Acceptability of a novel vaginal microbicide during a safety trial among low-risk women

CONTEXT: The increasing recognition that women who are unable or unwilling to discuss or use condoms with their sexual partners need female-controlled methods for preventing sexually transmitted diseases (STDs), including HIV, has led to considerable focus on the development of vaginal microbicides. While many such products are being tested for safety and effectiveness, clinical trials generally overlook another key factor in a product's impact on infection rates-its acceptability to users. METHODS: A Phase I clinical trial of a microbicidal gel included an assessment of the product's acceptability among 27 low-risk participants. Information on acceptability was gathered from structured interviews, participants' daily diaries and unstructured exit interviews. RESULTS: Participants reported only minor side effects of product use, such as itching, burning and difficulty urinating; two women developed candida infections while participating in the study. None of the side effects could be conclusively linked to use of the gel. Some women noted product discharge and messiness as drawbacks of the method, but this experience varied according to how often the women applied the gel. For example, one-third of those who used it once daily said that at least some of the time, it was too "wet or drippy," compared with two-thirds of women who inserted the gel twice a day. However, participants considered these "nuisance factors" that could be outweighed by the potential protective characteristics of the product. The majority reported that they would use the product if it were available and proven efficacious, and if they perceived that they were at risk of STD infection. CONCLUSIONS: Additional testing of this product is urgently needed. Furthermore, as other products approach Phase I testing, acceptability assessments should be a key component of clinical trials.     

GABRA2 alleles moderate the subjective effects of alcohol, which are attenuated by finasteride.

GABA(A) receptors are involved in the subjective effects of alcohol. Endogenous neuroactive steroids interact with GABA(A) receptors to mediate several behavioral effects of alcohol in rodents. Based on a haplotypic association of alcohol dependence with the gene encoding the GABA(A) receptor alpha-2 subunit (GABRA2), we examined whether GABRA2 alleles are associated with the subjective response to alcohol. We also examined whether finasteride (a 5-alpha steroid reductase inhibitor), which blocks the synthesis of some neuroactive steroids, reduces the subjective response to alcohol. In all, 27 healthy social drinkers (15 males) completed a randomized, double-blind, placebo-controlled study of high-dose finasteride. After being pretreated with study drug, subjects consumed three alcoholic drinks. Subjective effects were measured repeatedly over the ascending blood alcohol curve. To examine the moderating role of genetic variation in GABRA2, a single-nucleotide polymorphism that was informative in association studies was included as a factor in the analysis. Subjects homozygous for the more common A-allele (n=7) showed more subjective effects of alcohol than did individuals with one or two copies of the alcohol dependence-associated G-allele (n=20, including two homozygotes). Among the A-allele homozygotes, there was a greater reduction in several subjective effects during the finasteride session compared to the placebo session. These findings provide preliminary evidence that the risk of alcoholism associated with GABRA2 alleles may be related to differences in the subjective response to alcohol. The effects of finasteride provide indirect evidence for a mediating role of neuroactive steroids in some of the subjective effects of alcohol.     

Inaugural Christianson Syndrome Association conference: families meeting for the first time

Christianson syndrome (CS) is an X-linked neurodevelopmental disorder caused by deleterious mutations in SLC9A6. Affected families organized the inaugural Christianson Syndrome Association conference to advance CS knowledge and develop questions that may be prioritized in future research.     

Cross‐sector emergency planning for water supply utilities and healthcare facilities

The purpose of this article is to outline the criticality of water supply in sustained operations of healthcare facilities, particularly during community emergencies, and to advocate for enhanced cross‐sector support from the water utilities in meeting this need. Information and ideas presented here were developed in the course of a regional project sponsored by the Metropolitan Washington Council of Governments (MWCOG) for development of emergency water supply operations plans for critical water uses in the Washington, DC, area.     

Sun Exposure and Vitamin D Supplementation in Relation to Vitamin D Status of Breastfeeding Mothers and Infants in the Global Exploration of Human Milk Study

Although vitamin D (vD) deficiency is common in breastfed infants and their mothers during pregnancy and lactation, a standardized global comparison is lacking. We studied the prevalence and risk factors for vD deficiency using a standardized protocol in a cohort of breastfeeding mother-infant pairs, enrolled in the Global Exploration of Human Milk Study, designed to examine longitudinally the effect of environment, diet and culture. Mothers planned to provide breast milk for at least three months post-partum and were enrolled at four weeks postpartum in Shanghai, China (n = 112), Cincinnati, Ohio (n = 119), and Mexico City, Mexico (n = 113). Maternal serum 25(OH)D was measured by radioimmunoassay (<50 nmol/L was categorized as deficient). Serum 25(OH)D was measured in a subset of infants (35 Shanghai, 47 Cincinnati and 45 Mexico City) seen at 26 weeks of age during fall and winter seasons. Data collected prospectively included vD supplementation, season and sun index (sun exposure × body surface area exposed while outdoors). Differences and factors associated with vD deficiency were evaluated using appropriate statistical analysis. vD deficiency in order of magnitude was identified in 62%, 52% and 17% of Mexican, Shanghai and Cincinnati mothers, respectively (p < 0.001). In regression analysis, vD supplementation (p < 0.01), obesity (p = 0.03), season (p = 0.001) and sites (p < 0.001) predicted maternal vD status. vD deficiency in order of  magnitude was found in 62%, 28%, and 6% of Mexican, Cincinnati and Shanghai infants, respectively (p < 0.001). Season (p = 0.022), adding formula feeding (p < 0.001) and a higher sun index (p = 0.085) predicted higher infant vD status. vD deficiency appears to be a global problem in mothers and infants, though the prevalence in diverse populations may depend upon sun exposure behaviors and vD supplementation. Greater attention to maternal and infant vD status starting during pregnancy is warranted worldwide.