The broad phenotypic spectrum of 17α-hydroxylase/17,20-lyase (CYP17A1) deficiency: a case series

CONTEXT: 17α-Hydroxylase/17,20-lyase deficiency (17OHD) caused by mutations in the CYP17A1 gene is a rare form of congenital adrenal hyperplasia typically characterised by cortisol deficiency, mineralocorticoid excess and sex steroid deficiency. OBJECTIVE: To examine the phenotypic spectrum of 17OHD by clinical and biochemical assessment and corresponding in silico and in vitro functional analysis. DESIGN: Case series. PATIENTS AND RESULTS: We assessed eight patients with 17OHD, including four with extreme 17OHD phenotypes: two siblings presented with failure to thrive in early infancy and two with isolated sex steroid deficiency and normal cortisol reserve. Diagnosis was established by mass spectrometry-based urinary steroid profiling and confirmed by genetic CYP17A1 analysis, revealing homozygous and compound heterozygous sequence variants. We found novel (p.Gly111Val, p.Ala398Glu, p.Ile371Thr) and previously described sequence variants (p.Pro409Leu, p.Arg347His, p.Gly436Arg, p.Phe53/54del, p.Tyr60IlefsLys88X). In vitro functional studies employing an overexpression system in HEK293 cells showed that 17,20-lyase activity was invariably decreased while mutant 17α-hydroxylase activity retained up to 14% of WT activity in the two patients with intact cortisol reserve. A ratio of urinary corticosterone over cortisol metabolites reflective of 17α-hydroxylase activity correlated well with clinical phenotype severity. CONCLUSION: Our findings illustrate the broad phenotypic spectrum of 17OHD. Isolated sex steroid deficiency with normal stimulated cortisol has not been reported before. Attenuation of 17α-hydroxylase activity is readily detected by urinary steroid profiling and predicts phenotype severity. SIGNIFICANCE STATEMENT: Here we report, supported by careful phenotyping, genotyping and functional analysis, a prismatic case series of patients with congenital adrenal hyperplasia due to 17α-hydroxylase (CYP17A1) deficiency (17OHD). These range in severity from the abolition of function, presenting in early infancy, and unusually mild with isolated sex steroid deficiency but normal ACTH-stimulated cortisol in adult patients. These findings will guide improved diagnostic detection of CYP17A1 deficiency

Three Aphid-Transmitted Viruses Encourage Vector Migration From Infected Common Bean (Phaseolus vulgaris) Plants Through a Combination of Volatile and Surface Cues

Bean common mosaic virus (BCMV), bean common mosaic necrosis virus (BCMNV), and cucumber mosaic virus (CMV) are important pathogens of common bean (Phaseolus vulgaris), a crop vital for food security in sub-Saharan Africa. These viruses are vectored by aphids non-persistently, with virions bound loosely to stylet receptors. These viruses also manipulate aphid-mediated transmission by altering host properties. Virus-induced effects on host-aphid interactions were investigated using choice test (migration) assays, olfactometry, and analysis of insect-perceivable volatile organic compounds (VOCs) using gas chromatography (GC)-coupled mass spectrometry, and GC-coupled electroantennography. When allowed to choose freely between infected and uninfected plants, aphids of the legume specialist species Aphis fabae, and of the generalist species Myzus persicae, were repelled by plants infected with BCMV, BCMNV, or CMV. However, in olfactometer experiments with A. fabae, only the VOCs emitted by BCMNV-infected plants repelled aphids. Although BCMV, BCMNV, and CMV each induced distinctive changes in emission of aphid-perceivable volatiles, all three suppressed emission of an attractant sesquiterpene, α-copaene, suggesting these three different viruses promote migration of virus-bearing aphids in a similar fashion

Treatment strategies and prognostic factors of patients with primary germ cell tumors in the mediastinum

Se presenta una paciente que fue intervenida quirúrgicamente por presentar una lesión tumoral a nivel del mediastino anterior, totalmente asintomática y descubierta, de forma incidental (incidentaloma), en el estudio preoperatorio por padecer litiasis vesicular. La tumoración resultó ser, histológicamente, un teratoma quístico maduro. La paciente evolucionó satisfactoriamente.It presents a patient who was surgery because of a tumor at the level of the anterior mediastinum, totally asymptomatic and uncovered, incidentally (incidentaloma), in the preoperative study due to vesicular lithiasis. The tumor turned out to be, histologically, a mature cystic teratoma. The patient evolved satisfactorily

