Fötale Programmierung: Der Einfluss von pränatalem Stress auf Entwicklung, Temperament und HHNR-Achsen-Funktion des Säuglings – eine prospektive Studie

Hintergrund: Entsprechend dem Konzept der „Fötalen Programmierung“ wirkt sich pränataler Stress nachhaltig auf die Gesundheit des Nachkömmlings aus. Die HHNR-Achse wird als eine zugrunde liegende Struktur angenommen, über welche fötale Programmierung durch die intrauterine Umwelt vermittelt wird. Epigenetische Studien zeigen, dass die HHNR-Achsen-Funktion durch epigenetische Prozesse veränderbar ist. Ziel: Zu untersuchen, ob sich eine erhöhte pränatale berichtete Stressbelastung und erhöhte basale Kortisolausschüttung der Mütter negativ auf die motorische und kognitive Entwicklung sowie das Temperament des Säuglings auswirkt und ob diese mit einer veränderten basalen HHNR-Achsen-Funktion sowie einer stärkeren Kortisolreaktion unter Stressbedingung beim Säugling einher gehen. Methode: In einer prospektiven Untersuchung von N = 46 Mutter-Kind-Paaren wurde die mütterliche Stressbelastung anhand verschiedener Fragebögen sowie Speichelkortisoltagesprofilen zu drei Messzeitpunkten während der Schwangerschaft (Trim. 1/2/3) erfasst. Im Alter von fünf Monaten wurden Entwicklung und Temperament des Säuglings mittels Entwicklungstestbatterie und Fragebögen erfasst sowie die HHNR-Achsen-Funktion des Säuglings anhand eines Speichelkortisoltagesprofils und eines Speichelkortisolprofils in Reaktion auf einen milden Stressor erhoben. Ergebnis: Säuglinge von Müttern mit höherer pränatal berichteter Stressbelastung und Kortisolausschüttung zeigten entgegen der Erwartung eine leicht verbesserte motorische und kognitive Entwicklung. Entsprechend der Erwartungen zeigten sich jedoch ein etwas schwierigeres Temperament, eine tendenziell niedrigere basale Kortisolausschüttung sowie eine leicht erhöhte Kortisolausschüttung in Reaktion auf einen Stressor. Schlussfolgerung: Stress während der Schwangerschaft scheint differenzielle Effekte im Hinblick auf motorische und kognitive Entwicklung, Temperament, basale und Stresskortisolausschüttung zu haben. Die Effektgrößen im Alter von fünf Monaten waren insgesamt gering und es war kein zeitpunktspezifisches Muster erkennbar. Es ist anzunehmen, dass gesunde Schwangere und deren Föten vor Stress in einem „normalen“ Alltagsausmaß westlicher Zivilgesellschaften insgesamt gut geschützt sind. In wieweit Veränderungen am Lebensanfang im Sinne einer Anpassung langfristige Gesundheitsfolgen haben, bleibt anhand von Follow-Up-Studien bis ins Erwachsenenalter in Zukunft zu überprüfen

Präsentation der Sigmadivertikulitis in der Medizinischen und Chirurgischen Klinik des Klinikum Ingolstadt 2002 - 2004

Die Therapie einer Sigmadivertikulitis im Klinikum Ingolstadt wurde für den Zeitraum der Jahre 2002 bis 2004 retrospektiv untersucht. Dabei wurden 109 Fälle operiert und 159 Fälle konservativ behandelt. Bei den operierten Fällen ließ sich feststellen, dass es im Klinikum Ingolstadt keine höhere Komplikationsrate im Vergleich zu anderen Kliniken gibt. Die kon-servative Behandlung in der Chirurgischen Klinik I (Allgemeinchirurgie) unterschied sich in einigen Punkten von den Methoden in der Medizinischen Klinik II (Gastroenterologie). Bei einer Befragung der Patienten im Jahr 2008 gaben 59% der Operierten an, völlig beschwerde-frei zu sein, ein Rezidiv erlitt kein Patient, 5 von 7 aufgetretenen Narbenhernien mussten operativ versorgt werden. Eine Befragung der Hausärzte der operierten Patienten im Jahr 2010 zeigte, dass bei 6 von 77 verwertbaren Fällen eine Wiedervorstellung wegen einer Sigmadivertikulitis notwendig wurde, 2 mal sogar mit konsekutiver stationärer Behandlung, aber ohne Notwendigkeit eines erneuten Eingriffes

Glycoprotein biosynthesis in Saccharomyces cerevisiae: ngd29, an N-glycosylation mutant allelic to och1 having a defect in the initiation of outer chain formation

