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Objectives To compare teledermatology and face-to-face (F2F) agreement in primary diagnoses of dermatological conditions.Design Systematic review and meta-analysisMethods MEDLINE, Embase, Cochrane Library (Wiley), CINAHL and medRxiv were searched between January 2010 and May 2022. Observational studies and randomised clinical trials that reported percentage agreement or kappa concordance for primary diagnoses between teledermatology and F2F physicians were included. Titles, abstracts and full-text articles were screened in duplicate. From 7173 citations, 44 articles were included. A random-effects meta-analysis was conducted to estimate pooled estimates. Primary outcome measures were mean percentage and kappa concordance for assessing diagnostic matches between teledermatology and F2F physicians. Secondary outcome measures included the agreement between teledermatologists, F2F dermatologists, and teledermatology and histopathology results.Results 44 studies were extracted and reviewed. The pooled agreement rate was 68.9%, and kappa concordance was 0.67. When dermatologists conducted F2F and teledermatology consults, the overall diagnostic agreement was significantly higher at 71% compared with 44% for non-specialists. Kappa concordance was 0.69 for teledermatologist versus specialist and 0.52 for non-specialists. Higher diagnostic agreements were also noted with image acquisition training and digital photography. The agreement rate was 76.4% between teledermatologists, 82.4% between F2F physicians and 55.7% between teledermatology and histopathology.Conclusions and relevance Teledermatology can be an attractive option particularly in resource-poor settings. Future efforts should be placed on incorporating image acquisition training and access to high-quality imaging technologies.Trial registration number 10.17605/OSF.IO/FJDVG

Background and objectiveNeoadjuvant chemotherapy (NAC) followed by cystectomy is the standard of care in muscle-invasive bladder cancer (MIBC). Pathological response has been associated with longer survival, but no currently available clinicopathological variables can identify patients likely to respond, highlighting the need for predictive biomarkers. We sought to identify a predictive signature of response to NAC integrating clinical score, taxonomic subtype, and gene expression.Material and methodsFrom 1994 to 2014, pre-treatment tumor samples were collected from MIBC patients (stage T2-4N0/+M0) at two Spanish hospitals. A clinical score was determined based on stage, hydronephrosis and histology. Taxonomic subtypes (BASQ, luminal, and mixed) were identified by immunohistochemistry. A custom set of 41 genes involved in DNA damage repair and immune response was analyzed in 84 patients with the NanoString nCounter platform. Genes related to pathological response were identified by LASSO penalized logistic regression. NAC consisted of cisplatin/methotrexate/vinblastine until 2000, after which most patients received cisplatin/gemcitabine. The capacity of the integrated signature to predict pathological response was assessed with AUC. Overall survival (OS) and disease-specific survival (DSS) were analyzed with the Kaplan-Meier method.ResultsLASSO selected eight genes to be included in the signature (RAD51, IFNγ, CHEK1, CXCL9, c-MET, KRT14, HERC2, FOXA1). The highest predictive accuracy was observed with the inclusion in the model of only three genes (RAD51, IFNɣ, CHEK1). The integrated clinical-taxonomic-gene expression signature including these three genes had a higher predictive ability (AUC=0.71) than only clinical score plus taxonomic subtype (AUC=0.58) or clinical score alone (AUC=0.56). This integrated signature was also significantly associated with OS (p=0.02) and DSS (p=0.02).ConclusionsWe have identified a predictive signature for response to NAC in MIBC patients that integrates the expression of three genes with clinicopathological characteristics and taxonomic subtypes. Prospective studies to validate these results are ongoing.

