Medical-grade ultrasound devices are now pocket sized and can be easily transported to underserved parts of the world, allowing health care providers to have the tools to optimize diagnoses, inform management plans, and improve patient outcomes in remote locations. Other great advances in technology have recently occurred, such as artificial intelligence applied to mobile health devices and cloud computing, as augmented reality instructions make these devices more user friendly and readily applicable across health care encounters. However, broader awareness of the impact of these mobile health technologies is needed among health care providers, along with training on how to use them in valid and reproducible environments, for accurate diagnosis and treatment. This article provides a summary of a Mayo International Health Program journey to Bwindi, Uganda, with a portable mobile health unit. This article shows how point-of-care ultrasonography and other technologies can benefit remote clinical diagnosis and management in underserved areas around the world.

<p>Oxygen (O2) plays a crucial role in the energy metabolism of complex multicellular life on earth. Due to the small and finite energy stores in the body, fine-tuned changes within the body are required to meet metabolic demand during skeletal muscle contractions, such as during exercise and activities of daily living. The skeletal muscle microcirculation is one of the last steps in the O2 transport pathway from the lungs to muscle cells and represents the largest surface area for O2 and substrate exchange. When skeletal muscle O2 uptake increases during contractions to meet metabolic demand, there must be an increase in muscle O2 delivery. To achieve these elevations in O2 delivery, vessel (arteriole) diameter in the microcirculation is increased, known as vasodilation. This process in the skeletal muscle microcirculation is regulated by several factors, such as neurohumoral, mechanical, endothelial, paracrine, and metabolic influences, which are imperative in properly regulating O2 delivery at rest and during muscular contractions. Two vasodilatory pathways of interest in this dissertation are the cyclooxygenase (COX) and nitric oxide (NO) vasodilatory pathways.</p> <p>The primary aim of my dissertation studies was to determine the mechanisms that modulate skeletal muscle oxygenation in health and to define the impact of a potentially effective intervention, whole-body chronic heat therapy (HT), to treat heart failure with preserved ejection fraction (HFpEF). In Chapter 2, we report that acute selective COX-2 inhibition had no effect on resting or exercising skeletal muscle microvascular oxygenation, pulmonary oxygen uptake, or exercise tolerance in healthy young humans. In Chapter 3, we report that NO, via phosphodiesterase type 5 inhibition, regulates myocyte O2 transport at rest and during recovery from muscle contractions in healthy young rats. In Chapter 4, we show that whole-body chronic HT promotes central and peripheral adaptations, which impact positively exercise tolerance in a pre-clinical rat model of HFpEF. Specifically, whole-body chronic HT had beneficial influences on exercise tolerance, skeletal muscle oxygenation from rest to contractions (driven, at least in part, by enhanced NO bioavailability), body composition, and cardiac function. Chapter 5 is a summary of the results and limitations of the projects presented in Chapters 2-4, with a brief discussion of potential future research directions. </p>

Aims In heart failure with preserved ejection fraction (HFpEF), the reduction of nitric oxide (NO)-bioavailability and consequently endothelial dysfunction leads to LV stiffness and diastolic dysfunction of the heart. Besides shear stress, high-density lipoprotein (HDL) stimulates endothelial cells to increased production of NO via phosphorylation of endothelial nitric oxide synthase (eNOS). For patients with heart failure with reduced ejection fraction, earlier studies demonstrated a positive impact of exercise training (ET) on HDL-mediated eNOS activation. The study aims to investigate the influence of ET on HDL-mediated phosphorylation of eNOS in HFpEF patients. Methods and results The present study is a substudy of the OptimEx-Clin trial. The patients were randomized to three groups: (i) HIIT (high-intensity interval training; (ii) MCT (moderate-intensity continuous training); and (iii) CG (control group). Supervised training at study centres was offered for the first 3 months. From months 4–12, training sessions were continued at home with the same exercise protocol as performed during the in-hospital phase. Blood was collected at baseline, after 3, and 12 months, and HDL was isolated by ultracentrifugation. Human aortic endothelial cells were incubated with isolated HDL, and HDL-induced eNOS phosphorylation at Ser1177 and Thr495 was assessed. Subsequently, the antioxidative function of HDL was evaluated by measuring the activity of HDL-associated paraoxonase-1 (Pon1) and the concentration of thiobarbituric acid-reactive substances (TBARS). After 3 months of supervised ET, HIIT resulted in increased HDL-mediated eNOS-Ser1177 phosphorylation. This effect diminished after 12 months of ET. No effect of HIIT was observed on HDL-mediated eNOS-Thr495 phosphorylation. MCT had no effect on HDL-mediated eNOS phosphorylation at Ser1177 and Thr495. HIIT also increased Pon1 activity after 12 months of ET and reduced the concentration of TBARS in the serum after 3 and 12 months of ET. A negative correlation was observed between TBARS concentration and HDL-associated Pon1 activity in the HIIT group (r = −0.61, P < 0.05), and a trend was evident for the correlation between the change in HDL-mediated eNOS-Ser1177 phosphorylation and the change in peak V̇O2 after 3 months in the HIIT group (r = 0.635, P = 0.07). Conclusions The present study documented that HIIT but not MCT exerts beneficial effects on HDL-mediated eNOS phosphorylation and HDL-associated Pon1 activity in HFpEF patients. These beneficial effects of HIIT were reduced as soon as the patients switched to home-based ET.

