ZnO Decorated Graphene-Based NFC Tag for Personal NO2 Exposure Monitoring during a Workday.

This paper presents the integration of a sensing layer over interdigitated electrodes and an electronic circuit on the same flexible printed circuit board. This integration provides an effective technique to use this design as a wearable gas measuring system in a target application, exhibiting high performance, low power consumption, and being lightweight for on-site monitoring. The wearable system proves the concept of using an NFC tag combined with a chemoresistive gas sensor as a cumulative gas sensor, having the possibility of holding the data for a working day, and completely capturing the exposure of a person to NO2 concentrations. Three different types of sensors were tested, depositing the sensing layers on gold electrodes over Kapton substrate: bare graphene, graphene decorated with 5 wt.% zinc oxide nanoflowers, or nanopillars. The deposited layers were characterized using FESEM, EDX, XRD, and Raman spectroscopy to determine their crystalline structure, morphological and chemical compositions. The gas sensing performance of the sensors was analyzed against NO2 (dry and humid conditions) and other interfering species (dry conditions) to check their sensitivity and selectivity. The resultant-built wearable NFC tag system accumulates the data in a non-volatile memory every minute and has an average low power consumption of 24.9 µW in dynamic operation. Also, it can be easily attached to a work vest.

Light-Responsive and Dual-Targeting Liposomes: From Mechanisms to Targeting Strategies.

In recent years, nanocarriers have played an ever-increasing role in clinical and biomedical applications owing to their unique physicochemical properties and surface functionalities. Lately, much effort has been directed towards the development of smart, stimuli-responsive nanocarriers that are capable of releasing their cargos in response to specific stimuli. These intelligent-responsive nanocarriers can be further surface-functionalized so as to achieve active tumor targeting in a sequential manner, which can be simply modulated by the stimuli. By applying this methodological approach, these intelligent-responsive nanocarriers can be directed to different target-specific organs, tissues, or cells and exhibit on-demand controlled drug release that may enhance therapeutic effectiveness and reduce systemic toxicity. Light, an external stimulus, is one of the most promising triggers for use in nanomedicine to stimulate on-demand drug release from nanocarriers. Light-triggered drug release can be achieved through light irradiation at different wavelengths, either in the UV, visible, or even NIR region, depending on the photophysical properties of the photo-responsive molecule embedded in the nanocarrier system, the structural characteristics, and the material composition of the nanocarrier system. In this review, we highlighted the emerging functional role of light in nanocarriers, with an emphasis on light-responsive liposomes and dual-targeted stimuli-responsive liposomes. Moreover, we provided the most up-to-date photo-triggered targeting strategies and mechanisms of light-triggered drug release from liposomes and NIR-responsive nanocarriers. Lastly, we addressed the current challenges, advances, and future perspectives for the deployment of light-responsive liposomes in targeted drug delivery and therapy.

Mesenchymal stem cells attenuate the proinflammatory cytokine pattern in a guinea pig model of chronic cigarette smoke exposure.

AIMS: Cigarette smoke often induces pulmonary and systemic inflammation. In animal models, mesenchymal stem cells (MSC) tend to ameliorate these effects. We aimed to explore the local and systemic expression of cytokines in guinea pigs chronically exposed to cigarette smoke, and their modifications by MSC. MAIN METHODS: Concentrations of IL-1ß, IL-6, IL-8, IL-12, TNF-α, INF-É£, TSG-6, MMP-9, TIMP-1, and/or TIMP-2 in serum and bronchoalveolar lavage (BALF) from animals exposed to tobacco smoke (20 cigarettes/day, 5 days/week for 10 weeks) were determined, and mRNA expression of some of them was measured in lung tissue. Intratracheal instillation of allogeneic bone marrow MSC (5x106 cells in 1 ml) was done at week 2. KEY FINDINGS: After cigarette smoke, IL-6 and IFN-γ increased in serum and BALF, while IL-1ß and IL-12 decreased in serum, and TSG-6 and TIMP-2 increased in BALF. IL-1ß had a paradoxical increase in BALF. MSC had an almost null effect in unexposed animals. The intratracheal administration of MSC in guinea pigs exposed to cigarette smoke was associated with a statistically significant decrease of IL-12 and TSG-6 in serum, as well as a decrease of IL-1ß and IFN-γ and an increase in TIMP-1 in BALF. Concerning mRNA expression in lung tissue, cigarette smoke did not modify the relative amount of the studied transcripts, but even so, MSC decreased the IL-12 mRNA and increased the TIMP-1 mRNA. SIGNIFICANCE: A single intratracheal instillation of MSC reduces the pulmonary and systemic proinflammatory pattern induced by chronic exposure to cigarette smoke in guinea pigs. TRIAL REGISTRATION: Not applicable.

