Evaluation of the Confiance Totale Campaign in Togo: Associations Between Campaign Exposure and Family Planning Outcomes of Interest.

In Togo, family planning (FP) use remains low; only 24.1% of married woman ages 15 to 49 use modern FP. The West Africa Breakthrough ACTION (WABA) project developed the Confiance Totale radio campaign, which used a Saturation+ approach to encourage FP use. This study presents the results of an evaluation of Confiance Totale which investigates associations between campaign exposure and outcomes of interest. Following the broadcasts, the team conducted a cross-sectional household survey among 2,200 respondents ages 18 to 49. Combined and sex-stratified multivariable models predicting outcomes of interest controlled for sex, age, site, marital status, educational attainment, religion, and economic status. Upon hearing a campaign jingle, approximately 45% of participants had heard the campaign. Exposure to the campaign was associated with many ideational and behavioral outcomes including current use of a facility-dependent FP method (OR = 1.77, p < .001). In stratified models, several outcomes were significantly associated with exposure in the women-only models but not in the men-only models. Exposure to Confiance Totale was associated with nearly all ideational and behavioral outcomes of interest, particularly among women. This demonstrates that high dosage broadcasting may be effective in promoting confidence in the health system and improving perceptions of FP.

Changing the Script: Intergenerational Communication about Sexual and Reproductive Health in Niamey, Niger.

Most strategies to reduce adolescent pregnancies have been designed to educate adolescents directly about family planning (FP), while adolescents often cite peers and parents as their primary sources of sexual health information. Yet parents' lack of knowledge about sexual and reproductive health (SRH), low self-efficacy to initiate conversations, and adverse social norms act as barriers to open intergenerational communication. To better understand the normative environment influencing communication between parents and youth about FP/SRH in francophone West Africa, the USAID supported Breakthrough RESEARCH project conducted a multi-stage qualitative study in Niger. During Stage 1, the research team developed a screening tool (based on a literature review) to categorize research participants into those who practiced open intergenerational communication about FP/SRH, and those who did not. Stage 2 consisted of 40 in-depth interviews with young people (ages 15-24) and adults (≥25 years old), stratified by whether they practiced open intergenerational communication. Results showed restrictive social norms related to youth SRH and access to information and services. However, particularly among participants classified as open-communicators, there is a hierarchy of norms and normative beliefs, with abstinence as the most virtuous decision for youth, but approving communication about and access to SRH services in order to minimize harm. Participants rely on values such as the protection of youth, protection of family honor and promotion of well-being as means to act in counter-normative ways and communicate about FP/SRH. Implications for the field include demystifying and destigmatizing SRH topics, increasing adults' communication skills, and changing the "script" to a more life-affirming view of SRH.

Implementation research: reactive mass vaccination with single-dose oral cholera vaccine, Zambia.

OBJECTIVE: To describe the implementation and feasibility of an innovative mass vaccination strategy - based on single-dose oral cholera vaccine - to curb a cholera epidemic in a large urban setting. METHOD: In April 2016, in the early stages of a cholera outbreak in Lusaka, Zambia, the health ministry collaborated with Médecins Sans Frontières and the World Health Organization in organizing a mass vaccination campaign, based on single-dose oral cholera vaccine. Over a period of 17 days, partners mobilized 1700 health ministry staff and community volunteers for community sensitization, social mobilization and vaccination activities in 10 townships. On each day, doses of vaccine were delivered to vaccination sites and administrative coverage was estimated. FINDINGS: Overall, vaccination teams administered 424 100 doses of vaccine to an estimated target population of 578 043, resulting in an estimated administrative coverage of 73.4%. After the campaign, few cholera cases were reported and there was no evidence of the disease spreading within the vaccinated areas. The total cost of the campaign - 2.31 United States dollars (US$) per dose - included the relatively low cost of local delivery - US$ 0.41 per dose. CONCLUSION: We found that an early and large-scale targeted reactive campaign using a single-dose oral vaccine, organized in response to a cholera epidemic within a large city, to be feasible and appeared effective. While cholera vaccines remain in short supply, the maximization of the number of vaccines in response to a cholera epidemic, by the use of just one dose per member of an at-risk community, should be considered.