Die vorliegende Arbeit hatte zum Ziel, das Auftreten von Milchejektionsstörungen in Produktionsherden zu erfassen und deren Ursachen zu finden. Die Fragestellung wurde in fünf methodisch sehr unterschiedlichen Untersuchungsblöcken bearbeitet, die tierindividuelle Aufzeichnungen zu Kalbung und Verlauf des Einmelkens, Verhaltensbeobachtungen im Vorabkalbezeitraum und Messungen psychophysiologischer Parameter (Herzfrequenz, Elektromyogramm, Hautpotential und Hautwiderstand) während eines Tests auf Stressstabilität sowie während des Einmelkens beinhalteten. Es nahmen 9 sächsische Betriebe an der Untersuchung teil. Die Datenerfassung erfolgte über einen Zeitraum von 20 Monaten in den Jahren 2004 / 2005. Es konnten die Daten von 1767 Färsen erfasst werden. Es wurden eindeutige Zusammenhänge zwischen dem durch suboptimale Haltungsbedingungen verursachten Wirken sozialer Stressoren in der Tiergruppe und dem Auftreten von MES gefunden. Demnach trat MES verstärkt in Betrieben auf, in denen bereits im Vorfeld der Kalbung eine chronische Stresssituation für die Tiere bestand. Hierbei konnten bei gemischten Färsen – Kuh- Gruppen die Anwesenheit der Altkühe und bei reinen Färsengruppen das zu geringe Platzangebot im Laufbereich als Hauptursache gefunden werden. Die Umstände von Abkalbung und Einmelken sind in den untersuchten Betrieben nicht primäre Ursache von MES, können aber verstärkend oder mildernd wirken. So bewirken Umstallungen kurz vor dem Abkalbetermin, eine langer Verbleib des Kalbes an der Kuh, zu kurze Pausen zwischen der Kalbung und der ersten Melkung sowie gesundheitliche Beschwerden im peripartalen Zeitraum ein Ansteigen des MES-Risikos. Betroffen sind hierbei vor allem stresslabile und rangniedrige Tiere sowie Tiere, die unter Testbedingungen bevorzugt introvertierte Verhaltensweisen (ängstlich, demütig) zeigten. Es bestand kein Unterschied hinsichtlich der Stressstabilität der Herden zwischen den Betrieben. Während des Einmelkens unterschieden sich Tiere mit und ohne MES in ihrem Verhalten und den gemessenen Parametern kaum von einander. Tiere mit MES zeigen lediglich eine verstärkte Neigung zu Überreaktionen und eingeschränkter Reaktionsfähigkeit bei den elektrodermalen Parametern, wobei die Differenzen häufig nicht statistisch zu sichern waren. Es konnte keine genetische Veranlagung zur Ausbildung einer MES nachgewiesen werden. Die errechnete Heritabilität lag bei h² = 0,009. MES ist somit als ein betriebsspezifisches Problem zu bezeichnen, das in den hier untersuchten Betrieben vor allem haltungsbedingte Ursachen hat. / The present study was designed to describe the occurrence and determine the causes of disturbed milk ejection (= MES = Milchejektionsstörung) in production herds. The question was treated in an examination with five parts with difficult methods: record individually courses of calving and the first milkings, observe the behaviour in the last weeks before the calving, measure psychophysiological parameters (heartrate, elektromyogram, skin conduction and electrical skin resistance) during a test of stress sensitivity and during the first milkings and an genetic analysis. Nine saxonian herds were involved. The data record was for 20 months in the years 2004 / 2005 and cover 1767 heifers. We found clear connections between social strains, they work in the groups of animals and was caused through suboptimal environment, and the occurrence of MES. We found more MES in herds, where animals had a chronical stress situation in the last weeks bevor the calving. The most important stressors are the presence of multiparous cows in mixed groups with cows and heifers and the lack of room for motion in the box when heifers are alone. The circumstances of calving and the first milkings are not the primary causes of MES in this study, but they can influence this problem. So we found an increase of risk for MES, when 1. the time between the transport of animals in the calving box and the calving was too short, 2. the calf stayed with the cow, 3. the time between the calving and the first milking was too short 4. the animal has health problems in the time around the calving. The animals with the highest risk for MES have low stress resistance are unstable for stress, have a low range in the herd and showed an introverted behaviour (timid, humble) in the test. There was no difference in the stress sensitivity between the herds. During the first milkings we found just little differents at behaviour and at measured parameters between animals with and without MES. Animals with MES showed a small disposition to overreactions or to restrict the ability of reaction in elektrodermal parameters, but the differences are often not significant. We couldn´t found genetic causes of MES. The heritability was h² = 0,009. In conclusion, MES is an herd specific problem. In the herds that were examine, the important causes of MES are suboptimale environment and management of the groups of animals.

