Elimination of Schistosomiasis Transmission in Zanzibar: Baseline Findings before the Onset of a Randomized Intervention Trial.

Gaining and sustaining control of schistosomiasis and, whenever feasible, achieving local elimination are the year 2020 targets set by the World Health Organization. In Zanzibar, various institutions and stakeholders have joined forces to eliminate urogenital schistosomiasis within 5 years. We report baseline findings before the onset of a randomized intervention trial designed to assess the differential impact of community-based praziquantel administration, snail control, and behavior change interventions. In early 2012, a baseline parasitological survey was conducted in ∼20,000 people from 90 communities in Unguja and Pemba. Risk factors for schistosomiasis were assessed by administering a questionnaire to adults. In selected communities, local knowledge about schistosomiasis transmission and prevention was determined in focus group discussions and in-depths interviews. Intermediate host snails were collected and examined for shedding of cercariae. The baseline Schistosoma haematobium prevalence in school children and adults was 4.3% (range: 0-19.7%) and 2.7% (range: 0-26.5%) in Unguja, and 8.9% (range: 0-31.8%) and 5.5% (range: 0-23.4%) in Pemba, respectively. Heavy infections were detected in 15.1% and 35.6% of the positive school children in Unguja and Pemba, respectively. Males were at higher risk than females (odds ratio (OR): 1.45; 95% confidence interval (CI): 1.03-2.03). Decreasing adult age (OR: 1.04; CI: 1.02-1.06), being born in Pemba (OR: 1.48; CI: 1.02-2.13) or Tanzania (OR: 2.36; CI: 1.16-4.78), and use of freshwater (OR: 2.15; CI: 1.53-3.03) showed higher odds of infection. Community knowledge about schistosomiasis was low. Only few infected Bulinus snails were found. The relatively low S. haematobium prevalence in Zanzibar is a promising starting point for elimination. However, there is a need to improve community knowledge about disease transmission and prevention. Control measures tailored to the local context, placing particular attention to hot-spot areas, high-risk groups, and individuals, will be necessary if elimination is to be achieved

IDEAL-CRT: A Phase 1/2 Trial of Isotoxic Dose-Escalated Radiation Therapy and Concurrent Chemotherapy in Patients With Stage II/III Non-Small Cell Lung Cancer

Purpose To report toxicity and early survival data for IDEAL-CRT, a trial of dose-escalated concurrent chemoradiotherapy (CRT) for non-small cell lung cancer. Patients and Methods Patients received tumor doses of 63 to 73 Gy in 30 once-daily fractions over 6 weeks with 2 concurrent cycles of cisplatin and vinorelbine. They were assigned to 1 of 2 groups according to esophageal dose. In group 1, tumor doses were determined by an experimental constraint on maximum esophageal dose, which was escalated following a 6 + 6 design from 65 Gy through 68 Gy to 71 Gy, allowing an esophageal maximum tolerated dose to be determined from early and late toxicities. Tumor doses for group 2 patients were determined by other tissue constraints, often lung. Overall survival, progression-free survival, tumor response, and toxicity were evaluated for both groups combined. Results Eight centers recruited 84 patients: 13, 12, and 10, respectively, in the 65-Gy, 68-Gy, and 71-Gy cohorts of group 1; and 49 in group 2. The mean prescribed tumor dose was 67.7 Gy. Five grade 3 esophagitis and 3 grade 3 pneumonitis events were observed across both groups. After 1 fatal esophageal perforation in the 71-Gy cohort, 68 Gy was declared the esophageal maximum tolerated dose. With a median follow-up of 35 months, median overall survival was 36.9 months, and overall survival and progression-free survival were 87.8% and 72.0%, respectively, at 1 year and 68.0% and 48.5% at 2 years. Conclusions IDEAL-CRT achieved significant treatment intensification with acceptable toxicity and promising survival. The isotoxic design allowed the esophageal maximum tolerated dose to be identified from relatively few patients

Posthumanist Education

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Metabolic and endocrine profiles and reproductive parameters in dairy cows under grazing conditions: effect of polymorphisms in somatotropic axis genes

