Sinclairanderson1237

ty of plaques and abnormal lipid accumulation in ApoE-/- mice. Furthermore, these effects might be mediated through the p38 MAPK pathway.

In the absence of definitive diagnosis, healthcare providers are likely to prescribe empirical antibacterials to those who test negative for malaria. This problem is of critical importance in Southern Asia (SA) and South-eastern Asia (SEA) where high levels of antimicrobial consumption and high prevalence of antimicrobial resistance have been reported. To improve management and guide further diagnostic test development, better understanding is needed of the true causative agents of fever and their geographical variability.

We conducted a systematic review of published literature (1980-2015) to characterise the spectrum of pathogens causing non-malarial febrile illness in SA and SEA. We searched six databases in English and French languages MEDLINE, EMBASE, Global Health (CABI) database, WHO Global Health Library, PASCAL, and Bulletin de la Société Française de Parasitologie (BDSP). Selection criteria included reporting on an infection or infections with a confirmed diagnosis, defined as pathogens detected febrile illness in SA and SEA. The findings emphasise the need of standardising the reporting of aetiological studies to develop effective, evidence-based fever management and improved surveillance. Research and development of diagnostic tools would benefit from up-to-date epidemiological reporting of the regional diversities of non-malaria fever aetiologies.

PROSPERO registration, CRD42016049281.

PROSPERO registration, CRD42016049281.An amendment to this paper has been published and can be accessed via the original article.

In malaria-endemic countries, febrile episodes caused by diseases other than malaria are a growing concern. However, limited knowledge of the prevalent etiologic agents and their geographic distributions restrict the ability of health services to address non-malarial morbidity and mortality through effective case management. Here, we review the etiology of fever in Latin America (LA) between 1980 and 2015 and map significant pathogens commonly implicated in febrile infectious diseases.

A literature search was conducted, without language restrictions, in three distinct databases in order to identify fever etiology studies that report laboratory-confirmed fever-causing pathogens that were isolated from usually sterile body sites. Data analyses and mapping was conducted with Tableau Desktop (version 2018.2.3).

Inclusion criteria were met by 625 publications corresponding to data relative to 34 countries. Studies using serology (n = 339) predominated for viral infections, culture (n = 131) for bacteria, and and timely identify emerging infections threats.

PROSPERO systematic review registration number CRD42016049281.

PROSPERO systematic review registration number CRD42016049281.Traumatic brain injury (TBI) is still the worldwide leading cause of mortality and morbidity in young adults. selleckchem Improved safety measures and advances in critical care have improved chances of surviving a TBI, however, numerous secondary mechanisms contribute to the injury in the weeks and months that follow TBI. The past 4 decades of research have addressed many of the metabolic impairments sufficient to mitigate mortality, however, an enduring secondary mechanism, i.e. neuroinflammation, has been intractable to current therapy. Neuroinflammation is particularly difficult to target with pharmacological agents due to lack of specificity, the blood brain barrier, and an incomplete understanding of the protective and pathologic influences of inflammation in TBI. Recent insights into TBI pathophysiology have established microglial activation as a hallmark of all types of TBI. The inflammatory response to injury is necessary and beneficial while the death of activated microglial is not. This review presents new insights on the therapeutic and maladaptive features of the immune response after TBI with emphasis on microglial polarization, followed by a discussion of potential targets for pharmacologic and non-pharmacologic treatments. In aggregate, this review presents a rationale for guiding TBI inflammation towards neural repair and regeneration rather than secondary injury and degeneration, which we posit could improve outcomes and reduce lifelong disease burden in TBI survivors.Chemoresistance, which leads to the failure of chemotherapy and further tumor recurrence, presents the largest hurdle for the success of anticancer therapy. In recent years, metformin, a widely used first-line antidiabetic drug, has attracted increasing attention for its anticancer effects. A growing body of evidence indicates that metformin can sensitize tumor responses to different chemotherapeutic drugs, such as hormone modulating drugs, anti-metabolite drugs, antibiotics, and DNA-damaging drugs via selective targeting of cancer stem cells (CSCs), improving the hypoxic microenvironment, and by suppressing tumor metastasis and inflammation. In addition, metformin may regulate metabolic programming, induce apoptosis, reverse epithelial to mesenchymal transition (EMT) and multidrug resistance (MDR). In this review, we summarize the chemosensitization effects of metformin and focus primarily on its molecular mechanisms in enhancing the sensitivity of multiple chemotherapeutic drugs, through targeting of mTOR, ERK/P70S6K, NF-κB/HIF-1α, and mitogenactivated protein kinase (MAPK) signaling pathways, as well as by down-regulating the expression of CSC genes and pyruvate kinase isoenzyme M2 (PKM2). Through a comprehensive understanding of the molecular mechanisms of chemosensitization provided in this review, the rationale for the use of metformin in clinical combination medications can be more systematically and thoroughly explored for wider adoption against numerous cancer types.

Triple negative breast cancers (TNBCs) are having high morbidity and shorter survival rate in the population. These types of cancers are having high aggressiveness, lymphatic invasion and absence of receptors. The treatment options for these types of cancers are also scarce. Several studies have been conducted to investigate the effectiveness of seeds of Annona muricata for its anti cancer activities in various cancer cell lines such as lung A549, breast MCF7, colon HT-29, oral KB and human hepatoma cell lines. But works related to its anticancer effect and mechanism of action in TNBCs has not been elucidated.

The present study was undertaken to evaluate the in vitro, in vivo and in silico anticancer potential of chloroform fraction of methanolic extract of seeds of Annona muricata (CMAM) against TNBC along with elucidation of its mechanistic pathway.

In vitro cytotoxicity- and antiproliferative- studies in three triple negative breast cancer cell lines were conducted using MTT and SRB assays respectively.