Saving for delivery through technology: an inquiry into an electronic commitment savings product for maternal healthcare in Kenya.

Many women in low-income countries cannot afford maternal healthcare services. Changamka, a Kenyan company, developed an electronic, stored-value card to help pregnant women save for maternal healthcare at a Nairobi hospital. This paper reports results from a mixed-methods process evaluation of the card's implementation. The study found high levels of uptake and identified several benefits of the program, such as facilitating payment for services. The evaluation also identified several challenges. Most users completed only one transaction before discontinuing card use; only 6% of women who acquired the card used it to pay for delivery, and slightly less than 1% used it as it was originally intended-to pay for several antenatal care visits and for delivery. According to respondents, the main reason for this discontinuation was a lack of understanding about how to use the card. Users were, on average, of a higher socioeconomic and educational status than non-card users. Most users obtained the card in their third trimester, and among those who used the card to save for delivery, most started to do so too late in pregnancy to accumulate sufficient savings to pay for that service. Copyright © 2015 John Wiley & Sons, Ltd.

Can mobile phone messages to drug sellers improve treatment of childhood diarrhoea?--A randomized controlled trial in Ghana.

Oral rehydration solution (ORS) and zinc are the recommended treatment in developing countries for the management of uncomplicated diarrhoea in children under five (World Health Organization and UNICEF 2004). However, drug sellers often recommend costly and unnecessary treatments instead. This article reports findings from an experiment to encourage licensed chemical sellers (LCS) in Ghana to recommend ORS and zinc for the management of childhood diarrhoea. The intervention consisted of mobile phone text messages (Short Message Service or SMS) sent to a randomly assigned group of LCS who had been trained on the diarrhoea management protocols recommended by the World Health Organization (WHO). The SMS campaign comprised informational messages and interactive quizzes sent over an 8-week period. The study measured the impact of the SMS messages on both reported and actual practices. Analysis of data from both face-to-face interviews and mystery client visits shows that the SMS intervention improved providers' self-reported practices but not their actual practices. The study also finds that actual practices deviate substantially from reported practices.

Evaluation of the benzothiazole aggregation inhibitors riluzole and PGL-135 as therapeutics for Huntington's disease.

Huntington's disease (HD) is an inherited progressive neurological disorder for which there is no effective therapy. It is caused by a CAG/polyglutamine repeat expansion that leads to abnormal protein aggregation and deposition in the brain. Several compounds have been shown to disrupt the aggregation process in vitro, including a number of benzothiazoles. To further explore the therapeutic potential of the benzothiazole aggregation inhibitors, we assessed PGL-135 and riluzole in hippocampal slice cultures derived from the R6/2 mouse, confirming their ability to inhibit aggregation with an EC50 of 40 microM in this system. Preliminary pharmacological work showed that PGL-135 was metabolically unstable, and therefore, we conducted a preclinical trial in the R6/2 mouse with riluzole. At the maximum tolerated dose, we achieved steady-state riluzole levels of 100 microM in brain. However, this was insufficient to inhibit aggregation in vivo and we found no improvement in the disease phenotype.

Standardization and statistical approaches to therapeutic trials in the R6/2 mouse.

The R6/2 mouse is the most widely used animal model of Huntington's disease (HD), a genetic disorder causing movement disorders, personality changes, dementia, and premature death, for which there is currently no effective therapy. Use of animal models to assess novel therapeutic approaches to HD is currently a major focus of research. Progress in this field will depend upon careful standardization of experimental protocols, and a sophisticated statistical approach. Here we investigate the sources of phenotypic variability in R6/2, and make recommendations for the future use of such models in therapeutic trials.

Minocycline and doxycycline are not beneficial in a model of Huntington's disease.

Huntington's Disease (HD) is an inherited neurological disorder causing movement impairment, personality changes, dementia, and premature death, for which there is currently no effective therapy. The modified tetracycline antibiotic, minocycline, has been reported to ameliorate the disease phenotype in the R6/2 mouse model of HD. Because the tetracyclines have also been reported to inhibit aggregation in other amyloid disorders, we have investigated their ability to inhibit huntingtin aggregation and further explored their efficacy in preclinical mouse trials. We show that tetracyclines are potent inhibitors of huntingtin aggregation in a hippocampal slice culture model of HD at an effective concentration of 30 microM. However, despite achieving tissue levels approaching this concentration by oral treatment of R6/2 mice with minocycline, we observed no clear difference in their behavioral abnormalities, or in aggregate load postmortem. In the light of these new data, we would advise that caution be exercised in proceeding into human clinical trials of minocycline.

Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in a mouse model of Huntington's disease.

Huntington's disease (HD) is an inherited, progressive neurological disorder that is caused by a CAG/polyglutamine repeat expansion and for which there is no effective therapy. Recent evidence indicates that transcriptional dysregulation may contribute to the molecular pathogenesis of this disease. Supporting this view, administration of histone deacetylase (HDAC) inhibitors has been shown to rescue lethality and photoreceptor neurodegeneration in a Drosophila model of polyglutamine disease. To further explore the therapeutic potential of HDAC inhibitors, we have conducted preclinical trials with suberoylanilide hydroxamic acid (SAHA), a potent HDAC inhibitor, in the R6/2 HD mouse model. We show that SAHA crosses the blood-brain barrier and increases histone acetylation in the brain. We found that SAHA could be administered orally in drinking water when complexed with cyclodextrins. SAHA dramatically improved the motor impairment in R6/2 mice, clearly validating the pursuit of this class of compounds as HD therapeutics.

Abnormal phosphorylation of synapsin I predicts a neuronal transmission impairment in the R6/2 Huntington's disease transgenic mice.

Motor and cognitive deficits in Huntington's disease (HD) are likely caused by progressive neuronal dysfunction preceding neuronal cell death. Synapsin I is one of the major phosphoproteins regulating neurotransmitter release. We report here an abnormal phosphorylation state of synapsin I in the striatum and the cerebral cortex of R6/2 transgenic mice expressing the HD mutation. These changes are mostly characterized by an early overphosphorylation at sites 3-5, whereas phosphorylation at site 1 remains unchanged and at site 6 becomes reduced only close to the end stage of the disease. Such changes do not result from modification in protein expression levels. However, we show a decreased expression of the calcineurin regulatory subunit-B, which may contribute to an imbalance between kinase and phosphatase activities. Together the results suggest that an early impairment in synapsin phosphorylation-dephosphorylation may alter synaptic vesicle trafficking and lead to defective neurotransmission in HD.

Environmental enrichment slows disease progression in R6/2 Huntington's disease mice.

Huntington's disease is a genetic disorder that causes motor dysfunction, personality changes, dementia, and premature death. There is currently no effective therapy. Several transgenic models of Huntington's disease are available, the most widely used of which is the R6/2 mouse, because of its rapid disease progression. Environmental enrichment alters gene expression in the normal mouse brain, and modulates the course of several neurological disorders. Environmentally enriched mice may actually mimic human disease more accurately. We found that even limited environmental enrichment slows decline in RotaRod performance in R6/2 mice, despite rapid disease progression, whereas in normal littermates, maximal enrichment was required to induce a marked improvement in behavioral tests. Enrichment also delayed the loss of peristriatal cerebral volume in R6/2 brains. These results could provide the basis for a rational approach to ameliorate the effects of Huntington's disease.