<p>Abstract</p> <p>Background</p> <p>The present study hypothesized that GH-AluI and IGF-I-SnabI polymorphisms do change the metabolic/endocrine profiles in Holstein cows during the transition period, which in turn are associated with productive and reproductive parameters.</p> <p>Methods</p> <p>Holstein cows (Farm 1, primiparous cows, n = 110, and Farm 2, multiparous cows, n = 76) under grazing conditions were selected and GH and IGF-I genotypes were determined. Blood samples for metabolic/endocrine determinations were taken during the transition period and early lactation in both farms. Data was analyzed by farm using a repeated measures analyses including GH and IGF-I genotypes, days and interactions as fixed effects, sire and cow as random effects and calving date as covariate.</p> <p>Results and Discussion</p> <p>Frequencies of GH and IGF-I alleles were L:0.84, V:0.16 and A:0.60, B:0.40, respectively. The GH genotype was not associated with productive or reproductive variables, but interaction with days affected FCM yield in multiparous (farm 2) cows (LL yielded more than LV cows) in early lactation. The GH genotype affected NEFA and IGF-I concentrations in farm 1 (LV had higher NEFA and lower IGF-I than LL cows) suggesting a better energy status of LL cows.</p> <p>There was no effect of IGF-I genotype on productive variables, but a trend was found for FCM in farm 2 (AB cows yielded more than AA cows). IGF-I genotype affected calving first service interval in farm 1, and the interaction with days tended to affect FCM yield (AB cows had a shorter interval and yielded more FCM than BB cows). IGF-I genotype affected BHB, NEFA, and insulin concentrations in farm 1: primiparous BB cows had lower NEFA and BHB and higher insulin concentrations. In farm 2, there was no effect of IGF-I genotype, but there was an interaction with days on IGF-I concentration, suggesting a greater uncoupling somatropic axis in AB and BB than AA cows, being in accordance with greater FCM yield in AB cows.</p> <p>Conclusion</p> <p>The GH and IGF-I genotypes had no substantial effect on productive parameters, although IGF-I genotype affected calving-first service interval in primiparous cows. Besides, these genotypes may modify the endocrine/metabolic profiles of the transition dairy cow under grazing conditions.</p

FMRFamide-Like Peptides (FLPs) Enhance Voltage-Gated Calcium Currents to Elicit Muscle Contraction in the Human Parasite Schistosoma mansoni

Schistosomes are amongst the most important and neglected pathogens in the world, and schistosomiasis control relies almost exclusively on a single drug. The neuromuscular system of schistosomes is fertile ground for therapeutic intervention, yet the details of physiological events involved in neuromuscular function remain largely unknown. Short amidated neuropeptides, FMRFamide-like peptides (FLPs), are distributed abundantly throughout the nervous system of every flatworm examined and they produce potent myoexcitation. Our goal here was to determine the mechanism by which FLPs elicit contractions of schistosome muscle fibers. Contraction studies showed that the FLP Tyr-Ile-Arg-Phe-amide (YIRFamide) contracts the muscle fibers through a mechanism that requires Ca2+ influx through sarcolemmal voltage operated Ca2+ channels (VOCCs), as the contractions are inhibited by classical VOCC blockers nicardipine, verapamil and methoxyverapamil. Whole-cell patch-clamp experiments revealed that inward currents through VOCCs are significantly and reversibly enhanced by the application of 1 µM YIRFamide; the sustained inward currents were increased to 190% of controls and the peak currents were increased to 180%. In order to examine the biochemical link between the FLP receptor and the VOCCs, PKC inhibitors calphostin C, RO 31–8220 and chelerythrine were tested and all produced concentration dependent block of the contractions elicited by 1 µM YIRFamide. Taken together, the data show that FLPs elicit contractions by enhancing Ca2+ influx through VOCC currents using a PKC-dependent pathway

Shaping public opinion on the issue of childbirth; a critical analysis of articles published in an Australian newspaper

<p>Abstract</p> <p>Background</p> <p>The Australian government has announced a major program of reform with the move to primary maternity care, a program of change that appears to be at odds with current general public perceptions regarding how maternity care is delivered.</p> <p>Methods</p> <p>A critical discourse analysis of articles published in 'The Age', a newspaper with national distribution, subsequent to the release of the discussion paper by the Australian Government in 2008 was undertaken. The purpose was to identify how Australian maternity services are portrayed and what purpose is served by this representation to the general public.</p> <p>Results</p> <p>Findings from this critical discourse analysis revealed that Australian maternity services are being portrayed to the general public as an inflexible outdated service struggling to meets the needs of pregnant women and in desperate need of reform. The style of reporting employed in this newspaper involved presenting to the reader the range of expert opinion relevant to each topic, frequently involving polarised positions of the experts on the issue.</p> <p>Conclusions</p> <p>The general public are presented with a conflict, caught between the need for changes that come with the primary maternity model of care and fear that these change will undermine safe standards. The discourse; 'Australia is one of the safest countries in which to give birth or be born, what is must be best', represents the situation where despite major deficiencies in the system the general public may be too fearful of the consequences to consider a move away from reliance on traditional medical-led maternity care.</p

