Sentinel network for monitoring in vitro susceptibility of Plasmodium falciparum to antimalarial drugs in Colombia: a proof of concept

Drug resistance is one of the principal obstacles blocking worldwide malaria control. In Colombia, malaria remains a major public health concern and drug-resistant parasites have been reported. In vitro drug susceptibility assays are a useful tool for monitoring the emergence and spread of drug-resistant Plasmodium falciparum. The present study was conducted as a proof of concept for an antimalarial drug resistance surveillance network based on in vitro susceptibility testing in Colombia. Sentinel laboratories were set up in three malaria endemic areas. The enzyme linked immunosorbent assay-histidine rich protein 2 and schizont maturation methods were used to assess the susceptibility of fresh P. falciparum isolates to six antimalarial drugs. This study demonstrates that an antimalarial drug resistance surveillance network based on in vitro methods is feasible in the field with the participation of a research institute, local health institutions and universities. It could also serve as a model for a regional surveillance network. Preliminary susceptibility results showed widespread chloroquine resistance, which was consistent with previous reports for the Pacific region. However, high susceptibility to dihydroartemisinin and lumefantrine compounds, currently used for treatment in the country, was also reported. The implementation process identified critical points and opportunities for the improvement of network sustainability strategies.PAHO [057-1-3144141]; COLCIENCIAS [ID 2229-405-20319]info:eu-repo/semantics/publishedVersio

Intraosseous foreign body granuloma in rotator cuff repair with bioabsorbable suture anchor

Biodegradable implants lead to problems such as cyst formation, soft-tissue inflammation, loose implant fragments or local osteolysis. This report represents the first published case of an intraosseous foreign body granuloma in the humeral head after arthroscopic rotator cuff tear fixation with a poly-l-lactide (PLLA) suture anchor. A 48-year-old female patient presented with pain in her right shoulder. A refixation of her right supraspinatus tendon with a biodegradable suture anchor was performed 11 months ago at an external hospital. Laboratory tests showed normal values for C-reactive protein, leukocytes and the erythrocyte sedimentation rate. No signs of infection or instability were noted. The visual analogue scale (VAS) was 8, the simple shoulder test (SST) was 4 and the American shoulder and elbow surgeons score (ASES) was 44. Plain radiographs showed high lucency in the area of the tuberculum majus. MRI showed an intra- and extraosseous mass surrounded by fluid in this area. Surgical care involved arthroscopic debridement and removal of the suture anchor. Histological examination revealed a foreign body granuloma. At the 18-month follow-up the patient was nearly pain-free. The VAS was 2, SST was 10 and ASES was 88. Foreign body granulomas are a well known but rarely described complication that arises after the use of biodegradable suture anchors in shoulder surgery. Every patient presenting with shoulder pain after usage of a biodegradable fixation material should be evaluated closely. Orthopaedic surgeons should be aware of the possibility of delayed foreign body reactions, especially after using PLLA anchors

Absence of Ataxin-3 Leads to Enhanced Stress Response in C. elegans

Ataxin-3, the protein involved in Machado-Joseph disease, is able to bind ubiquitylated substrates and act as a deubiquitylating enzyme in vitro, and it has been involved in the modulation of protein degradation by the ubiquitin-proteasome pathway. C. elegans and mouse ataxin-3 knockout models are viable and without any obvious phenotype in a basal condition however their phenotype in stress situations has never been described

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference