Gesundheit und Gesundheitsversorgung von trans Personen während der COVID‑19-Pandemie: Eine Online-Querschnittstudie in deutschsprachigen Ländern

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Seit dem Frühjahr 2020 hat die COVID‑19-Pandemie nahezu alle Bereiche des gesellschaftlichen Lebens erheblich...     

Absence of MHC class II on cDCs results in microbial-dependent intestinal inflammation

Conventional dendritic cells (cDCs) play an essential role in host immunity by initiating adaptive T cell responses and by serving as innate immune sensors. Although both innate and adaptive functions of cDCs are well documented, their relative importance in maintaining immune homeostasis is poorly understood. To examine the significance of cDC-initiated adaptive immunity in maintaining homeostasis, independent of their innate activities, we generated a cDC-specific Cre mouse and crossed it to a floxed MHC class II (MHCII) mouse. Absence of MHCII on cDCs resulted in chronic intestinal inflammation that was alleviated by antibiotic treatment and entirely averted under germ-free conditions. Uncoupling innate and adaptive functions of cDCs revealed that innate immune functions of cDCs are insufficient to maintain homeostasis and antigen presentation by cDCs is essential for a mutualistic relationship between the host and intestinal bacteria.Conventional DCs (cDCs) are specialized immune cells that link the innate and adaptive immune system. Innate features of cDCs allow them to recognize and respond to pathogens by producing essential cytokines such as IL-6, IL-12, IL-23, and TNF. These cytokines contribute to the activation of other immune cells, including T and B cells and cells of the innate immune system. For example, in the intestine, cDCs sense bacteria and produce IL-23, which induces type III innate lymphoid cells (ILC3s) to produce IL-22, which in turn stimulates production of antimicrobial peptides (AMPs; Sonnenberg et al., 2011; Kinnebrew et al., 2012; Satpathy et al., 2013; Bernink et al., 2015). In addition to their innate functions, cDCs initiate adaptive immune responses by ingesting, processing, and presenting antigens to T cells (Nussenzweig et al., 1980; Steinman et al., 2003). In the intestine, cDCs are responsible for transport of antigen to the draining mesenteric LNs (mLNs). Under physiological conditions, the capacity of cDCs to migrate from tissue to draining LNs distinguishes them from more sessile macrophages (Schreiber et al., 2013). The importance of cDCs in adaptive immune function is exemplified by the fact that cDC depletion during viral and bacterial infection results in impaired T cell immunity and increased susceptibility to infection (Jung et al., 2002; Kassim et al., 2006; Hildner et al., 2008; Satpathy et al., 2013; Schreiber et al., 2013).In mice, expression of Itgax (CD11c) is a hallmark of the DC lineage, and its expression has been used to label (CD11c^YFP), deplete (CD11c^DTR), and conditionally target (CD11c^Cre) cDCs (Jung et al., 2002; Lindquist et al., 2004; Caton et al., 2007; Stranges et al., 2007). However, CD11c is also expressed by plasmacytoid DCs (pDCs), activated monocytes, macrophages, and some NK cells, and therefore CD11c-based labeling and targeting strategies are not entirely cDC specific (Serbina et al., 2003; Hohl et al., 2009; Meredith et al., 2012; Schreiber et al., 2013). Higher levels of specificity can be achieved by deletion of genes that regulate the development of specific subsets of cDCs, such as Batf3, Irf4, and Notch2; however, these methods have yet to be applied to dissect the relative contributions of the innate and adaptive functions of cDCs to immune homeostasis (Caton et al., 2007; Hildner et al., 2008; Persson et al., 2013; Schlitzer et al., 2013).To investigate the adaptive functions of cDCs independent of innate activities, we produced a cDC-restricted Cre mouse wherein Cre expression is directed by the Zbtb46 gene (zDC^Cre) and used it to delete MHCII in cDCs in vivo. These mice exhibited profound intestinal inflammation that was directly related to the presence of intestinal bacteria, as antibiotic-treated or germ-free mice lacking MHCII on cDCs showed no signs of intestinal inflammation. Colonization of germ-free mice allowed us to monitor adaptive immune responses against intestinal bacteria and revealed that mice lacking MHCII on cDCs have a defect in inducing proper adaptive immune responses against commensals. Collectively, our studies reveal the importance of the adaptive function of cDCs in maintaining intestinal homeostasis.     