A cost-effectiveness analysis of a preventive exercise program for patients with advanced head and neck cancer treated with concomitant chemo-radiotherapy

In recent years, concomitant chemo-radiotherapy (CCRT) has become an indispensable organ preserving treatment modality for advanced head and neck cancer, improving local control and overall survival in several anatomical sites [1]. Unfortunately, CCRT can have a detrimental effect on many functions of the upper respiratory and digestive system. Sequellae such as pain, oedema, xerostomia and fibrosis negatively affect mouth opening (trismus), chewing, swallowing and speech [1]. Several studies investigating long-term effects of CCRT have concluded that swallowing and nutritional dysfunction tend to be persistent and can be severe [2-4]. Not surprisingly, therefore, CCRT can have a negative effect on patients‟ quality of life (QoL) [2]. Moreover, even before onset of treatment patients may already present with pain, impaired swallowing, trismus, aspiration, dietary restrictions and tube dependency, and loss of body weight, because the tumour may disrupt the normal anatomy and thus interfere with normal function [1]. Many studies refer to the importance of rehabilitation after, and even during treatment, in order to support and improve those functions [2]. However, as yet, few studies have investigated the effects of (preventive) rehabilitation exercises on the predictable and inevitable swallowing and mouth opening problems for this patient group. In addition, little is known about the costs and benefits of such exercise programs for head and neck cancer. As the clinical effectiveness is established [4], it is now relevant to embark on cost-effectiveness as a contribution to decision making on coverage. The aim of this study was to analyze the incremental cost-effectiveness for a preventive exercise program (PREP) versus usual care (UC) for patients with advanced head and neck cancer treated at the Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital (NKI-AVL)

State–Space Forecasting of Schistosoma haematobium Time-Series in Niono, Mali

Adequate forecasting and early warning systems are based upon observations of human behavior, population, disease time-series, climate, environment, and/or a combination thereof, whichever option best compromises among realism, feasibility, robustness, and parsimony. Fully automatic and user-friendly state–space forecasting frameworks, incorporating myriad options (e.g., expert opinion, univariate, multivariate, and spatial-temporal), could considerably enhance disease control and hazard mitigation efforts in regions where vulnerability to neglected tropical diseases is pervasive and statistical expertise is scarce. The operational simplicity, generality, and flexibility of state–space frameworks, encapsulating multiple methods, could conveniently allow for 1) unsupervised model selection without disease-specific methodological tailoring, 2) on-line adaptation to disease time-series fluctuations, and 3) automatic switches between distinct forecasting methods as new time-series perturbations dictate. In this investigation, a univariate state–space framework with the aforementioned properties was successfully applied to the Schistosoma haematobium time-series for the district of Niono, Mali, to automatically generate contemporaneous on-line forecasts and hence, providing a basis for local re-organization and strengthening public health programs in this and potentially other Sahelian districts

CD271-selected mesenchymal stem cells from adipose tissue enhance cartilage repair and are less angiogenic than plastic adherent mesenchymal stem cells

CD271 is a marker of bone marrow MSCs with enhanced differentiation capacity for bone or cartilage repair. However, the nature of CD271+ MSCs from adipose tissue (AT) is less well understood. Here, we investigated the differentiation, wound healing and angiogenic capacity of plastic adherent MSCs (PA MSCs) versus CD271+ MSCs from AT. There was no difference in the extent to which PA MSCs and CD271+ MSCs formed osteoblasts, adipocytes or chondrocytes in vitro. In contrast, CD271+ MSCs transplanted into athymic rats significantly enhanced osteochondral wound healing with reduced vascularisation in the repair tissue compared to PA MSCs and control animals; there was little histological evidence of mature articular cartilage formation in all animals. Conditioned medium from CD271+ MSC cultures was less angiogenic than PA MSC conditioned medium, and had little effect on endothelial cell migration or endothelial tubule formation in vitro. The low angiogenic activity of CD271+ MSCs and improved early stage tissue repair of osteochondral lesions when transplanted, along with a comparable differentiation capacity along mesenchymal lineages when induced, suggests that these selected cells are a better candidate than PA MSCs for the repair of cartilaginous tissue