This paper develops a simple, cost-effective, fully Inkjet-printed flexible temperature sensor with easy fabrication steps using PiXDRO LP50 inkjet printer. The thermistor sensor employed a Poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonate) (PEDOT: PSS) as a temperature-sensitive layer with silver nanoparticles (AgNps) as a contact electrode. The sensor performance was evaluated on different dimensions and types of substrates. Epson Glossy paper with 255 $\mu \text{m}$ thickness and Polyimide (Kapton HN) with $50~\mu \text{m}$ thickness were used over temperatures ranging from room temperature up to 50 °C and 90 °C for paper and Kapton substrates, respectively. The sensor developed over Glossy paper showed the best sensitivity of −1.67 %/°C in the chosen temperature range while the sensor showed +0.113%/°C on PI substrate.

Abstract Background Wolbachia bacteria are widely distributed throughout terrestrial arthropod species. These bacteria can manipulate reproduction and influence the vector competence of their hosts. Recently, Wolbachia have been integrated into vector control programmes for mosquito management. A number of supergroups and strains exist for Wolbachia, and they have yet to be characterized for many mosquito species. In this study, we examined Wolbachia prevalence and their phylogenetic relationship to other Wolbachia, using mosquitoes collected in Merced County in the Central Valley of California. Methods Adult mosquitoes were collected from 85 sites in Merced County, California in 2017 and 2018. Traditional and quantitative PCR were used to investigate the presence or absence and the density of Wolbachia, using Wolbachia-specific 16S rRNA and Wolbachia-surface protein (wsp) genes. The supergroup of Wolbachia was determined, and Multilocus Sequence Typing (MLST) by sequencing five housekeeping genes (coxA, gatB, ftsZ, hcpA and fbpA) was also used to determine Wolbachia supergroup as well as strain. Results Over 7100 mosquitoes of 12 species were collected: Aedes melanimon, Ae. nigromaculis, Ae. vexans, Ae. aegypti, Culex pipiens, Cx. stigmatosoma, Cx. tarsalis, Anopheles franciscanus, An. freeborni, An. punctipennis, Culiseta incidens and Cs. inornata. Eight showed evidence of Wolbachia. To our knowledge, this study is the first to report detection of Wolbachia in five of these species (Ae. melanimon, Cx. stigmatosoma, Cx. tarsalis, Cs. incidens and Cs. inornata). Culex pipiens and Cx. stigmatosoma had a high frequency and density of Wolbachia infection, which grouped into supergroup B; Cs. inornata clustered with supergroup A. MLST comparisons identified Cx. pipiens and Cx. stigmatosoma as wPip strain type 9 supergroup B. Six species had moderate to low (< 14%) frequencies of Wolbachia. Four species were negative, Ae. nigromaculis, An. franciscanus, An. freeborni and Ae. aegypti. Conclusions New records of Wolbachia detection were found in mosquitoes from Merced County, California. Culex stigmatosoma and Cs. inornata were new records for Wolbachia supergroup B and A, respectively. Other species with Wolbachia occurred with low frequency and low density. Detection of Wolbachia in mosquitoes can be used to inform potential vector control applications. Future study of Wolbachia within Cx. stigmatosoma and Cs. inornata in California and through the range of these species could further explore Wolbachia infection in these two species.

