Dysfunktion der Hypothalamus-Hypophysen-Schilddrüsenachse bei Menschen mit Down-Syndrom

Menschen mit Down-Syndrom (DS; Synonyme: Morbus Down, Trisomie 21) sind prädisponiert für die Entwicklung thyroidaler Erkrankungen (Iughetti et al., 2014). Das zusätzliche Chromosom 21 scheint mit einer Dysfunktion der Hypothalamus-Hypophysen-Schilddrüsenachse assoziiert zu sein. Hierbei stehen vor allem zwei Probleme im Vordergrund. Dazu zählt zum einen das vermehrte Vorkommen autoimmuner Schilddrüsenerkrankungen und zum anderen die erhöhte Prävalenz für Schilddrüsenunterfunktionen, insbesondere für kongenitale (Synonyme: konnatale, angeborene) Hypothyreosen (Claret et al., 2013; Pierce et al., 2017; Van Trotsenburg et al., 2005). Ziel dieser Studie ist es, den Verlauf dieser Schilddrüsenerkrankungen hinsichtlich ihres Timings und der Prävalenz für die verschiedenen Funktionsstörungen besser erfassen und charakterisieren zu können. Auf der Basis dieser Ergebnisse wird die Reevaluation der Screening-Empfehlungen ermöglicht und ein Leitfaden für Therapiemaßnahmen erarbeitet. Außerdem soll die Ätiologie der Schilddrüsenerkrankungen bei Menschen mit Down-Syndrom genauer beleuchtet werden. Als Ursache wird eine milde Form der Schilddrüsen-Hypoplasie diskutiert (Fort et al., 1984).1.2 Summary 1.2.1 Introduction People with Down's syndrome have a predisposition to develop thyroid diseases (Iughetti et al., 2014). The additional chromosome 21 appears to be associated with a dysfunction of the hypothalamic-pituitary-thyroid axis. The focus is on two problems here; namely, the increased incidence of autoimmune thyroid diseases and the increased prevalence of hypothyroidism, especially congenital hypothyroidism (Claret et al., 2013; Pierce et al., 2017; Van Trotsenburg et al., 2005). The aim of this study is to better understand and characterize the course of these thyroid diseases in terms of their timing and prevalence for the different functional disorders. On the basis of these results, the re-evaluation of the screening recommendations will be made possible and a guideline for therapeutic measures will be developed. In addition, the etiology of thyroid diseases in people with Down's syndrome will be examined in more detail. A moderate form of thyroid hypoplasia is discussed as the cause (Fort et al., 1984). 1.2.2 Methods A retrospective analysis of thyroid-specific data from a cohort of 274 patients was performed. The patient collective comprised 134 male (49%) and 140 female (51%) volunteers who came to the Down's syndrome consultation hours of Saarland University Hospital between 2012 and 2018 with a confirmed diagnosis of trisomy 21. Among other things, data on the thyroid hormones TSH, fT3 and fT4 and the thyroid autoantibodies (thyroid peroxidase antibodies, thyroglobulin antibodies, TSH receptor antibodies) were collected. The diagnosed thyroid diseases were categorized under epidemiological and etiological aspects. Where available, the sonographic findings were also recorded and evaluated. The longitudinal data collection was followed by the evaluation and analysis of the data. 1.2.3 Results Thyroid dysfunction was detected in 127 patients (46%), of which 34 patients had congenital hypothyroidism. An autoimmune etiology was found in 24 patients. A high proportion of subclinical hypothyroidism was also found. This moderate form of hypothyroidism was diagnosed in 27 patients. With regard to timescale, it was noticed that thyroid diseases were manifested at an earlier age. About half of the diagnoses were made by the age of two. These results illustrate the extremely high proportion of connatal hypothyroidism. A further manifestation peak was emerging for young people between eleven and fifteen years. In addition, a strikingly high proportion of autoimmune thyroid diseases was found. These began at an earlier age and with increasing age, the proportion of thyroid peroxidase positive patients increased parallel to the thyroid peroxidase mean. These results formed the basis for the screening and treatment recommendations. Thyroid hypoplasia could not be excluded as a potential cause for the tendency to thyroid diseases. 1.2.4 Conclusion The predisposition for children with Down's syndrome to develop thyroid hormone disorders was clearly demonstrated and confirmed in this study. Regular screening measures are therefore absolutely necessary and should be intensified, especially in the first two years of the child's life (Luton et al., 2012). An additional control of the TSH values four to five weeks postnatally, as part of the U3 examination, is recommended in order not to overlook later forms of connatal hypothyroidism. Hormone replacement therapy proved to be useful under observation of TSH value normalization. Further studies are required to conclusively assess the protective effect of the therapy. Sensitization to thyroid dysfunction in children with Down's syndrome is extremely important in order to ensure adequate care of the children in everyday clinical practice. The establishment of the screening and therapy recommendations should enable an optimal functional adjustment of the thyroid gland and thus offer the children the best conditions for their quality of life

