96 research outputs found
Approach to the virilizing girl at puberty
Virilization is the medical term for describing a female who develops characteristics associated with male hormones (androgens) at any age, or when a newborn girl shows signs of prenatal male hormone exposure at birth. In girls, androgen levels are low during pregnancy and childhood. A first physiologic rise of adrenal androgens is observed at the age of 6 to 8 years and reflects functional activation of the zona reticularis of the adrenal cortex at adrenarche, manifesting clinically with first pubic and axillary hairs. Early adrenarche is known as âpremature adrenarche.â It is mostly idiopathic and of uncertain pathologic relevance but requires the exclusion of other causes of androgen excess (eg, nonclassic congenital adrenal hyperplasia) that might exacerbate clinically into virilization. The second modest physiologic increase of circulating androgens occurs then during pubertal development, which reflects the activation of ovarian steroidogenesis contributing to the peripheral androgen pool. However, at puberty initiation (and beyond), ovarian steroidogenesis is normally devoted to estrogen production for the development of secondary female bodily characteristics (eg, breast development). Serum total testosterone in a young adult woman is therefore about 10- to 20-fold lower than in a young man, whereas midcycle estradiol is about 10- to 20-fold higher. But if androgen production starts too early, progresses rapidly, and in marked excess (usually more than 3 to 5 times above normal), females will manifest with signs of virilization such as masculine habitus, deepening of the voice, severe acne, excessive facial and (male typical) body hair, clitoromegaly, and increased muscle development. Several medical conditions may cause virilization in girls and women, including androgen-producing tumors of the ovaries or adrenal cortex, (non)classical congenital adrenal hyperplasia and, more rarely, other disorders (also referred to as differences) of sex development (DSD). The purpose of this article is to describe the clinical approach to the girl with virilization at puberty, focusing on diagnostic challenges. The review is written from the perspective of the case of an 11.5-year-old girl who was referred to our clinic for progressive, rapid onset clitoromegaly, and was then diagnosed with a complex genetic form of DSD that led to abnormal testosterone production from a dysgenetic gonad at onset of puberty. Her genetic workup revealed a unique translocation of an abnormal duplicated Y-chromosome to a deleted chromosome 9, including the Doublesex and Mab-3 Related Transcription factor 1 (DMRT1) gene
Bioplastic (PHBV) addition to soil alters microbial community structure and negatively affects plant-microbial metabolic functioning in maize
Field response of N2O emissions, microbial communities, soil biochemical processes and winter barley growth to the addition of conventional and biodegradable microplastics
LDPE and biodegradable PLA-PBAT plastics differentially affect plant-soil nitrogen partitioning and dynamics in a Hordeum vulgare mesocosm
Increasing concentration of pure micro- and macro-LDPE and PP plastic negatively affect crop biomass, nutrient cycling, and microbial biomass
Clinical and Molecular Characteristics and Outcome of Cystic Partially Differentiated Nephroblastoma and Cystic Nephroma: A Narrative Review of the Literature
In children presenting with a predominantly cystic renal tumor, the most likely diagnoses
include cystic partially differentiated nephroblastoma (CPDN) and cystic nephroma (CN). Both
entities are rare and limited information on the clinical and molecular characteristics, treatment, and
outcome is available since large cohort studies are lacking. We performed an extensive literature
review, in which we identified 113 CPDN and 167 CN. The median age at presentation for CPDN
and CN was 12 months (range: 3 weeksâ4 years) and 16 months (prenatal diagnosisâ16 years),
respectively. No patients presented with metastatic disease. Bilateral disease occurred in both entities.
