Bakterielle Pneumonien sind weltweit eine der häufigsten Todesursachen und S. pneumoniae ist das häufigste klinische Isolat. Neutrophile Granulozyten gehören zur Klasse der myeloiden Zellen und sind eine wichtige Komponente der angeborenen Immunität gegen bakterielle Infektionen. Krüppel-like factor 4 (KLF4) spielt dabei nicht nur eine Rolle in der Differenzierung der Zellen des Immunsystems, sondern auch während der Infektion bei der Vermittlung inflammatorischer Signale in unterschiedlichen Zelltypen. Diese Studie zeigt zum ersten Mal in vivo, dass myeloides KLF4 Einfluss auf den Krankheitsverlauf hat und die mit einer bakteriellen Pneumonie einhergehende Entzündungsreaktion reguliert. Die hier aufgeführten Ergebnisse demonstrieren, dass der Transkriptionsfaktor KLF4 während einer Pneumokokken Pneumonie in humanen und murinen neutrophilen Granulozyten induziert wird. Diese Induktion ist Zeit- und Dosisabhängig. Außerdem wird die Expression von myeloidem KLF4 durch die Autolyse von S. pneumoniae reguliert, aber nicht über Toll-like Rezeptor 2 (TLR2), TLR4 oder TLR9 vermittelt. Studien in einem Maus-Pneumonie Modell zeigen, dass myeloides KLF4 einen proinflammatorischen Phänotyp bewirkt. Mäuse mit einem KLF4 knockout (KLF4-/-) in myeloiden Zellen haben im Vergleich zu Wildtyp (KLF4+/+) Mäusen eine höhere Bakterienlast in Lunge, Blut und Milz. Obwohl die Produktion proinflammatorischer Zytokine (wie TNF-α, IL-1β und KC) in BALF und Plasma von KLF4-/- Mäusen geringer war, gab es keine Unterschiede bei der Zellrekrutierung in der BALF von KLF4-/- und KLF4+/+ Mäusen. Allerdings war die Zellrekrutierung im Blut der KLF4-/- Mäuse geringer als bei den KLF4+/+ Mäusen. Außerdem wurde eine erhöhte vaskuläre Permeabilität verbunden mit perivaskulären Ödemen und Pleuritis bei KLF4-/- Mäusen während der S. pneumoniae-induzierten Infektion beobachtet. Diese Mäuse erreichten auch eher die humanen Endpunkte als die vergleichbaren KLF4+/+ Mäuse. / Bacterial pneumonia is one of the leading causes of death worldwide. Streptococcus pneumoniae is the most frequently isolated pathogen from clinical pneumonia samples. Neutrophils belong to the class of myeloid cells and forms an important component of this innate immune system against bacterial infections. Krüppel-like factor 4 (KLF4) has been reported to not only play a role in differentiation of cells of the immune system but also in mediating inflammatory signals in different kinds of host cells during infection. This study shows myeloid KLF4 has an impact on pneumococcal pneumonia outcome and regulates the inflammation associated with bacterial pneumonia in vivo in mice. The results presented in the work show that the transcription factor KLF4 is induced in human and mice neutrophils during pneumococcal pneumonia. The induction of KLF4 is time and dose dependent. Additionally, the expression of myeloid KLF4 is regulated by the autolysis of S. pneumoniae but is not mediated via Toll-like receptor (TLR) 2, TLR4 or TLR9. Studies using a mouse pneumonia model showed that myeloid KLF4 exhibits a pro-inflammatory phenotype. Mice with KLF4 knockout (KO) or KLF4-/- in myeloid cells had higher bacterial load in their lungs, blood and spleen in comparison to wildtype (WT) or KLF4+/+ mice. Although there was less pro-inflammatory cytokine (such as TNF-α, IL-1β and KC) production in the broncho-alveolar lavage fluid (BALF) and plasma of KLF4-/- mice yet there no differences in cell recruitment in the BALF of the KLF4-/- and KLF4+/+ mice. There was however less cell recruitment in the blood of KLF4-/- mice in comparison to KLF4+/+ mice. Additionally, an increased vascular permeability associated with perivascular edema and pleuritis was seen during Streptococcus pneumoniae-induced infection in KLF4-/- mice, which also reached earlier the human endpoints than the KLF4+/+ mice.