Favouritism: exploring the 'uncontrolled' spaces of the leadership experience

In this paper, we argue that a focus on favouritism magnifies a central ethical ambiguity in leadership, both conceptually and in practice. The social process of favouritism can even go unnoticed, or misrecognised if it does not manifest in a form in which it can be either included or excluded from what is (collectively interpreted as) leadership. The leadership literature presents a tension between what is an embodied and relational account of the ethical, on the one hand, and a more dispassionate organisational ‘justice’ emphasis, on the other hand. We conducted 23 semi-structured interviews in eight consultancy companies, four multinationals and four internationals. There were ethical issues at play in the way interviewees thought about favouritism in leadership episodes. This emerged in the fact that they were concerned with visibility and conduct before engaging in favouritism. Our findings illustrate a bricolage of ethical justifications for favouritism, namely utilitarian, justice, and relational. Such findings suggest the ethical ambiguity that lies at the heart of leadership as a concept and a practice

The present and future of serum diagnostic tests for testicular germ cell tumours.

Testicular germ cell tumours (GCTs) are the most common malignancy occurring in young adult men and the incidence of these tumours is increasing. Current research priorities in this field include improving overall survival for patients classified as being 'poor-risk' and reducing late effects of treatment for patients classified as 'good-risk'. Testicular GCTs are broadly classified into seminomas and nonseminomatous GCTs (NSGCTs). The conventional serum protein tumour markers α-fetoprotein (AFP), human chorionic gonadotrophin (hCG) and lactate dehydrogenase (LDH) show some utility in the management of testicular malignant GCT. However, AFP and hCG display limited sensitivity and specificity, being indicative of yolk sac tumour (AFP) and choriocarcinoma or syncytiotrophoblast (hCG) subtypes. Furthermore, LDH is a very nonspecific biomarker. Consequently, seminomas and NSGCTs comprising a pure embryonal carcinoma subtype are generally negative for these conventional markers. As a result, novel universal biomarkers for testicular malignant GCTs are required. MicroRNAs are short, non-protein-coding RNAs that show much general promise as biomarkers. MicroRNAs from two 'clusters', miR-371-373 and miR-302-367, are overexpressed in all malignant GCTs, regardless of age (adult or paediatric), site (gonadal or extragonadal) and subtype (seminomas, yolk sac tumours or embryonal carcinomas). A panel of four circulating microRNAs from these two clusters (miR-371a-3p, miR-372-3p, miR-373-3p and miR-367-3p) is highly sensitive and specific for the diagnosis of malignant GCT, including seminoma and embryonal carcinoma. In the future, circulating microRNAs might be useful in diagnosis, disease monitoring and prognostication of malignant testicular GCTs, which might also reduce reliance on serial CT scanning. For translation into clinical practice, important practical considerations now need addressing.The authors would like to acknowledge grant funding from CwCUK/GOSHCC (M.J.M. N.C. grant W1058), SPARKS (M.J.M. N.C. grant 11CAM01), CRUK (N.C. grant A13080) MRC (M.J.M. grant MC_EX_G0800464) and National Health Service funding to the Royal Marsden/Institute of Cancer Research National Institute for Health Research Biomedical Research Centre for Cancer (R.A.H.). The authors also thank the Max Williamson Fund, the Josh Carrick Foundation and The Perse Preparatory School, Cambridge for support.This is the author accepted manuscript. The final version is available fromNature Publishing Group via https://doi.org/10.1038/nrurol.2016.17

Intervenir sobre la cultura organizacional: ¿qué aspectos se pueden considerar?

La cultura organizacional (co) es un macroconstructo que involucra una gran variedad de componentes y funciones organizacionales (Warner, 2014). Reyes y Moros (2018) señalan que tiene su origen en el estudio realizado en Hawthorne por Elton Mayo y otros investigadores de la Escuela de las Relaciones Humanas de la Administración, en el que buscaban identificar la influencia de las condiciones físicas y ambientales en el desempeño individual. Para Reyes y Moros (2018), la co se siguió desarrollando en los años setenta con Pettigrew, para ser entendida como un sistema de significados que tanto pública como colectivamente es aceptado para operar en un tiempo y por un grupo determinado. Los autores la definen como “… un sistema de significados compartidos por los miembros de la organización, los cuales son el resultado de una construcción social constituida a través de símbolos y como tal deben ser interpretados”1a edició