No description available.

L’insuffisance cardiaque (IC) est définie comme l’incapacité du cœur à fournir un débit cardiaque suffisant lorsque la demande augmente. L’IC survient lors d’une diminution 1) de la fonction contractile, définie comme l’IC à fraction d’éjection réduite (IC-FER) ou 2) de remplissage reliée à une rigidité du myocarde ou du péricarde, définie comme l’IC à FE préservée (IC-FEP). Les altérations de la fonction cardiaque contribuent à l’activation neuro-hormonale et à l’inflammation sous-clinique lors de l’apparition et l’évolution de l’IC. L’IC est caractérisée par de multiples anomalies du système vasculaire et musculaire périphériques. La diminution de la perfusion périphérique peut causer de multiples désordres au niveau vasculaire et musculaire chez les IC. L’inflammation sous-clinique contribue significativement à la progression de l’IC. Puisque les neutrophiles sont les principaux acteurs dans la sécrétion de cytokines inflammatoires, l’objectif de cette thèse est de caractériser le profil pro- et anti-inflammatoire dérivé des neutrophiles chez les patients souffrant d’IC-FER et IC-FEP, ainsi que l’impact du diabète (DM) sur ce profil. Les biomarqueurs plasmatiques et relâchés par les neutrophiles isolés à partir du sang provenant de 20 volontaires sains (CTL), 52 IC-FER et 25 IC-FEP et 22 DM ont été quantifiés. L’observation majeure de notre étude est la réduction importante (>90%) des taux circulants de Vascular endothelial growth factor (VEGF) chez les patients IC-FER et IC-FEP avec ou sans DM par rapport aux CTL. En parallèle, nous avons observé une diminution significative de la sécrétion du VEGF par les neutrophiles des patients IC-FER et IC-FEP avec une réduction maximale (92%) chez les IC-FEP+DM comparé aux CTL après une stimulation avec des médiateurs pro-inflammatoires. La diminution du VEGF associée à une inflammation accrue de l'endothélium micro-vasculaire coronarien conduit à une dérégulation de la génération de l’oxyde nitrique (NO). Une diminution marquée des taux circulants de NO a été observée chez les patients diabétiques et atteints d'IC comparé aux CTL. Les niveaux circulants d'IL-6 et d'IL-8 sont significativement augmentés chez les patients IC et DM et de manière synergique chez les IC-FEP avec DM. Ces données, combinées à une diminution du VEGF et du NO, suggèrent une altération significative de la fonction macro-vasculaire et micro-vasculaire chez les patients IC-FEP, qui est intensifiée par la présence de diabète. La libération d’IL-8 et d’IL-6 par les neutrophiles était significativement augmentée chez les patients DM et IC-FEP+DM après un traitement au lipopolysaccharide (LPS). Nous avons aussi démontré une augmentation de l'IL-1RA circulante, une cytokine anti-inflammatoire dans toutes les cohortes de patients. Cependant, la sécrétion de l’IL-1RA par les neutrophiles était diminuée dans toutes les cohortes par rapport aux CTL, indépendamment de l’agoniste utilisé. Ces observations suggèrent que les neutrophiles ne sont pas les principales cellules qui secrètent l'IL-1RA, mais bien les monocytes, les hépatocytes, les cellules épithéliales et les adipocytes. Les données scientifiques provenant de ces études nous ont permis de mieux caractériser le rôle du