Normally swallowing occurs completely without effort. Should the act of swallowing for some reason be impaired, it becomes difficult to eat and drink. Dysphagia is the medical term for eating and swallowing disorders. Dysphagia is common in people with dementia, but the prevalence is not yet fully evaluated. The most common cause of death in people with dementia is aspiration pneumonia, which can be caused by dysphagia. In Sweden investigation and treatment of dysphagia are performed by speech and language pathologists (SLPs) but few of them work with dementia care. This study aims to identify the prevalence of dysphagia in people with dementia, living in a nursing home. The screening methods SSA-S and LtL were used to test the swallowing of 38 participants between 68-96 years of age (M = 86 years). To examine the participants’ oral health the risk assessment tool ROAG was used. When tested with the water swallowing test SSA-S 71,1% of the participants showed signs of aspiration, 36,8% had an oral transit time over 5 seconds, measured with LtL and 92% of the participants had an affected oral health, showing one or more symptoms of severity grade 2 according to ROAG. When adding up the results from the two screening tests a total of 86,8% of the participants showed signs of some kind of swallowing difficulty. Correlation analysis did not show any statistically significant correlations between SSA-S, oral transit time, oral health, or age. The present study found that there is a great need for interventions from speech and language pathologists in people with dementia. / Normalt sker sväljning helt utan ansträngning. Skulle sväljningen av någon anledning inte fungera som den ska, blir det svårt att äta och dricka. Den medicinska termen för ät- och sväljsvårigheter är dysfagi. Dysfagi är vanligt hos personer med demens men det är ännu inte helt kartlagt hur vanligt det är. Hos personer med demens är den vanligaste dödsorsaken aspirationspneumoni, vilket kan orsakas av dysfagi. I Sverige är det logopeder som utreder och behandlar dysfagi men det är få som är verksamma inom demensvården. Den här studien syftar till att kartlägga förekomst av dysfagi hos personer med demenssjukdom boende på ett vård- och omsorgsboende. Med screeningmetoderna SSA-S och LtL genomfördes undersökningar av sväljförmågan hos 38 personer mellan 68-96 års ålder (M = 86 år). För att undersöka deltagarnas munhälsa användes riskbedömningsverktyget ROAG. Av deltagarna fick 71,1 % utslag på vattensväljningstestet SSA-S, 36,8 % hade en oral transporttid över 5 sekunder, mätt med LtL och 92 % av deltagarna hade en nedsatt munhälsa med ett eller flera symptom av grad 2 i munhålan, enligt ROAG. Vid sammanräkning av resultaten från de två screeningtesten uppvisade totalt 86,8 % av deltagarna tecken på någon form av sväljsvårighet. Korrelationsberäkningar visade inga statistiskt signifikanta samband mellan resultat på SSA-S, oral transporttid, munhälsa eller ålder. Studien visar på ett stort behov av logopediska insatser hos gruppen personer med demenssjukdom.

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Introduction: La pneumonie associée à la ventilation mécanique (VM) est fréquente chez les patients ventilés. L’étirement cyclique (EC) induit par la VM pourrait amorcer le poumon vers une réponse inflammatoire en cas d'exposition à des bactéries. Les Toll-like Receptors (TLR) reconnaissent les bactéries et déclenchent l'immunité. La VM pourrait moduler l'expression des TLR et leur réactivité aux agonistes. Le décubitus ventral (DV) réduit l’étirement du poumon. Méthodes: Les niveaux de TLR2 et la réponse à ses agonistes ont été mesures dans des cellules pulmonaires soumises à un EC, et dans un modèle de lapin ventilé. Une stimulation ex vivo du sang total prélevé sur lapins ventilés a été réalisée. Une pneumonie a été induite chez des lapins soumis à VM et maintenus en décubitus dorsal ou tournés en DV. Résultats: L’EC des cellules ainsi que des poumons de lapins augmente les niveaux de TLR2 et la réponse inflammatoire à ses agonistes. La VM et l’exposition du poumon à des agonistes TLR2 induisent synergiquement des lésions. Chez des lapins avec pneumonie sous VM la clairance bactérienne pulmonaire est réduite, la probabilité de bactériémie et le taux des cytokines circulantes augmentés. Le sang total provenant d'animaux sous VM libère de grandes quantités de cytokines après stimulation. Le DV est associe à des niveaux plus faibles de concentrations bactériennes et d'inflammation. Conclusions: La VM sensibilise le poumon aux ligands bactériens de TLR2, modifie la clairance bactérienne pulmonaire, favorise les lésions pulmonaires et de l'inflammation. La surexpression de TLR2 induite par l’EC pourrait expliquer ces différences. Le DV pourrait avoir un effet protecteur. / Introduction: Ventilator-associated pneumonia is common in patients subjected to mechanical ventilation (MV). Cyclic stretch subsequent to MV could prime the lung toward an inflammatory response if exposed to bacteria. Toll-like receptors (TLRs) recognize pathogens thus triggering immunity. MV could modulate TLRs expression and responsiveness to agonists. The prone position (PP) reduces lung stretch.Methods:TLR2 levels and response to the TLR2 ligands were measured in human pulmonary cells submitted to cyclic stretch, and either spontaneously breathing (SB) or MV rabbits. Ex vivo stimulation of whole blood taken from SB or MV rabbits was performed.Enterobacter aerogenes pneumonia was induced in rabbits subjected to MV and kept supine or turned to the PP. Results: Cyclic stretch of human cells as well as rabbitsÕ lung increased both TLR2 levels and inflammatory response to its agonist. MV and airways exposure to TLR2 ligands acted synergistically in causing lung injury.A decrease of lung bacterial clearance and a greater likelihood of bacteremia were observed in MV rabbits with S. aureus pneumonia. Circulating cytokines rose significantly only in these animals. MV induced TLR2 spleen overexpression. Whole blood obtained from MV animals released larger amounts of cytokines after stimulation. PP was associated with lower levels of bacterial concentrations and inflammation. Conclusions: MV sensitizes the lung to bacterial TLR2 ligands, alters lung bacterial clearance, promotes lung injury and inflammation. Both pulmonary and peripheral blood stretch-induced TLR2 overexpression could account at least in part for such differences. The PP could be protective.