AbstractOuter chain glycosylation in Saccharomyces cerevisiae leads to heterogeneous and immunogenic asparagine-linked saccharide chains containing more than 50 mannose residues on secreted glycoproteins. Using a [3H]mannose suicide selection procedure a collection of N-glycosylation defective mutants (designated ngd) was isolated. One mutant, ngd29, was found to have a defect in the initiation of the outer chain and displayed a temperature growth sensitivity at 37°C allowing the isolation of the corresponding gene by complementation. Cloning, sequencing and disruption of NGD29 showed that it is a non lethal gene and identical to OCH1. It complemented both the glycosylation and growth defect. Membranes isolated from an ngd29 disruptant or an ngd29mnn1 double mutant were no longer able, in contrast to membranes from wild type cells, to transfer mannose from GDPmannose to Man8GlcNAc2, the in vivo acceptor for building up the outer chain. Heterologous expression of glucose oxidase from Aspergillus niger in an ngd29mnn1 double mutant produced a secreted uniform glycoprotein with exclusively Man8GlcNAc2 structure that in wild type yeast is heavily hyperglycosylated. The data indicate that this mutant strain is a suitable host for the expression of recombinant glycoproteins from different origin in S. cerevisiae to obtain mammalian oligomannosidic type N-linked carbohydrate chains

The Dengue virus in Nepal: gaps in diagnosis and surveillance.

BACKGROUND: The introduction of the dengue virus (DENV) in Nepal is recent, first reports date back to 2004 from a Japanese traveller and limited information is available about DENV infection in the Nepali population. Within a decade after the first DENV detection, it is now endemic in multiple districts of Nepal with approximately 11.2 million people residing in the Terai belt being at risk of DENV infection. Sporadic cases of DENV infection have been reported every year for the past decade during the monsoon season, mainly in the Terai region. METHODS: Medline/Embase/Cochrane databases were reviewed for reports on the burden of dengue infection, diagnostic methods, and national surveillance. RESULTS: Four outbreaks were reported since 2004 including the diagnosis of all serotypes in 2006 and predominance of a single serotype in 2010 (DENV-1), 2013 (DENV-2), and 2016 (DENV-1). The clinical diagnoses showed a predominance of dengue fever while 4/917 (0.4%), 8/642 (1.2%) and 8/1615 (0.4%) dengue haemorrhagic fever/dengue shock syndrome cases were identified during the outbreaks in 2010, 2013 and 2016, respectively. The number of cases reported in males was significantly higher (67.4%) than in females. Disease occurrence was primarily found in the Terai region until 2010 and was increasingly detected in the Hilly region in 2016. CONCLUSION: In Nepal currently weak diagnostic facilities, very limited research on mosquitoes vectors, and poor surveillance of dengue leading to inappropriate detection and control of DENV. We surmise that improved basic research and epidemiological training courses for local scientists and laboratory personal at national and international level will help better understand the evolution and distribution of DENV transmission and its eventual control

Surge of Typhoid Intestinal Perforations as Possible Result of COVID-19-Associated Delays in Seeking Care, Madagascar.

During the coronavirus disease pandemic, we observed a 6.4-fold increase in typhoid intestinal perforation incidence in Antananarivo, Madagascar. Thirteen perforations occurred within 6 months (February 2020-July 2020), compared with 13 perforations during the previous 41 months (August 2016-January 2020). The increase may be attributable to delayed healthcare seeking during the pandemic

Current perspectives on invasive nontyphoidal Salmonella disease.

PURPOSE OF REVIEW: We searched PubMed for scientific literature published in the past 2 years for relevant information regarding the burden of invasive nontyphoidal Salmonella disease and host factors associated with nontyphoidal Salmonella infection and discuss current knowledge on vaccine development. The following search terms were used: Salmonella, non typhoidal/nontyphoidal, NTS, disease, bloodstream infection, invasive, sepsis/septicaemia/septicemia, bacteraemia/bacteremia, gastroenteritis, incidence, prevalence, morbidity, mortality, case fatality, host/risk factor, vaccination, and prevention/control. RECENT FINDINGS: Estimates of the global invasive nontyphoidal Salmonella disease burden have been recently updated; additional data from Africa, Asia, and Latin America are now available. New data bridge various knowledge gaps, particularly with respect to host risk factors and the geographical distribution of iNTS serovars. It has also been observed that Salmonella Typhimurium sequence type 313 is emergent in several African countries. Available data suggest that genetic variation in the sequence type 313 strain has led to increased pathogenicity and human host adaptation. A bivalent efficacious vaccine, targeting Salmonella serovars Typhimurium and Enteritidis, would significantly lower the disease burden in high-risk populations. SUMMARY: The mobilization of surveillance networks, especially in Asia and Latin America, may provide missing data regarding the invasive nontyphoidal Salmonella disease burden and their corresponding antimicrobial susceptibility profiles. Efforts and resources should be directed toward invasive nontyphoidal Salmonella disease vaccine development

