Synchrotron phase-contrast X-ray imaging reveals fluid dosing dynamics for gene transfer into mouse airways

Although airway gene transfer research in mouse models relies on bolus fluid dosing into the nose or trachea, the dynamics and immediate fate of delivered gene transfer agents are poorly understood. In particular, this is because there are no in vivo methods able to accurately visualize the movement of fluid in small airways of intact animals. Using synchrotron phase-contrast X-ray imaging, we show that the fate of surrogate fluid doses delivered into live mouse airways can now be accurately and non-invasively monitored with high spatial and temporal resolution. This new imaging approach can help explain the non-homogenous distributions of gene expression observed in nasal airway gene transfer studies, suggests that substantial dose losses may occur at deliver into mouse trachea via immediate retrograde fluid motion and shows the influence of the speed of bolus delivery on the relative targeting of conducting and deeper lung airways. These findings provide insight into some of the factors that can influence gene expression in vivo, and this method provides a new approach to documenting and analyzing dose delivery in small-animal models.M Donnelley, KKW Siu, RA Jamison and DW Parson

Cost-effectiveness of adding indoor residual spraying to case management in Afghan refugee settlements in Northwest Pakistan during a prolonged malaria epidemic.

INTRODUCTION: Financing of malaria control for displaced populations is limited in scope and duration, making cost-effectiveness analyses relevant but difficult. This study analyses cost-effectiveness of adding prevention through targeted indoor residual spraying (IRS) to case management in Afghan refugee settlements in Pakistan during a prolonged malaria epidemic. METHODS/FINDINGS: An intervention study design was selected, taking a societal perspective. Provider and household costs of vector control and case management were collected from provider records and community survey. Health outcomes (e.g. cases and DALYs averted) were derived and incremental cost-effectiveness ratios (ICERs) for cases prevented and DALYs averted calculated. Population, treatment cost, women's time, days of productivity lost, case fatality rate, cases prevented, and DALY assumptions were tested in sensitivity analysis. Malaria incidence peaked at 44/1,000 population in year 2, declining to 14/1,000 in year 5. In total, 370,000 malaria cases, 80% vivax, were diagnosed and treated and an estimated 67,988 vivax cases and 18,578 falciparum and mixed cases prevented. Mean annual programme cost per capita was US$0.56. The additional cost of including IRS over five years per case prevented was US$39; US$50 for vivax (US$43 in years 1-3, US$80 in years 4-5) and US$182 for falciparum (US$139 in years 1-3 and US$680 in years 4-5). Per DALY averted this was US$266 (US$220 in years 1-3 and US$486 in years 4-5) and thus 'highly cost-effective' or cost-effective using WHO and comparison thresholds. CONCLUSIONS: Adding IRS was cost-effective in this moderate endemicity, low mortality setting. It was more cost-effective when transmission was highest, becoming less so as transmission reduced. Because vivax was three times more common than falciparum and the case fatality rate was low, cost-effectiveness estimations for cases prevented appear reliable and more definitive for vivax malaria

Is vaccine the magic bullet for malaria elimination? A reality check

Malaria remains a major health burden especially for the developing countries. Despite concerted efforts at using the current control tools, such as bed nets, anti malarial drugs and vector control measures, the disease is accountable for close to a million deaths annually. Vaccines have been proposed as a necessary addition to the armamentarium that could work towards elimination and eventual eradication of malaria in view of their historical significance in combating infectious diseases. However, because malaria vaccines would work differently depending on the targeted parasite stage, this review addresses the potential impact various malaria vaccine types could have on transmission. Further, because of the wide variation in the epidemiology of malaria across the endemic regions, this paper proposes that the ideal approach to malaria control ought to be tailor-made depending on the specific context. Finally, it suggests that although it is highly desirable to anticipate and aim for malaria elimination and eventual eradication, many affected regions should prioritize reduction of mortality and morbidity before aspiring for elimination

Progress towards early detection services for infants with hearing loss in developing countries

