The effects of improved sanitation on diarrheal prevalence, incidence, and duration in children under five in the SNNPR State, Ethiopia: study protocol for a randomized controlled trial.

BACKGROUND: Diarrhea is one of the leading causes of death, killing 1.3 million in 2013 across the globe, of whom, 0.59 million were children under 5 years of age. Globally, about 1 billion people practice open defecation, and an estimated 2.4 billion people were living without improved sanitation facilities in 2015. Much of the previous research investigating the effect of improved sanitation has been based on observational studies. Recent studies have executed a cluster-randomized controlled trial to investigate the effect of improved sanitation. However, none of these recent studies achieved a sufficient level of latrine coverage. Without universal or at least a sufficient level of latrine coverage, a determination of the effect of improved latrines on the prevention of diarrheal disease is difficult. This cluster-randomized trial aims to explore the net effect of improved latrines on diarrheal prevalence and incidence in children under five and to investigate the effect on the diarrheal duration. METHOD/DESIGN: A phase-in and factorial design will be used for the study. The intervention for improving latrines will be implemented in an intervention arm during the first phase, and the comparable intervention will be performed in the control arm during the second phase. During the second phase, a water pipe will be connected to the gotts (villages) in the intervention arm. After the second phase is completed, the control group will undergo the intervention of receiving a water pipe connection. For diarrheal prevalence, five rounds of surveying will be conducted at the household level. The first four rounds will be carried out in the first phase to explore the effect of improved latrines, and the last one, in the second phase to examine the combined effects of improved water and sanitation. For documentation of diarrheal incidence and duration, the mother or caregiver will record the diarrheal episodes of her youngest child on the "Sanitation Calendar" every day. Of 212 gotts in the project area, 48 gotts were selected for the trial, and 1200 households with a child under 5 will be registered for the intervention or control arm. Informed consent from 1200 households will be obtained from the mother or caregiver in written form. DISCUSSION: To our knowledge, this is the second study to assess the effects of improved latrines on child diarrheal reduction through the application of Community-Led Total Sanitation. TRIAL REGISTRATION: Current Controlled Trials, ISRCTN82492848

Benefits and Costs of a Community-Led Total Sanitation Intervention in Rural Ethiopia-A Trial-Based ex post Economic Evaluation.

We estimated the costs and benefits of a community-led total sanitation (CLTS) intervention using the empirical results from a cluster-randomized controlled trial in rural Ethiopia. We modelled benefits and costs of the intervention over 10 years, as compared to an existing local government program. Health benefits were estimated as the value of averted mortality due to diarrheal disease and the cost of illness arising from averted diarrheal morbidity. We also estimated the value of time savings from avoided open defecation and use of neighbours' latrines. Intervention delivery costs were estimated top-down based on financial records, while recurrent costs were estimated bottom-up from trial data. We explored methodological and parameter uncertainty using one-way and probabilistic sensitivity analyses. Avoided mortality accounted for 58% of total benefits, followed by time savings from increased access to household latrines. The base case benefit-cost ratio was 3.7 (95% CI: 1.9-5.4) and the net present value was Int'l $1,193,786 (95% CI: 406,017-1,977,960). The sources of the largest uncertainty in one-way sensitivity analyses were the effect of the CLTS intervention and the assumed lifespan of an improved latrine. Our results suggest that CLTS interventions can yield favourable economic returns, particularly if follow-up after the triggering is implemented intensively and uptake of improved latrines is achieved (as opposed to unimproved)

Blood-Stage Plasmodium Berghei ANKA Infection Promotes Hepatic Fibrosis by Enhancing Hedgehog Signaling in Mice