BackgroundComposition of tissue types within a wound is a useful indicator of its healing progression. Tissue composition is clinically used in wound healing tools (eg, Bates-Jensen Wound Assessment Tool) to assess risk and recommend treatment. However, wound tissue identification and the estimation of their relative composition is highly subjective. Consequently, incorrect assessments could be reported, leading to downstream impacts including inappropriate dressing selection, failure to identify wounds at risk of not healing, or failure to make appropriate referrals to specialists. ObjectiveThis study aimed to measure inter- and intrarater variability in manual tissue segmentation and quantification among a cohort of wound care clinicians and determine if an objective assessment of tissue types (ie, size and amount) can be achieved using deep neural networks. MethodsA data set of 58 anonymized wound images of various types of chronic wounds from Swift Medical’s Wound Database was used to conduct the inter- and intrarater agreement study. The data set was split into 3 subsets with 50% overlap between subsets to measure intrarater agreement. In this study, 4 different tissue types (epithelial, granulation, slough, and eschar) within the wound bed were independently labeled by the 5 wound clinicians at 1-week intervals using a browser-based image annotation tool. In addition, 2 deep convolutional neural network architectures were developed for wound segmentation and tissue segmentation and were used in sequence in the workflow. These models were trained using 465,187 and 17,000 image-label pairs, respectively. This is the largest and most diverse reported data set used for training deep learning models for wound and wound tissue segmentation. The resulting models offer robust performance in diverse imaging conditions, are unbiased toward skin tones, and could execute in near real time on mobile devices. ResultsA poor to moderate interrater agreement in identifying tissue types in chronic wound images was reported. A very poor Krippendorff α value of .014 for interrater variability when identifying epithelization was observed, whereas granulation was most consistently identified by the clinicians. The intrarater intraclass correlation (3,1), however, indicates that raters were relatively consistent when labeling the same image multiple times over a period. Our deep learning models achieved a mean intersection over union of 0.8644 and 0.7192 for wound and tissue segmentation, respectively. A cohort of wound clinicians, by consensus, rated 91% (53/58) of the tissue segmentation results to be between fair and good in terms of tissue identification and segmentation quality. ConclusionsThe interrater agreement study validates that clinicians exhibit considerable variability when identifying and visually estimating wound tissue proportion. The proposed deep learning technique provides objective tissue identification and measurements to assist clinicians in documenting the wound more accurately and could have a significant impact on wound care when deployed at scale.

Orthopedic tumor resection, trauma, or degenerative disease surgeries can result in large bone defects and often require bone grafting. However, standard autologous bone grafting has been associated with donor site morbidity and/or limited quantity. As an alternate, allografts with or without metallic or polyether-etherketone have been used as grafting substitutes. However, these may have drawbacks as well, including stress shielding, pseudarthrosis, disease-transmission, and infection. There is therefore a need for alternative bone substitutes, such as the use of mechanically compliant three-dimensional (3D)-printed scaffolds. Several off-the-shelf materials are available for low-cost fused deposition 3D printing such as polylactic acid (PLA) and polycaprolactone (PCL). We have previously described the feasibility of 3D-printed PLA scaffolds to support cell activity and extracellular matrix deposition. In this study, we investigate two medical-grade filaments consistent with specifications found in American Society for Testing and Materials (ASTM) standard for semi-crystalline polylactide polymers for surgical implants, a pure polymer (100M) and a copolymeric material (7415) for their cytocompatibility and suitability in bone tissue engineering. Moreover, we assessed the impact on osteo-inductive properties with the addition of beta-tricalcium phosphate (β-TCP) minerals and assessed their mechanical properties. 100M and 7415 scaffolds with the additive β-TCP demonstrated superior mesenchymal stem cells (MSCs) differentiation detected via increased alkaline phosphatase activity (6-fold and 1.5-fold, respectively) and mineralized matrix deposition (14-fold and 5-fold, respectively) in vitro. Furthermore, we evaluated in vivo compatibility, biosafety and bone repair potential in a rat femur window defect model. 100M+β-TCP implants displayed a positive biosafety profile and showed significantly enhanced new bone formation compared to 100M implants evidenced by μCT (39 versus 25% bone volume/tissue volume ratio) and histological analysis 6 weeks post-implantation. These scaffolds are encouraging composite biomaterials for repairing bone applications with a great potential for clinical translation. Further analyses are required with appropriate evaluation in a larger critical-sized defect animal model with long-term follow-up.

