Current Issue : January - March Volume : 2018 Issue Number : 1 Articles : 5 Articles
Background: The clinical development of a single encounter treatment for uncomplicated malaria has the potential to\nsignificantly improve the effectiveness of antimalarials. Exploratory data suggested that the combination of artefenomel\nand piperaquine phosphate (PQP) has the potential to achieve satisfactory cure rates as a single dose therapy. The\nprimary objective of the study was to determine whether a single dose of artefenomel (800 mg) plus PQP in ascending\ndoses is an efficacious treatment for uncomplicated Plasmodium falciparum malaria in the 'target' population of\nchildren ââ?°Â¤ 5 years of age in Africa as well as Asian patients of all ages.\nMethods: Patients in six African countries and in Vietnam were randomised to treatment with follow-up for 42ââ?¬â??63\ndays. Efficacy, tolerability, safety and pharmacokinetics were assessed. Additional key objectives were to characterise the\nexposureââ?¬â??response relationship for polymerase chain reaction (PCR)-adjusted adequate clinical and parasitological\nresponse at day 28 post-dose (ACPR28) and to further investigate Kelch13 mutations. Patients in Africa (n = 355) and\nVietnam (n = 82) were included, with 85% of the total population being children < 5 years of age. Results: ACPR28 in the per protocol population (95% confidence interval) was 70.8% (61.13ââ?¬â??79.19), 68.4% (59.13ââ?¬â??76.66)\nand 78.6% (70.09ââ?¬â??85.67) for doses of 800 mg artefenomel with 640 mg, 960 mg and 1440 mg of PQP respectively.\nACPR28 was lower in Vietnamese than in African patients (66.2%; 54.55ââ?¬â??76.62 and 74.5%; 68.81ââ?¬â??79.68) respectively.\nWithin the African population, efficacy was lowest in the youngest age group of ââ?°Â¥ 0.5 to ââ?°Â¤ 2 years, 52.7% (38.80ââ?¬â??66.35).\nInitial parasite clearance was twice as long in Vietnam than in Africa. Within Vietnam, the frequency of the Kelch13\nmutation was 70.1% and was clearly associated with parasite clearance half-life (PCt1/2). The most significant tolerability\nfinding was vomiting (28.8%).\nConclusions: In this first clinical trial evaluating a single encounter antimalarial therapy, none of the treatment arms\nreached the target efficacy of > 95% PCR-adjusted ACPR at day 28. Achieving very high efficacy following single dose\ntreatment is challenging, since > 95% of the population must have sufficient concentrations to achieve cure across a\nrange of parasite sensitivities and baseline parasitaemia levels. While challenging, the development of tools suitable for\ndeployment as single encounter curative treatments for adults and children in Africa and to support elimination\nstrategies remains a key development goal....
In todayââ?¬â?¢s aging society, more people are living with lifestyle-related noncommunicable diseases (NCDs) such as cardiovascular\ndisease, type 2 diabetes, obesity, and cancer. Numerous opinion-leader organizations recommend lifestyle medicine as the firstline\napproach in NCD prevention and treatment. However, there is a strong need for a personalized approach as ââ?¬Å?one-size-fits-allââ?¬Â\npublic health recommendations have been insufficient in addressing the interindividual differences in the diverse populations.\nAdvancement in systems biology and the ââ?¬Å?omicsââ?¬Â technologies has allowed comprehensive analysis of how complex biological\nsystems are impacted upon external perturbations (e.g., nutrition and exercise), and therefore is gradually pushing personalized\nlifestyle medicine toward reality. Clinicians and healthcare practitioners have a unique opportunity in advocating lifestyle\nmedicine because patients see them as a reliable source of advice. However, there are still numerous technical and logistic\nchallenges to overcome before personal ââ?¬Å?big dataââ?¬Â can be translated into actionable and clinically relevant solutions. Clinicians are\nalso facing various issues prior to bringing personalized lifestyle medicine to their practice. Nevertheless, emerging groundbreaking\nresearch projects have given us a glimpse of how systems thinking and computational methods may lead to personalized\nhealth advice. It is important that all stakeholders work together to create the needed paradigm shift in healthcare before the rising\nepidemic of NCDs overwhelm the society, the economy, and the dated health system....
