Prevalence of intestinal protozoa infection among school-aged children on Pemba Island, Tanzania, and effect of single-dose albendazole, nitazoxanide and albendazole-nitazoxanide.

Pathogenic intestinal protozoa infections are common in school-aged children in the developing world and they are frequently associated with malabsorption syndromes and gastrointestinal morbidity. Since diagnosis of these parasites is difficult, prevalence data on intestinal protozoa is scarce. We collected two stool samples from school-aged children on Pemba Island, Tanzania, as part of a randomized controlled trial before and 3 weeks after treatment with (i) single-dose albendazole (400 mg); (ii) single-dose nitazoxanide (1,000 mg); (iii) nitazoxanide-albendazole combination (1,000 mg--400 mg), with each drug given separately on two consecutive days; and (iv) placebo. Formalin-fixed stool samples were examined for the presence of intestinal protozoa using an ether-concentration method to determine the prevalence and estimate cure rates (CRs). Almost half (48.7%) of the children were diagnosed with at least one of the (potentially) pathogenic protozoa Giardia intestinalis, Entamoeba histolytica/E. dispar and Blastocystis hominis. Observed CRs were high for all treatment arms, including placebo. Nitazoxanide showed a significant effect compared to placebo against the non-pathogenic protozoon Entamoeba coli. Intestinal protozoa infections might be of substantial health relevance even in settings where they are not considered as a health problem. Examination of a single stool sample with the ether-concentration method lacks sensitivity for the diagnosis of intestinal protozoa, and hence, care is indicated when interpreting prevalence estimates and treatment effects

Nonlocal Astroparticles in Einstein's Universe

Gravitational probes should maintain spatial flatness for Einsten-Infeld-Hoffmann dynamics of relativistic matter-energy. The continuous elementary source/particle in Einstein's gravitational theory is the r^{-4} radial energy density rather than the delta-operator density in empty-space gravitation. The space energy integral of such an infinite (astro)particle is finite and determines its nonlocal gravitational charge for the energy-to-energy attraction of other nonlocal (astro)particles. The non-empty flat space of the undivided material Universe is charged continuously by the world energy density of the global ensemble of overlapping radial particles. Nonlocal gravitational/inertial energy-charges incorporate Machian relativism quantitatively into Einstein's gravitation for self-contained SR-GR dynamics without references on Newton's mass-to-mass attraction.Comment: 9 pages, typos and arguments adde

Identification of antischistosomal leads by evaluating peroxides of beta-dicarbonyl compounds and their heteroanalogs : bridged 1,2,4,5-tetraoxanes and alphaperoxides, and beta,delta-triketones: tricyclic monoperoxides

Although antischistosomal properties of peroxides were studied in recent years, systematic structure-activity relationships have not been conducted. We evaluated the antischistosomal potential of 64 peroxides belonging to bridged 1,2,4,5-tetraoxanes, alphaperoxides and beta,delta-triketones. Thirty-nine compounds presented IC50 values > 15 microM on newly transformed schistosomula. Active drugs featured phenyl-, adamantane- or alkyl residues at the methylene bridge. Lower susceptibility was documented on adult schistosomes, with most hit compounds being tricyclic monoperoxides (IC50: 7.7-13.4 microM). A bridged 1,2,4,5-tetraoxane characterized by an adamantane residue showed the highest activity (IC50: 0.3 microM) on adult Schistosoma mansoni. Studies with hemin and heme supplemented medium indicated that antischistosomal activation of peroxides is not necessarily triggered by iron porphyrins. Two compounds (tricyclic monoperoxide; bridged 1,2,4,5-tetraoxane) revealed high worm burden reductions in the chronic (WBR: 75.4-82.8 %) but only moderate activity in the juvenile (WBR:18.9-43.1%) S. mansoni mouse model. Our results might serve as starting point for the preparation and evaluation of related derivative

Adult triclabendazole-resistant Fasciola hepatica: morphological changes in the tegument and gut following in vivo treatment with artemether in the rat model

A study has been carried out to determine the morphological changes to the adult liver fluke, Fasciola hepatica after treatment in vivo with artemether. Rats were infected with the triclabendazole-resistant Sligo isolate of F. hepatica, dosed orally with artemether at a concentration of 200mg/kg and flukes recovered at 24, 48 and 72h post-treatment (p.t.). Surface changes were monitored by scanning electron microscopy and fine structural changes to the tegument and gut by transmission electron microscopy. Twenty-four hours p.t., the external surface showed minor disruption, in the form of mild swelling of the tegument. The tegumental syncytium and sub-tegumental tissues appeared relatively normal. Forty-eight and seventy-two hours p.t., disruption to the tegumental system increased, with isolated patches of surface blebbing and reduced production of secretory bodies by the tegumental cells being the main changes seen. The gastrodermal cells showed a relatively normal morphology 24h p.t. By 48h, large numbers of autophagic vacuoles and lipid droplets were present. Autophagy increased in magnitude by 72h p.t. and substantial disruption to the granular endoplasmic reticulum was observed. Results from this study show that flukes treated in vivo with artemether display progressive and time-dependent alterations to the tegument and gut. Disruption to the gut was consistently and substantially more severe than that to the tegument, suggesting that an oral route of uptake for this compound predominates. This is the first study providing ultrastructural information on the effect of an artemisinin compound against liver fluk

