Pilot study to identify missed opportunities for prevention of childhood tuberculosis

Tuberculosis (TB) in exposed children can be prevented with timely contact tracing and preventive treatment. This study aimed to identify potential barriers and delays in the prevention of childhood TB in a low-incidence country by assessing the management of children subsequently diagnosed with TB. A pilot retrospective cohort study included children (< 15 years) treated for TB between 2009 and 2016 at a tertiary care hospital in Berlin, Germany. Clinical data on cases and source cases, information on time points of the diagnostic work up, and preventive measures were collected and analyzed. Forty-eight children (median age 3 years [range 0.25-14]) were included; 36 had been identified through contact tracing, the majority (26; 72.2%) being < 5 years. TB source cases were mostly family members, often with advanced disease. Thirty children (83.3%) did not receive prophylactic or preventive treatment, as TB was already prevalent when first presented. Three cases developed TB despite preventive or prophylactic treatment; in three cases (all < 5 years), recommendations had not been followed. Once TB was diagnosed in source cases, referral, assessment, TB diagnosis, and treatment were initiated in most children in a timely manner with a median duration of 18 days (interquartile range 6-60, range 0-252) between diagnosis of source case and child contact (information available for 35/36; 97.2%). In some cases, notable delays in follow-up occurred. Conclusion: Prompt diagnosis of adult source cases appears to be the most important challenge for childhood TB prevention. However, improvement is also needed in the management of exposed children

Correction to: Pilot study to identify missed opportunities for prevention of childhood tuberculosis

Peer Reviewe

Pilot study to identify missed opportunities for prevention of childhood tuberculosis

Tuberculosis (TB) in exposed children can be prevented with timely contact tracing and preventive treatment. This study aimed to identify potential barriers and delays in the prevention of childhood TB in a low-incidence country by assessing the management of children subsequently diagnosed with TB. A pilot retrospective cohort study included children (< 15 years) treated for TB between 2009 and 2016 at a tertiary care hospital in Berlin, Germany. Clinical data on cases and source cases, information on time points of the diagnostic work up, and preventive measures were collected and analyzed. Forty-eight children (median age 3 years [range 0.25–14]) were included; 36 had been identified through contact tracing, the majority (26; 72.2%) being < 5 years. TB source cases were mostly family members, often with advanced disease. Thirty children (83.3%) did not receive prophylactic or preventive treatment, as TB was already prevalent when first presented. Three cases developed TB despite preventive or prophylactic treatment; in three cases (all < 5 years), recommendations had not been followed. Once TB was diagnosed in source cases, referral, assessment, TB diagnosis, and treatment were initiated in most children in a timely manner with a median duration of 18 days (interquartile range 6–60, range 0–252) between diagnosis of source case and child contact (information available for 35/36; 97.2%). In some cases, notable delays in follow-up occurred. Conclusion: Prompt diagnosis of adult source cases appears to be the most important challenge for childhood TB prevention. However, improvement is also needed in the management of exposed children.Peer Reviewe

Финансовые аспекты реформирования дошкольного образования (на примере МАДОУ ДСКВ №7 «Дарование»)

Актуальность работы тем, что в условиях нестабильной экономической ситуации в РФ и без того не слишком высокий уровень финансирования системы образования всех уровней имеет тенденции к снижению, так что образовательные учреждения вынуждены искать дополнительные (к бюджетному) источники финансирования, в том числе, за счет коммерческой деятельности. Объектом исследований является финансирование образовательной сферы РФ Предметом исследований является процесс реформирования и текущее состояние финансирования системы образования на примере МАДОУ ДСКВ №7 "Дарование". Целью ВКР является оптимизация финансовых аспектов реформирования дошкольного образования (на примере МАДОУ ДСКВ №7 "Дарование").The relevance of the work is that in the unstable economic situation in the Russian Federation, the already not too high level of funding for the education system at all levels tends to decrease, so that educational institutions are forced to look for additional (to the budget) sources of funding, including through commercial activities. The object of research is the financing of the educational sphere of the Russian Federation The subject of research is the process of reformation and the current state of financing of the education system on the example of MADOU DSKV №7 "Darovanie". The purpose of WRC is to optimize the financial aspects of reforming preschool education (on the example of MADOU DSKV №7 "Darovanie")

SPSS Einsatz auf unterschiedlichen Plattformen in einem Netzwerk: Daten- und Ergebnisaustausch

