A novel validated assay to support the discovery of new anti-malarial gametocytocidal agents

Additional file 1. Graphical representation of the expression of 12 selected genes throughout the 30 days of gametocytogenesis. Y-axis shows the gene expression represented as (Ctgene−Ct18S rRNA)Ttime × −(Ctgene−Ct18S rRNA)T0, considering the time 0 as the basal expression. Although only the gametocytogenesis during 30 days is presented, similar results were obtained from day 0 to day 15 in both assays

A Reliable and Standardizable Differential PCR and qPCR Methodology Assesses HER2 Gene Amplification in Gastric Cancer

We have applied two PCR techniques, differential PCR (diffPCR) and qPCR for the identification of HER2 gene amplifications in genomic DNA of tumor and distal gastric samples from patients with gastric cancer. The diffPCR technique consists of the simultaneous amplification of the HER2 gene and a housekeeping gene by conventional PCR and the densitometric analysis of the bands obtained. We established a cut-off point based on the mean and standard deviation analyzing the DNA of 30 gastric tissues from patients undergoing non-cancer gastrectomy. diffPCR and qPCR yielded consistent results. HER2-overexpression was detected in 25% of patients and was further confirmed by immunohistochemistry and immunofluorescence. The approaches herein described may serve as complementary and reliable methods to assess HER2 amplification

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Adiciones y correcciones al Catalogo florístico de Alava, Vizcaya y Guipúzcoa.

Citamos 83 especies de plantas vasculares que constituyen novedad   provincial o territorial para Alava, Vizcaya y Guipúzcoa; también   hemos podido comprobar en el campo varias citas anteriores y   hacemos alguna corrección taxonómica

Investigation of relationships between Aedes aegypti egg, larvae, pupae, and adult density indices where their main breeding sites were located indoors.

Aedes aegypti (L.) density indices obtained in a dengue fever (DF) endemic area were compared. One hundred and twenty premises, in an urban area of Colombia where dengue type-1 and type-2 virus cocirculated, were randomly selected and sampled for 7 months. The geometric mean monthly numbers (density index, DI) of Ae. aegypti eggs (ODI), 4th instar larvae (LDI), pupae (PDI), and adults (ADI) were calculated based on the use of ovitraps, nets, and manual aspirators, respectively. A negative temporal correlation was observed between the LDI and the ODI (r = -0.83, df = 5, and P < 0.01). Positive temporal correlations were only observed between the LDI and the PDI (r = 0.90, df = 5, and P < 00.5) and the Breteau and House indices (r = 0.86, df = 5, and P < 0.01). No other correlations were found between these indices and any of the other density indices or the incidence of suspected DF cases in residents, the temperature, the rainfall, or seasonal fluctuations. Our results were, therefore, probably due to the most productive Ae. aegypti breeding sites (large water containers) being located indoors within this study area. The number of adult female Ae. aegypti/person (n = 0.5) and pupae/person (n = 11) in our study area were lower and dramatically higher than the transmission thresholds previously reported for adult and pupae, respectively. Because there were confirmed DF cases during the study period, the transmission threshold based on the Ae. aegypti pupae was clearly more reliable. We found that the mean ovitrap premise index (OPI) was 98.2% during this study and that the mean larval (L-4th instars) premise index (LPI) was 59.2%, and therefore we suggest that the OPI and LPI would be more sensitive methods to gauge the effectiveness of A. aegypti control programs

Devotee or fan: The town of Orizaba, 1762-1834 [De devoto a fanático: El pueblo de Orizaba, 1762-1834]

The objective of this study was to determine some of the most important bionomic parameters related to the capacity of transmission of Trypanosoma cruzi and to estimate the potential transmission capacity and role of 3 groups of recent colonized Mexican Triatoma barberi, T. rubida sonoriana, and Meccus (formerly Triatoma) mazzottii in the prevalence of Chagas disease cases based on the distribution area of each species. Among the studied Triatominae species, the life cycle was shorter in T. r. sonoriana and longer in T. barberi, by as much as 4 times. The 1st and 5th instars had the highest rates of mortality in most of the studied species. Statistically significant shorter duration of feeding of instars was observed for T. r. sonoriana and longer duration was found for M. mazzottii when the species were compared. The mean number of blood meals per nymphal stadium was statistically greater in T. barberi than in T. r. sonoriana and M. mazzottii. Triatoma r. sonoriana and M. mazzotti had shorter defecation delay than in T. barberi and the delay was uniform in all instars. Most of the studied parameters showed that T. r. sonoriana and M. mazzotti could have an important potential role in the prevalence of Chagas disease cases where these species are commonly found. Copyright " 2005 by the American Mosquito Control Association, Inc.",,,,,,,,,"http://hdl.handle.net/20.500.12104/40607","http://www.scopus.com/inward/record.url?eid=2-s2.0-26844474152&partnerID=40&md5=c1f3d7cc95dc45c11568b8fcd59f2b7

Functional screening of selective mitochondrial inhibitors of Plasmodium

Phenotypic screening has produced most of the new chemical entities currently in clinical development for malaria, plus many lead compounds active against Plasmodium falciparum asexual stages. However, lack of knowledge about the mode of action of these compounds delays and may even hamper their future development. Identifying the mode of action of the inhibitors greatly helps to prioritise compounds for further development as novel antimalarials. Here we describe a whole-cell method to detect inhibitors of the mitochondrial electron transport chain, using oxygen consumption as high throughput readout in 384-well plate format. The usefulness of the method has been confirmed with the Tres Cantos Antimalarial Compound Set (TCAMS). The assay identified 124 respiratory inhibitors in TCAMS, seven of which were novel anti-plasmodial chemical structures never before described as mitochondrial inhibitors. Keywords: Plasmodium falciparum, Plasmodium yoelii, Oxygen consumption, Mitochondrial inhibitors and cytochrom

QM/MM with Auxiliary DFT

International audienceThis chapter describes the theoretical background of the quantum mechanical/molecular mechanical (QM/MM) implementation in deMon2k within the framework of auxiliary density functional theory (ADFT). It aims to give the reader an overview of the current state of the art of this QM/MM implementation and perspectives for its future development. To this end, we first derive the ADFT working equations for the QM and QM/MM energy and gradient expressions. Based on the joint QM/MM gradient expression, we present algorithms for QM/MM structure optimizations, transition-state searches and molecular dynamics simulations. The use of auxiliary density perturbation theory (ADPT) in the framework of QM/MM is discussed using illustrative implementations including analytic second-order ADFT energy derivatives, nuclear magnetic resonance chemical shift calculations and excited state calculations using time-dependent ADFT. The chapter closes with the description of a transformation program used to generate deMon2k QM/MM inputs