Mechanisms for the Spread of Antibiotic Resistance in Tuberculosis

Tuberculosis (TB) is currently the ninth leading cause of death for humans worldwide, causing 10.4 million new infections in 2016. According to the World Health Organization, of these infections, 600,000 were antibiotic resistant. However, the treatment success rate for resistant TB was only 54%. The potential for emergent epidemics of drug resistant TB highlights the need to understand the mechanisms for the spread of resistance. Mycobacterium tuberculosis, the bacterium that causes TB, evolves resistant strains within individuals who are being treated with antibiotics. It has been assumed previously that the resistant characteristics of these strains are spread primarily by the transmission of the strains themselves through the air, by coughing. However, in other bacterial diseases, genes for resistance often spread by horizontal gene transfer, or the movement of DNA between cells. In this study, I asked whether resistant genes in Mycobacterium tuberculosis (Mtb) could also spread by the same mechanism. One way to show evidence of horizontal transfer is to look for places in the cell’s DNA where new DNA has recently been incorporated, or recombined. I analyzed 67 whole genomes of drug resistant Mtb for recombination, using the program FastGEAR. I found evidence of ancestral recombination in 3 different places, and of recent recombination in 30 different places. This discovery may lead to new approaches for treating drug resistant tuberculosis

How Does Antibiotic Resistance Spread in Tuberculosis?

The ancient bacterial disease of tuberculosis (TB) is curable with antibiotics, but according to the World Health Organization, in 2016 over 10 million people became infected with the disease. 600,000 of these cases were resistant to antibiotics, yet the worldwide treatment success rate for drug resistant TB is only 54%. Furthermore, strains exist now that are resistant to all known antibiotics. In the current environment of global travel, this poses a risk for emergent epidemics of drug resistant TB. In this study, I asked: after an antibiotic resistant strain has evolved in someone’s lungs, how does it spread? It is well known that a strain may be transmitted when an infected person coughs, and then another person inhales the aerosol droplets containing the bacterium that causes the disease. However, resistance may also spread by the movement of DNA directly from cell to cell. One way this happens is when the tiny viruses that attack bacteria carry genes back and forth between bacterial cells. I analyzed 67 whole genomes, and found evidence of recently acquired genes in 30 different places in the DNA. Many of the genes involved have functions related to antibiotic resistance or evasion of the human immune system. These results may open the way for the development of new treatments for tuberculosis

Prévention du cancer de la peau : pertinence des messages de prévention de la Ligue vaudoise contre le cancer

Introduction: La Ligue vaudoise contre le cancer (LVC) mène, entre autres activités, des campagnes d'information et de sensibilisation afin de prévenir les risques de développer un cancer. L'une de ces campagnes porte sur la prévention du cancer de la peau. L'incidence du mélanome est en constante augmentation et la Suisse est le pays d'Europe le plus touché par ce type de cancer, avec la Norvège. C'est la prévention primaire qui se montre la plus efficace pour prévenir ce type de cancer, mais dans un contexte sociétal où le bronzage et les représentations qui lui sont associées restent souvent connotés positivement, il est difficile de connaître la portée et le degré d'application des messages de sensibilisation. Sur ce constat, la LVC a mandaté l'IUMSP afin d'évaluer la pertinence des messages préventifs qu'elle délivre. Méthodologie: Afin de répondre aux questions de recherche, une méthode exploratoire et qualitative a été privilégiée. La récolte des données s'est principalement faite par l'intermédiaire des groupes de discussion (focus groups) : 4 focus groups, structurés par âge (18 à 25 ans et 26 à 40 ans) et par sexe, ont été organisés et une analyse thématique menée sur les retranscriptions de ces discussions. Une séance de restitution des résultats de l'étude a été organisée avec différents experts - des représentant-e-s de la LVC (responsables et bénévoles), de la Ligue suisse contre le cancer et du CHUV - afin de susciter une discussion autour de la résonance des résultats pour les personnes présentes et d'élaborer ensemble des recommandations afin d'adapter si besoin les messages de prévention de la LVC

Conservative Treatment for Meniscus Rehabilitation

The purpose of this review is to produce a nonsurgical treatment plan for meniscus injuries using therapeutic exercise, to eventually prepare the athlete for return to play after the sustained injury. Using therapeutic exercises, a rehabilitation program can be created for athletes who do not wish to pursue surgery. The treatment plan was designed for a soccer player who had a partially torn meniscus