Background/Aims: Malaria is the most deadly parasitic infection in the world, resulting in damage to various organs, including the liver, of the infected organism; however, the mechanism causing this damage in the liver remains unclear. Liver fibrosis, a major characteristic of liver diseases, occurs in response to liver injury and is regulated by a complex network of signaling pathways. Hedgehog (Hh) signaling orchestrates a number of hepatic responses including hepatic fibrogenesis. Therefore, we investigated whether Hh signaling influenced the liver’s response to malarial infection. Methods: Eight-week-old male C57BL/6 mice inoculated with blood containing Plasmodium berghei ANKA (PbA)-infected erythrocytes were sacrificed when the level of parasitemia in the blood reached 10% or 30%, and the livers were collected for biochemical analysis. Liver responses to PbA infection were examined by hematoxylin and eosin staining, real-time polymerase chain reaction, immunohistochemistry and western blot. Results: Severe hepatic injury, such as ballooned hepatocytes, sinusoidal dilatation, and infiltrated leukocytes, was evident in the livers of the malaria-infected mice. Hypoxia was also induced in 30% parasitemia group. With the accumulation of Kupffer cells, inflammation markers, TNF-α, interleukin-1β, and chemokine (C-X-C motif) ligand 1, were significantly upregulated in the infected group compared with the control group. Expression of fibrotic markers, including transforming growth factor-β, α-smooth muscle actin (α-SMA), collagen 1a1, thymosin β4, and vimentin, were significantly higher in the infected groups than in the control group. With increased collagen deposition, hepatic stellate cells expressing α-SMA accumulated in the liver of the PbA-infected mice, whereas those cells were rarely detected in the livers of the control mice. The levels of Hh signaling and Yes-associated protein (YAP), two key regulators for hepatic fibrogenesis, were significantly elevated in the infected groups compared with the control group. Treatment of mice with Hh inhibitor, GDC-0449, reduced hepatic inflammation and fibrogenesis with Hh suppression in PbA-infected mice. Conclusion: Our results demonstrate that HSCs are activated in and Hh and YAP signaling are associated with this process, contributing to increased hepatic fibrosis in malaria-infected livers

A Hop Extract Lifenol® Improves Postmenopausal Overweight, Osteoporosis, and Hot Flash in Ovariectomized Rats

Objective. In order to assess the effectiveness of a hop extract (HE) for postmenopausal symptoms, the effects of Lifenol on ovariectomy-induced osteoporosis, hyperlipidemia, body weight increase, and hot flash were investigated in rats. Methods. Female Sprague-Dawley rats were ovariectomized and subjected to a daily scheduled exercise training (15 min at 15 m/min) or treated with HE (30 or 100 mg/kg, oral) or 17β-estradiol (100 μg/kg, intraperitoneal) for 12 weeks. Body and visceral fat weights, serum lipid profiles, osteoporotic parameters in serum, and femoral bones were analyzed. Separately, forced running-induced dermal and rectal temperatures and blood flow velocity were measured in ovariectomized rats. Results. Ovariectomy increased blood lipids including triglycerides, total cholesterol, and low-density lipoproteins, leading to visceral fat accumulation and overweight. Estrogen depletion caused osteoporosis, displaying decreased femoral bone weight, bone mineral density and content, and blood phosphorus level. The disturbances in lipid metabolism and bone resorption were recovered by treatment with HE in a dose-dependent manner. In addition, HE treatment shortened the duration of forced running-induced alterations in skin and rectal temperatures by reducing blood flow velocity. Conclusion. The results indicate that HE attenuated overweight, osteoporosis, and hot flash in estrogen-deficient animals by regulating blood lipid profile and fat accumulation, blood estrogen and bone resorption factors, and dermal blood flow

Neuroprotective properties of Hsp90 inhibitor NXD30001 in a primary culture model of amyotrophic lateral sclerosis