Summary: Anopheles gambiae mosquitoes that have been infected with Plasmodium mount a more effective immune response to a subsequent infection. Priming is established when Plasmodium invasion of the mosquito midgut allows contact of the gut microbiota with epithelial cells. This event is followed by a systemic release of a hemocyte differentiation factor (HDF) consisting of Lipoxin A4 bound to Evokin, a lipocalin carrier, which increases the proportion of circulating hemocytes. We show that mosquito midgut cells produce and release prostaglandin E2 (PGE2), which attracts hemocytes to the midgut surface and enhances their patrolling activity. Systemic injection of prostaglandins (PGs) recapitulates the priming response and enhances antiplasmodial immunity by triggering HDF production. Although insects lack cyclooxygenases, two heme peroxidases, HPX7 and HPX8, catalyze essential steps in PG biosynthesis in mosquitoes. Mosquito midgut PGE2 release attracts hemocytes and establishes a long-lasting enhanced systemic cellular immune response to Plasmodium infection. : Biological Sciences; Immunology; Immune System; Microbiology; Oral Microbiology; Microbial Interactions Subject Areas: Biological Sciences, Immunology, Immune System, Microbiology, Oral Microbiology, Microbial Interactions

Abstract Background Early skin-to-skin contact promotes infant physiologic stability, provides warmth and makes breast milk readily available. Despite the known benefits of early skin-to-skin contact, this practice is not included within standard care in the Mexican public healthcare system. After birth, newborns are usually taken to an incubator in the nursery where they transition to extrauterine life and receive either dextrose 5% or infant formula for their first feed. The aim of this study was to assess if a dual educational intervention in a rural hospital in Mexico could modify current practice and accomplish early skin-to-skin contact and early breastfeeding. Methods A two-step educational intervention was designed. The first step was to educate the labor and birthing staff of the hospital, and the second step was to educate all pregnant women with uncomplicated pregnancies at 36 weeks’ gestation. The educational intervention explored the benefits, implications and steps of early skin-to-skin contact and early breastfeeding. All births were registered for the three month period following the intervention. The time of onset of skin-to-skin (SSC) contact, its duration and time of initiation of breastfeeding were recorded and analyzed using ANOVA testing. Results A total of 142 births met our inclusion criteria, from those, 77% (n = 109) received skin-to-skin contact and early breastfeeding. The average time of initiation of skin-to-skin contact in the first and last month of the study was 18.5 (± 2.2) and 9.6 (± 2.2) minutes of life, respectively (p

Culturing the entomopathogenic fungus, Beauveria bassiana, under high glucose concentrations coupled with high aeration results in a fungal developmental shift from hyphal growth to mostly blastospores (yeast-like cells). The underlying molecular mechanisms involved in this shift remain elusive. A systematic transcriptome analysis of the differential gene expression was preformed to uncover the fungal transcriptomic response to osmotic and oxidative stresses associated with the resulting high blastospore yield. Differential gene expression was compared under moderate (10% w/v) and high (20% w/v) glucose concentrations daily for three days. The RNAseq-based transcriptomic results depicted a higher proportion of downregulated genes when the fungus was grown under 20% glucose than 10%. Additional experiments explored a broader glucose range (4, 8, 12, 16, 20% w/v) with phenotype assessment and qRT-PCR transcript abundance measurements of selected genes. Antioxidant, calcium transport, conidiation, and osmosensor-related genes were highly upregulated in higher glucose titers (16-20%) compared to growth in lower glucose (4-6%) concentrations. The class 1 hydrophobin gene (Hyd1) was highly expressed throughout the culturing. Hyd1 is known to be involved in spore coat rodlet layer assembly, and indicates that blastospores or another cell type containing hydrophobin 1 is expressed in the haemocoel during the infection process. Furthermore, we found implications of the HOG signaling pathway with upregulation of homologous genes Ssk2 and Hog1 for all fermentation time points under hyperosmotic medium (20% glucose). These findings expand our knowledge of the molecular mechanisms behind blastospore development and may help facilitate large-scale industrial production of B. bassiana blastospores for pest control applications.