Evaluating the Usefulness and Ease of Use of a Next-Generation–Connected Drug Delivery Device for Growth Hormone Therapy: Qualitative Study of Health Care Professionals’ Perceptions

Background: Digital solutions targeting children’s health have become an increasingly important element in the provision of integrated health care. For the treatment of growth hormone deficiency (GHD), a unique connected device is available to facilitate the delivery of recombinant human growth hormone (r-hGH) by automating the daily injection process and collecting injection data such that accurate adherence information is available to health care professionals (HCPs), caregivers, and patients. The adoption of such digital solutions requires a good understanding of the perspectives of HCPs as key stakeholders because they leverage data collection and prescribe these solutions to their patients. Objective: This study aimed to evaluate the third generation of the easypod device (EP3) for the delivery of r-hGH treatment from the HCP perspective, with a focus on perceived usefulness and ease of use. Methods: A qualitative study was conducted, based on a participatory workshop conducted in Zaragoza, Spain, with 10 HCPs experienced in the management of pediatric GHD from 7 reference hospitals in Spain. Several activities were designed to promote discussion among participants about predefined topics based on the Technology Acceptance Model and the Unified Theory of Acceptance and Use of Technology to provide their perceptions about the new device. Results: Participants reported 2 key advantages of EP3 over previous easypod generations: the touch screen interface and the real-time data transmission functionality. All participants (10/10, 100%) agreed that the new device should be part of a digital health ecosystem that provides complementary functionalities including data analysis. Conclusions: This study explored the perceived value of the EP3 autoinjector device for the treatment of GHD by HCPs. HCPs rated the new capabilities of the device as having substantial improvements and concluded that it was highly recommendable for clinical practice. EP3 will enhance decision-making and allow for more personalized care of patients receiving r-hGH

Electron microscopical study to assess the in vitro effects of the synthetic trioxolane OZ78 against the liver fluke, Fasciola hepatica

Adult Fasciola hepatica were incubated for 48 h in vitro in the synthetic peroxide, OZ78 at a concentration of 100 μg/ml and then prepared for scanning and transmission electron microscopy. There was limited disruption to the external fluke surface, with only slight swelling and blebbing of the interspinal tegument in the midbody and ventral tail regions. By contrast, significant disruption was observed to the ultrastructure of the tegument and subtegumental tissues. There was severe swelling of the basal infolds in the tegumental syncytium and the flooding spread internally to affect the subtegumental tissues. In the tegumental system, there was swelling of the cisternae of granular endoplasmic reticulum and of the mitochondria, with the latter showing signs of breaking down. Autophagic vacuoles and lipid droplets were present and the synthesis of tegumental secretory bodies was much reduced. The gastrodermal cells were severely affected, with swelling and degeneration of the mitochondria and the presence of autophagic vacuoles and lipid droplets. The granular endoplasmic reticulum was swollen and vesiculated and the cells contained few secretory bodies. Both the vitelline and testis follicles showed evidence of extensive cellular disruption and degeneration. This study confirms previous data indicating the potential flukicidal activity of OZ7

Simultaneous Triggered Collapse of the Presolar Dense Cloud Core and Injection of Short-Lived Radioisotopes by a Supernova Shock Wave

Cosmochemical evidence for the existence of short-lived radioisotopes (SLRI) such as $^{26}$Al and $^{60}$Fe at the time of the formation of primitive meteorites requires that these isotopes were synthesized in a massive star and then incorporated into chondrites within $\sim 10^6$ yr. A supernova shock wave has long been hypothesized to have transported the SLRI to the presolar dense cloud core, triggered cloud collapse, and injected the isotopes. Previous numerical calculations have shown that this scenario is plausible when the shock wave and dense cloud core are assumed to be isothermal at $\sim 10$ K, but not when compressional heating to $\sim 1000$ K is assumed. We show here for the first time that when calculated with the FLASH2.5 adaptive mesh refinement (AMR) hydrodynamics code, a 20 km/sec shock wave can indeed trigger the collapse of a 1 $M_\odot$ cloud while simultaneously injecting shock wave isotopes into the collapsing cloud, provided that cooling by molecular species such as H$_2$O, CO$_2$, and H$_2$ is included. These calculations imply that the supernova trigger hypothesis is the most likely mechanism for delivering the SLRI present during the formation of the solar system.Comment: 12 pages, 4 color figures. Astrophysical Journal Letters (in press

Efficacy and Safety of Artemether in the Treatment of Chronic Fascioliasis in Egypt: Exploratory Phase-2 Trials

Fasciola hepatica and F. gigantica are two liver flukes that parasitize herbivorous large size mammals (e.g., sheep and cattle), as well as humans. A single drug is available to treat infections with Fasciola flukes, namely, triclabendazole. Recently, laboratory studies and clinical trials in sheep and humans suffering from acute fascioliasis have shown that artesunate and artemether (drugs that are widely used against malaria) also show activity against fascioliasis. Hence, we were motivated to assess the efficacy and safety of oral artemether in patients with chronic Fasciola infections. The study was carried out in Egypt and artemether administered according to two different malaria treatment regimens. Cure rates observed with 6×80 mg and 3×200 mg artemether were 35% and 6%, respectively. In addition, high efficacy was observed when triclabendazole, the current drug of choice against human fascioliasis, was administered to patients remaining Fasciola positive following artemether treatment. Concluding, monotherapy with artemether does not represent an alternative to triclabendazole against fascioliasis, but its role in combination chemotherapy regimen remains to be investigated