Prevalence and correlates of autism spectrum disorder in Qatar: a national study.

BACKGROUND: Few epidemiological data on autism spectrum disorders (ASD) exist for Arabic countries. We conducted the first survey of ASD in Qatar, a population with high consanguinity level. METHODS: This cross-sectional survey was conducted from 2015 to 2018 in Qatar school-age children (N = 176,960) from national and immigrant families. Children diagnosed with ASD were identified through medical centers and special needs schools. Records were abstracted and supplemented by parental interviews. Additionally, children attending 93 schools were screened; ASD case status was confirmed in random samples of screen-positive and screen-negative children. Prevalence was estimated after taking into account different sampling fractions and participation rates at each survey phase. RESULTS: One thousand three hundred and ninety-three children already diagnosed with ASD were identified. Among 9,074 school survey participants, 760 screen-negative children and 163 screen-positive children were evaluated; 17 were confirmed to have ASD including five children newly diagnosed. Prevalence was 1.14% (95% CI: 0.89-1.46) among 6- to 11-year-olds. ASD was reported in full siblings/extended relatives in 5.9% (95% CI: 0.042-0.080)/11.8% (95% CI: 0.095-0.146) families. First-degree consanguinity in Qatari cases (45%) was comparable to known population levels. Among 844 ASD cases (mean age: 7.2 years; 81% male), most children experienced language delay (words: 75.1%; phrase speech: 91.4%), and 19.4% reported developmental regression. At the time of the survey, persisting deficits in expressive language (19.4%) and peer interactions (14.0%) were reported in conjunction with behavioral problems (ADHD: 30.2%; anxiety: 11.0%). In multivariate logistic regression, ASD severity was associated with parental consanguinity, gestational diabetes, delay in walking, and developmental regression. CONCLUSIONS: ASD prevalence in Qatar is consistent with recent international studies. The methods employed in this study should help designing comparable surveys in the region. We estimated that 187,000 youths under age 20 have ASD in Gulf countries. This figure should assist in planning health and educational services for a young, fast-growing population.

Prevalence of Autism Spectrum Disorders in Guanajuato, Mexico: The Leon survey.

There are no epidemiological data on autism for Mexico. This study was conducted to generate a first estimate of ASD prevalence in Mexico. We surveyed children age eight in Leon (Guanajuato). The sample was stratified in two strata: (1) children having special education and medical records (SEMR; N = 432) and (2) children attending regular schools (GSS; N = 11,684). GSS children were screened with the SRS and those with the highest scores were invited to a diagnostic evaluation. The final sample comprised 36 children (80.6 % male) who had confirmed ASD. A third had intellectual disability, 25 % were non-verbal, 69 % had co-occurring behavioral problems. The prevalence overall was 0.87 % (95 % CI 0.62, 1.1 %). This survey provides an estimate for ASD prevalence in Mexico that is consistent with recent studies.

Decreased androgen receptor levels and receptor function in breast cancer contribute to the failure of response to medroxyprogesterone acetate.

Previously, we reported that androgen receptor (AR), but not estrogen receptor (ER) or progesterone receptor (PR), is predictive of response to the synthetic progestin, medroxyprogesterone acetate (MPA), in a cohort of 83 patients with metastatic breast cancer. To further investigate the role of AR in determining response to MPA in this cohort, we analyzed AR levels by immunohistochemistry with two discrete antisera directed at either the NH2 or the COOH termini of the receptor. Compared with tumors that responded to MPA (n = 31), there was a significant decrease in the intensity and extent of AR immunoreactivity with both AR antisera in tumors from nonresponders (n = 52). Whereas only a single AR immunostaining pattern was detected in responders to MPA, reflecting concordance of immunoreactivity with the two AR antisera, tumors from nonresponders exhibited four distinct AR immunostaining patterns: (a) concordance with the two antibodies (31%), (b) staining only with the COOH-terminal antibody (33%), (c) staining only with the NH2-terminal antibody (22%), or (d) no immunoreactivity with either NH2- or COOH-terminal antibody (14%). DNA sequencing and functional analysis identified inactivating missense gene mutations in the ligand-binding domain of the AR in tumors from two of nine nonresponders positive with the NH2-terminal AR antisera but negative for COOH-terminal immunoreactivity and lacking specific, high-affinity dihydrotestosterone binding in tumor cytosol fractions. Tumors with more AR than the median level (37 fmol/mg protein) had significantly lower levels of PR (30 fmol/mg protein) than tumors with low AR (PR; 127 fmol/mg protein) despite comparable levels of ER. Ligand-dependent activation of the AR in human T47D and MCF-7 breast cancer cells resulted in inhibition of estradiol-stimulated cell proliferation and a reduction in the capacity of the ER to induce expression of the PR. These effects could be reversed using a specific AR antisense oligonucleotide. Increasing the ratio of AR to ER resulted in a greater androgen-dependent inhibition of ER function. Collectively, these data suggest that reduced levels of AR or impaired AR function contribute to the failure of MPA therapy potentially due to abrogation of the inhibitory effect of AR on ER signaling.