Protein misfolding and aggregation are important features in the pathogenesis of amyotrophic lateral sclerosis (ALS). Upregulation of protein chaperones (heat shock proteins; HSPs) protects against cellular stress, as well as in models of ALS. Treatment with Hsp90 inhibitors upregulates multiple HSPs in motor neurons without requiring additional cellular stress; however, currently available Hsp90 inhibitors have unfavourable properties for therapeutic use. A novel Hsp90 inhibitor, NXD30001 (NexGenix Pharmaceuticals) shows improved safety, stability and bioactivity, which make it a favourable candidate for therapeutic development. NXD30001 induced expression of stress-inducible Hsp70 and its co-chaperone Hsp40 in motor neurons of dissociated cultures of murine spinal cord-dorsal root ganglia, at least in part mediated by the transcription factor, heat shock factor 1. In a primary culture model of familial ALS1 due to mutation in the SOD1 gene, NXD30001 protected against mutant SOD1-induced toxicity in cultured motor neurons, delaying accumulation of SOD1G93A, preventing formation of mutant SOD1 inclusions, and prolonging viability. This study of NXD30001 in culture paves the way for further testing in transgenic mouse models.Les erreurs de repliements de protéines et l'aggregation des protéines sont deux importantes caractéristiques de la pathogenèse de la Sclérose Latérale Amyotrophique (SLA). Une augmentation de l'activité des protéines chaperons (protéines de choc thermique – Hsp-) procure une certaine protection contre le stress cellulaire et contre la SLA dans des modèles animaux. Un traitement menant à l'inhibition du complexe Hsp90 augmente l'activité de plusieurs autres Hsp dans les neurones et nerfs moteurs sans ajout de stress cellulaire. Cependant, les inhibiteurs couramment utilisés ont des propriétés qui ne sont pas favorables à une utilisation thérapeutique. Un inhibiteur du complexe Hsp90 nouvellement créé, le NXD30001 (NexGenix Pharmaceutic), démontre une meilleure bioactivité et stabilité, ce qui le rend plus sécuritaire et plus apte à une utilisation thérapeutique. Grâce au facteur de traduction heat shock factor 1, NXD30001 induit l'expression du complexe Hsp70 ainsi que la protéine co-chaperonne Hsp40 dans des cultures dissociées de neurones moteurs spinaux provenant des ganglions des cornes lombaires de souris. Dans l'étude primaire d'une culture d'un model familial de SLA1 causé par une mutation du gène SOD1; NXD30001 a protégé les neurones moteurs d'une toxicité induite par la mutation, a retardé l'accumulation de SOD1G93A, a empêché la formation d'agrégats de protéines produites par le gène mutant et a prolongé la viabilité des neurones. Cette étude portant sur les effets du NXD30001 en culture, ouvre la voie à d'autres recherches, pouvant être faites sur des souris transgéniques, qui permettraient d'explorer le potentiel thérapeutique de cette nouvelle drogue

Precipitation Probability Prediction through NWP Bias Correction for South Korea Using Random Forest

This study presents the results of an effort to improve the forecast of precipitation (> 0.1 mm/hr or > 0.1 mm/3hr) in the Local Data Assimilation and Prediction System (LDAPS) and the Global Data Assimilation and Prediction System (GDAPS) by applying the Random Forest (RF) model in South Korea. LDAPS and GDAPS are Numerical Weather Prediction (NWP) models operated by the Korea Meteorological Administration (KMA) for weather forecasting. GDAPS operates the Unified Model (UM) and the Korean Integrated Model (KIM). This study used weather forecast data from LDAPS, GDAPS/KIM, and GDAPS/UM. Precipitation forecasts from LDAPS and GDAPS were corrected by RF training with rain gauge observations from about 685 stations. Approximately 35 selected NWP model output variables were used as inputs to the RF training. To reflect recent trends in biases between observations and NWP, the precipitation probability prediction model was designed for real-time learning using a sliding window technique. In addition, the precipitation data had a data imbalance problem with more precipitation cases than non-precipitation cases, so an under-sampling method was applied to solve this problem. Comparing the performance of the proposed method with NWP in predicting precipitation, the CSI was improved by 14.7-23.1% (LDAPS), 33.9% (GDAPS/KIM), and 6.7%-38% (GDAPS/UM) over NWP, and the accuracy was also better. In future research, automating the sampling rate selection to reflect recent weather trends when under-sampling is likely to improve forecast performance

Can Architectural Surfaces Capture Atmospheric Particulate Matter Like Trees? A Design Strategy to Mimic Leaf Traits

