Interactions Between Clostridioides difficile and Fecal Microbiota in in Vitro Batch Model: Growth, Sporulation, and Microbiota Changes

Disturbance in gut microbiota is crucial for the development of Clostridioides difficile infection (CDI). Different mechanisms through which gut microbiota influences C. difficile colonization are known. However, C. difficile could also affect gut microbiota balance as previously demonstrated by cultivation of fecal microbiota in C. difficile conditioned medium. In current study, the interactions of C. difficile cells with gut microbiota were addressed. Three different strains (ribotypes 027, 014/020, and 010) were co-cultivated with two types of fecal microbiota (healthy and dysbiotic) using in vitro batch model. While all strains showed higher sporulation frequency in the presence of dysbiotic fecal microbiota, the growth was strain dependent. C. difficile either proliferated to comparable levels in the presence of dysbiotic and healthy fecal microbiota or grew better in co-culture with dysbiotic microbiota. In co-cultures with any C. difficile strain fecal microbiota showed decreased richness and diversity. Dysbiotic fecal microbiota was more affected after co-culture with C. difficile than healthy microbiota. Altogether, 62 OTUs were significantly changed in co-cultures of dysbiotic microbiota/C. difficile and 45 OTUs in co-cultures of healthy microbiota/C. difficile. However, the majority of significantly changed OTUs in both types of microbiota belonged to the phylum Firmicutes with Lachnospiraceae and Ruminococcaceae origin

Coulomb dissociation of O-16 into He-4 and C-12

We measured the Coulomb dissociation of O-16 into He-4 and C-12 within the FAIR Phase-0 program at GSI Helmholtzzentrum fur Schwerionenforschung Darmstadt, Germany. From this we will extract the photon dissociation cross section O-16(alpha,gamma)C-12, which is the time reversed reaction to C-12(alpha,gamma)O-16. With this indirect method, we aim to improve on the accuracy of the experimental data at lower energies than measured so far. The expected low cross section for the Coulomb dissociation reaction and close magnetic rigidity of beam and fragments demand a high precision measurement. Hence, new detector systems were built and radical changes to the (RB)-B-3 setup were necessary to cope with the high-intensity O-16 beam. All tracking detectors were designed to let the unreacted O-16 ions pass, while detecting the C-12 and He-4

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Kako in zakaj analiziramo mikrobioto

Mikrobno združbo, ki naseljuje določen del človeškega telesa, imenujemo mikrobiota. Najbolj poznana je črevesna mikrobiota, vendar se zmeraj več raziskav izvaja tudi na področju mikrobiote ust, vagine in kože. Danes vemo, da imajo tudi številna področja, ki so nekoč veljala za sterilna, svojo specifično mikrobioto. Mikrobiote igrajo pomembno vlogo pri delovanju organov ter pri zdravju in razvoju bolezni in so zato predmet obsežnih raziskav, katerih namen je ugotavljanje možnih označevalcev zdravja oziroma bolezni ali možnosti uporabe mikrobiote v terapevtske namene. Skupaj z razvojem metod za analizo mikrobiote literatura na tem področju eksponentno narašča. Razumevanje osnovnih načel in izrazov, ki se uporabljajo v raziskavah mikrobiote, bo zato postalo pomemben del splošnega znanja zdravnikov

CONCEPTION OF SUSTAINABLE FAMILY HOUSES IN SUBURBAN AREA

V diplomskem delu smo obravnavali trajnostni razvoj v obmestnem prostoru, kjer model za preurejanje in razvoj sodobnih naselij predstavljajo strnjene skupine stavb v obliki samooskrbnega naselja. Za oblikovanje takšnega naselja smo na podlagi teoretičnih izhodišč zbrali vidike, ki jih moramo upoštevati za doseganje ˝trajnosti˝. Vidike smo razdelili glede na njihov vpliv na različnih nivojih načrtovanja in sicer na lokalni nivo, nivo strnjenega naselja in nivo stavb. Pri tem smo izpostavili nivo naselja. S pomočjo teoretičnih izhodišč, spoznanj, referenčnih primerov in analiz lokacije smo zasnovali vzorčni model trajnostnega naselja družinskih hiš.In this thesis we deal with sustainable development in the suburban area, where a model, for the reorganization and development of sustainable neighbourhood, are compact groups of buildings in form of self-sufficiency settlement. In order to create such neighbourhood gathered from certain aspects on tha basis of the principles, which we have to consider in order to achieve ˝sustainability˝. Those aspects were divided on different levels of planning according to their impact: on the local level, the level of density and the level of buildings. In doing so, we pointed out the density of the neighbourhood. With the help of theoretical principles, insights, reference examples and location analysis, we designed a model of sustainable neighbourhood of family houses