Background: Danggui Buxue Tang (DBT), a phytoestrogen-enriched Chinese herbal formula, serves as dietary supplement\nin stimulating the ââ?¬Å?Bloodââ?¬Â functions of menopausal women. In traditional Chinese medicine (TCM) theory,\nââ?¬Å?Bloodââ?¬Â has a strong relationship with brain activities. Previous studies supported that some ingredients of DBT possessed\nneuronal beneficial functions. Therefore, the neurotrophic function and the mechanistic action of DBT were\nsystematically evaluated in cultured human neuroblastoma SH-SY5Y cells.\nMethods: The DBT-triggered protein expressions were analyzed by western blotting, while the transcriptional activities\nof promoters coding for related genes were revealed by luciferase assays. For mechanistic analysis of DBT, Erk1/2\nand its inhibitor U0126 were analyzed.\nResults: The application of DBT in cultured neuroblastoma cells showed the efficacies in: (1) up-regulation of nerve\ngrowth factor (NGF), brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF);\n(2) activation of transcriptional activities of promoters coding for NGF, BDNF, GDNF; (3) activation of Erk1/2 and CREB;\nand (4) attenuation of the neurotrophic factor expression by the treatment of an Erk1/2 inhibitor.\nConclusions: Our study supports that MAPK/Erk pathway acts as fundamental role in monitoring DBT-induced\nexpression of neurotrophic factors in cultured human neuroblastoma cell. These results shed light in developing the\nworking mechanism of this ancient herbal decoction for its neuronal function....
Background: Stroke is the second most common cause of death and may result in various disabilities; thus, identification\nof neuroprotective therapeutic agents is important. Peucedani Radix (PR), the root of Angelica decursiva, is\na well-known remedy for damp and phlegm in Korean medicine and has also been shown to exert antioxidant and\nanti-inflammatory activities. This study was performed to investigate the mechanism underlying the anti-inflammatory\neffect of methanol extract of PR (PRex) on cerebral ischemic injury.\nMethods: C57BL/6 male mice were orally administered PRex (20, 60, or 200 mg/kg) at 2 days, 1 day, and 1 h prior to\nmiddle cerebral artery occlusion (MCAO). Twenty-four hours after MCAO, the infarct volume was measured and the\nneurological deficit score was assessed. The inflammatory-related substances in the ipsilateral hemisphere were determined\nby western blotting, DCFH-DA assay, TBARS assay, and ELISA.\nResults: PRex pretreatment significantly decreased the infarct volume at 24 h after MCAO. Moreover, PRex effectively\nsuppressed the expression of iNOS, ROS, MDA, and pro-inflammatory cytokines, such as IL-1�² and TNF-�±, in brain tissue\nof mice with MCAO-induced brain injury.\nConclusions: PRex protected neurons from ischemic brain injury in mice through its antioxidant and anti-inflammatory\nactivities. Our results suggested that PR could be a promising candidate in the therapy of ischemia-induced brain\ndamage....
Background: Wild type 2 poliovirus was last observed in 1999. The Sabin-strain oral polio vaccine type 2 (OPV2)\nwas critical to eradication, but it is known to revert to a neurovirulent phenotype, causing vaccine-associated\nparalytic poliomyelitis. OPV2 is also transmissible and can establish circulating lineages, called circulating vaccinederived\npolioviruses (cVDPVs), which can also cause paralytic outbreaks. Thus, in April 2016, OPV2 was removed\nfrom immunization activities worldwide. Interrupting transmission of cVDPV2 lineages that survive cessation will\nrequire OPV2 in outbreak response, which risks seeding new cVDPVs. This potential cascade of outbreak responses\nseeding VDPVs, necessitating further outbreak responses, presents a critical risk to the OPV2 cessation effort.\nMethods: The EMOD individual-based disease transmission model was used to investigate OPV2 use in outbreak\nresponse post-cessation in West African populations. A hypothetical outbreak response in northwest Nigeria is modeled,\nand a cVDPV2 lineage is considered established if the Sabin strain escapes the response region and continues circulating\n9 months post-response. The probability of this event was investigated in a variety of possible scenarios.\nResults: Under a broad range of scenarios, the probability that widespread OPV2 use in outbreak response\n(~2 million doses) establishes new cVDPV2 lineages in this model may exceed 50% as soon as 18 months or\nas late as 4 years post-cessation.\nConclusions: The risk of a cycle in which outbreak responses seed new cVDPV2 lineages suggests that OPV2\nuse should be managed carefully as time from cessation increases. It is unclear whether this risk can be\nmitigated in the long term, as mucosal immunity against type 2 poliovirus declines globally. Therefore,\ncurrent programmatic strategies should aim to minimize the possibility that continued OPV2 use will be\nnecessary in future years: conducting rapid and aggressive outbreak responses where cVDPV2 lineages are\ndiscovered, maintaining high-quality surveillance in all high-risk settings, strengthening the use of the\ninactivated polio vaccine as a booster in the OPV2-exposed and in routine immunization, and gaining access\nto currently inaccessible areas of the world to conduct surveillance....
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