Burkholderia pseudomallei Misidentified by Automated System

After returning from Thailand, a 35-year-old man from Switzerland was hospitalized with an abscess of the head. Material cultured from the abscess and adjacent bone grew a gram-negative rod, which was misidentified by an automated microbiology system as Burkholderia cepacia. The organism was eventually identified by molecular methods as B. pseudomallei

Yersinia pestis DNA from Skeletal Remains from the 6(th) Century AD Reveals Insights into Justinianic Plague.

Yersinia pestis, the etiologic agent of the disease plague, has been implicated in three historical pandemics. These include the third pandemic of the 19(th) and 20(th) centuries, during which plague was spread around the world, and the second pandemic of the 14(th)-17(th) centuries, which included the infamous epidemic known as the Black Death. Previous studies have confirmed that Y. pestis caused these two more recent pandemics. However, a highly spirited debate still continues as to whether Y. pestis caused the so-called Justinianic Plague of the 6(th)-8(th) centuries AD. By analyzing ancient DNA in two independent ancient DNA laboratories, we confirmed unambiguously the presence of Y. pestis DNA in human skeletal remains from an Early Medieval cemetery. In addition, we narrowed the phylogenetic position of the responsible strain down to major branch 0 on the Y. pestis phylogeny, specifically between nodes N03 and N05. Our findings confirm that Y. pestis was responsible for the Justinianic Plague, which should end the controversy regarding the etiology of this pandemic. The first genotype of a Y. pestis strain that caused the Late Antique plague provides important information about the history of the plague bacillus and suggests that the first pandemic also originated in Asia, similar to the other two plague pandemics

Mycobacterium microti Infections in Free-Ranging Red Deer (Cervus elaphus)

Infections with Mycobacterium microti, a member of the M. tuberculosis complex, have been increasingly reported in humans and in domestic and free-ranging wild animals. At postmortem examination, infected animals may display histopathologic lesions indistinguishable from those caused by M. bovis or M. caprae, potentially leading to misidentification of bovine tuberculosis. We report 3 cases of M. microti infections in free-ranging red deer (Cervus elaphus) from western Austria and southern Germany. One diseased animal displayed severe pyogranulomatous pleuropneumonia and multifocal granulomas on the surface of the pericardium. Two other animals showed alterations of the lungs and associated lymph nodes compatible with parasitic infestation. Results of the phylogenetic analysis including multiple animal strains from the study area showed independent infection events, but no host-adapted genotype. Personnel involved in bovine tuberculosis–monitoring programs should be aware of the fastidious nature of M. microti, its pathogenicity in wildlife, and zoonotic potential