SALDI-MS and SERS Multimodal Imaging: One Nanostructured Substrate to Rule Them Both.

Imaging techniques based on mass spectrometry or spectroscopy methods inform in situ about the chemical composition of biological tissues or organisms, but they are sometimes limited by their specificity, sensitivity, or spatial resolution. Multimodal imaging addresses these limitations by combining several imaging modalities; however, measuring the same sample with the same preparation using multiple imaging techniques is still uncommon due to the incompatibility between substrates, sample preparation protocols, and data formats. We present a multimodal imaging approach that employs a gold-coated nanostructured silicon substrate to couple surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS) and surface-enhanced Raman spectroscopy (SERS). Our approach integrates both imaging modalities by using the same substrate, sample preparation, and data analysis software on the same sample, allowing the coregistration of both images. We transferred molecules from clean fingertips and fingertips covered with plasticine modeling clay onto our nanostructure and analyzed their chemical composition and distribution by SALDI-MS and SERS. Multimodal analysis located the traces of plasticine on fingermarks and provided chemical information on the composition of the clay. Our multimodal approach effectively combines the advantages of mass spectrometry and vibrational spectroscopy with the signal enhancing abilities of our nanostructured substrate.

Very low peroneal nerve compound muscle action potential amplitude predicts poor outcome in patients with Guillain-Barré syndrome: a prospective cohort.

INTRODUCTION: Twenty percent of patients with Guillain-Barré syndrome (GBS) have poor outcomes despite proper management. The aim of the study was to characterize electrophysiological factors related to poor outcome in patients with GBS. METHODS: We conducted an observational study from a prospective cohort of 91 patients with GBS in a tertiary healthcare center in Mexico, from 2017 to 2019. Demographics and nerve conduction studies were performed on admission, and a 3-month follow-up for GBS disability score was ensued, allocating patients in good (GBS disability score ≤ 2) and poor outcome (GBS disability score ≥ 3) groups. A logistic regression analysis for independent walk at 3 months was performed. Kaplan-Meier estimator curves for independent walk in very low (< 20% LLN) and low-normal ( ≥20% LLN) peroneal nerve CMAPs are presented. RESULTS: From the 91 GBS patients included, 37 (40.6%) did not regain independent walk at 3 months. Axonal variants were more common in the poor outcome group (31.4% vs 59.4%, p = 0.01) as well as AIDP variants with motor conduction block (6.6% vs 42.4%, p = 0.018). Univariable analysis was statistically significant for very low median, ulnar, tibial, and peroneal CMAP amplitudes in poor outcome patients; however, multivariable analysis was only significant for very low peroneal nerve CMAP amplitude (OR 3.6 [1.1-11.5, p = 0.024]). Conversely, a greater proportion of GBS patients with low-normal CMAPs recovered independent walk at 90 days (75% vs 30%, p < 0.001). CONCLUSION: Severe axonal injury of the peroneal nerve, axonal, and AIDP with motor conduction block variants predicts worse functional outcome regarding independent walk at 3 months.

Effects of dietary ferulic acid on growth performance, carcass traits and meat quality of heifers.

