Survey of caregivers in Kenya to assess perceptions of zinc as a treatment for diarrhea in young children and adherence to recommended treatment behaviors

In 2004, the United Nations Children’s Fund (UNICEF) and the World Health Organization (WHO) revised their recommendations for management of acute diarrhea in children to include zinc treatment as well as oral rehydration solution (ORS). Little is known about how caregivers in low–resource settings perceive and use zinc treatment

Znaczenie kliniczne badań nad aromatazą

Aromatase is a member of the cytochrome P450 superfamily that catalyzes the conversion of androgens (C19), namely testosterone and androstenedione, into oestrogens (C18), oestradiol, and oestrone, respectively. The enzyme is active in various tissues in both females and males, thus oestrogens are produced not only in gonads but also in extra-gonadal localizations such as brain, adipose tissue, breast, skin, and bone. Aromatase gene CYP19A1 located on chromosome 15 comprises nine coding exons and a number of alternative non-coding first exons that regulate tissue-specific expression. Studies on local regulation of aromatase expression and activity are important for understanding processes such as growth of oestrogen-dependent breast cancer. Rare clinical conditions of aromatase deficiency and excess have revealed some new and unexpected oestrogen functions in metabolism and bone health in both women and men. They were further studied using transgenic animal models such as aromatase knockout mice (ArKO) or (AROM+) mice overexpressing human aromatase. Research on aromatase was important for its practical outcome as it contributed to the development of aromatase inhibitors (AIs), an effective and safe group of drugs for the first-line endocrine therapy of breast cancer. Further studies are needed to establish AIs application in other oestrogen-dependent conditions, to overcome the resistance in breast cancer patients, and to develop tissue-specific selective inhibitors. (Pol J Endocrinol 2010; 61 (1): 126–134)Aromataza jest enzymem należącym do rodziny cytochromu P450. Katalizuje reakcję hydroksylacji prowadzącą do powstania estrogenów: estradiolu i estronu z androgenowych substratów, odpowiednio: testosteronu i androstendionu. Aktywność enzymu i produkcję estrogenów wykazano w różnych tkankach zarówno u kobiet, jak i u mężczyzn. Poza gonadami aromataza jest aktywna na przykład w mózgu, tkance tłuszczowej, gruczole piersiowym, skórze i kościach. Gen aromatazy CYP19A1, zlokalizowany na chromosomie 15, składa się z dziewięciu kodujących egzonów i alternatywnych niekodujących pierwszych egzonów, których swoista tkankowo transkrypcja reguluje ekspresję genu. Poznanie mechanizmów regulujących lokalną ekspresję i aktywność aromatazy przyczynia się między innymi do lepszego zrozumienia procesów istotnych dla rozwoju estrogenozależnego raka piersi. Opisy klinicznych przypadków niedoboru i nadmiaru aromatazy oraz analiza fenotypu myszy transgenicznych pozbawionych aromatazy (ArKO) lub z jej nadekspresją (AROM+) ujawniły dotychczas nieznane i często zaskakujące funkcje estrogenów u obu płci. Badania podstawowe nad aromatazą znalazły swoje praktyczne zastosowanie w pracach nad inhibitorami aromatazy. Stanowią one obecnie pierwszoplanowe leczenie hormonalne raka piersi kobiet po menopauzie, w przypadku obecności receptorów estrogenowych w komórkach guza. Potrzebne są dalsze badania nad zastosowaniem inhibitorów aromatazy w innych schorzeniach zależnych od estrogenów, nad przeciwdziałaniem rozwojowi oporności powstającej w trakcie terapii oraz opracowaniem selektywnych inhibitorów swoistych tkankowo. (Endokrynol Pol 2010; 61 (1): 126-134

Assessing the Organizational Readiness of the Zambia Ministry of Health to Adopt a New Immunization Supply Chain Distribution System

In 1974 the World Health Organization launched the Expanded Program on Immunization (EPI) with the goal of vaccinating all children. To implement the EPI, a standardized in-country immunization supply chain (iSC) design was developed and implemented by most low-income countries in Asia and Africa. Today, the iSC design faces an influx of new and more expensive vaccines putting additional strain on an already antiquated system, and little attention is being paid to the ability of the traditional iSC to absorb this increase. To do so, global health and vaccine experts are calling for a change to the current iSC. Implementation science proposes that organizational readiness for change (ORC)—such as that being proposed to the iSC—is a critical antecedent to the successful adoption of evidence-based programs and the uptake of new systems and innovations (Weiner 2009). Scaccia and colleagues (2015) provide a useful approach to measuring ORC. Their formula consists of determining the relative strengths and weaknesses of three ORC components: (1) motivation for carrying out a program or innovation, (2) general organizational capacity for implementation, and (3) innovation-specific capacity, which is specific to the program or innovation being considered (Scaccia et al. 2015). Using a modified version of Scaccia’s theoretical framework for ORC, an assessment was made of the readiness of key EPI staff at district and provincial levels in Zambia to adopt a new iSC distribution system. Using focus groups (n=17) and key informant interviews (n=6), the assessment revealed a high level of motivation, but relatively low levels of general capacity and innovation-specific capacity. Specifically, the lack of infrastructure, particularly transport, energy, and communications, as well as low-skill levels of facility staff, are a barrier to ORC in Zambia. A plan for change is proposed to build greater ORC among EPI staff in Zambia by implementing a demonstration project that builds general capacity and innovation-specific capacity through three objectives: (1) consistent and regular training of facility-level staff, (2) placing professionally trained logisticians at the provincial level, and (3) demonstrating the effectiveness of unmanned aerial vehicles (UAVs; aka “drones”) to delivery vaccines to remote and isolated areas.Doctor of Public Healt