The S. Cerevisiae HAP Complex, a Key Regulator of Mitochondrial Function, Coordinates Nuclear and Mitochondrial Gene Expression

We have compared Saccharomyces cerevisiae global gene expression in wild-type and mutants (Δhap2 and Δhap4) of the HAP transcriptional complex, which has been shown to be necessary for growth on respiratory substrates. Several hundred ORFs are under positive or negative control of this complex and we analyse here in detail the effect of HAP on mitochondria. We found that most of the genes upregulated in the wild-type strain were involved in organelle functions, but practically none of the downregulated ones. Nuclear genes encoding the different subunits of the respiratory chain complexes figure in the genes more expressed in the wild-type than in the mutants, as expected, but in this group we also found key components of the mitochondrial translation apparatus. This control of mitochondrial translation may be one of the means of coordinating mitochondrial and nuclear gene expression in elaborating the respiratory chain. In addition, HAP controls the nuclear genes involved in several other mitochondrial processes (import, mitochondrial division) that define the metabolic state of the cell, but not mitochondrial DNA replication and transcription. In most cases, a putative CCAAT-binding site is present upstream of the ORF, while in others no such sites are present, suggesting the control to be indirect. The large number of genes regulated by the HAP complex, as well as the fact that HAP also regulates some putative transcriptional activators of unknown function, place this complex at a hierarchically high position in the global transcriptional regulation of the cell

The epidemiology of dengue outbreaks in 2016 and 2017 in Ouagadougou, Burkina Faso.

BACKGROUND: Dengue is prevalent in as many as 128 countries with more than 100 million clinical episodes reported annually and four billion people estimated to be at risk. While dengue fever is systematically diagnosed in large parts of Asia and South America, the disease burden in Africa is less well investigated. This report describes two consecutive dengue outbreaks in Ouagadougou, Burkina Faso in 2016 and 2017. METHODS: Blood samples of febrile patients received at Schiphra laboratory in Ouagadougou, Burkina Faso, were screened for dengue infection using SD Bioline Dengue Duo rapid diagnostic test kits (Standard Diagnostics, Suwon, Republic of Korea). RESULTS: A total of 1,397 and 1,882 cases were reported by a single laboratory in 2016 and 2017, respectively. Most cases were at least 15 years of age and the results corroborated reports from WHO indicating the circulation of three dengue virus serotypes in Burkina Faso. CONCLUSION: This study complements data from other, simultaneously conducted surveillance efforts, and indicates that the dengue disease burden might be underestimated in sub-Saharan African nations. Dengue surveillance should be enhanced in African settings to determine the burden more accurately, and accelerated efforts towards a dengue vaccine should be put in place

Challenges to the Fight against Rabies-The Landscape of Policy and Prevention Strategies in Africa.

Nearly 59,000 human deaths worldwide are attributable to rabies annually, of which more than a third occur in Africa. In recent years, progress has been made in both action and collaboration including implementation of surveillance and prevention measures. In this review we assess the scale of surveillance, preventive, and control efforts of canine-transmitted human rabies in African countries. We reviewed literature published from 2014 to 2018, retrieved from electronic databases including MEDLINE, Global Index Medicus, BIOSIS, Science Citation Index, and EMBASE. WHO reports, national disease control program reports, and conference proceedings were also reviewed. The database search was conducted using keywords including rabies, control, and prevention. In forty countries (40/54), some level of rabies control and prevention strategy was available while in fourteen (14/54) countries, no specific national control and prevention strategy for human rabies could be retrieved. Thirty-four (34/54) countries utilized the Stepwise Approach towards Rabies Elimination (SARE) tool to monitor the national rabies control efforts-five of these countries were at the lowest tier (0/5) of the SARE scoring system while no country had achieved the highest score (5/5). High burden countries need to step up the implementation of context specific national rabies control, prevention, and monitoring strategies. As a zoonosis, rabies control and elimination require coordination between human and veterinarian health sectors under the "One Health" umbrella and with national master plans on the prevention and control of neglected tropical diseases ending in 2020, the time to act is now