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BACKGROUND AND OBJECTIVES: Childhood immunization may influence the development of asthma, possibly due to lack of infections or a shift in the T-helper cell type 1/T-helper cell type 2/regulatory T cells balance. We therefore investigated whether pertussis immunization in infancy is associated with asthma medication in adolescence. METHODS: After 14 years of no general pertussis vaccination, almost 82 000 Swedish children were immunized for pertussis in a vaccination trial between June 1, 1993, and June 30, 1994. In a follow-up analysis of almost 80 000 children, their data were compared with those of ~100 000 nonvaccinated children, born during a 5-month period before and a 7-month period after the vaccination trial. Data for the main outcome variable (ie, dispensed prescribed asthma medication for each individual in the cohort during 2008-2010) were obtained from the national prescription database. Multivariate regression models were used to calculate the effect size of vaccination on dispensed asthma medication (odds ratios [OR], 95% confidence intervals [Cl]). Approaches similar to intention-to-treat and per-protocol methods were used. RESULTS: The prevalence rates of various asthma medications for study patients at 15 years of age differed between 4.6% and 7.0%. The crude ORs for any asthma medication and antiinflammatory treatment in pertussis-vaccinated children after intention-to-treat analysis were 0.97 (95% Cl: 0.93-1.00) and 0.94 (95% Cl: 0.90-0.98), respectively. Corresponding adjusted ORs were 0.99 (95% Cl: 0.95-1.03) and 0.97 (95% Cl: 0.92-1.01). Similar ORs were found after per-protocol analysis. CONCLUSIONS: Pertussis immunization in infancy does not increase the risk of asthma medication use in adolescents. Our study presents evidence that pertussis immunization in early childhood can be considered safe with respect to long-term development of asthma. [ABSTRACT FROM AUTHOR]

Cord blood IgE has previously been studied as a possible predictor of asthma and allergic diseases. Results from different studies have been contradictory, and most have focused on high-risk infants and early infancy. Few studies have followed their study population into adulthood. This study assessed whether cord blood IgE levels and a family history of asthma were associated with, and could predict, asthma medication and allergy-related respiratory symptoms in adults. A follow-up was carried out in a Swedish birth cohort comprising 1,701 consecutively born children. In all, 1,661 individuals could be linked to the Swedish Prescribed Drug Register and the Medical Birth Register, and 1,227 responded to a postal questionnaire. Cord blood IgE and family history of asthma were correlated with reported respiratory symptoms and dispensed asthma medication at 32–34 years. Elevated cord blood IgE was associated with a two- to threefold increased risk of pollen-induced respiratory symptoms and dispensed anti-inflammatory asthma medication. Similarly, a family history of asthma was associated with an increased risk of pollen-induced respiratory symptoms and anti-inflammatory medication. However, only 8% of the individuals with elevated cord blood IgE or a family history of asthma in infancy could be linked to current dispensation of anti-inflammatory asthma medication at follow-up. In all, 49 out of 60 individuals with dispensed anti-inflammatory asthma medication at 32–34 years of age had not been reported having asthma at previous check-ups of the cohort during childhood. Among those, only 5% with elevated cord blood IgE and 6% with a family history of asthma in infancy could be linked to current dispensation of anti-inflammatory asthma medication as adults. Elevated cord blood IgE and a positive family history of asthma were associated with reported respiratory symptoms and dispensed asthma medication in adulthood, but their predictive power was poor in this long-time follow-up. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Preterm birth is associated with respiratory morbidity later in life, including asthma. Previous studies have mainly focused on asthma in early childhood in children born extremely preterm. In this study, we examined the risk of asthma in a national cohort of schoolchildren grouped according to degree of immaturity expressed as completed gestational weeks at birth. METHODS: This was a register study in a Swedish national cohort of 1 100 826 children 6 to 19 years old. Retrieval of at least 1 prescription of inhaled corticosteroids (ICS) during 2006 was used as the main indicator for asthma. Logistic regression was used to test hypotheses, with adjustment for multiple socioeconomic and perinatal indicators. RESULTS: Degree of immaturity, expressed as completed gestational weeks at birth, had an inverse dose-response relationship with ICS use. Compared with children born between 39 and 41 weeks' gestation, the odds ratio for ICS use increased with the degree of prematurity, from 1.10 (95% confidence interval: 1.08-1.13) for children born in weeks 37 to 38, to 2.28 (95% confidence interval: 1.96-2.64) for children born in weeks 23 to 28, after adjustment for confounders The increase in ICS use with decreasing gestational age at delivery was similar in boys and girls, and declined with older age. CONCLUSION: Preterm birth increased the risk of ICS use in these 6-to 19-year-olds by degree of immaturity, from extremely preterm to early term birth. [ABSTRACT FROM AUTHOR]

