Technological infrastructure, sleep, and rest-activity patterns in a Kaqchikel Maya community.

Sleep duration, quality, and rest-activity pattern-a measure for inferring circadian rhythm-are influenced by multiple factors including access to electricity. Recent findings suggest that the safety and comfort afforded by technology may improve sleep but negatively impact rest-activity stability. According to the circadian entrainment hypothesis, increased access to electric lighting should lead to weaker and less uniform circadian rhythms, measured by stability of rest-activity patterns. Here, we investigate sleep in a Maya community in Guatemala who are in a transitional stage of industrialization. We predicted that (i) sleep will be shorter and less efficient in this population than in industrial settings, and that (ii) rest-activity patterns will be weaker and less stable than in contexts with greater exposure to the natural environment and stronger and more stable than in settings more buffered by technologic infrastructure. Our results were mixed. Compared to more industrialized settings, in our study population sleep was 4.87% less efficient (78.39% vs 83.26%). We found no significant difference in sleep duration. Rest-activity patterns were more uniform and less variable than in industrial settings (interdaily stability = 0.58 vs 0.43; intradaily variability = 0.53 vs 0.60). Our results suggest that industrialization does not inherently reduce characteristics of sleep quality; instead, the safety and comfort afforded by technological development may improve sleep, and an intermediate degree of environmental exposure and technological buffering may support circadian rhythm strength and stability.

Social and Biological Transgenerational Underpinnings of Adolescent Pregnancy.

Adolescent pregnancy (occurring < age 20) is considered a public health problem that creates and perpetuates inequities, affecting not only women, but societies as a whole globally. The efficacy of current approaches to reduce its prevalence is limited. Most existing interventions focus on outcomes without identifying or addressing upstream social and biological causes. Current rhetoric revolves around the need to change girls' individual behaviours during adolescence and puberty. Yet, emerging evidence suggests risk for adolescent pregnancy may be influenced by exposures taking place much earlier during development, starting as early as gametogenesis. Furthermore, pregnancy risks are determined by complex interactions between socio-structural and ecological factors including housing and food security, family structure, and gender-based power dynamics. To explore these interactions, we merge three complimentary theoretical frameworks: "Eco-Social", "Life History" and "Developmental Origins of Health and Disease". We use our new lens to discuss social and biological determinants of two key developmental milestones associated with age at first birth: age at girls' first menstrual bleed (menarche) and age at first sexual intercourse (coitarche). Our review of the literature suggests that promoting stable and safe environments starting at conception (including improving economic and social equity, in addition to gender-based power dynamics) is paramount to effectively curbing adolescent pregnancy rates. Adolescent pregnancy exacerbates and perpetuates social inequities within and across generations. As such, reducing it should be considered a key priority for public health and social change agenda.

Access to fludrocortisone and to hydrocortisone in children with congenital adrenal hyperplasia in the WHO Eastern Mediterranean Region: it takes a village .

Congenital adrenal hyperplasia (CAH), if untreated, carries high morbidity and mortality. A higher incidence of CAH is expected in countries where consanguinity is common, such as in the countries of the WHO Eastern Mediterranean Region (EMRO). CAH is managed through lifelong treatment with fludrocortisone and hydrocortisone. In this analysis, performed in the 22 EMRO countries and territories plus Algeria, we review which countries offer a neonatal screening programme for CAH and describe the barriers and opportunities to access oral fludrocortisone and oral and injectable hydrocortisone. Neonatal CAH screening was only available nationally in Qatar, Kuwait and partially in Lebanon and Saudi Arabia. We reviewed the national lists of essential medicines (NEMLs) and found that 13/23 (57%) countries included fludrocortisone and 18/23 (78%) included oral hydrocortisone. Fludrocortisone was not included by any of the low-income countries and oral hydrocortisone was only included by one low-income country. We then contacted paediatric endocrinologists in each country to assess perceived availability of these medicines. Overall, there was a relatively good consistency between inclusion of fludrocortisone and hydrocortisone in the NEML and their actual availability in a country. We propose several mechanisms to improve access, including prequalification by the WHO, a common registration process for groups of countries, pooled procurement, working with local pharmaceutical companies, special access status for medicines not yet registered in a country and compounding. We suggest that access to medicines requires a collaboration between health professionals, families of patients, health authorities, pharmaceutical companies and the WHO.

Parthenolide prevents the expression of cocaine-induced withdrawal behavior in planarians.

We recently reported that parthenolide and related sesquiterpene lactones are able to prevent and reverse behavioral responses in planarian worms induced by acute cocaine exposure. Previous reports indicate that when planarians are chronically exposed to microM concentrations of cocaine, they display stereotypical withdrawal-like behaviors when the cocaine is removed. Here we report that parthenolide prevents this cocaine-induced expression of planarian withdrawal-like behaviors.

Reversal of cocaine-induced planarian behavior by parthenolide and related sesquiterpene lactones.

Here we report the prevention and reversal of cocaine-induced behaviors in planarian worms by parthenolide and two related cyclic sesquiterpene lactones (SL), costunolide and santonin. Using established protocols, we studied two cocaine-induced behavioral effects in planaria; the induction of motility decrease and the induction of C-like hyperkinesia. Cocaine, parthenolide, costunolide, santonin, and a lactone-less cyclic sesquiterpene, beta-eudesmol, decreased planarian motility in a concentration-dependent manner. Only cocaine induced C-like hyperkinesia. At concentrations that did not show any motility decrease, parthenolide, costunolide and santonin, but not beta-eudesmol, significantly reduced the cocaine-induced motility decrease and C-like hyperkinesia, in a concentration-dependent manner. Furthermore, parthenolide, costunolide and santonin were able to rescue planaria from C-like hyperkinesia, after the worms were exposed to cocaine. Conversely, cocaine at a concentration that did not show any measurable effects (10 microM), was able to alleviate the SL-, but not the beta-eudesmol-induced motility decrease. Liquid Chromatography/Mass Spectrometry experiments demonstrated that cocaine does not interact directly with any of the cyclic sesquiterpenoids, which suggests specific biochemical targets for these compounds in planarians. Our data suggests a common binding site for cocaine and the sesquiterpene lactones in planarians.