Evidence for a decrease in transmission of Ebola virus--Lofa County, Liberia, June 8-November 1, 2014.

Lofa County has one of the highest cumulative incidences of Ebola virus disease (Ebola) in Liberia. Recent situation reports from the Liberian Ministry of Health and Social Welfare (MoHSW) have indicated a decrease in new cases of Ebola in Lofa County. In October 2014, the Liberian MoHSW requested the assistance of CDC to further characterize recent trends in Ebola in Lofa County. Data collected during June 8-November 1, 2014 from three sources were analyzed: 1) aggregate data for newly reported cases, 2) case-based data for persons admitted to the dedicated Ebola treatment unit (ETU) for the county, and 3) test results for community decedents evaluated for Ebola. Trends from all three sources suggest that transmission of Ebola virus decreased as early as August 17, 2014, following rapid scale-up of response activities in Lofa County after a resurgence of Ebola in early June 2014. The comprehensive response strategy developed with participation from the local population in Lofa County might serve as a model to implement in other affected areas to accelerate control of Ebola.

Improving provider and client communication around family planning in Togo: Results from a cross-sectional survey.

Previous research has shown that clients are better able to achieve their reproductive intentions when family planning (FP) services meet their needs and they have satisfying client provider interactions. There are several areas of quality provider-client communication, including providers taking a complete reproductive history of their clients to best gauge their needs, communication around alternative FP methods and side effects captured in the method information index, and communication around sexually transmitted infections and HIV risk as it relates to FP choices. This study examines data from a clinic-based intervention in Togo that focuses on strengthening health provider counseling related to FP, including improving in these three areas of provider-client communication. A clustered sampling approach was used to select 650 FP clients from 23 intervention facilities and 235 clients from 17 control facilities in the Lomé and Kara districts of Togo. The FP clients' interactions with providers were observed and clients exit interviews were conducted in December 2021. For each communication area measured through client interviews and observations, principal components analysis and Cronbach's alpha scores were used to ensure that the individual components could be indexed. Outcomes variables based on an index of sub-questions were then created for those who had fulfilled each of the components within an index. Multivariate multilevel mixed-effects logit models accounted for clients nested within facilities and included independent variables capturing client demographic and facility variables. Multivariate results show that all three outcome variables representing the three provider-client communication areas were statistically significantly better for FP clients in intervention clinics versus control clinics (p<0.05). The results speak to the emphasis that the Togo Ministry of Health has placed on building the provider capacity to provide quality counseling and administration of FP methods and working to assist in achieving health programming goals through well-designed interventions.

Evaluating a youth-designed sexual and reproductive health mass and social media campaign in Côte d'Ivoire: triangulation of three independent evaluations.

Merci Mon Héros (MMH) is a youth-designed multi-media campaign seeking to improve sexual and reproductive health and family planning (SRH/FP) outcomes among youth living in nine francophone countries. A mixed methods approach was implemented to assess the MMH campaign progress and impact in Côte d'Ivoire. Three data sources were triangulated to evaluate the campaign: social media listening (October 2019-January 2021); a quantitative cross-sectional monitoring survey (September 2020) with 412 youth (aged 16-24) and 597 adults (aged 25-49); and a qualitative study using a Most Significant Change approach (March 2021), including a total of 24 focus group discussions with youth (aged 15-24) and adults (aged 25+) exposed to the MMH campaign. Data from all three studies were analysed independently and then brought together through a triangulation workshop where the study team compared findings to achieve convergence in evaluation results. Social listening results showed topic-specific online conversations related to MMH campaign spiked significantly during the two-week period after topic-specific campaign posts (p < .05), suggesting potential campaign impact. Survey results showed both adults and youth were more likely to have spoken with someone about FP in the past five months if exposed to the campaign (p < 0.01). Qualitative findings support the campaign's effect on shifting attitudes and behavioural uptake of intergenerational communication among adults and youth. This evaluation shows evidence of MMH's strong potential for impact in encouraging communication and the need to focus efforts on strategies to strengthen supportive adults' communication competencies and redefine what it means to act in support of SRH/FP for youth.