neutrophile dans l’IC et permettront de valider l’hypothèse stipulant que les biomarqueurs dérivés des neutrophiles jouent un rôle significatif dans l’IC. / Heart failure (HF) is characterized by the inability of the heart to provide sufficient cardiac output when there is an increase in demand. This may result from a decrease in 1) contractile function, defined as heart failure with reduced ejection fraction (HF-REF) or 2) filling related to stiffness of the myocardium or pericardium, defined as HF with preserved EF (HF-PEF). Alterations in cardiac function contribute to neuro-hormonal activation and subclinical inflammation during the onset and progression of HF. HF is characterized by multiple abnormalities in the peripheral vascular and muscular system. Decreased peripheral perfusion can cause vascular and peripheral muscular disorders in HF-REF and HF-PEF. However, the cellular mechanisms involved in these observations remain unknown. Subclinical inflammation significantly contributes to the progression of HF. Since neutrophils are the first players for the inflammatory cytokines release, the main objective of this doctoral thesis is to characterize the pro and anti-inflammatory profile derived from neutrophils in patients suffering from HF-REF and HF-PEF, as well as the impact of diabetes (DM) on this profile. The plasma and neutrophil released biomarkers from the blood of 20 healthy control volunteers (CTL), 52 HF-REF and 25 HF-PEF and 22 DM were quantified. The major finding of our study is the significant reduction (>90%) of the circulating levels of vascular endothelial growth factor (VEGF) in HF-REF and HF-PEF patients with or without diabetes compared to CTL. In parallel, we observed a significant decrease of the VEGF secretion by the neutrophils from HF-REF and HF-PEF patients with a maximal reduction (92%) in HF-PEF+DM compared to CTL after pro-inflammatory agonists stimulation. The decrease of VEGF associated with an increased inflammation of the coronary microvascular endothelium leads to a deregulation of nitric oxide (NO) generation. A marked decrease in circulating NO levels was indeed observed in diabetic and HF patients compared to CTL. Circulating levels of IL-6 and IL-8 increased significantly in HF and DM patients, being maximal in HFPEF+DM. These data, when combined with a decrease in VEGF and NO, support a significant impairment of macrovascular and microvascular function in HF-PEF patients, which is increased by the presence of diabetes. The release of IL-8 and IL-6 from neutrophils was significantly increased in DM and HF-PEF+DM patients after treatment with lipopolysaccharide (LPS). We also observed an increase in circulating IL-1RA, an anti-inflammatory cytokine in all patients’ cohorts. However, IL-1RA secretion by the neutrophils was decreased in all cohorts compared to CTL, independently of the agonist used. These observations suggest that neutrophils are not the main cells that secrete IL-1RA, but rather monocytes, hepatocytes, epithelial cells and adipocytes. The scientific data from these studies have allowed us to better characterize the role of neutrophils in HF and will validate the hypothesis that biomarkers derived from neutrophils play a significant role in the HF.