Trees’ ability to capture atmospheric Particular Matter (PM) is related to morphological traits (shape, size, and micro-morphology) of the leaves. The objectives of this study were (1) to find out whether cluster pattern of the leaves is also a parameter that affects trees’ PM capturing performance and (2) to apply the cluster patterns of the leaves on architectural surfaces to confirm its impact on PM capturing performance. Two series of chamber experiments were designed to observe the impact of cluster patterns on PM capturing performance whilst other influential variables were controlled. First, we exposed synthetic leaf structures of different cluster patterns (a large and sparsely arranged cluster pattern and a small and densely arranged cluster pattern) to artificially generated PM in a chamber for 60 min and recorded the changing levels of PM2.5 and PM10 every minute. The results confirmed that the small and densely arranged cluster pattern has more significant effect on reducing PM2.5 and PM10 than the large and sparsely arranged cluster pattern. Secondly, we created three different types of architectural surfaces mimicking the cluster patterns of the leaves: a base surface, a folded surface, and a folded and porous surface. The surfaces were also exposed to artificially generated PM in the chamber and the levels of PM2.5 and PM10 were recorded. The results confirmed that the folded and porous surface has a more significant effect on reducing PM2.5 and PM10 than other surfaces. The study has confirmed that the PM capturing performance of architectural surfaces can be improved by mimicking cluster pattern of the leaves

Analysis of the strong propensity for the delocalized diamagnetic pi electronic structure of hydrogenated graphenes

The conformation and electronic structure of hydrogen-treated graphenes are investigated using the density-functional theory (DFT) method. We show that the overall energetics of the hydrogen chemisorption configuration can be analyzed with two energy components: the electronic pairing effect in the hyper-conjugated pi electron network and the strain effect in the C-C bond at the boundary between sp(3)- and sp(2)-bonded regions. Some unpaired hydrogenation configurations can show magnetic ground states, but these were found to be unstable. The least strained paired configurations strongly favored the delocalized pi electronic states. This suggests that appropriate annealing following a hydrogen plasma treatment of graphene can lead to a semiconducting state with a stable finite bandgap.close3

Effect of Floor Openings on Evacuation Efficiency in Multipurpose Commercial Buildings: IFC Mall in Yeouido, Seoul, Korea

To achieve evacuation-optimized design at the architectural planning phase, this study analyzed the effect of floor openings in multipurpose commercial buildings on their evacuation efficiency. Herein, the IFC Mall in Yeouido, Seoul, Korea was considered the study site, because all the factors influencing the evacuation efficiency can be controlled owing to the underground location of all floors. Therefore, all evacuees followed the same evacuation direction. Comprehensively, a spatial analysis methodology (Cellular ECEM) was employed to derive the evacuation costs through the sum of visibility cost and distance cost. Subsequently, the evacuation costs were compared in all cases to review the hindrances in evacuation according to the type and area ratio of the planned floor opening, and several causes of evacuation cost deviations were discussed. Overall, increasing the area of the floor opening deteriorates the evacuation efficiency. The evacuation efficiency increased if the area of the floor opening is appropriately separated and a bridge is constructed in the middle to connect a path. Furthermore, following the longer path around the floor opening to use the main vertical means of circulation, owing to the connection between the atrium and floor opening, is more vulnerable toward evacuation efficiency than other floor opening types

Electronic Effect on the Molecular Motion of Aromatic Amides: Combined Studies Using VT-NMR and Quantum Calculations

Rotational barrier energy studies to date have focused on the amide bond of aromatic compounds from a kinetic perspective using quantum calculations and nuclear magnetic resonance (NMR). These studies provide valuable information, not only regarding the basic conformational properties of amide bonds but also the molecular gear system, which has recently gained interest. Thus, we investigate the precise motion of the amide bonds of two aromatic compounds using an experimental rotational barrier energy estimation by NMR experiments and a theoretical evaluation of the density functional theory calculation. The theoretical potential energy surface scan method combined with the quadratic synchronous transit 3 method and consideration of additional functional group rotation with optimization and frequency calculations support the results of the variable temperature 1H NMR, with deviations of less than 1 kcal/mol. This detailed experimental and theoretical research strongly supports molecular gear motion in the aromatic amide system, and the difference in kinetic energy indicates that the electronic effect from the aromatic structure has a key role in conformational movements at different temperatures. Our study provides an enhanced basis for future amide structural dynamics research.© 2018 by the authors