Development and validation of a luminescence-based, medium-throughput assay for drug screening in Schistosoma mansoni

Schistosomiasis, one of the world's greatest neglected tropical diseases, is responsible for over 280,000 human deaths per annum. Praziquantel, developed in the 1970s, has high efficacy, excellent tolerability, few and transient side effects, simple administration procedures and competitive cost and it is currently the only recommended drug for treatment of human schistosomiasis. The use of a single drug to treat a population of over 200 million infected people appears particularly alarming when considering the threat of drug resistance. Quantitative, objective and validated methods for the screening of compound collections are needed for the discovery of novel anti-schistosomal drugs. METHODOLOGY/PRINCIPAL FINDINGS: The present work describes the development and validation of a luminescence-based, medium-throughput assay for the detection of schistosomula viability through quantitation of ATP, a good indicator of metabolically active cells in culture. This validated method is demonstrated to be fast, highly reliable, sensitive and automation-friendly. The optimized assay was used for the screening of a small compound library on S. mansoni schistosomula, showing that the proposed method is suitable for a medium-throughput semi-automated screening. Interestingly, the pilot screening identified hits previously reported to have some anti-parasitic activity, further supporting the validity of this assay for anthelminthic drug discovery. CONCLUSIONS: The developed and validated schistosomula viability luminescence-based assay was shown to be successful and suitable for the identification of novel compounds potentially exploitable in future schistosomiasis therapies

Exploring the coordination chemistry of isomerizable terpyridine derivatives for successful analyses of cis and trans isomers by travelling wave ion mobility mass spectrometry

The photochemical cis-trans isomerization of the 4-{4-[2-(pyridin-4-yl)ethenyl]phenyl}-2,2': 6',2''-terpyridine ligand (vpytpy) was investigated by UV-vis, NMR and TWIM-MS. Ion mobility mass spectrometry was performed pursuing the quantification of the isomeric composition during photolysis, however an in-source trans-to-cis isomerization process was observed. In order to overcome this inherent phenomenon, the isomerization of the vpytpy species was suppressed by complexation, reacting with iron(II) ions, and forming the [Fe(vpytpy)(2)](2+) complex. The strategy of "freezing" the cis-trans isomerizable ligand at a given geometric conformation was effective, preventing further isomerization, thus allowing the distinction of each one of the isomers in the photolysed mixture. In addition, the experimental drift times were related to the calculated surface areas of the three possible cis-cis, cis-trans and trans-trans iron(II) complex isomers. The stabilization of the ligand in a given conformation also allows us to obtain the cis-cis and cis-trans complexes exhibiting the ligand in the metastable cis-conformation, as well as in the thermodynamically stable trans-conformation.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq

Fluctuations in export productivity over the last century from sediments of a southern Chilean fjord (44°S)

Author Posting. © The Authors, 2005. This is the author's version of the work. It is posted here by permission of Elsevier B. V. for personal use, not for redistribution. The definitive version was published in Estuarine, Coastal and Shelf Science 65 (2005): 587-600, doi:10.1016/j.ecss.2005.07.005.Here we present the first reconstruction of changes in surface primary production during the last century from the Puyuhuapi fjord in southern Chile, using a variety of parameters (diatoms, biogenic silica, total organic carbon, chlorins, and proteins) as productivity proxies. Two sediment cores from the head and the center of the fjord were analyzed and compared to gain insights on past changes in productivity in these two different depositional environments. Higher sedimentation rates found at the head of the fjord result from the combination of a shallower water column and a restricted circulation by the occurrence of a sill. Additionally, sediment mixing depths estimated from 210Pb data suggest that suboxic conditions may dominate the bottom water and the sediment-water interface in this location. Productivity of the Puyuhuapi fjord during the last century was characterized by a constant increase from the late 19th century to the early 1980s, then decreased until the late-1990s, and then rose again to present-day values. The influence of rainfall on productivity was most noticeable during periods of low rainfall, which coincided with decreased overall productivity within the Puyuhuapi fjord. Simultaneous variations in productivity and rainfall in the study area suggest that marine productivity could respond to atmospheric-oceanic interactions at a local scale. At a regional scale, marine productivity of the area may be related to other large-scale processes such as the El Niño Southern Oscillation.We are grateful to the Ministerio de Hacienda de Chile (Chilean Ministry of Treasury) and the National Oceanographic Committee (CONA) for financial support to carry out the Cimar-7 Fiordo Program (Grant C7F 01-10 to Silvio Pantoja), the FONDAP-COPAS Center, and Grant 200.031.085-1 (UdeC) for financial support. Sepúlveda was funded by a scholarship from the Graduate School of the University of Concepción and by the FONDAP-COPAS Center. Additional support was given by Fundación Andes through the Woods Hole Oceanographic Institution/University of Concepción agreement

Debridement, antibiotics, and implant retention (DAIR) for the early prosthetic joint infection of total knee and hip arthroplasties: a systematic review

International audienceEarly periprosthetic joint infection (PJI) represents one of the most fearsome complications of joint replacement. No international consensus has been reached regarding the best approach for early prosthetic knee and hip infections. The aim of this updated systematic review is to assess whether debridement, antibiotics, and implant retention (DAIR) is an effective choice of treatment in early postoperative and acute hematogenous PJI. Methods: This systematic review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The diagnostic criteria defining a PJI, the most present pathogen, and the days between the index procedure and the onset of the PJI were extracted from the selected articles. Additionally, the mean follow-up, antibiotic regimen, and success rate of the treatment were also reported. Results: The articles included provided a cohort of 970 patients. Ten studies specified the joint of their cohort in PJIs regarding either hip prostheses or knee prostheses, resulting in 454 total knees and 460 total hips. The age of the patients ranged from 18 to 92 years old. Success rates for the DAIR treatments in the following cohort ranged from 55.5% up to a maximum of 90% (mean value of 71%). Conclusion: Even though the DAIR procedure is quite limited, it is still considered an effective option for patients developing an early post-operative or acute hematogenous PJI. However, there is a lack of studies, in particular randomized control trials (RCTs), comparing DAIR with one-stage and two-stage revision protocols in the setting of early PJIs, reflecting the necessity to conduct further high-quality studies to face the burden of early PJI