Yersinia pestis Lineages in Mongolia

BACKGROUND: Whole genome sequencing allowed the development of a number of high resolution sequence based typing tools for Yersinia (Y.) pestis. The application of these methods on isolates from most known foci worldwide and in particular from China and the Former Soviet Union has dramatically improved our understanding of the population structure of this species. In the current view, Y. pestis including the non or moderate human pathogen Y. pestis subspecies microtus emerged from Yersinia pseudotuberculosis about 2,600 to 28,600 years ago in central Asia. The majority of central Asia natural foci have been investigated. However these investigations included only few strains from Mongolia. METHODOLOGY/PRINCIPAL FINDINGS: Clustered Regularly Interspaced Short Prokaryotic Repeats (CRISPR) analysis and Multiple-locus variable number of tandem repeats (VNTR) analysis (MLVA) with 25 loci was performed on 100 Y. pestis strains, isolated from 37 sampling areas in Mongolia. The resulting data were compared with previously published data from more than 500 plague strains, 130 of which had also been previously genotyped by single nucleotide polymorphism (SNP) analysis. The comparison revealed six main clusters including the three microtus biovars Ulegeica, Altaica, and Xilingolensis. The largest cluster comprises 78 isolates, with unique and new genotypes seen so far in Mongolia only. Typing of selected isolates by key SNPs was used to robustly assign the corresponding clusters to previously defined SNP branches. CONCLUSIONS/SIGNIFICANCE: We show that Mongolia hosts the most recent microtus clade (Ulegeica). Interestingly no representatives of the ancestral Y. pestis subspecies pestis nodes previously identified in North-western China were identified in this study. This observation suggests that the subsequent evolution steps within Y. pestis pestis did not occur in Mongolia. Rather, Mongolia was most likely re-colonized by more recent clades coming back from China contemporary of the black death pandemic, or more recently in the past 600 years

A Novel Mutation Involving the Initiation Codon of FGF3 in a Family Described with Complete Inner Ear Agenesis, Microtia and Major Microdontia (LAMM Syndrome)

LAMM syndrome (OMIM #610706) is a rare autosomal recessive syndrome characterized by the association of Michel aplasia, microdontia and malformation of the external ear. Different mutations in FGF3 gene were reported in several families presenting with this syndrome. Clinical features and genetic results observed in a family with LAMM syndrome are reported. The diagnosis of isolated Michel aplasia was initially made in this family composed of two affected children. Microtia and microdontia was recently evidenced in both patients suggesting the diagnosis of LAMM syndrome. New auditory and orodental iconography was performed permitting to describe the patients’ phenotype in depth and to report rare findings of LAMM syndrome. The sequencing of FGF3 gene identified a novel missense mutation (c.2T>G), substituting the first initiator methionine in arginine, in the fibroblast growth factor 3 (FGF3) at the homozygous state in both patients. LAMM syndrome was confirmed and appropriate genetic counseling performed

Parallel independent evolution of pathogenicity within the genus Yersinia

Peer reviewe

Antimicrobial Susceptibility from a One Health Perspective Regarding Porcine Escherichia coli from Bavaria, Germany

Antimicrobial resistance is one of the most crucial One Health topics worldwide. Consequently, various national and international surveillance programs collect data and report trends regularly. Ceftiofur, colistin and enrofloxacin belong to the most important and critical class of anti-infective medications in both human and veterinary medicine. In the present study, antimicrobial resistance was analyzed using the epidemiological cut-off (ECOFF) value on 6569 Escherichia coli isolated from pigs in Bavaria, Germany, during five years, from 2016 to 2020. The statistically relevant results regarding antimicrobial resistance revealed a decrease for colistin, an increase for enrofloxacin, and a constant level for ceftiofur. In Germany, the usage of all three antimicrobial substances in livestock has fallen by 43.6% for polypeptides, 59.0% for fluoroquinolones and 57.8% for the 3rd + 4th generation cephalosporines during this time. Despite the decline in antimicrobial usage, a reduction regarding antimicrobial resistance was solely observed for colistin. This finding illustrates that in addition to the restriction of pharmaceutical consumption, further measures should be considered. Improved biosecurity concepts, a reduction in crowding, and controlled animal movements on farms may play a key role in finally containing the resistance mechanisms of bacteria in farm animals