Minocycline can rescue the dendritic spine and synaptic structural abnormalities in the fragile X knock-out mouse. This is a review and preliminary survey to document side effects and potential outcome measures for minocycline use in the treatment of individuals with fragile X syndrome. We surveyed 50 patients with fragile X syndrome who received minocycline for at least 2 weeks and found that the most common reported side effect is gastrointestinal difficulty, including loss of appetite. The families reported an improvement in language and behavioral areas. Outcome measures in the design of future randomized clinical trials should include both behavioral and language measures. As with any other treatments, we emphasize that randomized clinical trials are needed to determine the efficacy of minocycline in fragile X syndrome.

Many studies have focused on the behavior and cognitive problems in young patients with fragile X syndrome (FXS), but there are no studies about the problems in aging for those with FXS. The discovery of the fragile X-associated tremor ataxia syndrome (FXTAS), a neurodegenerative disorder related to elevated FMR1-mRNA, in elderly men and some women with the premutation, intensified the need for aging studies in FXS. Approximately 40% of males with FXS have repeat size mosaicism and as a result, some of these individuals also have elevated levels of FMR1-mRNA which theoretically puts them at risk for FXTAS. Here, we have surveyed all of the aging patients with FXS that we have followed over the years to clarify the medical complications of aging seen in those with FXS. Data was collected from 62 individuals with the FXS full mutation (44 males; 18 females) who were at least 40 years old at their most recent clinical examination. We found that the five most frequent medical problems in these patients were neurological problems (38.7%), gastrointestinal problems (30.6%), obesity (28.8%), hypertension (24.2%) and heart problems (24.2%). Movement disorders were significantly different between males and females (38.6% vs.10.2%, p = 0.029). We did not find any differences in medical problems between those with a full mutation and those with mosaicism. Identification of medical problems associated with aging in FXS is important to establish appropriate recommendations for medical screening and treatment considerations.

Context and objective We describe clinical features and biochemical characteristics of a unique population of severely affected untreated patients with congenital adrenal hyperplasia (CAH) from an Indonesian population, with proven cortisol deficiency but without clinical signs of cortisol deficiency. We evaluated the in vitro glucocorticoid activity of all relevant adrenal steroid precursors occurring in CAH patients. Design Cross sectional cohort study and translational research. Intervention/Main Outcome Measures Adrenal steroid precursor concentrations before and 60 minutes after ACTH administration of 24 untreated CAH patients (3-46years) with proven cortisol deficiency (< 500nmol/L post-ACTH) measured by liquid chromatography tandem-mass spectrometry (LC-MS/MS) were compared to 6 control patients (Mann-Whitney U test). Glucocorticoid receptor (GR) activation was determined by dual-luciferase assays in human embryonic kidney cells transfected with the GR and exposed to increasing amounts of adrenal steroid precursors for 24hours. Results Blood concentrations of the steroid precursors 11-deoxycortisol (457nmol/L, p=0.003), 11-deoxycorticosterone (55nmol/L, p=0.003), 17-hydroxyprogesterone (610nmol/L , p<0.001), progesterone (29nmol/L, p<0.001), and 21-deoxycortisol (73 nmol/L) were strongly elevated compared to controls. The GR was activated with comparable potency to cortisol by corticosterone and 21-deoxycortisol or with 4-100x lower potency by 11-hydroxyprogesterone, 11-deoxycortisol, aldosterone, 11-deoxycorticosterone, progesterone, and 17-hydroxyprogesterone. Conclusions We identified strongly elevated adrenal steroid precursor concentrations in blood from untreated CAH patients and demonstrated glucocorticoid activity of these adrenal precursors in vitro – suggesting a possible role of these precursors in the clinical phenotype of these patients. Further studies are necessary to evaluate the role of these precursors in more detail.

The rising epidemic of childhood obesity worldwide is a major public health challenge. Despite its urgency, there is a lack of data on the awareness and implementation of preventative measures. This study aims to identify areas for improvement in the prevention and management of childhood obesity worldwide. A cross-sectional electronic survey was distributed to 132 national pediatric societies members of the International Pediatric Association. Twenty-eight participants from different countries across six WHO regions completed the survey. Most participants reported that national prevalence data of childhood obesity is available (78.6%), and the number increased during the COVID-19 pandemic (60.7%). In most countries (78.6%), the amount of sugar and salt is provided in children's products, but only 42.9% enacted regulations on children-targeted advertising. Childhood obesity prevention programs from the government (64.3%) and schools (53.6%) are available with existing support from private or non-profit organizations (71.4%). Participants were aware of WHO's guidance concerning childhood obesity (78.6%), while fewer were aware of UNICEF's guidance (50%). Participants reported that WHO/UNICEF guidance acted as a reference to develop policies, regulations and national programs. However, progress is hindered by poor compliance. Lastly, participants provided suggestions on tackling obesity with responses ranging from developing and reinforcing policies, involvement of schools, and prevention across all life stages. There are different practices in implementing prevention measures against childhood obesity globally, particularly in statutory regulation on food advertising and national programs. While support and awareness is relatively high, its implementation is hindered. This reflects the need for prompt country-specific evaluation and interventions.

Pesticide Exposure and Thyroid Function in Elementary School Children Living in an Agricultural Area, Brebes District, Indonesia