Processing carbon nanotubes with holographic optical tweezers

We report the first demonstration that carbon nanotubes can be trapped and manipulated by optical tweezers. This observation is surprising because individual nanotubes are substantially smaller than the wavelength of light, and thus should not be amenable to optical trapping. Even so, nanotube bundles, and perhaps even individual nanotubes, can be transported at high speeds, deposited onto substrates, untangled, and selectively ablated, all with visible light. The use of holographic optical tweezers, capable of creating hundreds of independent traps simultaneously, suggests opportunities for highly parallel nanotube processing with light.Comment: 3 pages, 1 figur

Treatment of diarrhea in young children: Results from surveys on the perception and use of oral rehydration solutions, antibiotics, and other therapies in India and Kenya

Diarrheal disease is a leading cause of morbidity and mortality among children under five. Although oral rehydration solution (ORS) has tremendous therapeutic benefits, coverage of and demand for this product have remained low in many developing countries. This study surveyed caregivers and health care providers in India and Kenya to gather information about perceptions and use of various diarrhea treatments, assess reasons for low ORS use, and identify opportunities for expanding ORS use

Use of formative research in developing a knowledge translation approach to rotavirus vaccine introduction in developing countries

BACKGROUND: Rotavirus gastroenteritis is the leading cause of diarrheal disease mortality among children under five, resulting in 450,000 to 700,000 deaths each year, and another 2 million hospitalizations, mostly in the developing world. Nearly every child in the world is infected with rotavirus at least once before they are five years old. Vaccines to prevent rotavirus or minimize its severity are now becoming available, and have already been introduced into the public vaccine programs of several Latin American countries. The World Health Organization (WHO) has made rotavirus vaccine introduction in developing countries a high priority. The WHOs Guidelines for Vaccine Introduction indicates that a key determinant to achieving vaccine introduction is the public health priority of the disease, suggesting that where the disease is not a priority uptake of the vaccine is unlikely. WHO recommends conducting a qualitative analysis of opinions held by the public health community to determine the perceptions of the disease and the priority given to the vaccine. METHODS: This paper presents the formative research results of a qualitative survey of public health providers in five low- and middle-income countries to determine if and to what degree rotavirus is perceived to be a problem and the priority of a vaccine. Open-ended surveys were carried out through focus group discussions and one-on-one interviews. RESULTS: Researchers discovered that in all five countries knowledge of rotavirus was extremely low, and as a result was not considered a high priority. However, diarrhea among young children was considered a high priority among public health providers in the three poorest countries with relatively high levels of child mortality: India, Indonesia, and Nicaragua. CONCLUSION: In the poorest countries, advocacy and communication efforts to raise awareness about rotavirus sufficient for prioritization and accelerated vaccine introduction might benefit from a knowledge translation approach that delivers information and evidence about rotavirus through the broader context of diarrheal disease control, an existing priority, and including information about other new interventions, specifically low-osmolarity oral rehydration solution and zinc treatment

Aromatase Is a Direct Target of FOXL2: C134W in Granulosa Cell Tumors via a Single Highly Conserved Binding Site in the Ovarian Specific Promoter

BACKGROUND: Granulosa cell tumors (GCT) of the ovary often express aromatase and synthesize estrogen, which in turn may influence their progression. Recently a specific point mutation (C134W) in the FOXL2 protein was identified in >94% of adult-type GCT and it is likely to contribute to their development. A number of genes are known to be regulated by FOXL2, including aromatase/CYP19A1, but it is unclear which are direct targets and whether the C134W mutation alters their regulation. Recently, it has been reported that FOXL2 forms a complex with steroidogenic factor 1 (SF-1) which is a known regulator of aromatase in granulosa cells. METHODOLOGY/PRINCIPAL FINDINGS: In this work, the human GCT-derived cell lines KGN and COV434 were heterozygous and wildtype for the FOXL2:C134W mutation, respectively. KGN had abundant FOXL2 mRNA expression but it was not expressed in COV434. Expression of exogenous FOXL2:C134W in COV434 cells induced higher expression of a luciferase reporter for the ovarian specific aromatase promoter, promoter II (PII) (-516bp) than expression of wildtype FOXL2, but did not alter induction of a similar reporter for the steroidogenic acute regulatory protein (StAR) promoter (-1300bp). Co-immunoprecipitation confirmed that FOXL2 bound SF-1 and that it also bound its homologue, liver receptor homologue 1 (LRH-1), however, the C134W mutation did not alter these interactions or induce a selective binding of the proteins. A highly conserved putative binding site for FOXL2 was identified in PII. FOXL2 was demonstrated to bind the site by electrophoretic mobility shift assays (EMSA) and site-directed mutagenesis of this element blocked its differential induction by wildtype FOXL2 and FOXL2:C134W. CONCLUSIONS/SIGNIFICANCE: These findings suggest that aromatase is a direct target of FOXL2:C134W in adult-type GCT via a single distinctive and highly conserved binding site in PII and therefore provide insight into the pathogenic mechanism of this mutation