Bmi1 distinguishes immature retinal progenitor/stem cells from the main progenitor cell population and is required for normal retinal development.

The developing mammalian retina is generated by the proliferation and differentiation of multipotent retinal progenitor cells (RPCs) giving rise to neuronal and glial lineages. Whether an immature progenitor/stem cell subpopulation is present in the developing mammalian retina remains undefined. Deficiency in the polycomb group gene Bmi1 results in reduced proliferation and postnatal depletion of neural and hematopoietic stem cells. Here, we show that Bmi1 is required for the self-renewal of most immature RPCs and for postnatal retinal development. In the embryo, Bmi1 is highly enriched in a rare stage-specific embryonic antigen-1-positive RPC subpopulation expressing the stem cell markers Sox2, Lhx2, and Musashi. Gain-of-function experiments revealed that Bmi1 overexpression could convert RPCs having limited proliferation capacity into RPCs showing extensive proliferation and multiple differentiation capacities over time. At all developmental stages analyzed using the neurosphere assay, Bmi1 deficiency resulted in reduced proliferation and self-renewal of most immature RPCs. Reduced RPCs proliferation was also observed in the peripheral retina of Bmi1(-/-) fetus and newborn mice. The biological impact of these developmental anomalies was revealed by the reduced retinal diameter of Bmi1-deficient pups. P19(Arf) and p16(Ink4a) were upregulated in vivo and in vitro and coinactivation of p53, which lies downstream of p19(Arf), partially restored Bmi1-deficient RPCs self-renewal phenotype. Bmi1 thus distinguishes immature RPCs from the main RPC population and is required for normal retinal development.

P-glycoprotein and cytochrome P450 3A4 involvement in risperidone transport using an in vitro Caco-2/TC7 model and an in vivo model.

The possible involvement of P-glycoprotein (P-gp) and cytochrome P450 (CYP) 3A4 in risperidone transport was investigated using in vitro and in vivo models. Firstly, uptake studies were performed on a Caco-2/TC7 cell monolayer; the effects of 1 microg ml(-1) risperidone on apparent permeability were determined for secretory and absorptive directions, in the presence or absence of various P-gp and CYP3A4 inhibitors (verapamil, ketoconazole, erythromycin), and of an associated multidrug-resistant protein inhibitor (indomethacin). Secondly, on a conscious rat model, risperidone pharmacokinetic parameters, notably absorption parameters, were determined using compartmental and deconvolution methods. Three groups of seven rats received respectively an IV risperidone dose, an oral risperidone dose (PO group) and the same oral risperidone dose after verapamil administration (POV group). No formation of 9-hydroxyrisperidone was observed on Caco-2 cells after risperidone administration; there was no evidence that intestinal CYP3A4 is involved in risperidone metabolising. Risperidone secretory permeation was higher than absorptive permeation. Verapamil increased risperidone absorption permeation and decreased its secretory permeation. Indomethacin did not modify these permeation values. In rats, verapamil led to an increase in both risperidone and 9-hydroxyrisperidone plasmatic concentrations. The fraction absorbed in the verapamil group was 3.18 times higher than in the oral group (65.9% and 20.7% for POV group and PO group). The absorption rate constant was lower in the verapamil group. Our results indicate that P-gp decreases the intestinal absorption of risperidone and that intestinal CYP3A4 is not involved in risperidone metabolism.

Analytical and semipreparative enantioseparation of 9-hydroxyrisperidone, the main metabolite of risperidone, using high-performance liquid chromatography and capillary electrophoresis. Validation and determination of enantiomeric purity.