A Systematic Review of Oxygen Therapy for the Management of Medication-Related Osteonecrosis of the Jaw (MRONJ)

Background: Medication-related osteonecrosis of the jaw (MRONJ) can be a life changing iatrogenic complication of antiresorptive and antiangiogenic drug therapy. It is most often associated with high doses of these medications that are used to prevent skeletal-related events in patients with cancer and bone pathologies. Unfortunately, managing MRONJ lesions has proven difficult and remains a major challenge for clinicians. Due to the lack of efficacy in treating MRONJ by surgical modalities (local debridement and free flap reconstruction), the nonsurgical management of MRONJ is still advocated to aid healing or avoid disease progression. The aim of this systematic review is to identify, analyse and understand the published evidence related to the success of oxygen therapies such as ozone (OT) and hyperbaric oxygen (HBO) in treating MRONJ. Material and methods: A multi-database (PubMed, MEDLINE, EMBASE, CINAHL and Cochrane CENTRAL) systematic search was performed by three authors. The identified articles were independently assessed for their risk of bias. Any type of study evaluating humans treated with antiresorptive and antiangiogenic drugs were considered. The aim is primarily to evaluate the success of OT and HBO in resolving MRONJ and secondarily to identify any improvements in quality of life (QoL), rate of complications, time-to-event and severity of side effects related to these treatments. Results: In total, just 13 studies were eligible for analysis. A pooled total of 313 patients (HBO group n = 82; OT group n = 231) described in these studies have shown good tolerance for oxygen therapies. Complete resolution of MRONJ was reported in 44.58% of OT patients but only 5.17% of the HBO group. Progression of MRONJ was reported only in the HBO studies in 10.34% of cases (6 patients). The quality of evidence was low or very low in all studies. This was due to limitations in how the studies were designed, run and reported. Conclusions: Based on the limited data available, it is difficult to suggest OT is better or worse than HBO or whether it is better than a placebo. As the level of evidence available is low, this necessitates larger well-designed trials to justify these interventions for patients affected by MRONJ

Optical motion capture systems for 3D kinematics analysis in patients with musculoskeletal shoulder disorders

To the best of our knowledge, no updated systematic review focused on the application of optical motion capture systems for the kinematic analysis of patients with musculoskeletal shoulder disorders is available in the literature. This systematic review aims to retrieve the current knowledge about the use of optical motion capture systems for 3D shoulder kinematics analysis in patients with Shoulder dysfunctions and its corresponding clinical relevance

The Role of Humeral Neck-Shaft Angle in Reverse Total Shoulder Arthroplasty: 155° versus <155°—A Systematic Review

The aim of this study was to have updated scrutiny of the influence of the humeral neck-shaft angle (HNSA) in patients who underwent reverse shoulder arthroplasty (RSA). A PRISMA-guided literature search was conducted from May to September 2021. Clinical outcome scores, functional parameters, and any complications were reviewed. Eleven papers were identified for inclusion in this systematic review. A total of 971 shoulders were evaluated at a minimum-follow up of 12 months, and a maximum of 120 months. The sample size for the “HNSA 155°” group is 449 patients, the “HNSA 145°” group involves 140 patients, and the “HSNA 135°” group comprises 291 patients. The HNSA represents an important variable in choosing the RSA implant design for patients with rotator cuff arthropathy. Positive outcomes are described for all the 155°, 145°, and 135° HSNA groups. Among the different implant designs, the 155° group show a better SST score, but also the highest rate of revisions and scapular notching; the 145° cohort achieve the best values in terms of active forward flexion, abduction, ASES score, and CMS, but also the highest rate of infections; while the 135° design obtains the best results in the external rotation with arm at side, but also the highest rate of fractures. High-quality studies are required to obtain valid results regarding the best prosthesis implant

Exploring the coordination chemistry of isomerizable terpyridine derivatives for successful analyses of cis and trans isomers by travelling wave ion mobility mass spectrometry

The photochemical cis–trans isomerization of the 4-{4-[2-(pyridin-4-yl)ethenyl]phenyl}-2,2′:6′,2′′-terpyridine ligand (vpytpy) was investigated by UV-vis, NMR and TWIM-MS. Ion mobility mass spectrometry was performed pursuing the quantification of the isomeric composition during photolysis, however an in-source trans-to-cis isomerization process was observed. In order to overcome this inherent phenomenon, the isomerization of the vpytpy species was suppressed by complexation, reacting with iron(II) ions, and forming the [Fe(vpytpy)2]2+ complex. The strategy of “freezing” the cis–trans isomerizable ligand at a given geometric conformation was effective, preventing further isomerization, thus allowing the distinction of each one of the isomers in the photolysed mixture. In addition, the experimental drift times were related to the calculated surface areas of the three possible cis–cis, cis–trans and trans–trans iron(II) complex isomers. The stabilization of the ligand in a given conformation also allows us to obtain the cis–cis and cis–trans complexes exhibiting the ligand in the metastable cis-conformation, as well as in the thermodynamically stable trans-conformation13740454051CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPSem informaçãoSem informaçã