Insights from the WHO and National Lists of Essential Medicines: Focus on Pediatric Diabetes Care in Africa.

BACKGROUND: Access to essential medicines in pediatric endocrinology and diabetes is limited in resource-limited countries. The World Health Organization (WHO) maintains two non-binding lists of essential medicines (EMLs) which are often used as a template for developing national EMLs. METHODS: We compared a previously published master list of medicines for pediatric endocrinology and diabetes with the WHO EMLs and national EMLs for countries within the WHO African region. To better understand actual access to medicines by patients, we focused on diabetes and surveyed pediatric endocrinologists from 5 countries and assessed availability and true cost for insulin and glucagon. RESULTS: Most medicines that are essential in pediatric endocrinology and diabetes were included in the national EMLs. However, essential medicines, such as fludrocortisone, were present in less than 30% of the national EMLs despite being recommended by the WHO. Pediatric endocrinologists from the 5 focus countries reported significant variation in terms of availability and public access to insulin, as well as differences between urban and rural areas. Except for Botswana, glucagon was rarely available. There was no significant relationship between Gross National Income and the number of medicines included in the national EMLs. CONCLUSIONS: Governments in resource-limited countries could take further steps to improve EMLs and access to medicines such as improved collaboration between health authorities, the pharmaceutical industry, patient groups, health professionals, and capacity-building programs such as Paediatric Endocrinology Training Centres for Africa.

Toxicity and behavioral effects of dimethylsulfoxide in planaria.

In this work, we describe aspects of the toxicity and behavioral effects of dimethylsulfoxide (DMSO) in planaria. Planarian worms have traditionally been a favored animal model in developmental biology. More recently, this organism is being recognized as an animal model in neuropharmacology research. DMSO is often used in cell and tissue culture as a cryoprotectant agent and is also commonly used to enhance the solubility of hydrophobic drugs in aqueous solutions. This compound can elicit various physiological effects in both vertebrates and invertebrates. Many drugs and drug candidates are hydrophobic, needing solvents like DMSO to be able to reach their physiological targets. As planaria becomes increasingly popular in neuropharmacology research, a description of the DMSO effects in this organism is essential. We found that DMSO is toxic to planarians at concentrations above 5% (705 mM), with an LD(50) of 10% (1.4M) at exposure times above 5 min. At sub-toxic concentrations, DMSO decreases planarian exploratory behavior in a concentration-dependent manner. This reduction in locomotor behavior is reversible and preincubation-independent. DMSO at a concentration of 0.1% (14.1 mM), which is usually enough to solubilize hydrophobic substances in aqueous solutions, did not display any toxic or behavioral effects in planaria. Therefore, in this animal model, DMSO concentrations above 0.1% should be avoided in order to be able to reliably observe any behavioral or toxic effects of hydrophobic drugs.

WHO and national lists of essential medicines in Mexico, Central and South America, and the Caribbean: are they adequate to promote paediatric endocrinology and diabetes care?

Paediatric endocrinology and diabetes is a paediatric specialty with less common conditions and higher cost medicines. Access to medicines for our specialty in low and middle income countries remains limited. We analysed the content of the WHO (children and adults) and of all available national Model Lists of Essential Medicines (EMLs) for Mexico, the Caribbean, Central and South America from a paediatric endocrinology and diabetes standpoint. A master list of medicines deemed necessary in paediatric endocrinology and diabetes was established and compared with the WHO and national EMLs, taking into account the gross national income. The WHO EMLs, which are largely recognised as an international benchmark and drive the content of the national EMLs, included many but not all medicines present on our master list. Interestingly, several national EMLs from richer countries included medicines that were not present in the WHO EMLs. Our analysis suggests that these medicines could be considered by the WHO for inclusion in their EMLs, which may promote the adoption of more medicines by individual countries. We also propose several changes to the WHO and national EMLs that could facilitate access to medicines in our specialty: age cut-off for a child using physical maturity rather than a set age limit; greater standardisation of the formatting of the national EMLs for easier comparison and collaborations between countries; greater emphasis on age-specificity and population-specificity for some medicines; and formatting of the EMLs in a disease-focused manner rather than as individual medicines.

A cembranoid from tobacco prevents the expression of nicotine-induced withdrawal behavior in planarian worms.

Using an adaptation of published behavioral protocols, we determined that acute exposure to the cholinergic compounds nicotine and carbamylcholine decreased planarian motility in a concentration-dependent manner. A tobacco cembranoid (1S,2E,4R,6R,7E,11E)-cembra-2,7,11-triene-4,6-diol (4R-cembranoid), also decreased planarian motility. Experiments in the presence of 1 microM 4R-cembranoid did increase the IC50 for nicotine- but not carbamylcholine-induced decrease in planarian motility. When planarians were exposed for 24 h to either nicotine or carbamylcholine at concentrations near their respective IC50 values and then transferred to plain media, nicotine-exposed, but not carbamylcholine- or cembranoid-exposed worms displayed withdrawal-like distress behaviors. In experiments where planarians were pre-exposed to 100 microM nicotine for 24 h in the presence of 1 microM 4R-cembranoid, the withdrawal-like effects were significantly reduced. These results indicate that the 4R-cembranoid might have valuable applications for tobacco abuse research. This experimental approach using planarians is useful for the initial screening of compounds relevant to drug abuse and dependence.