Seit einiger Zeit gibt es in der PC-Welt drei Versionen von SPSS: SPSS für OS/2, SPSS/PC+ und SPSS für Windows. Als problematisch erweist sich für viele Anwender der Datenaustausch zwischen diesen verschiedenen Versionen. Auf einige der in der Praxis auftretenden Probleme wird im vorliegenden Bericht eingegangen. Die Autoren beziehen sich auf die Systeme SPSS/PC+ (Version 4.0.1 und 5.0.1), SPSS für Windows (Version 5.0.2), SPSS für Macintosh (Version 4.0.3) und SPSS für HP-UX (Release 4.0 für HP900/8xx). Erläutert werden Neuheiten der einzelnen Versionen und Vergleichsergebnisse. Es geht u.a. auch um Unterschiede beim Arbeiten mit verschiedenen SPSS-Versionen in bezug auf fehlende Werte. (psz

Screening and treatment for tuberculosis in a cohort of unaccompanied minor refugees in Berlin, Germany

INTRODUCTION: In 2015, 4062 unaccompanied minor refugees were registered in Berlin, Germany. According to national policies, basic clinical examination and tuberculosis (TB) screening is a prerequisite to admission to permanent accommodation and schooling for every refugee. This article evaluates the use of an interferon-γ-release-assay (IGRA) during the initial examination and TB screening of 970 unaccompanied minor refugees. RESULTS: IGRA test were obtained during TB screening for 301 (31.0%) of 970 adolescents not previously screened for TB. Positive IGRA results were obtained in 13.9% (42/301). Most of the 42 IGRA-positive refugees originated from Afghanistan or Syria (n?20 and 10 respectively). Two IGRA-positive adolescents were lost to follow-up, 2 were diagnosed with TB and the remaining 38 diagnosed with latent TB infection (LTBI). Demographic features of the 40 patients with positive IGRA result were as follows: 39 male, median age 16.8 years (IQR 16.0-17.2y), none meeting underweight criteria (median BMI 21.3kg/m2). On initial chest X-ray 2/40 participants had signs of active TB, while in 38 active disease was excluded and the diagnosis of latent TB infection (LTBI) made. Active hepatitis B-co-infection was diagnosed in 3/38 patients. All patients with LTBI received Isoniazid and Rifampicin for 3 months without occurrence of severe adverse events. The most frequently observed side effect was transient upper abdominal pain (n = 5). Asymptomatic elevation of liver transaminases was seen in 2 patients. 29 patients completed treatment with no signs of TB disease at the end of chemoprevention and 9 were lost to follow up. CONCLUSION: Screening for TB infection in minor refugees was feasible in our setting with a relatively high rate of TB infection detected. Chemopreventive treatment was tolerated well regardless of underlying hepatitis-B-status. Minor refugees migrating to Germany should be screened for TB infection, instead of TB disease only, regardless of the background TB incidence

PDGF and TGF-β contribute to the natural course of human IgA glomerulonephritis

PDGF and TGF-β contribute to the natural course of human Ig-A glomerulonephritis. PDGF and TGF-β are known mediators of mesangial cell proliferation and matrix expansion. The presence of these regulatory factors was examined in 30 renal biopsies from patients with IgA glomerulonephritis (IgA-GN) at the mRNA and protein level. Normal renal tissue served as control. The mRNA expression of PDGF A/B chains, PDGF-βR and TGF-β1 was evaluated by means of RT/PCR with subsequent Southern blot hybridization and/or non-radiactive in situ hybridization. In addition, PDGF-AB/BB, PDGF-βR, TGF-β isoforms (β1, β1+2, β2+3), the small TGF-β1 latency associated peptide (TGF-β1 LAP) and the extracellular matrix proteins tenascin and decorin were analyzed by immunocytochemistry. The expression of growth factors was correlated with light microscopic and clinical features. Compared to normal control kidneys, an increased expression of PDGF-BB/PDGF-βR mRNAs and the corresponding proteins was observed in all biopsies with IgA-GN. Up-regulation was related to the degree of glomerular proliferation and the extent of fibrosing interstitial lesions. In contrast, there was a discordance between TGF-β1 mRNA and protein expression (evaluated by immunocytochemistry). In all biopsies, irrespective of the stage of the disease, abundant TGF-β1 transcripts were detected, whereas TGF-β1 immunoreactivity was expressed to a lesser degree and disclosed a more variable staining pattern. In patients with significant proliferative glomerular lesions and minor tubulointerstitial alterations, TGF-β1 positivity was confined to areas of glomerular proliferation, whereas in cases with more severe histology including sclerosing lesions TGF-β1 immunoreactivity was less prominent. The distribution and the intensity of TGF-β1 LAP staining commonly exceeded the positivity noted for TGF-β1, indicating only limited TGF-β1 activation. A decreased reactivity for tenascin accompanied the morphological features of glomerular sclerosis. The staining patterns and the fact that only very few inflammatory cells, particularly CD68 positive monocytes/macrophages, were detected in glomeruli confirm that predominantly resident glomerular cells (mesangial and endothelial cells) are the major source of up-regulated growth factor production in IgA-GN. Since the expression of PDGF-AB/BB paralleled the severity of proliferative glomerular changes, PDGF seems to represent a potential indicator of activity in this condition. It is suggested that an imbalance between PDGF and TGF-β (by restricted translation and/or activation) production contribute to the progressive nature of IgA-GN

