Compound heterozygosity for a whole gene deletion and p.R124C mutation in CYP21A2 causing nonclassic congenital adrenal hyperplasia

We present a family with 2 members who received long-term steroid treatment for presumed classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, until molecular testing revealed nonclassic CAH, not necessarily requiring treatment. A 17-year-old male presented to our clinic on glucocorticoid and mineralocorticoid treatment for classic CAH. He was diagnosed at 4 years of age based on mild-moderate elevations of 17-hydroxyprogesterone (17-OHP) and adrenocorticotropic hormone (ACTH), but without evidence of precocious adrenarche/puberty. Due to his diagnosis, his clinically asymptomatic 3-year-old sister was tested and also found to have elevated ACTH and 17-OHP levels and was started on glucocorticoids for classic CAH. Family history revealed a healthy sibling who had no biochemical evidence of CAH and consanguineous healthy parents. We questioned the diagnosis of classic CAH and performed an ACTH1-24 stimulation test, which showed a level of 17-OHP in the borderline range between classic and nonclassic CAH. Molecular testing, using sequencing and multiplex ligation-dependent probe amplification analysis of CYP21A2, revealed that both affected siblings were compound heterozygotes for a whole-gene deletion and a, likely pathogenic (nonclassical), sequence variant, p.R124C. The asymptomatic father had the same genotype, while the mother showed one deleted copy and 2 active copies, making her an asymptomatic carrier. Our report demonstrates the importance of molecular testing in atypical cases of CAH, as well as the importance of both sequencing and deletion analysis. The results of molecular testing should be interpreted in clinical context, and treatment should be prescribed according to guidelines when available

Motives for choosing university and specialty applicants Ukraine (for example, students NTU "KPI")

Стаття присвячена аналізу портрета абітурієнта НТУ "ХПІ", де, крім визначення мотивів професійного вибору, самооцінки особистих здібностей, розглядаються і основні цілі навчання в НТУ "ХПІ". У статті підкреслюється, що проблема професійного самовизначення стояла перед молоддю завжди, а сьогодні вона особливо актуальна, тому що сучасні умови ринку праці ведуть до того, що більшість випускників не мають ясної життєвої перспективи. Аналізуються мотиви отримання абітурієнтами вищої освіти, мотивація вступу до НТУ "ХПІ", мотиви вибору спеціальності, період формування професійного інтересу. Проаналізовано мотиви професійного вибору абітурієнтів; період формування інтересу молодих людей до обраної спеціальності (процес самовизначення, коли здійснено вибір спеціальності, ВНЗ); специфіку вибору ВНЗ (яким за рахунком був ХПІ, хто допоміг визначитися з вибором); уявлення про процес навчання в університеті; відповідність уявлень про навчання в університеті реаліям університетського життя.This article analyzes portrait applicant NTU "KPI", where in addition to determining the reasons professional choice, self-personal skills, and discusses the main goals of training at NTU "KPI". The article highlights the problem of professional self -determination was always the youth, and today it is particularly urgent because the current labor market conditions lead to the fact that most graduates do not have a clear life perspective. Analyzed the motives of applicants receiving higher education, motivation admission to NTU "KPI" motives choice of specialty, during the formation of professional interest. Analyzed the motives of professional selection of applicants; during the formation of young people's interest to the chosen profession (the process of self-selection made when specialty Universities); the specific choice of university (how the account was HPI, who helped to choose); understanding of the learning process at the university; line ideas about university studies realities of university life

The Role of the PAX8/PPARγ Fusion Oncogene in Thyroid Cancer

Thyroid cancer is uncommon and exhibits relatively low mortality rates. However, a subset of patients experience inexorable growth, metastatic spread, and mortality. Unfortunately, for these patients, there have been few significant advances in treatment during the last 50 years. While substantial advances have been made in recent years about the molecular genetic events underlying papillary thyroid cancer, the more aggressive follicular thyroid cancer remains poorly understood. The recent discovery of the PAX8/PPARγ translocation in follicular thyroid carcinoma has promoted progress in the role of PPARγ as a tumor suppressor and potential therapeutic target. The PAX8/PPARγ fusion gene appears to be an oncogene. It is most often expressed in follicular carcinomas and exerts a dominant-negative effect on wild-type PPARγ, and stimulates transcription of PAX8-responsive promoters. PPARγ agonists have shown promising results in vitro, although very few studies have been conducted to assess the clinical impact of these agents

Organizational and activational androgens, lemur social play, and the ontogeny of female dominance

The role of androgens in shaping “masculine” traits in males is a core focus in behavioral endocrinology, but relatively little is known about an androgenic role in female aggression and social dominance. In mammalian models of female dominance, including the ring-tailed lemur (Lemur catta), links to androgens in adulthood are variable. We studied the development of ring-tailed lemurs to address the behavioral basis and ontogenetic mechanisms of female dominance. We measured behavior and serum androgen concentrations in 24 lemurs (8 males, 16 females) from infancy to early adulthood, and assessed their ‘prenatal’ androgen milieu using serum samples obtained from their mothers during gestation. Because logistical constraints limited the frequency of infant blood sampling, we accounted for asynchrony between behavioral and postnatal hormone measurements via imputation procedures. Imputation was unnecessary for prenatal hormone measurements. The typical sex difference in androgen concentrations in young lemurs was consistent with adult conspecifics and most other mammals; however, we found no significant sex differences in rough-and-tumble play. Female (but not male) aggression increased beginning at approximately 15 months, coincident with female puberty. In our analyses relating sexually differentiated behavior to androgens, we found no relationship with activational hormones, but several significant relationships with organizational hormones. Notably, associations of prenatal androstenedione and testosterone with behavior were differentiated, both by offspring sex and by type of behavior within offspring sexes. We discuss the importance of considering (1) missing data in behavioral endocrinology research, and (2) organizational androgens other than testosterone in studies of female dominance