The HPLC semipreparative enantioseparation of 9-hydroxyrisperidone (9-OHRisp) was studied by optimizing various experimental conditions: the nature of the chiral stationary phase (CSP), mobile phase composition, temperature and analyte loading. This semipreparative enantioseparation was successfully completed using the polysaccharide Chiralcel OJ chiral stationary phase and a n-hexane/ethanol/methanol (50/35/15, v/v/v) ternary mobile phase. To assess the enantiomeric purity of both isolated isomers, three analytical methods using UV detection were developed and validated: one CE method using dual cyclodextrin mode and two HPLC methods using either the Chiralcel OJ CSP in normal-phase mode or the alpha-acid glycoprotein (alpha-AGP) CSP in reversed-phase mode. The three methods make it possible to obtain excellent enantioseparations (R(s) >3) with analysis times lower than 15 min, and the calculated limits of detection allow for the determination of minor enantiomeric impurities (0.1%). Enantiomeric purity obtained for dextrorotatory and levorotatory enantiomers was superior to 99.9% and equal to 98.9%, respectively, which proved the success of the semipreparative enantioseparation. A brief comparison of the performances of the analytical methods completes this work.

Effect of oil-in-water submicron emulsion surface charge on oral absorption of a poorly water-soluble drug in rats.

The effect of oil-in-water submicron emulsion (SE) droplet surface charge on absolute bioavailability of a poorly water-soluble drug (griseofulvin, as model drug) after oral administration was studied in conscious rat. Positively, negatively, and neutrally charged SE were designed and characterized (size, polydispersity index, zeta potential, and pH). Three emulsion formulations, whose compositions included 40% oil phase and differed only in the nature of the emulsifying agent, were retained. Only the positively charged SE showed a higher area under the plasma concentration-time curve (AUC(0 --> infinity)) in comparison with the tablet and with the other SE.

Pax6 controls the proliferation rate of neuroepithelial progenitors from the mouse optic vesicle.

In vertebrates, a limited number of homeobox-containing transcription factors are expressed in the optic vesicle primordium and are required and sufficient for eye formation. At present, little is known about the distinct functions of these factors in optic vesicle growth and on the nature of the main neuroepithelial (NE) progenitor population present in this organ. We have characterized a multipotent cell population present in the mouse optic vesicle that shows extensive proliferation potential and which expresses NE progenitor and retinal markers in vitro. In Pax6 mutant embryos, which form an optic vesicle, we found that the number of resident NE progenitors was greater than normal. In vitro, Pax6-null NE progenitors overproliferate and display reduced p16(Ink4a), p19(Arf), p27(kip1), p57(kip2), and p21(cip1) expression. Pax6 overexpression repressed cellular proliferation and secondary colonies formation, supporting the hypothesis that Pax6 acts cell-autonomously on NE progenitors cell cycle. Notably, these in vitro data correlated with aberrant numbers of mitosis observed in the optic vesicle of early stage Pax6 mutants, with Pax6 association with the chromatin upstream of p27(kip1) promoter region, and with reduced expression levels of p27(kip1), p57(kip2), and p21(cip1) in the primitive forebrain of Pax6 mutants. Taken together, our results suggest that, prior to retinal progenitor cell identity and neurogenesis, Pax6 is required to regulate the proliferation rate of NE progenitors present in the mouse optic vesicle.

Pax6 is required for delta-catenin/neurojugin expression during retinal, cerebellar and cortical development in mice.

The transcription factor Pax6 regulates multiple aspects of central nervous system (CNS) development. At the cellular level, the Pax6 mutation was reported to affect homophilic and heterophilic cellular adhesion, neuron polarity and neurite outgrowth. These abnormalities were observed in multiple regions of Pax6-mutant CNS, suggesting a common function for Pax6 in regulating cytoskeletal dynamics. However, target genes mediating Pax6 function in cytoskeletal dynamics remain largely unknown. Using DNA microarrays, we identified delta-catenin (delta-catenin /neurojugin) as a potential direct target of Pax6 in the CNS. delta-catenin encodes a large cytoskeletal protein that localizes at adherens junction in the CNS and that can modulate neurite outgrowth and N-cadherin turnover. delta-catenin was found to be co-expressed with Pax6 in several regions of the developing CNS. In Pax6 mutant embryos, delta-catenin expression was severely reduced in the optic vesicle neural ectoderm, in the ventricular zone of the neocortex and in the external granule layer of the cerebellum. We identified a Pax6 binding site in delta-catenin promoter that is conserved between mice and humans and which is effectively bound by Pax6 in vitro. Our results suggest that Pax6 regulates delta-catenin expression during CNS development in mice.