Surgery was the main treatment for both. Two/113 CPDN patients and 26/167 CN patients had
previous, concomitant, or subsequent other tumors. Unlike CPDN, CN was strongly associated with
somatic (n = 27/29) and germline (n = 12/12) DICER1-mutations. Four CPDN patients and one CN
patient relapsed. Death was reported in six/103 patients with CPDN and six/118 CN patients, none
directly due to disease. In conclusion, children with CPDN and CN are young, do not present with
metastases, and have an excellent outcome. Awareness of concomitant or subsequent tumors and
genetic testing is important. International registration of cystic renal tumor cohorts is required to
enable a better understanding of clinical and genetic characteristics
Reproducibility via coordinated standardization:A multi-center study in a Shank2 genetic rat model for Autism Spectrum Disorders
Inconsistent findings between laboratories are hampering scientific progress and are of increasing public concern. Differences in laboratory environment is a known factor contributing to poor reproducibility of findings between research sites, and well-controlled multisite efforts are an important next step to identify the relevant factors needed to reduce variation in study outcome between laboratories. Through harmonization of apparatus, test protocol, and aligned and non-aligned environmental variables, the present study shows that behavioral pharmacological responses in Shank2 knockout (KO) rats, a model of synaptic dysfunction relevant to autism spectrum disorders, were highly replicable across three research centers. All three sites reliably observed a hyperactive and repetitive behavioral phenotype in KO rats compared to their wild-type littermates as well as a dose-dependent phenotype attenuation following acute injections of a selective mGluR1 antagonist. These results show that reproducibility in preclinical studies can be obtained and emphasizes the need for high quality and rigorous methodologies in scientific research. Considering the observed external validity, the present study also suggests mGluR1 as potential target for the treatment of autism spectrum disorders
Modelling hurricane track memory
It has been observed that hurricanes that are close in time often follow similar paths. If this can be shown to be statistically significant, it could have implications for how insurance premiums are calculated in areas of the US prone to hurricanes.
We developed two independent path distance metrics and while one suggested that sequential storms within a given hurricane season are more likely to follow each other than any other pair of storms within that season, this conclusion was not supported by the other metric.
Some considerations of how local and large scale air pressure gradients might affect hurricane paths were considered. A point vortex model in the presence of a steering flow field was developed and used to simulate the path of two time displaced vortices. In order for the vortices to follow each other they had to be relatively weak compared to the steering flow field. At realistic vortex strength, the trajectories became chaotic.
In summary, our metrics provided conflicting evidence towards the no- tion of hurricane track memory. A large-scale steering flow field did not appear to provide sufficient explanation for hurricanes following each other, though this does not preclude hurricane track memory being due to localised physical changes following a large storm
Outcome of Stage IV Completely Necrotic Wilms Tumour and Local Stage III Treated According to the SIOP 2001 Protocol
Objective: Wilms tumour (WT) patients with a localised completely necrotic nephroblastoma after preoperative chemotherapy are a favourable outcome group. Since the introduction of the
SIOP 2001 protocol, the SIOPâ Renal Tumour Study Group (SIOPâRTSG) has omitted radiotherapy
for such patients with low-risk, local stage III in an attempt to reduce treatment burden. However,
for metastatic patients with local stage III, completely necrotic WT, the recommendations led to
ambiguous use. The purpose of this descriptive study is to demonstrate the outcomes of patients with
metastatic, completely necrotic and local stage III WT in relation to the application of radiotherapy or
not. Methods and materials: all metastatic patients with local stage III, completely necrotic WT after
6 weeks of preoperative chemotherapy who were registered in the SIOP 2001 study were included
in this analysis. The pattern of recurrence according to the usage of radiation treatment and 5 year
event-free survival (EFS) and overall survival (OS) was analysed. Results: seven hundred and three
metastatic WT patients were registered in the SIOP 2001 database. Of them, 47 patients had a completely necrotic, local stage III WT: 45 lung metastases (11 combined localisations), 1 liver/peritoneal, and 1 tumour thrombus in the renal vein and the inferior vena cava with bilateral pulmonary arterial
embolism. Abdominal radiotherapy was administered in 29 patients (62%; 29 flank/abdominal
irradiation and 9 combined with lung irradiation). Eighteen patients did not receive radiotherapy.
Median follow-up was 6.6 years (range 1â151 months). Two of the 47 patients (4%) developed disease
recurrence in the lung (one combined with abdominal relapse) and eventually died of the disease.
Both patients had received abdominal radiotherapy, one of them combined with lung irradiation.
Five-year EFS and OS were 95% and 95%, respectively. Conclusions: the outcome of patients with
stage IV, local stage III, completely necrotic Wilms tumours is excellent. Our results suggest that
abdominal irradiation in this patient category may not be of added value in first-line treatment,
consistent with the current recommendation in the SIOPâRTSG 2016 UMBRELLA protocol
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