Like in most eukaryotes, the linear chromosomes of Trypanosoma cruzi end in a nucleoprotein structure called the telomere, which is preceded by regions of variable length called subtelomeres. Together telomeres and subtelomeres are dynamic sites where DNA sequence rearrangements can occur without compromising essential interstitial genes or chromosomal synteny. Good examples of subtelomeres involvement are the expansion of human olfactory receptors genes, variant surface antigens in Trypanosoma brucei, and Saccharomyces cerevisiae mating types. T. cruzi telomeres are made of long stretches of the hexameric repeat 5′-TTAGGG-OH-3′, and its subtelomeres are enriched in genes and pseudogenes from the large gene families RHS, TS and DGF1, DEAD/H-RNA helicase and N-acetyltransferase, intermingled with sequences of retrotransposons elements. In particular, members of the Trans-sialidase type II family appear to have played a role in shaping the current T. cruzi telomere structure. Although the structure and function of T. cruzi telomeric and subtelomeric regions have been documented, recent experiments are providing new insights into T. cruzi's telomere-subtelomere dynamics. In this review, I discuss the co-evolution of telomere, subtelomeres and the TS gene family, and the role that these regions may have played in shaping T. cruzi's genome.

In the phase II MAJA trial, maintenance therapy with vinflunine resulted in longer progression-free survival compared to best supportive care in advanced urothelial cell carcinoma (aUCC) patients who did not progress after first-line platinum-based chemotherapy. However, despite an initial benefit observed in some patients, unequivocal resistance appears which underlying mechanisms are presently unknown. We have performed gene expression and functional enrichment analyses to shed light on the discovery of these underlying resistance mechanisms. Differential gene expression profile of eight patients with poor outcome and nine with good outcome to vinflunine administered in the MAJA trial were analyzed. RNA was isolated from tumor tissue and gene expression was assessed by microarray. Differential expression was determined with linear models for microarray data. Gene Set Enrichment Analysis (GSEA) was used for the functional classification of the genes. In vitro functional studies were performed using UCC cell lines. Hierarchical clustering showed a differential gene expression pattern between patients with good and poor outcome to vinflunine treatment. GSEA identified epithelial-to-mesenchymal transition (EMT) as the top negatively enriched hallmark in patients with good outcome. In vitro analyses showed that the polyphenol curcumin downregulated EMT markers and sensitized UCC cells to vinflunine. We conclude that EMT mediates resistance to vinflunine and suggest that the reversion of this process could enhance the effect of vinflunine in aUCC patients.

Abstract Malaria is a mosquito-borne disease affecting millions of people every year. The rodent parasite Plasmodium berghei has served as a model for human malaria transmission studies and played a pivotal role in dissecting the mosquito immune response against infection. The 6-cysteine protein P47, known to be important for P. berghei female gamete fertility, is shown to serve a different function in Plasmodium falciparum, protecting ookinetes from the mosquito immune response. Here, we investigate the function of P. berghei P47 in Anopheles gambiae mosquito infections. We show that P47 is expressed on the surface of both female gametocytes and ookinetes where it serves distinct functions in promoting gametocyte-to-ookinete development and protecting ookinetes from the mosquito complement-like response, respectively. The latter function is essential, as ookinetes lacking P47 are targeted for killing while traversing the mosquito midgut cells and eliminated upon exposure to hemolymph proteins of the complement-like system. Silencing key factors of the complement-like system restores oocyst development and disease transmission to rodent hosts. Our data establish a dual role of P. berghei P47 in vivo and reinforce the use of this parasite to study the impact of the mosquito immune response on human malaria transmission.

On 15 July 2020 was the 15th anniversary of the Science Magazine issue that reported three trypanosomatid genomes, namely Leishmania major, Trypanosoma brucei, and Trypanosoma cruzi. That publication was a milestone for the research community working with trypanosomatids, even more so, when considering that the first draft of the human genome was published only four years earlier after 15 years of research. Although nowadays, genome sequencing has become commonplace, the work done by researchers before that publication represented a huge challenge and a good example of international cooperation. Research in neglected diseases often faces obstacles, not only because of the unique characteristics of each biological model but also due to the lower funds the research projects receive. In the case of Trypanosoma cruzi the etiologic agent of Chagas disease, the first genome draft published in 2005 was not complete, and even after the implementation of more advanced sequencing strategies, to this date no final chromosomal map is available. However, the first genome draft enabled researchers to pick genes a la carte, produce proteins in vitro for immunological studies, and predict drug targets for the treatment of the disease or to be used in PCR diagnostic protocols. Besides, the analysis of the T. cruzi genome is revealing unique features about its organization and dynamics. In this work, I briefly summarize the actions of Latin American researchers that contributed to the first publication of the T. cruzi genome and discuss some features of the genome that may help to understand the parasite’s robustness and adaptive capabilities.