CXCR4 mediates leukemic cell migration and survival in the testicular microenvironment

The testis is the second most frequent extramedullary site of relapse in pediatric acute lymphoblastic leukemia (ALL). The mechanism for B-cell (B) ALL cell migration towards and survival within the testis remains elusive. Here, we identified CXCL12-CXCR4 as the leading signaling axis for B-ALL cell migration and survival in the testicular leukemic niche. We combined analysis of primary human ALL with a novel patient-derived xenograft (PDX)-ALL mouse model with testicular involvement. Prerequisites for leukemic cell infiltration in the testis were prepubertal age of the recipient mice, high surface expression of CXCR4 on PDX-ALL cells, and CXCL12 secretion from the testicular stroma. Analysis of primary pediatric patient samples revealed that CXCR4 was the only chemokine receptor being robustly expressed on B-ALL cells both at the time of diagnosis and relapse. In affected patient testes, leukemic cells localized within the interstitial space in close proximity to testicular macrophages. Mouse macrophages isolated from affected testes, in the PDX model, revealed a macrophage polarization towards a M2-like phenotype in the presence of ALL cells. Therapeutically, blockade of CXCR4-mediated functions using an anti-CXCR4 antibody treatment completely abolished testicular infiltration of PDX-ALL cells and strongly impaired the overall development of leukemia. Collectively, we identified a prepubertal condition together with high CXCR4 expression as factors affecting the leukemia permissive testicular microenvironment. We propose CXCR4 as a promising target for therapeutic prevention of testicular relapses in childhood B-ALL. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland

Leistung und Stresslevel bei Maultieren während eines fünftägigen Gotthardtrecks

Während einer fünftägigen Gotthardüberquerung im Sommer 2016 haben drei Maultiere als Tragtiere mit einer Gepäcklast von je 80 kg rund 94,46 Kilometer und 3’364 Höhenmeter bewältigt. Die Leistungsanforderung wurde anhand der Erholungswerte der Vitalparameter Herzfrequenz, Atemfrequenz und Körpertemperatur, sowie durch kontinuierliche Herzfrequenzmessung während der Belastung evaluiert. Die Bestimmung der Glucokortikoid- Metabolit Konzentration im Kot diente zur Einschätzung des Stresslevels der drei Maultiere. Die Erholungswerte der Herzfrequenzen der drei Maultiere lagen während allen Trekkingetappen in einem Bereich, der nicht auf eine Leistungsüberforderung schliessen liess. Anhand der kontinuierlichen Herzfrequenzaufzeichnung bei einem der Maultiere konnte gezeigt werden, dass die physische Leistungsanforderung im Ausdauerbereich lag. Wie als normale physiologische Reaktion des Körpers nach einer fünftägigen körperlichen Belastung erwartet, stieg Stresslevel gemessen an den Glucokortikoid-Metaboliten im Kot gegen Ende des Trecks bei allen Maultieren an. In der vorliegenden Studie konnte gezeigt werden, dass die Maultiere während des Gotthardtrecks ausdauernd belastbar waren, ohne durch die Anstrengung beeinträchtigt zu sein, die schon historisch von Maultieren abverlangt wurde

CD70 Deficiency Associated With Chronic Epstein-Barr Virus Infection, Recurrent Airway Infections and Severe Gingivitis in a 24-Year-Old Woman

Most of the few patients with homozygous CD70 deficiency described to date suffered from EBV-related malignancies in early childhood. We present a woman with CD70 deficiency diagnosed in adulthood. She presented in childhood with recurrent airway infections due to encapsulated bacteria, herpes zoster and a fulminant EBV infection followed by chronic EBV infection with mild lymphoproliferation and severe gingivitis/periodontal disease with high EBV viral load in saliva and gingival plaques as an adult. Up to the age of 24 years she developed no malignancy despite constant EBV viremia since primary EBV infection 15 years previously. Immunologic evaluation in childhood showed hypogammaglobulinemia with impaired polysaccharide responsiveness. She has been stable on immunoglobulin substitution with no further severe viral infections and no bacterial airway infections in adulthood. Targeted panel sequencing at the age of 20 years revealed a homozygous CD70 missense mutation (ENST00000245903.3:c.2T>C). CD70 deficiency was confirmed by absent CD70 expression of B cells and activated T cell blasts. The patient finished high school, persues an academic career and has rarely sick days at college. The clinical course of our patient may help to counsel parents of CD70-deficient patients with regard to prognosis and therapeutic options including haematopoetic stem cell transplantation