Citizenship of the European Union in the case law of the European Court of Justice

Državljanstvo Unije je institut, ki se je od uvedbe naprej vsebinsko spremenil in dopolnil predvsem z aktivnim delovanjem Sodišča EU. Čeprav ne gre zanemariti njegov postopni razvoj v zakonodaji EU vse odkar je leta 1993 bilo uvedeno, je prav Sodišče EU tisto, ki je (vsaj v določeni meri) pojasnilo vsebino državljanstva Unije. To je sicer tesno povezano z nacionalnim državljanstvom, kar izhaja že iz primarne zakonodaje in se kaže tudi v tem, da so države članice pristojne za določanje pogojev za pridobitev in izgubo državljanstva, vendar pa ob tem še vedno morajo spoštovati temeljna načela EU. Prelomni korak v razvoju sodne prakse na področju državljanstva Unije in z njim tesno povezano pravico do prostega gibanja, je prinesla novejša sodna praksa z uvedbo merila dejanskega izvrševanja bistvene vsebine pravic, ki so podeljene zaradi statusa državljana Unije. Pristop Sodišča EU namreč daje podlago za širšo uporabo prava EU. Merilo omogoča, da se v primerih, kadar bi bilo onemogočeno dejansko izvrševanje bistvene vsebine pravic, ali kadar bi bilo oteženo izvrševanje pravic državljana Unije, pravo EU lahko uporabi, čeprav ni podanega čezmejnega elementa. Takšen pristop Sodišča EU, kljub restriktivni razlagi, je sicer omogočil sklicevanje na pravo EU tudi v primerih, ki po prejšnjem pristopu z njim niso bili zajeti, vendar pa v ospredju še vedno ostaja problem obratne diskriminacije v povezavi s popolnoma notranjimi položaji in vprašanje razmerja s temeljnimi pravicami. Tako se tudi niso uresničili strahovi držav članic, da bi takšen pristop razširil področje uporabe prava EU. Vsekakor gre za področje, ki je z nacionalno zakonodajo držav članic tesno povezano, in ki bo v prihodnosti vplivalo predvsem na oblikovanje politike priseljevanja držav članic. To se kaže tudi v velikem številu intervencij držav članic v zadeve s področja državljanstva Unije, saj je državljanstvo institut in eden izmed pokazateljev suverenosti, ki se jim države članice niso pripravljene odpovedati v celoti. Tako je državljanstvo Unije predmet nenehnih sprememb, ki je v marsičem olajšalo življenje svojih državljanov, je pa za njegovo učinkovito varstvo potrebno vnesti več jasnosti, določnosti in predvidljivosti, zato da se bodo državljani Unije na te pravice z gotovostjo lahko zanesli.The master\u27s thesis titled ‘Citizenship of the European Union in the case law of the European Court of Justice’ deals with citizenship of the Union (also Union citizenship). Citizenship of the Union has changed substantially since its introduction in 1993 and has been defined mainly by the Court of Justice of the European Union (hereinafter: CJEU, European Court of Justice). Union citizenship has evolved over time through European legislation, although more significant changes are apparent in ECJ case law. The CJEU has determined that Union citizenship is subject to national citizenship of a member state. This determination is derived from primary legislation, and is also reflected in the fact that Member States have the power to define the conditions for acquiring and losing citizenship, but they still have to respect the fundamental principles of the European Union (EU). European Court of Justice case law has, in the areas of Union citizenship and free movement, led to significant developments including the enforcement of genuine enjoyment of the substance of rights conferred by virtue of the status as a citizen of the Union. This provides a basis for the wider application of EU law and allows an individual to invoke the provisions of EU law on Union citizenship in cases where European citizen would be in danger of being deprived of the ‘genuine enjoyment of the substance of rights’. In these exceptional cases individuals can refer to Union citizenship rights, even if there is no sign of a cross-border element. According to the CJEU the loss of rights itself constitutes a sufficient link with the EU law. In other words, despite restrictions imposed by the CJEU it is possible for a Union citizen to refer to EU law in purely internal situations, but only in certain cases. However this approach still presents issues of reverse discrimination, and fundamental rights. Despite initial concerns from Member States, wide application of EU law is not guaranteed, as the application of ‘genuine enjoyment’ is more restrictive than initially thought. It is clear that Union citizenship is closely linked to national legislation and will influence the immigration policy of a Member State. The importance of Union citizenship is also obvious due to the numerous interventions by Member States in CJEU proceedings. This is not surprising given that citizenship is an indicator of sovereignty, which Member States are not willing to relinquish. Union citizenship is subject to continual changes, which to date, in many ways have made life easier for European citizens. But for more effective protection, it is necessary to provide more clarity, precision and predictability into case law, so Union citizens can rely on the provisions of EU law with certainty