Les pneumonies chez l’enfant de moins de 5 ans restent à l’heure actuelle un enjeu majeur de santé publique. Afin d’étudier les agents étiologiques des pneumonies chez les enfants de moins de 5 ans dans les pays à revenu faible ou intermédiaire, une étude cas-témoins a été réalisée entre 2010 et 2014 dans cette population par le réseau Global Approach for Biological Research on Infectious Epidemics in Low Income Countries (GABRIEL). Notre travail s’est attaché à décrire la distribution des sérotypes de Streptococcus pneumoniae retrouvés dans la population de l’étude, d’évaluer la prévalence du virus infuenza et d’évaluer l’effet du virus sur la gravité de la pneumonie, et enfin d’étudier la fréquence des co-détections bactériennes et virales au niveau nasopharyngé ainsi que leur effet sur le risque de pneumonie. Les résultats montraient que la majorité des sérotypes pneumococciques retrouvés étaient inclus dans le vaccin pneumococcique conjugué 13-valent (PCV13) et suggèraient que les souches de S. pneumoniae retrouvées au niveau nasopharyngé et au niveau sanguin étaient identiques chez un même individu atteint de pneumonie. L’importance du virus influenza, et particulièrement d’influenza A H1N1 a été soulignée. Enfin, de nombreuses co-détections nasopharyngées de microorganismes étaient observées chez les cas mais aussi chez les témoins. Leur pathogénicité semblait différer selon les espèces et pourrait dépendre des interactions avec le microbiome du tractus respiratoire. Les résultats suggèraient que la mise en œuvre de campagnes de vaccination par PCV13 pourrait être efficace dans les pays étudiés. Néanmoins, de nouvelles études précisant le rôle des co-détections entre bactéries et virus dans la physiopathologie de la pneumonie sont nécessaires pour guider les décisions de santé publique de façon optimale / Pneumonia remains a public health issue in children under 5 years old. In order to study the etiological agents of pneumonia in this population, a case-control study was carried out between 2010 and 2014 by the Global Approach for Biological Research on Infectious Epidemics in Low Income Countries (GABRIEL) Network in 9 study sites located in 8 low or middle-income countries. The objectives of the present work were to describe the distribution of Streptococcus pneumoniae serotypes, to assess the burden of influenza virus and its effect on the severity of pneumonia, and to study bacterial/viral co-detection in nasopharyngeal samples and their effect on the risk of pneumonia. Results showed that most of S. pneumoniae serotypes detected were included in the pneumococcal 13-Valent conjugate vaccine (PCV13) and confirmed the assumption that the isolate carrying or causing disease in an individual were of the same serotype. The importance of the burden of influenza virus in pneumonia cases, and particularly A H1N1 influenza, was highlighted. Finally, numerous nasopharyngeal co-detections were found both in pneumonia cases and in control subjects. Pathogenicity of microorganisms differs between species and might depend of the interactions with the microbiome of the respiratory tract. Results suggested that the implementation of PCV13 vaccination policies might be effective in the study population. Nevertheless, further studies focused on the most important co-detections of micro-organisms are needed to improve the understanding of their role in the pathogenesis of pneumonia and to guide appropriate public health interventions

<p>Moždani udar predstavlja drugi uzrok smrti u celom svetu i neurolo&scaron;ku bolest sa najvećim stepenom invaliditeta. Za povoljan ishod moždanog udara veoma je važno sprečavanje i lečenje somatskih kompikacija (SK), pri čemu je njihova učestalost i značaj za oporavak pacijenata potcenjena, a uticaj na ishod moždanog udara zanemaren. Ciljevi istraživanja su bili da se utvrdi učestalost pacijenata sa somatskim komplikacijama u akutnoj fazi moždanog udara; zatim da se utvrdi učestalost svake pojedinačne somatske komplikacije: pneumonije, urinarnih infekcija, duboke venske tromboze, tromboembolije pluća, dijarealnog sindroma i akutnog koronarnog sindroma; zatim da se utvrde faktori rizika za nastanak svake pojedinačne SK, kao i da se utvrdi uticaj SK na ishod bolesti - iskazan kroz njihovu povezanost sa funkcionalnim statusom, dužinom hospitalizacije i mortalitetom pacijenata. Istraživanje je sprovedeno kao prospektivno i obuhvatilo je 403 pacijenta hospitalizovanih zbog akutnog moždanog udara na Klinici za