BACKGROUND: Ferulic acid is a natural occurring compound with antioxidant and antimicrobial bioactive properties, and recently was proposed as a new alternative growth promoter in meat-producing animals without changing meat quality parameters. The present study aimed to evaluate the impact of two doses of ferulic acid (FA) on the feedlot performance, carcass traits, and physicochemical and sensory characteristics of meat quality in commercial heifers. Ninety heifers (3/4 Bos taurus; n = 270; body weight = 480 ± 10 kg) were randomly assigned to one of the following treatments (30 days): Control, fed with a basal diet; FA250 or FA500 offered the same diet further supplemented with FA at 250 or 500 mg kg-1 feed, respectively. Feedlot performance, carcass traits, and physicochemical and meat sensory characteristics were evaluated. RESULTS: FA supplementation increased average daily gain (ADG) by 21%, hot carcass weight by 1.8% and cold carcass weight by 1.6% with respect to the control (P < 0.05). FA500 treatment caused a decrease (P < 0.05) in some carcass traits. However, carcass characteristics of economic importance, such as cold carcass dressing and LT muscle area, were improved by FA250 supplementation (P < 0.05), causing a possible growth promoter effect. Physicochemical and sensory parameters of meat were not altered by FA supplementation (P > 0.05). CONCLUSION: Ferulic acid has the potential for use as a growth promoter additive in finishing heifers without negatively affecting the meat quality, as occurs with some synthetic growth promotants compounds used in animal production. © 2020 Society of Chemical Industry.

Assessment of scattered radiation from hand-held dental x-ray equipment using the Monte Carlo method.

The objective of the present study was to evaluate the intensity and spatial distribution of the scattered radiation caused by the use of hand-held x-ray equipment in the zone occupied by the operator, using the Monte Carlo simulation for radiographic views of the upper and lower incisor teeth, and the consequent evaluation of the equivalent dose in the lens. In order to carry out this evaluation, the geometry of a typical dental facility with plaster walls containing the scattering object was used for the computational scenario implemented for the Monte Carlo method simulation. The PENELOPE code for Monte Carlo simulation of electron and photon transport was used with the radiation beam represented by a 60 kV spectrum, 1.5 mm Al and tungsten target. The simulations were carried out with typical parameters for workload and the number of radiographs/week. The results showed that the exposure levels varied significantly according to the angle of the x-ray beam and with the distance to the scattering object. It is concluded that the incorporation of hand-held equipment in dental radiology must be accompanied by the surveillance of occupational exposure levels and a review of the training structure of professionals in dental radiology regarding aspects of radiological protection and the particularities of using this type of equipment.

Effect of naturally occurring Wolbachia in Anopheles gambiae s.l. mosquitoes from Mali on Plasmodium falciparum malaria transmission.

A naturally occurring Wolbachia strain (wAnga-Mali) was identified in mosquitoes of the Anopheles gambiae complex collected in the Malian villages of Dangassa and Kenieroba. Phylogenetic analysis of the nucleotide sequence of two 16S rRNA regions showed that wAnga-Mali clusters with Wolbachia strains from supergroup A and has the highest homology to a Wolbachia strain isolated from cat fleas (Ctenocephalides). wAnga-Mali is different from two Wolbachia strains previously reported in A. gambiae from Burkina Faso (wAnga_VK5_STP and wAnga_VK5_3.1a). Quantitative analysis of Wolbachia and Plasmodium sporozoite infection in field-collected mosquitoes indicates that the prevalence and intensity of Plasmodium falciparum sporozoite infection is significantly lower in Wolbachia-infected females. The presence of Wolbachia in females from a laboratory Anopheles coluzzii (A. gambiae, M form) colony experimentally infected with P. falciparum (NF54 strain) gametocyte cultures slightly enhanced oocyst infection. However, Wolbachia infection significantly reduced the prevalence and intensity of sporozoite infection, as observed in the field. This indicates that wAnga-Mali infection does not limit early stages of Plasmodium infection in the mosquito, but it has a strong deleterious effect on sporozoites and reduces malaria transmission.

5 protein-based signature for resectable lung squamous cell carcinoma improves the prognostic performance of the TNM staging.