BACKGROUND:The clinical evaluation of a burn wound alone may not be adequate to predict the severity of the injury nor to guide clinical decision making. Infrared thermography provides information about soft tissue viability and has previously been used to assess burn depth. The objective of this study was to determine if temperature differences in burns assessed by infrared thermography could be used predict the treatment modality of either healing by re-epithelization, requiring skin grafts, or requiring amputations, and to validate the clinical predication algorithm in an independent cohort. METHODS AND FINDINGS:Temperature difference (ΔT) between injured and healthy skin were recorded within the first three days after injury in previously healthy burn patients. After discharge, the treatment modality was categorized as re-epithelization, skin graft or amputation. Potential confounding factors were assessed through multiple linear regression models, and a prediction algorithm based on the ΔT was developed using a predictive model using a recursive partitioning Random Forest machine learning algorithm. Finally, the prediction accuracy of the algorithm was compared in the development cohort and an independent validation cohort. Significant differences were found in the ΔT between treatment modality groups. The developed algorithm correctly predicts into which treatment category the patient will fall with 85.35% accuracy. Agreement between predicted and actual treatment for both cohorts was weighted kappa 90%. CONCLUSION:Infrared thermograms obtained at first contact with a wounded patient can be used to accurately predict the definitive treatment modality for burn patients. This method can be used to rationalize treatment and streamline early wound closure.

Abstract Exposure of Anopheles gambiae mosquitoes to Plasmodium infection enhances the ability of their immune system to respond to subsequent infections. However, the molecular mechanism that allows the insect innate immune system to ‘remember’ a previous encounter with a pathogen has not been established. Challenged mosquitoes constitutively release a soluble haemocyte differentiation factor into their haemolymph that, when transferred into Naive mosquitoes, also induces priming. Here we show that this factor consists of a Lipoxin/Lipocalin complex. We demonstrate that innate immune priming in mosquitoes involves a persistent increase in expression of Evokin (a lipid carrier of the lipocalin family), and in their ability to convert arachidonic acid to lipoxins, predominantly Lipoxin A4. Plasmodium ookinete midgut invasion triggers immune priming by inducing the release of a mosquito lipoxin/lipocalin complex.

In the adult skeleton, cells of the immune system interact with those of the skeleton during all phases of bone repair to influence the outcome. Mast cells are immune cells best known for their pathologic role in allergy, and may be involved in chronic inflammatory and fibrotic disorders. Potential roles for mast cells in tissue homeostasis, vascularization and repair remain enigmatic. Previous studies in combined mast cell- and Kit-deficient KitW-sh/W-sh mice (KitW-sh) implicated mast cells in bone repair but KitW-sh mice suffer from additional Kit-dependent hematopoietic and non- hematopoietic deficiencies that could have confounded the outcome. The goal of the current study was to compare bone repair in normal wild type (WT) and Cpa3Cre/+ mice, which lack mast cells in the absence of any other hematopoietic or non- hematopoietic deficiencies. Repair of a femoral window defect was characterized using micro CT imaging and histological analyses from the early inflammatory phase, through soft and hard callus formation, and finally the remodeling phase. The data indicate 1) mast cells appear in healing bone of WT mice but not Cpa3Cre/+ mice, beginning 14 days after surgery; 2) re-vascularization of repair tissue and deposition of mineralized bone was delayed and dis-organised in Cpa3Cre/+ mice compared with WT mice; 3) the defects in Cpa3Cre/+ mice were associated with little change in anabolic activity and biphasic alterations in osteoclast and macrophage activity. The outcome at 56 days postoperative was complete bridging of the defect in most WT mice and fibrous mal-union in most Cpa3Cre/+ mice. The results indicate that mast cells promote bone healing, possibly by recruiting vascular endothelial cells during the inflammatory phase and coordinating anabolic and catabolic activity during tissue remodeling. Taken together the data indicate that mast cells have a positive impact on bone repair.