neurologiju Kliničkog centra Vojvodine u periodu od godinu dana. Pacijenti su podeljeni u dve grupe, gde su prvu grupu sačinjavali pacijenti sa registrovanom jednom ili vi&scaron;e somatskih komplikacija (n = 162), a drugu su činili pacijenti koji nisu imali somatske komplikacije (n = 241). Evaluacija pacijenata obuhvatila je registrovanje sociodemografskih karakteristika, ličnu i porodičnu anamnezu, karakteristike moždanog udara, neurolo&scaron;ki status na prijemu i otpustu, funkcionalni status na prijemu i otpustu, laboratorijske analize krvi i urina na prijemu, vrstu i vreme nastanka pojedinačne somatske komplikacije, sve relevantne dijagnostičke metode za postavljenje dijagnoze i definisanje potencijalnih faktora rizika. Somatske komplikacije se če&scaron;će javljaju kod starijih osoba, prosečne starosti 72,9 godina, kod osoba ženskog pola i kod pacijenata sa hemoragijskim moždanim udarom. Somatske komplikacije registrovane su kod 40,2% pacijenata, pri tome urinarnu infekciju imalo je 20,3% pacijenata, pneumoniju 16,3%, infarkt miokarda 4,7%, plućnu tromboemboliju 3,4%, duboku vensku trombozu 2,4% i dijarealni sindrom 2,9% pacijenata. Nezavisni prediktori pneumonije su disfagija, naru&scaron;eno stanje svesti, hronična opstruktivna bolest pluća, mRS veći od 3. Prediktori urinarnih infekcija su: podatak o rekurentnim urinarnim infekcijama, ženski pol, starost preko 70 godina, mRS veći od 3 i NIHSS skor veći od 16. Kao nezavisni prediktori plućnog tromboembolizma dobijeni su duboka venska tromboza, naru&scaron;eno stanje svesti i gojaznost, dok se jedinim nezavisnim prediktorom dijarealnog sindroma pokazala starost pacijenta preko 70 godina. Prediktori akutnog koronarnog sindroma su: starost veća od 70 godina i hemoragijski moždani udar. Pacijenti sa SK, na kraju hospitalnog lečenja imaju značajno lo&scaron;iji funkcionalni status u odnosu na pacijente bez somatskih komplikacija. Somatske komplikacije statistički značajno produžavaju hospitalizaciju. Kod četvrtine pacijenata (25,9%) sa somatskim komplikacijama u akutnoj fazi moždanog udara registrovan je letalni ishod. Najveći procenat smrtnih ishoda kod pacijenata sa somatskim komplikacijama registrovan je kod pacijenata sa infarktom miokarda (63,2%), a najmanji kod pacijenata sa urinarnom infekcijom (18,3%).</p> / <p>Stroke is the second cause of death worldwide and neurological disease with the highest level of disability. For a favorable outcome of stroke, the prevention and treatment of somatic complications are of great importance, while their frequency and the importance of the recovery of patients are underestimated, and the influence on the outcome of stroke is neglected. The aims of the study were: to determine the frequency of patients with somatic complications in the acute phase of stroke; to determine the frequency of each somatic complication: pneumonia, urinary infections, deep venous thrombosis, lung thromboembolism, diarrheal syndrome, and acute coronary syndrome; to identify risk factors for the emergence of each somatic complication, as well as to determine the effect of those complications on the outcome of the disease - expressed through their association with the functional status, length of hospitalization and mortality of patients. The study was conducted as a prospective and included 403 patients hospitalized due to acute stroke at the Clinic for Neurology of the Clinical Center of Vojvodina for a period of one year. Patients were divided into two groups; the first group included patients with one or more somatic complications registered (n = 162), and the second group consisted of patients without any somatic complication (n = 241). Patient evaluation included registration of socio-demographic characteristics, personal and family history, stroke characteristics, neurological and functional status at the time of admission and discharge, laboratory analysis of blood and urine at admission, type and time of emergence of each somatic complication, all relevant diagnostic methods for setting diagnosis and defining potential risk factors. Somatic complications are more common in older people (the average age of 72.9 years) in females and in patients with hemorrhagic stroke. Somatic complications were reported in 40.2% of patients, 20.3% of patients had urinary infection, 16.3% pneumonia, 4.7% myocardial infarction, 3.4% pulmonary thromboembolism, deep venous thrombosis 2.4% and diarrheal syndrome 2.9% of patients. Independent predictors of pneumonia were