Impairment of neuropsychological functions in children with medulloblastomas and astrocytomas in the posterior fossa

Neuropsychological impairment after removal of posterior fossa tumors is a recurrent issue in child neuropsychology and neurosurgery. The aim of this study was to assess verbal and performance intelligence, as well as immediate and sustained attention, in children with medulloblastoma or astrocytoma operated on for total removal of the lesion. Surgical treatment of medulloblastoma was always followed by chemoradiotherapy. Siblings of both tumor groups (without a history of neurological disease, even suspected) were examined as controls. The results were as follows: the cognitive performances were significantly poorer than the controls in both groups; the children with medulloblastoma scored below normal. Attention deficits were present in both groups as well when the usual clinical tests were used. When assessed by means of computerized methodology, the same function was normal. Considering that both groups of children underwent the same surgical treatment and all had hydrocephalus, the severe intellectual impairment reported only in patients with medulloblastoma can be ascribed to chemoradiotherapy. In contrast, the attention deficits present in both groups could be ascribed to the proximity of lesions to the ascending activating system. Malfunctioning of the activating system seems to be bypassed by the computerized administration of stimuli, which supplies motivation and kindles attention.Presented at the XIthe Meeting of the European Society for Paediatric Neurosurgery, Naples, 1988     

Synthesis of New Congeners of 1‐methyl‐3‐aminoisoquinolines,Evaluation of Their Cytotoxic Activity,In Silico and In Vitro Study of Their Molecular Targets as PDE4B

To examine the cytotoxic activity of congeners of 3‐amino‐isoquinoline, we performed the phenotypic screening using panel of 60 cell lines and found that (N‐(6,7‐dimethoxy‐1‐methyl‐isoquinolin‐3‐yl)‐4‐{[(1‐ethyl‐4‐methyl‐1H‐pyrazol‐3‐yl)methyl]amino}benzamide ( 4d )) exhibited the significant effect against different tumor cell lines while showing the high activity toward human colorectal cancer HCT‐116 cells (IC₅₀ = 18 μm ) and human breast cancer T‐47D cells (GI₅₀ = 1.9 μm ). Virtual screening indicated that these compounds target protein kinases and phosphodiesterases (PDE). However, wet screening among panel of protein kinases did not show any significant activity. By contrast, 50 μm of 4c and 4d inhibited the growth of HKe3‐mtKRAS spheroids in the 3D floating (3DF) culture suggesting that 4c and 4d target PDE4B which is selectively upregulated by mtKRAS in 3DF culture.     

Comparative genome analysis of global and Russian strains of community-acquired methicillin-resistant Staphylococcus aureus ST22, a ‘Gaza clone’

In this study, we identified the relationship between the genetic lineage of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) sequence type 22 (ST22) from Russia and other regions. Sixty ST22 isolates from Russia were characterised through whole-genome sequencing. To evaluate the phylogenetic relationship of Russian isolates with the global ST22 population, we analysed 1283 genomes obtained from NCBI's GenBank. The phylogenetic tree of the ST22 global population consisted of three main clusters (A, B and C). The first (cluster A) was represented by EMRSA-15 isolates, the second (cluster B) by heterogeneous isolates from different regions harbouring different sets of virulence genes, and the third (cluster C) by isolates from the Middle East previously recognised as ‘Gaza clone’ and similar isolates from Russia. Presence of the toxic shock syndrome toxin (tsst) and elastin-binding protein S (ebpS) genes as well as the hypothetical proteins NCTC13616_00051 and NCTC13616_00047 were the most useful factors in discriminating ST22 lineages. Although the CA-MRSA ‘Gaza clone’ was mainly recovered from carriers, its widespread occurrence is a cause for concern. Differentiation of the ‘Gaza clone’ from other MRSA lineages is necessary for planning infection control measures.     

Preoperative assessment of ovarian tumors by CA 125 measurement and transvaginal color Doppler ultrasound

The accuracy of combined use of serum CA 125 and transvaginal color Doppler for preoperative assessment of ovarian lesions in premenopausal patients was evaluated. Seventy-six ovarian lesions were analyzed the day before surgery using transvaginal color Doppler ultrasound. On the same day, serum CA 125 was measured in each patient. A novel index is proposed for the detection of ovarian malignancy combining resistance index (RI) obtained from newly formed vessels within the ovarian lesion and serum CA 125 level: (RI/CA 125) x 100. Values below the cut-off value of 1.5 were associated with a high risk of ovarian malignancy. Assessment of ovarian lesions by the novel index had a sensitivity and specificity of 94.44% and 100%, while positive and negative predictive values were 100% and 98.31%, respectively. The best prediction of ovarian malignancy was achieved by a combined use of transvaginal color Doppler ultrasound and serum CA 125 in the form of index: (RI/CA 125) x 100.     

The effect of DEAE-Dextran on the infectivity of a feline calicivirus and its RNA

Summary The polycation DEAE-Dextran increases the plating efficiency of an intact feline calicivirus in primary kitten kidney cells by up to 10 times. Both pretreated virus and pretreated cells show a similar dose response curve with a peak at 250 g/ml DEAE-Dextran. Above this concentration, the polycation appeared toxic to the cell monolayers. Pretreated washed cells showed an increased plaque count of intact virus but this was only in the order of a two fold increase.Low titres of infectious RNA could be assayed from the virus. No infectious RNA could be detected in the absence of DEAE-Dextran and titres of RNA were 10^–6 of the intact virus.