BACKGROUND: Early detection of infants with permanent hearing loss through infant hearing screening is recognised and routinely offered as a vital component of early childhood care in developed countries. This article investigates the initiatives and progress towards early detection of infants with hearing loss in developing countries against the backdrop of the dearth of epidemiological data from this region. METHODS: A cross-sectional, descriptive study based on responses to a structured questionnaire eliciting information on the nature and scope of early hearing detection services; strategies for financing services; parental and professional attitudes towards screening; and the performance of screening programmes. Responses were complemented with relevant data from the internet and PubMed/Medline. RESULTS: Pilot projects using objective screening tests are on-going in a growing number of countries. Screening services are provided at public/private hospitals and/or community health centres and at no charge only in a few countries. Attitudes amongst parents and health care workers are typically positive towards such programmes. Screening efficiency, as measured by referral rate at discharge, was generally found to be lower than desired but several programmes achieved other international benchmarks. Coverage is generally above 90% but poor follow-up rates remain a challenge in some countries. The mean age of diagnosis is usually less than six months, even for community-based programmes. CONCLUSION: Lack of adequate resources by many governments may limit rapid nationwide introduction of services for early hearing detection and intervention, but may not deter such services altogether. Parents may be required to pay for services in some settings in line with the existing practice where healthcare services are predominantly financed by out-of-pocket spending rather than public funding. However, governments and their international development partners need to complement current voluntary initiatives through systematic scaling-up of public awareness and requisite manpower development towards sustainable service capacities at all levels of healthcare delivery

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Examination of Urinary Iodine Status from a Sample of Malian Adolescent Girls

Iodine deficiency disorders are common throughout the developing world, yet they are considered one of the most preventable causes of mental retardation. Iodine deficiency has tremendous consequences on women and girls and can not only impair a woman's reproductive health, but it also has serious consequences for a growing fetus. In pregnant women, this deficiency can lead to congenital hypothyroidism in newborn infants. Congenital hypothyroidism is a disorder associated with a low IQ, deaf mutism, and neurological problems. Many studies have revealed that iodine deficiency is common throughout West Africa. While several of these studies have investigated the prevalence of iodine deficiency among women in West Africa, few have examined the problem among adolescent girls. Thus this study aimed to quantify iodine levels in a representative sample of adolescent girls aged 10 to 15 years from the Segou Region of Mali, West Africa. Casual urine samples were collected, and urinary iodine excretion was analyzed using the Sandell-Kolthoff reaction. Clinical signs of iodine deficiency, the presence or absence of goiters, were noted and ethnographic interviews were conducted to examine dietary behaviors. Mean urinary iodine excretion was 9.3 µg iodine/dl (95% CI 7.6-10.9). Forty girls were iodine deficient (66.6%, 95% CI 53.3-78.3) of whom 19 (31.7% CI 20.3-45.0) showed moderate or severe deficiency. These results show that the majority of these Malian adolescent girls are at a mild to moderate risk for iodine deficiency, however no statistically significant differences were found between girls from the urban and rural communities. These findings suggest that not only can iodine deficiency affect the individual health of these girls, but iodine deficiency can have many ramifications concerning the socioeconomic status of their communities. Because adolescent girls are still growing and preparing to have children, these findings have major implications for their health and the health for their future children. These results provide one of the first analyses concerning iodine deficiency among adolescent girls in Mali. Key words - Iodine deficiency, Mali, nutrition, adolescent girls Résumé EXAMEN DU NIVEAU D'IODE URINAIRE A PARTIR D'UN ECHANTILLON DE FILLES ADOLESCENTES MALIENNES Contexte : Les troubles dus à la carence en iode sont courants dans le Tiers-monde. Chez les femmes, cette carence peut conduire à un hypothyroïdisme congénital avec des troubles de croissance chez les nouveaux-nés, associés à un bas Q I et une surdité et aphonie. But : Cette étude avait pour but d'évaluer de façon quantitative, le niveau d'iode dans un échantillon représentatif de filles âgées de 10 à 15 ans au Mali (Afrique de l'ouest). Méthode: Des échantillons d'iode ont été collectés dans la région de Ségou au Mali et l'iode contenu dans l'urine a été analysé en employant le réactif Sandell-Kolthoff. La présence ou absence de goitre ont été notée et des enquêtes ethnographiques conduites pour examiner leurs habitudes alimentaires. Résultats: le taux moyen d'iode retrouvé dans les urine étaient de 9,3mg iode /dl (95% IC 7.6 - 10, 9 ) quarante filles avaient manifesté une déficience en iode (66,6% , 95% IC 53,3-78,3) parmi lesquels dix neuf (31,7% IC 20,3 - 45.0) ont manifesté une carence modérée ou sévère. Discussion: Ces résultats démontrent que la majorité de ces adolescentes maliennes courent un risque plus ou moins grand de carence en iode. Ces résultats fournissent l'une des premières analyses concernant la carence en iode chez les adolescentes du Mali. Etant donné que les adolescentes sont en pleine croissance et en âge de procréer, ces découvertes ont des implications majeures pour leur santé et celle de leur futurs enfants. Mots clefs - carences en iode, le Mali, nutrition, adolescentes IC : Intervalle de confiance (Af. J. of Food, Agriculture, Nutrition and Development: 2003 3(1): 20-28