La fraction d’éjection du ventricule gauche est un excellent marqueur de la fonction cardiaque. Plusieurs techniques invasives ou non sont utilisées pour son calcul : l’angiographie, l’échocardiographie, la résonnance magnétique nucléaire cardiaque, le scanner cardiaque, la ventriculographie radioisotopique et l’étude de perfusion myocardique en médecine nucléaire. Plus de 40 ans de publications scientifiques encensent la ventriculographie radioisotopique pour sa rapidité d’exécution, sa disponibilité, son faible coût et sa reproductibilité intra-observateur et inter-observateur. La fraction d’éjection du ventricule gauche a été calculée chez 47 patients à deux reprises, par deux technologues, sur deux acquisitions distinctes selon trois méthodes : manuelle, automatique et semi-automatique. Les méthodes automatique et semi-automatique montrent dans l’ensemble une meilleure reproductibilité, une plus petite erreur standard de mesure et une plus petite différence minimale détectable. La méthode manuelle quant à elle fournit un résultat systématiquement et significativement inférieur aux deux autres méthodes. C’est la seule technique qui a montré une différence significative lors de l’analyse intra-observateur. Son erreur standard de mesure est de 40 à 50 % plus importante qu’avec les autres techniques, tout comme l’est sa différence minimale détectable. Bien que les trois méthodes soient d’excellentes techniques reproductibles pour l’évaluation de la fraction d’éjection du ventricule gauche, les estimations de la fiabilité des méthodes automatique et semi-automatique sont supérieures à celles de la méthode manuelle. / Left ventricular ejection fraction is an excellent indicator of cardiac function. Many invasive and non-invasive techniques can be used for its assessment: angiography, echocardiography, cardiac MRI, computed tomography of the heart, multigated radionuclide angiography and myocardial perfusion imaging. More than 40 years of scientific publication praise the multigated radionuclide angiography for its execution speed, its availability, its low cost and intrarater and interrater reproducibility. The left ventricular ejection fraction was calculated twice for 47 patients, using two raw data acquisitions, two technologists and three software platforms: one fully manual, one semi-automatic and one fully automatic. In general, the automatic and semi-automatic methods showed greater reproducibility, a smaller standard error of measurement and minimal detectable change than the manual method, whereas the manual method systematically gave a significantly lower quality of result. It was the only technique that showed significant intrarater difference, and its standard error of measurement and minimal detectable change were 40% to 50% higher than those of automatic and semi-automatic methods. Even though all three techniques are all excellent and reliable options, reliability coefficient estimations were superior using automatic and semi-automatic methods as compared to the manual method.

Développement de diagnostics expérimentaux permettant d'étudier les masses éjectées obtenues a partir de défauts de surface reparties ou localises. Evaluation de la masse éjectée en fonction de la vitesse des particules moyennant l'hypothèse du transfert inélastique de la quantité de mouvement entre l'éjecta et une cible mince placée initialement devant la surface libre et dont on suit la vitesse par interférométrie doppler laser. Etude de la structure spatiale des éjecta au moyen d'un générateur de rayons-x pulse et de l'évolution des contours a l'aide d'une camera ultrarapide a images intégrales. Elaboration d'un modèle.

Experiments show that MgSO4 salt has a non-monotonic effect as a function of MgSO4 concentration on the ejection of DNA from bacteriophage lambda. There is a concentration, N0, at which the minimum amount of DNA is ejected. At lower or higher concentrations, more DNA is ejected. We propose that this non-monotonic behavior is due to the overcharging of DNA at high concentration of Mg⁺² counterions. As the Mg⁺² concentration increases from zero, the net charge of ejected DNA changes its sign from negative to positive. N0 corresponds to the concentration at which DNA is neutral. Our theory fits experimental data well. The DNA-DNA electrostatic attraction is found to be -0.004 kBT/nucleotide. Simulations of DNA-DNA interaction of a hexagonal DNA bundle support our theory. They also show the non-monotonic DNA-DNA interaction and reentrant behavior of DNA condensation by divalent counterions. Three problems in understanding the capsid assembly for a retrovirus are studied: First, the way in which the viral membrane affects the structure of in vivo assembled HIV-1 capsid is studied. We show that conical and cylindrical capsids have similar energy at high surface tension of the viral membrane, which leads to the various shapes of HIV-1 capsids. Secondly, the problem of RNA genome packaging inside spherical viruses is studied using RNA condensation theory. For weak adsorption strength of capsid protein, most RNA genomes are located at the center of the capsid. For strong adsorption strength, RNA genomes peak near the capsid surface and the amount of RNA packaged is proportional to the capsid area instead its volume. Theory fits experimental data reasonably well. Thirdly, the condensation of RNA molecules by nucleocapsid (NC) protein is studied. The interaction between RNA molecules and NC proteins is important for the reverse transcription of viral RNA which relates to the viral infectivity. For strong adsorption strength of the NC protein, there is a screening effect by RNA molecules around a single NC protein.

No description available.