INTRODUCTION: Prognostic biomarkers have been very elusive in the lung squamous cell carcinoma (SCC) and none is currently being used in the clinical setting. We aimed to identify and validate the clinical utility of a protein-based prognostic signature to stratify patients with early lung SCC according to their risk of recurrence or death. METHODS: Patients were staged following the new International Association for the Study of Lung Cancer (IASLC) staging criteria (eighth edition, 2018). Three independent retrospective cohorts of 117, 96 and 105 patients with lung SCC were analysed to develop and validate a prognostic signature based on immunohistochemistry for five proteins. RESULTS: We identified a five protein-based signature whose prognostic index (PI) was an independent and significant predictor of disease-free survival (DFS) (p<0.001; HR=4.06, 95% CI 2.18 to 7.56) and overall survival (OS) (p=0.004; HR=2.38, 95% CI 1.32 to 4.31). The prognostic capability of PI was confirmed in an external multi-institutional cohort for DFS (p=0.042; HR=2.01, 95% CI 1.03 to 3.94) and for OS (p=0.031; HR=2.29, 95% CI 1.08 to 4.86). Moreover, PI added complementary information to the newly established IASLC TNM 8th edition staging system. A combined prognostic model including both molecular and anatomical (TNM) criteria improved the risk stratification in both cohorts (p<0.05). CONCLUSION: We have identified and validated a clinically feasible protein-based prognostic model that complements the updated TNM system allowing more accurate risk stratification. This signature may be used as an advantageous tool to improve the clinical management of the patients, allowing the reduction of lung SCC mortality through a more accurate knowledge of the patient's potential outcome.

Performance of Flexible Chemoresistive Gas Sensors after Having Undergone Automated Bending Tests.

Many sensors are developed over flexible substrates to be used as wearables, which does not guarantee that they will actually withstand being bent. This work evaluates the gas sensing performance of metal oxide devices of three different types, before and after having undergone automated, repetitive bending tests. These tests were aimed at demonstrating that the fabricated sensors were actually flexible, which cannot be taken for granted beforehand. The active layer in these sensors consisted of WO3 nanowires (NWs) grown directly over a Kapton foil by means of the aerosol-assisted chemical vapor deposition. Their response to different H2 concentrations was measured at first. Then, they were cyclically bent, and finally, their response to H2 was measured again. Sensors based on pristine WO3-NWs over Ag electrodes and on Pd-decorated NWs over Au electrodes maintained their performance after having been bent. Ag electrodes covered with Pd-decorated NWs became fragile and lost their usefulness. To summarize, two different types of truly flexible metal oxide gas sensor were fabricated, whereas a third one was not flexible, despite being grown over a flexible substrate following the same method. Finally, we recommend that one standard bending test procedure should be established to clearly determine the flexibility of a sensor considering its intended application.

Nifurtimox response of Trypanosoma cruzi isolates from an outbreak of Chagas disease in Caracas, Venezuela.

BACKGROUND & OBJECTIVES: In Venezuela, Chagas disease (ChD) is considered a serious health problem, with about 6 million people at risk; and acute outbreaks due to oral transmission of Chagas Disease (OChD) are becoming increasingly important. In 2007 there was a major outbreak of OChD and although patients from this episode were treated with nifurtimox (Lampit®-Bayer), about 70% therapeutic failure was registered. These results led us to examine whether parasite's drug susceptibility was related to this therapeutic failure. METHODS: The Trypanosoma cruzi parasites were isolated by haemoculture of the peripheral blood drawn from the pre- and post-nifurtimox treated patients infected in the 2007 OChD outbreak at Caracas, Venezuela. The in vitro assays for drug testing were performed by the MTT methodology followed by calculation of inhibitory concentration-50 (IC50) values. RESULTS: Parasite isolates obtained from the infected patients prior and after nifurtimox treatment when subjected to variable concentrations of the drug showed great heterogeneity in susceptibility with IC50 values ranging from 4.07 ± 1.82 to 94.92 ± 7.24 µM. INTERPRETATION & CONCLUSION: The high heterogeneity in nifurtimox IC50 values in the isolates and clones from the OChD patients, suggests that the therapeutic failure to nifurtimox could be due in part to a phenotypic variability that existed in the wild parasite population at the original source of contamination. Though, further pharmacological studies are needed to confirm the existence of natural nifurtimox resistance in the parasite.

