myopia. Expression levels of 2,302 genes correlated with the baseline refractive state of the eye, whereas 1,917 genes correlated with susceptibility to induced myopia. Genome-wide gene-based association analysis in the CREAM and UK Biobank human cohorts revealed that 985 of the above genes were associated with myopia in humans, including 847 genes which were implicated in the development of human myopia for the first time. Although the gene sets controlling baseline refractive development and those regulating susceptibility to myopia overlapped, these two processes appeared to be controlled by largely distinct sets of genes. Conclusions: Comparison with data for other animal models of myopia revealed that the genes identified in this study comprise a well-defined set of retinal signaling pathways, which are highly conserved across different vertebrate species. These results identify major signaling pathways involved in refractive eye development and provide attractive targets for the development of anti-myopia drugs

Genome-wide association studies for corneal and refractive astigmatism in UK Biobank demonstrate a shared role for myopia susceptibility loci.

Previous studies have suggested that naturally occurring genetic variation contributes to the risk of astigmatism. The purpose of this investigation was to identify genetic markers associated with corneal and refractive astigmatism in a large-scale European ancestry cohort (UK Biobank) who underwent keratometry and autorefraction at an assessment centre. Genome-wide association studies for corneal and refractive astigmatism were performed in individuals of European ancestry (N = 86,335 and 88,005 respectively), with the mean corneal astigmatism or refractive astigmatism in fellow eyes analysed as a quantitative trait (dependent variable). Genetic correlation between the two traits was calculated using LD Score regression. Gene-based and gene-set tests were carried out using MAGMA. Single marker-based association tests for corneal astigmatism identified four genome-wide significant loci (P < 5 × 10-8) near the genes ZC3H11B (1q41), LINC00340 (6p22.3), HERC2/OCA2 (15q13.1) and NPLOC4/TSPAN10 (17q25.3). Three of these loci also demonstrated genome-wide significant association with refractive astigmatism: LINC00340, HERC2/OCA2 and NPLOC4/TSPAN10. The genetic correlation between corneal and refractive astigmatism was 0.85 (standard error = 0.068, P = 1.37 × 10-35). Here, we have undertaken the largest genome-wide association studies for corneal and refractive astigmatism to date and identified four novel loci for corneal astigmatism, two of which were also novel loci for refractive astigmatism. These loci have previously demonstrated association with axial length (ZC3H11B), myopia (NPLOC4), spherical equivalent refractive error (LINC00340) and eye colour (HERC2). The shared role of these novel candidate genes for astigmatism lends further support to the shared genetic susceptibility of myopia and astigmatism

Revue narrative de la littérature sur la formation en soins ambulatoires en médecine interne au Canada

Background: The Canadian healthcare system faces increasing patient volumes and complexity amidst funding constraints. Ambulatory care offers a potential solution to some of these challenges. Despite growing emphasis on the provision of ambulatory care, there has been a relative paucity of ambulatory care training curricula within Canadian internal medicine residency programs. We conducted a narrative review to understand the current state of knowledge on postgraduate ambulatory care education (ACE), in order to frame a research agenda for Canadian Internal Medicine ACE. Methods: We searched OVID Medline, Embase, and PsycINFO for articles that included the concepts of ambulatory care and medical or health professions education from 2005-2015. After sorting for inclusion/exclusion, we analyzed 30 articles, looking for dominant claims about ACE in Internal Medicine literature. Results: We found three claims. First, ACE is considered to be a necessary component of medical training because of its distinction from inpatient learning environments. Second, current models of ambulatory care clinics do not meet residency education needs. Third, ACE presents opportunities to develop non-medical expert roles.&nbsp; Conclusions: The findings of our narrative review highlight a need for additional research regarding ACE in Canada to inform optimal ambulatory internal medicine training structures and alignment of educational and societal needs.&nbsp;Contexte&nbsp;: Le système canadien des soins de santé fait face à des volumes croissants de patients et de cas complexes en même temps qu’à des contraintes budgétaires. Les soins ambulatoires offrent une solution pour relever certains de ces défis.&nbsp; Malgré l’importance grandissante portée aux soins ambulatoires, on observe un manque relatif de cursus de formation en soins ambulatoires dans les programmes de résidence en médecine interne.&nbsp; On a effectué une revue narrative en vue de comprendre l’état actuel des connaissances sur la formation en soins ambulatoires (FSA) postgraduée afin d’encadrer un programme de recherche portant sur la FSA à l’intention des étudiants en médecine interne canadiens. Méthodologie&nbsp;: On a consulté OVID Medline, Embase et PsycINFO pour trouver des articles publiés entre 2005 et 2015, portant sur les concepts de soins ambulatoires et d’éducation médicale ou des professionnels de la santé. Après la sélection d’articles selon des critères d’inclusion et d’exclusion, nous en avons examiné 30 en recherchant les affirmations dominantes sur la FSA dans la littérature en médecine interne. Résultats&nbsp;:&nbsp; On a dégagé trois affirmations soit 1) la FSA est tenue pour une composante nécessaire de tout programme d’études de médecine parce qu’elle se distingue de l’environnement d’apprentissage hospitalier; 2) les modèles actuels de cliniques de soins ambulatoires ne répondent pas aux besoins de formation des résidents; 3) la FSA permet de développer des rôles autres que ceux de l’expert médical.&nbsp; Conclusions&nbsp;: Les conclusions de notre analyse documentaire mettent en lumière la nécessité d’effectuer d’autres recherches sur la FSA au Canada pour connaître quelles seraient les structures optimales pour dispenser la formation en soins ambulatoires pour la médecine interne et établir une adéquation entre les besoins de formation et les besoins de la société. &nbsp

Time Outdoors at Specific Ages During Early Childhood and the Risk of Incident Myopia.

PURPOSE: Time outdoors during childhood is negatively associated with incident myopia. Consequently, additional time outdoors has been suggested as a public health intervention to reduce the prevalence of myopia. We investigated whether there were specific ages during early childhood when the time outdoors versus incident myopia association was strongest. METHODS: Children participating in the Avon Longitudinal Study of Parents and Children (ALSPAC) were studied from age 2 to 15 years. Parentally reported time outdoors and time spent reading were assessed longitudinally in early childhood (ages 2, 3, 4, 5, 7, and 9 years). Noncycloplegic autorefraction was carried out longitudinally in later childhood (ages 10, 11, 12, and 15 years). Information was available for 2833 participants. Cox proportional hazards regression was used to test for association between time outdoors and incident myopia. RESULTS: From 3 years of age onward, greater time outdoors was associated with a reduced risk of incident myopia. The hazard ratio for myopia changed progressively from 0.90 (95% CI 0.83-0.98, P = 0.012) at age 3 years, to 0.86 (95% CI 0.78-0.93, P = 0.001) at age 9 years, for each additional SD of time spent outdoors per day. These associations were independent of two major risk factors for myopia: time reading and number of myopic parents. CONCLUSIONS: Additional time spent outdoors across the 3 to 9 years age range was associated with a reduced incidence of myopia between ages 10 and 15 years. There was a trend for the association to increase toward the older end of the 3 to 9 years range.Supported by the UK Medical Research Council. The Wellcome Trust (Grant 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. This research was specifically funded by National Institute for Health Research Career Development Fellowship CDF-2009-02-35 (CW) and a Wellcome Trust Institutional Strategic Support Fund Populations Pilot Award (Grant 508353/509506)