Nowadays, the development or improvement of soft actuation mechanisms is a crucialtopic for the achievement of dexterous manipulation using. Then, a primary target of research is thedesign of actuation and driving devices. Consequently, in this paper, we introduce a soft drivingepicyclical mechanism that mimics human muscle behavior and fulfills motion requirements toachieve grasping gestures using a robotic finger. The prototype is experimentally assessed, andresults show that our approach has enough performance for the implementation in grasping tasks.Furthermore, we introduce the basis for a new soft epicyclical mechanism merger with shape memoryalloys to allow active stiffness control of the mechanism.

A castanha-do-brasil (Bertholletia excelsa H.B.K.) é uma matéria-prima importante que constitui a base de subsistência para os povos da região Amazônica. Em razão do alto teor de lipídios insaturados, cerca de 60 a 70% torna-se altamente perecível. Inadequadas práticas de beneficiamento fazem com que o descascamento resulte alto índice de amêndoas quebradas ou danificadas. Neste trabalho objetivou-se fazer um comparativo das propriedades físico-químicas, teor de minerais, ácidos graxos e perfil de aminoácidos essenciais de amêndoas que sofreram danos mecânicos em comparação a amêndoas intactas, que foram beneficiadas, embaladas e armazenadas nas mesmas condições. O teor de minerais totais de amêndoas danificadas e intactas, armazenadas durante três meses à temperatura ambiente, não apresentaram diferenças significativas entre si. Entretanto, resultou em perdas significativas de ácidos graxos insaturados, como o oléico e o linoléico, além de aminoácidos essenciais, principalmente a lisina. Isso pode implicar na redução do valor biológico da castanha, principalmente na sua qualidade sensorial.Brazil nut (Bertholletia excelsa H.B.K.) is an important raw material. It constitutes a basic stable of the population living in the Amazon region. Due to high unsaturated lipid content, around 60 to 70% is highly perishable. Moreover, inadequate processing practices result in high broken or damaged nuts. The objective this work was to make a comparative study of the physicochemical properties, mineral contents, lipids, and essential amino acid profiles between intact and highly damaged Brazil nut. All samples were stored in the same conditions. Samples were stored during three months at room temperature.The mineral profile of both samples did not show significant variation in total contents. It resulted, however, in significant loss of unsaturated fatty acids such as oleic and linoleic acid, besides essential amino acid, specially lysine. This fact can imply a reduction in the nutritional and sensory properties of the nut.

The characterisation of the gene encoding Trypanosoma cruzi CL Brener phosphofructokinase (PFK) and the biochemical properties of the expressed enzyme are reported here. In contradiction with previous reports, the PFK genes of CL Brener and YBM strain T. cruzi were found to be similar to their Leishmania mexicana and Trypanosoma brucei homologs in terms of both kinetic properties and size, with open reading frames encoding polypeptides with a deduced molecular mass of 53,483. The predicted amino acid sequence contains the C-terminal glycosome-targeting tripeptide SKL; this localisation was confirmed by immunofluorescence assays. In sequence comparisons with the genes of other eukaryotes, it was found that, despite being an adenosine triphosphate-dependent enzyme, T. cruzi PFK shows significant sequence similarity with inorganic pyrophosphate-dependent PFKs.