Acute effects of Hibiscus sabdariffa calyces on postprandial blood pressure, vascular function, blood lipids, biomarkers of insulin resistance and inflammation in humans

The acute impact of Hibiscus sabdariffa calyces (HSC) extract on postprandial vascular function and other cardiometabolic risk factors have not been studied previously. This study investigated the acute impact of HSC extract consumption on blood pressure (BP), vascular function and other cardiometabolic risk markers. Twenty-five men with 1% to 10% cardiovascular disease (CVD) risk (determined by QRISK 2) were randomised to consume either 250 mL of the aqueous extract of HSC or water with breakfast in a randomised, controlled, single-blinded, 2-meal cross-over study (ClinicalTrials.gov, NTC02165553) with a two weeks washout period between study days. BP was measured at baseline and hourly for 4 h. Flow mediated dilatation (FMD) of the branchial artery was measured at baseline, 2 and 4 h post intervention drink consumption. Acute consumption of aqueous extract of HSC caused a significant increase in % FMD ( < 0.001), a non-significant decrease in systolic BP (SBP) and diastolic BP (DBP); non-significant increase in urinary and plasma nitric oxide (NOx) and reduced response of serum glucose, plasma insulin, serum triacylglycerol and C-reactive protein (CRP) levels; significant ( = 0.026) improvement in the area under systemic antioxidant response curve (0 to 2 h); no significant changes in arterial stiffness following the acute consumption of the extract of HSC. Gallic acid, 4-O-methylgallic acid, 3-O-methylgallic acid and hippuric acid reached a maximum plasma concentration at 1 to 2 h post consumption of the extract of HSC. The extract of HSC improved postprandial vascular function and may be a useful dietary strategy to reduce endothelial dysfunction and CVD risk, although this requires confirmation

Platelet-mediated metabolism of the common dietary flavonoid, quercetin.

BACKGROUND: Flavonoid metabolites remain in blood for periods of time potentially long enough to allow interactions with cellular components of this tissue. It is well-established that flavonoids are metabolised within the intestine and liver into methylated, sulphated and glucuronidated counterparts, which inhibit platelet function. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate evidence suggesting platelets which contain metabolic enzymes, as an alternative location for flavonoid metabolism. Quercetin and a plasma metabolite of this compound, 4'-O-methyl quercetin (tamarixetin) were shown to gain access to the cytosolic compartment of platelets, using confocal microscopy. High performance liquid chromatography (HPLC) and mass spectrometry (MS) showed that quercetin was transformed into a compound with a mass identical to tamarixetin, suggesting that the flavonoid was methylated by catechol-O-methyl transferase (COMT) within platelets. CONCLUSIONS/SIGNIFICANCE: Platelets potentially mediate a third phase of flavonoid metabolism, which may impact on the regulation of the function of these cells by metabolites of these dietary compounds

Decreased temperature variance associated with biotic composition enhances coastal shrub encroachment

Regime shift from grasslands to shrub-dominated landscapes occur worldwide driven by altered land-use and climate change, affecting landscape function, biodiversity, and productivity. Warming winter temperatures are a main driver of expansion of the native, evergreen shrub, Morella cerifera, in coastal landscapes. Shrub establishment in these habitats alters microclimate, but little is known about seasonal differences and microclimate variance. We assessed influence of shrubs on microclimate variance, community composition, and community physiological functioning across three vegetation zones: grass, transitional, and shrub in a coastal grassland. Using a novel application of a time-series analysis, we interpret microclimatic variance modification and elucidate mechanisms of shrub encroachment at the Virginia Coast Reserve, Long-Term Ecological Research site. As shrub thickets form, diversity is reduced with little grass/forb cover, while transpiration and annual productivity increase. Shrub thickets significantly reduced temperature variance with a positive influence of one day on the next in maximum air, minimum air, and maximum ground temperature. We also show that microclimatic temperature moderation reduces summer extreme temperatures in transition areas, even before coalescence into full thickets. Encroachment of Morella cerifera on the Virginia barrier islands is driven by reduced local exposure to cold temperatures and enhanced by abiotic microclimatic modification and biotic physiological functioning. This shift in plant community composition from grassland to shrub thicket alters the role of barrier islands in productivity and can have impacts on the natural resilience of the islands