A RELIC OF THE PAST OR PRIVILEGED HOMICIDE IN MODERN CRIMINAL LAW

Čedomorstvo, koje se u suvremenom kaznenom pravu javlja kao privilegirano usmrćenje, poznato je još od davnina, a sam pojam čedomorstva podrazumijeva ubijanje tek rođenog djeteta od strane njegove majke. Većina autora čedomorstvo određuje kao usmrćenje novorođenčeta od strane njegove majke tijekom ili neposredno nakon poroda i to pod utjecajem jakog duševnog opterećenja koje su kod nje izazvali trudnoća ili porod. Budući da se radi o izuzetno delikatnom kaznenom djelu, oduvijek su postojale posebnosti u određivanju i sankcioniranju ovog kaznenog djela. Stoga će u ovome radu biti prikazano podrijetlo, razvoj, problematika i najvažnije odrednice čedomorstva s naglaskom na različita zakonodavna rješenja navedenog kaznenog djela kroz povijest pa sve do suvremenog kaznenog zakonodavstva. Iz rada se također može dobiti uvid u položaj žena i njihovo sankcioniranje tijekom različitih povijesnih razdoblja, ali i promjene stavova prema čedomorstvu te njegovim počiniteljicama polazeći od okrutnih smrtnih kazni do privilegiranja, dok središnji dio rada pruža uvid u suvremeno uređenje čedomorstva u Hrvatskoj. Nakon analize kaznenog djela čedomorstva u okviru Krivičnog zakona Republike Hrvatske iz 1977. te prvog hrvatskog Kaznenog zakona iz 1997. godine, u radu se analiziraju definicija i značajke djela na način kako je ono trenutno uređeno Kaznenim zakonom iz 2011. godine. Osim toga, u radu se obrađuje fenomenološko kretanje kaznenog djela čedomorstva, odnosno njegova učestalost u određenom vremenskom razdoblju, a potom se metodom studije slučaja obrađuje kazneno djelo čedomorstva u praksi Općinskog suda u Čakovcu. Obzirom da istraživanja pokazuju kako su počiniteljice čedomorstva većinom mlade, ekonomski ovisne o drugima te dolaze najčešće iz ruralnih sredina bit će objašnjeno kako društvena sredina utječe na počiniteljice i njihov odnos prema vlastitom djetetu, trudnoći i čedomorstvu, a također pruža se uvid u različiti splet motiva koji navode majke na ubojstvo novorođenčeta. Radi se o fenomenu koji se ne smatra prirodnim pa izaziva zgražanje društva i javnosti te, unatoč brojim istraživanjima, i dalje za sobom povlači brojna pitanja kako i zašto se događa.Infanticide, which appears in modern criminal law as a privileged killing, has been known since ancient times, and the very term infanticide implies the killing of a newborn child by its mother. Most authors define infanticide as the killing of a newborn by its mother during or immediately after childbirth under the influence of a strong mental burden caused by pregnancy or childbirth. Since it is an extremely delicate crime, there have always been peculiarities in determining and sanctioning this crime. Therefore, this paper will present the origin, development, issues and most important determinants of infanticide with an emphasis on the various legislative solutions of the mentioned criminal offense throughout history and up to modern criminal legislation. The work also provides an insight into the position of women and their sanctioning during different historical periods, as well as changes in attitudes towards infanticide and its perpetrators, from cruel death sentences to privileging, while the central part of the thesis provides an insight into the contemporary regulation of infanticide in Croatia. After analyzing the criminal offense of infanticide within the Criminal Code of the Republic of Croatia from 1977 and the first Croatian Criminal Code from 1997th, the paper analyzes the definition and characteristics of the crime as it is currently regulated by the Criminal Code from 2011. In addition, the thesis elaborates the phenomenological movement of the criminal offense of infanticide, i.e. its frequency in a certain period of time, followed by a description of the criminal offense of infanticide in the practice of the Municipal Court in Čakovec through the case study method. Given that research shows that the perpetrators of infanticide are mostly young, economically dependent on others and most often come from rural areas, it will be explained how the social environment affects the perpetrators and their attitude towards their own child, pregnancy and infanticide, and also provides an insight into the different complex of motives that lead mothers to kill their newborns. It is a phenomenon that is not considered natural, so it causes outrage in society and the public, and despite numerous studies, it still raises many questions about how and why it happens