Plasmodium and dengue virus, the causative agents of the two most devastating vector-borne diseases, malaria and dengue, are transmitted by the two most important mosquito vectors, Anopheles gambiae and Aedes aegypti, respectively. Insect-bacteria associations have been shown to influence vector competence for human pathogens through multi-faceted actions that include the elicitation of the insect immune system, pathogen sequestration by microbes, and bacteria-produced anti-pathogenic factors. These influences make the mosquito microbiota highly interesting from a disease control perspective. Here we present a bacterium of the genus Chromobacterium (Csp_P), which was isolated from the midgut of field-caught Aedes aegypti. Csp_P can effectively colonize the mosquito midgut when introduced through an artificial nectar meal, and it also inhibits the growth of other members of the midgut microbiota. Csp_P colonization of the midgut tissue activates mosquito immune responses, and Csp_P exposure dramatically reduces the survival of both the larval and adult stages. Ingestion of Csp_P by the mosquito significantly reduces its susceptibility to Plasmodium falciparum and dengue virus infection, thereby compromising the mosquito's vector competence. This bacterium also exerts in vitro anti-Plasmodium and anti-dengue activities, which appear to be mediated through Csp_P -produced stable bioactive factors with transmission-blocking and therapeutic potential. The anti-pathogen and entomopathogenic properties of Csp_P render it a potential candidate for the development of malaria and dengue control strategies.

The EURTAC trial demonstrated that the tyrosine kinase inhibitor (TKI) erlotinib was superior to chemotherapy as first-line therapy for advanced non-small cell lung cancers (NSCLC) that harbor EGFR activating mutations in a predominantly Caucasian population. Based on EURTAC and several Asian trials, anti-EGFR TKIs are standard of care for EGFR mutation-positive NSCLC. We sought to validate a rapid multiplex EGFR mutation assay as a companion diagnostic assay to select patients for this therapy. Samples from the EURTAC trial were prospectively screened for EGFR mutations using a combination of laboratory-developed tests (LDTs), and tested retrospectively with the cobas EGFR mutation test (EGFR PCR test). The EGFR PCR test results were compared to the original LDT results and to Sanger sequencing, using a subset of specimens from patients screened for the trial. Residual tissue was available from 487 (47%) of the 1044 patients screened for the trial. The EGFR PCR test showed high concordance with LDT results with a 96.3% overall agreement. The clinical outcome of patients who were EGFR-mutation detected by the EGFR PCR test was very similar to the entire EURTAC cohort. The concordance between the EGFR PCR test and Sanger sequencing was 90.6%. In 78.9% of the discordant samples, the EGFR PCR test result was confirmed by a sensitive deep sequencing assay. This retrospective study demonstrates the clinical utility of the EGFR PCR test in the accurate selection of patients for anti-EGFR TKI therapy. The EGFR PCR test demonstrated improved performance relative to Sanger sequencing.

Dengue virus is one of the most important arboviral pathogens and the causative agent of dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. It is transmitted between humans by the mosquitoes Aedes aegypti and Aedes albopictus, and at least 2.5 billion people are at daily risk of infection. During their lifecycle, mosquitoes are exposed to a variety of microbes, some of which are needed for their successful development into adulthood. However, recent studies have suggested that the adult mosquito's midgut microflora is critical in influencing the transmission of human pathogens. In this study we assessed the reciprocal interactions between the mosquito's midgut microbiota and dengue virus infection that are, to a large extent, mediated by the mosquito's innate immune system. We observed a marked decrease in susceptibility to dengue virus infection when mosquitoes harbored certain field-derived bacterial isolates in their midgut. Transcript abundance analysis of selected antimicrobial peptide genes suggested that the mosquito's microbiota elicits a basal immune activity that appears to act against dengue virus infection. Conversely, the elicitation of the mosquito immune response by dengue virus infection itself influences the microbial load of the mosquito midgut. In sum, we show that the mosquito's microbiota influences dengue virus infection of the mosquito, which in turn activates its antibacterial responses.