High school reform: a case study using the Breaking Ranks II framework

The purpose of this case study is to unpack the complex process of high school reform in six different high schools in the Seaboro School District. Seaboro School District, like others across the United States, is facing the many challenges that are surfacing in high schools. In the study, the researcher examined how a school district implemented the thirty-one strategic recommendations for high school reform identified in Breaking Ranks II. Specifically, the case study was aimed at discerning if: (1) a recommendation perceived as being more important than others by stakeholders was related to the depth and breadth of the implementation of the recommendation; (2) those recommendations perceived as having a higher degree of importance resulted in a more successful longitudinal implementation after three years of implementing the district reform plan; and (3) those recommendations perceived as having a higher degree of implementation resulted in a more successful longitudinal implementation after three years. The data revealed that the Breaking Ranks II recommendations were perceived as being important by the stakeholders at the beginning of the reform effort, as well as after three years. Additionally, the Seaboro School District increased the level of implementation from 2004 to 2007. However, there was not a relationship between the degree of importance of the recommendations and the longitudinal implementation (as measured by the difference in current practice from 2004 to 2007). Moreover, there was a slight relationship between the degree of current practice of the recommendations in 2004 and the longitudinal implementation (as measured by the difference in current practice from 2004 to 2007). Those recommendations that had a lesser degree of implementation in 2004 saw the greatest gains after three years while the recommendations that had a greater degree of implementation in 2004 saw smaller gains in practice after three years. Chapter Five presents implications and recommendations for school districts that are interested in doing a reform effort similar to the one that Seaboro initiated

TOWARDS RATIONAL DESIGN OF PRECURSORS FOR FOCUSED ELECTRON BEAM INDUCED DEPOSITION

Focused electron beam induced deposition (FEBID) is an emerging method to fabricate nanostructures without the use of resists or masks. In the FEBID process, a gas phase precursor is introduced into a vacuum chamber and transiently adsorbed onto a substrate. A focused electron beam is used to irradiate the precursor, which decomposes under electron beam irradiation. The non-volatile portions of the precursor molecule remain behind on the surface as a deposit, while the volatile portions are pumped away into the vacuum. FEBID has a great deal of potential, but it is currently limited by significant amounts of contamination that remain in the nanostructures. Most precursors that are used for FEBID were designed as chemical vapor deposition (CVD) precursors and were optimized for the thermal process of CVD. Under the electron-based process of FEBID, precursors which produce pure metal films in CVD often produce FEBID deposits with significant levels of contamination, due to the different mechanisms of the two processes. This highlights the need to develop precursors specifically for FEBID. This research used an ultrahigh vacuum surface science approach to investigate the process by which FEBID precursors decompose under electron beam interaction. Specifically, the tools of x-ray photoelectron spectroscopy (XPS) and mass spectrometry (MS) were used to evaluate precursors adsorbed onto cooled substrates under 500 eV electron beam irradiation; this process allowed investigation of both species that remain on the surface and those released into the gas phase. This surface science approach provides kinetic and mechanistic details of precursor decomposition that are not available in the electron microscopes typically used for FEBID. During this work, several precursors were investigated: η3-C3H5(Ru(CO)3Br/Cl, cis-Pt(CO)2Cl2, Co2(CO)8, and CpFe(CO)2Mn(CO)5. Purification of cis-Pt(CO)2Cl2 by electrons and atomic hydrogen radicals was also investigated. Certain ligand types are preferable for FEBID precursors. A small number of carbonyl ligands may desorb under electron beam irradiation. Carbon-rich ligands (η3-C3H5, η5-C5H5) remain behind in deposits as contamination, and halogens are somewhat of a free ligand, as they desorb under a slower, electron stimulated desorption process. Our success in achieving pure Pt films from electron beam irradiation of cis-Pt(CO)2Cl2 prompted further purification studies using atomic hydrogen radicals, which were found to efficiently purify deposits of Cl; however, this resulted in mobility and dispersion of the platinum, creating a porous structure. These results will inform rational design of FEBID precursors as research continues to address contamination in FEBID nanostructures