dysphagia, impaired state of consciousness, chronic obstructive pulmonary disease, mRS higher than 3. Predictors of urinary infections were: data on recurrent urinary tract infections, female sex, age over 70 years, mRS higher than 3 and NIHSS score higher than 16. As independent predictors of pulmonary thromboembolism, deep venous thrombosis, impaired state of consciousness and obesity were obtained, while the only independent predictor of diarrheal syndrome proved to be the age of the patient over 70 years. Predictors of acute coronary syndrome were: age over 70 years and haemorrhagic stroke. Patients with somatic complications at the end of hospital treatment had significantly worse functional status compared to patients without somatic complications. Somatic complications statistically significantly prolong hospitalization. A quarter of patients (25.9%) with somatic complications in the acute phase of the stroke had a lethal outcome. The highest percentage of deaths in patients with somatic complications was registered in patients with myocardial infarction (63.2%) and the lowest was registered in patients with urinary tract infections (18.3%).</p>

The purpose of this study is to evaluate the value of systematic thoracic ultrasonography (TUS) for detecting bovine respiratory disease (BRD) related lung damage in Holstein x Angus crossbred calves. Because the dairy industry is known to operate on small profit margins, it is important to assess the potential of this technology to help prevent the main source of financial loss related to calf production that dairy producers face. Studies have shown that BRD may impact nearly a fourth of all dairy calves before weaning. In an industry that is currently growing and evolving, it is important that producers have all the necessary resources to operate efficiently. TUS is known to be a quick and accurate predictor of BRD related lung damage, but this study focuses on the financial implications of BRD related lung damage on calf growth and efficiency—average daily gain (ADG) and milk-to-gain (M:G)—and the value of implementing TUS information to make sound management decisions. TUS along with BRD diagnosis information give producers a unique perspective on future growth and development of calves and could be part of the solution to promote larger profit margins for dairy producers. We find that the value associated with TUS and BRD diagnosis information is between $0.88/head and $13.44/head and depends on BRD incidence rate, feed price, and feeder price. Depending on the cost to the farm, it may be beneficial to implement this as a way to manage BRD damage, which we know to influence calf growth and efficiency.

<p><strong>Background</strong>: Human rhinovirus/enterovirus (HRV/ENT) infections are commonly identified in children with acute respiratory infections (ARIs), but data on their clinical severity remains limited. We compared the clinical severity of HRV/ENT to respiratory syncytial virus (RSV), influenza A/B (FLU) and other common respiratory virus in children.</p> <p><strong>Methods</strong>: Retrospective study of children with ARIs and confirmed single positive viral infections on mid-turbinate swabs by molecular assays. Outcome measures included hospital admission and, for inpatients, a composite end-point consisting of intensive care admission, hospitalization greater than 5 days, oxygen requirements or death.</p> <p><strong>Results</strong>: A total of 116 HRV/ENT, 102 RSV, 99 FLU and 64 other common respiratory viruses were identified. Children with single HRV/ENT infections presented with significantly higher rates of underlying immunosuppressive conditions compared to those with RSV (37.9% vs 13.6%; p</p> <p><strong>Conclusions</strong>: Children with HRV/ENT had a more severe clinical course than those with RSV and FLUA/B infections and often had significant comorbidities. These findings emphasize the importance of considering HRV/ENT infection in children presenting with severe acute respiratory tract infections.</p> / Master of Science (MSc)

The diagnosis and treatment of respiratory tract infections in ambulatory adults is challenging. The prevalence of these conditions outstrips the medical profession's efficiency and effectiveness in dealing with them. However, selecting diagnostic techniques that identify causative organisms and therapeutic agents targeted to those organisms should lead to a reduction in the morbidity and mortality associated with these illnesses.