This article discusses a study on the haemostasis (blood clotting) during the early treatment of childhood acute lymphoblastic leukaemia (ALL) using the ALLTogether protocol. The study compared the coagulation parameters, thromboses, and bleeding events between patients treated with the ALLTogether protocol and those treated with the previous protocol. The results showed that low fibrinogen levels were more pronounced in the ALLTogether group, but the number of bleeding events did not increase. Thrombotic events were also observed in both groups, but the timing may differ between the protocols. The study suggests further research to identify children at risk of bleeding and those who may benefit from thromboprophylaxis. [Extracted from the article]

PURPOSE: Several studies have indicated that broad genomic characterization of childhood cancer provides diagnostically and/or therapeutically relevant information in selected high-risk cases. However, the extent to which such characterization offers clinically actionable data in a prospective broadly inclusive setting remains largely unexplored. METHODS: We implemented prospective whole-genome sequencing (WGS) of tumor and germline, complemented by whole-transcriptome sequencing (RNA-Seq) for all children diagnosed with a primary or relapsed solid malignancy in Sweden. Multidisciplinary molecular tumor boards were set up to integrate genomic data in the clinical decision process along with a medicolegal framework enabling secondary use of sequencing data for research purposes. RESULTS: During the study's first 14 months, 118 solid tumors from 117 patients were subjected to WGS, with complementary RNA-Seq for fusion gene detection in 52 tumors. There was no significant geographic bias in patient enrollment, and the included tumor types reflected the annual national incidence of pediatric solid tumor types. Of the 112 tumors with somatic mutations, 106 (95%) exhibited alterations with a clear clinical correlation. In 46 of 118 tumors (39%), sequencing only corroborated histopathological diagnoses, while in 59 cases (50%), it contributed to additional subclassification or detection of prognostic markers. Potential treatment targets were found in 31 patients (26%), most commonly ALK mutations/fusions (n = 4), RAS/RAF/MEK/ERK pathway mutations (n = 14), FGFR1 mutations/fusions (n = 5), IDH1 mutations (n = 2), and NTRK2 gene fusions (n = 2). In one patient, the tumor diagnosis was revised based on sequencing. Clinically relevant germline variants were detected in 8 of 94 patients (8.5%). CONCLUSION: Up-front, large-scale genomic characterization of pediatric solid malignancies provides diagnostically valuable data in the majority of patients also in a largely unselected cohort. Countrywide establishment of whole-genome sequencing for childhood cancers to improve diagnostics [ABSTRACT FROM AUTHOR]

Summary: Patients undergoing treatment for acute lymphoblastic leukaemia (ALL) are at risk of coagulopathy, especially thromboembolism. We conducted a survey on practices in the assessment and management of coagulopathy during the new ALLTogether protocol in 29 (17 paediatric, 12 adult) Nordic and Baltic cancer centres. While 92% of adult centres used thromboprophylaxis with low‐molecular‐weight heparin, no paediatric centre did. Almost all providers performed baseline coagulation studies, but only 59% continued the assessment. Fibrinogen replacement was conducted in 59%, and antithrombin replacement in 28% of the centres. The survey highlights the need for guidelines in the management of coagulopathy during ALL therapy. [ABSTRACT FROM AUTHOR]

Pediatric T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy resulting from overproduction of immature T-cells in the thymus and is typified by widespread alterations in DNA methylation. As survival rates for relapsed T-ALL remain dismal (10 to 25%), development of targeted therapies to prevent relapse is key to improving prognosis. Whereas mutations in the DNA demethylating enzyme TET2 are frequent in adult T-cell malignancies, TET2 mutations in T-ALL are rare. Here, we analyzed RNA-sequencing data of 321 primary T-ALLs, 20 T-ALL cell lines, and 25 normal human tissues, revealing that TET2 is transcriptionally repressed or silenced in 71% and 17% of T-ALL, respectively. Furthermore, we show that TET2 silencing is often associated with hypermethylation of the TET2 promoter in primary T-ALL. Importantly, treatment with the DNA demethylating agent, 5-azacytidine (5-aza), was significantly more toxic to TET2-silenced T-ALL cells and resulted in stable re-expression of the TET2 gene. Additionally, 5-aza led to up-regulation of methylated genes and human endogenous retroviruses (HERVs), which was further enhanced by the addition of physiological levels of vitamin C, a potent enhancer of TET activity. Together, our results clearly identify 5-aza as a potential targeted therapy for TET2-silenced T-ALL. [ABSTRACT FROM AUTHOR]