High lipid order of Arabidopsis cell‐plate membranes mediated by sterol and DYNAMIN‐RELATED PROTEIN1A function

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109568/1/tpj12674.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/109568/2/tpj12674-sup-0002-FigS2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/109568/3/tpj12674-sup-0001-FigS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/109568/4/tpj12674-sup-0003-FigS3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/109568/5/tpj12674-sup-0004-FigS4.pd

a prospective ‘before/after’ cohort study

Objectives Antibiotic resistance has risen dramatically over the past years. For individual patients, adequate initial antibiotic therapy is essential for clinical outcome. Computer-assisted decision support systems (CDSSs) are advocated to support implementation of rational anti-infective treatment strategies based on guidelines. The aim of this study was to evaluate long- term effects after implementation of a CDSS. Design This prospective ‘before/after’ cohort study was conducted over four observation periods within 5 years. One preinterventional period (pre) was compared with three postinterventional periods: directly after intensive implementation efforts (post1), 2 years (post2) and 3 years (post3) after implementation. Setting Five anaesthesiological-managed intensive care units (ICU) (one cardiosurgical, one neurosurgical, two interdisciplinary and one intermediate care) at a university hospital. Participants Adult patients with an ICU stay of >48 h were included in the analysis. 1316 patients were included in the analysis for a total of 12 965 ICU days. Intervention Implementation of a CDSS. Outcome measures The primary end point was percentage of days with guideline adherence during ICU treatment. Secondary end points were antibiotic-free days and all-cause mortality compared for patients with low versus high guideline adherence. Main results Adherence to guidelines increased from 61% prior to implementation to 92% in post1, decreased in post2 to 76% and remained significantly higher compared with baseline in post3, with 71% (p=0.178). Additionally, antibiotic-free days increased over study periods. At all time periods, mortality for patients with low guideline adherence was higher with 12.3% versus 8% (p=0.014) and an adjusted OR of 1.56 (95% CI 1.05 to 2.31). Conclusions Implementation of computerised regional adapted guidelines for antibiotic therapy is paralleled with improved adherence. Even without further measures, adherence stayed high for a longer period and was paralleled by reduced antibiotic exposure. Improved guideline adherence was associated with reduced ICU mortality

Endocytosis restricts Arabidopsis KNOLLE syntaxin to the cell division plane during late cytokinesis

Cytokinesis represents the final stage of eukaryotic cell division during which the cytoplasm becomes partitioned between daughter cells. The process differs to some extent between animal and plant cells, but proteins of the syntaxin family mediate membrane fusion in the plane of cell division in diverse organisms. How syntaxin localization is kept in check remains elusive. Here, we report that localization of the Arabidopsis KNOLLE syntaxin in the plane of cell division is maintained by sterol-dependent endocytosis involving a clathrin- and DYNAMIN-RELATED PROTEIN1A-dependent mechanism. On genetic or pharmacological interference with endocytosis, KNOLLE mis-localizes to lateral plasma membranes after cell-plate fusion. Fluorescence-loss-in-photo-bleaching and fluorescence-recovery-after-photo-bleaching experiments reveal lateral diffusion of GFP-KNOLLE from the plane of division to lateral membranes. In an endocytosis-defective sterol biosynthesis mutant displaying lateral KNOLLE diffusion, KNOLLE secretory trafficking remains unaffected. Thus, restriction of lateral diffusion by endocytosis may serve to maintain specificity of syntaxin localization during late cytokinesis

Weichselzeitliche Kryocalcite als Hinweise für Eisseen in der Hüttenbläserschachthöhle (Iserlohn/NRW)

C/O-stable isotope composition (VPDB) of speleothems from the Makkaronihalle of the Hüttenbläserschacht Cave in Iserlohn shows a clear separation between glacial and interglacial calcites. In contrast to normal speleothems (stalagmites, excentriques, crystals in cave ponds, draperies; δ18O: –4.0 to –6.1 ‰, δ13C: –4.9 to –10.9 ‰), rhombohedral crystal sinter and spherulitic speleoparticles are characterised by lower δ18O (–8.9 to –17.9 ‰) and higher δ13C values (+0.7 to –6.1 ‰). This suggests that these speleogenetic particles were formed in slowly freezing waterpools on ice during the transition from a stadial to an interstadial phase. Precise 230Th/U-dating shows younger Weichselian ages of 28.6 to 33.0 ka for these speleogenetic particles from north-west Germany. These formation periods indicate freezing conditions overlain by 34 m of hostrock and provide the minimum depth of permafrost penetration for the younger Weichselian in the area of the northern Sauerland (north-west Germany).researc