• Establishment of a reference model for cortical follicular density for ages 0–25 years. • Average Z-score indicates normal reserve in patients exposed to chemotherapy. • Average Z-score indicates significantly reduced ovarian reserve in patients with Turner syndrome. • Young age predicts lower Z-scores in patients exposed to chemotherapy. • Depleted ovarian reserve cut-off (Z-score <-1.7) identifies patients with genetic conditions. Are age-normalized reference values for human ovarian cortical follicular density adequate for tissue quality control in fertility preservation? Published quantitative data on the number of follicles in samples without known ovarian pathology were converted into cortical densities to create reference values. Next, a sample cohort of 126 girls (age 1–24 years, mean ± SD 11 ± 6) with cancer, severe haematological disease or Turner syndrome were used to calculate Z-scores for cortical follicular density based on the reference values. No difference was observed between Z-scores in samples from untreated patients (0.3 ± 3.5, n = 30) and patients treated with (0.5 ± 2.9, n = 48) and without (0.1 ± 1.3, n = 6) alkylating chemotherapy. Z-scores were not correlated with increasing cumulative exposure to cytostatics. Nevertheless, Z-scores in young treated patients (0–2 years -2.1 ± 3.1, n = 10, P = 0.04) were significantly lower than Z-scores in older treated patients (11–19 years, 2 ± 1.9, n = 15). Samples from patients with Turner syndrome differed significantly from samples from untreated patients (-5.2 ± 5.1, n = 24, P = 0.003), and a Z-score of -1.7 was identified as a cut-off showing good diagnostic value for identification of patients with Turner syndrome with reduced ovarian reserve. When this cut-off was applied to other patients, analysis showed that those with indications for reduced ovarian reserve (n = 15) were significantly younger (5.9 ± 4.2 versus 10.7 ± 5.9 years, P = 0.004) and, when untreated, more often had non-malignant haematologic diseases compared with those with normal ovarian reserve (n = 24, 100% versus 19%, P = 0.009). Z-scores allow the estimation of genetic- and treatment-related effects on follicular density in cortical tissue from young patients stored for fertility preservation. Understanding the quality of cryopreserved tissue facilitates its use during patient counselling. More research is needed regarding the cytostatic effects found in this study. [ABSTRACT FROM AUTHOR]

Of late, decrease in mineral oil supplies has stimulated research on use of biomass as an alternative energy source. Climate change has brought problems such as increased drought and erratic rains. This, together with a rise in land degeneration problems with concomitant loss in soil fertility has inspired the scientific world to look for alternative bio-energy species. Euphorbia tirucalli L., a tree with C3/CAM metabolism in leaves/stem, can be cultivated on marginal, arid land and could be a good alternative source of biofuel. We analyzed a broad variety of E. tirucalli plants collected from different countries for their genetic diversity using AFLP. Physiological responses to induced drought stress were determined in a number of genotypes by monitoring growth parameters and influence on photosynthesis. For future breeding of economically interesting genotypes, rubber content and biogas production were quantified. Cluster analysis shows that the studied genotypes are divided into two groups, African and mostly non-African genotypes. Different genotypes respond significantly different to various levels of water. Malate measurement indicates that there is induction of CAM in leaves following drought stress. Rubber content varies strongly between genotypes. An investigation of the biogas production capacities of six E. tirucalli genotypes reveals biogas yields higher than from rapeseed but lower than maize silage. [ABSTRACT FROM AUTHOR]

Fertility preservation for male childhood cancer survivors not yet capable of producing mature spermatozoa, relies on experimental approaches such as testicular explant culture. Although the first steps in somatic maturation can be observed in human testicular explant cultures, germ cell depletion is a common obstacle. Hence, understanding the spermatogonial stem cell (SSC) niche environment and in particular, specific components such as the seminiferous basement membrane (BM) will allow progression of testicular explant cultures. Here, we revealed that the seminiferous BM is established from 6 weeks post conception with the expression of laminin alpha 1 (LAMA 1) and type IV collagen, which persist as key components throughout development. With prepubertal testicular explant culture we found that seminiferous LAMA 1 expression is disrupted and depleted with culture time correlating with germ cell loss. These findings highlight the importance of LAMA 1 for the human SSC niche and its sensitivity to culture conditions. [ABSTRACT FROM AUTHOR]