Entomopathogen ID: a curated sequence resource for entomopathogenic fungi.

We report the development of a publicly accessible, curated nucleotide sequence database of hypocrealean entomopathogenic fungi. The goal is to provide a platform for users to easily access sequence data from taxonomic reference strains. The database can be used to accurately identify unknown entomopathogenic fungi based on sequence data for a variety of phylogenetically informative loci. The database provides full multi-locus sequence alignment capabilities. The initial release contains data compiled for 525 strains covering the phylogenetic diversity of three important entomopathogenic families: Clavicipitaceae, Cordycipitaceae, and Ophiocordycipitaceae. Furthermore, Entomopathogen ID can be expanded to other fungal clades of insect pathogens, as sequence data becomes available. The database will allow isolate characterisation and evolutionary analyses. We contend that this freely available, web-accessible database will facilitate the broader community to accurately identify fungal entomopathogens, which will allow users to communicate research results more effectively.

Plasmodium evasion of mosquito immunity and global malaria transmission: The lock-and-key theory.

Plasmodium falciparum malaria originated in Africa and became global as humans migrated to other continents. During this journey, parasites encountered new mosquito species, some of them evolutionarily distant from African vectors. We have previously shown that the Pfs47 protein allows the parasite to evade the mosquito immune system of Anopheles gambiae mosquitoes. Here, we investigated the role of Pfs47-mediated immune evasion in the adaptation of P. falciparum to evolutionarily distant mosquito species. We found that P. falciparum isolates from Africa, Asia, or the Americas have low compatibility to malaria vectors from a different continent, an effect that is mediated by the mosquito immune system. We identified 42 different haplotypes of Pfs47 that have a strong geographic population structure and much lower haplotype diversity outside Africa. Replacement of the Pfs47 haplotypes in a P. falciparum isolate is sufficient to make it compatible to a different mosquito species. Those parasites that express a Pfs47 haplotype compatible with a given vector evade antiplasmodial immunity and survive. We propose that Pfs47-mediated immune evasion has been critical for the globalization of P. falciparum malaria as parasites adapted to new vector species. Our findings predict that this ongoing selective force by the mosquito immune system could influence the dispersal of Plasmodium genetic traits and point to Pfs47 as a potential target to block malaria transmission. A new model, the "lock-and-key theory" of P. falciparum globalization, is proposed, and its implications are discussed.

Flexible Gas Sensors Employing Octahedral Indium Oxide Films.

Indium oxide octahedral nanopowders were obtained from an ionic precursor compound after an oxidation process conducted under a low-oxygen atmosphere. This method was found to produce contamination-free indium oxide nanomaterial with very similar morphological and crystalline properties to the one produced by vapor-phase transport, but at significantly lower temperatures and higher yield. The as-synthesized indium oxide was mixed to an organic vehicle and microdrop deposited to form a film bridging the interdigitated silver electrodes patterned on top of a flexible, polyimide (Kapton®), substrate. The gas sensing properties of the flexible chemoresistors towards ammonia vapors, hydrogen, and nitrogen dioxide were investigated. It was found that these sensors were remarkably sensitive to nitrogen dioxide at a low operating temperature of 150 °C. These results are consistent with the performance of vapor-phase transport synthesized indium oxide octahedra sensors on rigid, ceramic substrates. Therefore, the results presented here pave the way for the mass production of inexpensive gas sensors onto flexible substrates via additive manufacturing.

Characteristic plethysmographic findings in a guinea pig model of COPD.

AIM OF THE STUDY: Long-term exposure to cigarette smoke generates chronic obstructive pulmonary disease (COPD) in guinea pigs, but a comprehensive evaluation of changes in lung function, as assessed by barometric whole body plethysmography (WBP), is lacking. MATERIALS AND METHODS: Female guinea pigs were exposed to the smoke of 20 cigarettes/day, 5 days/week, during 10 weeks (COPD group, n = 8), and were compared with unexposed female guinea pigs of the same age (control group, n = 8). WBP was performed in both groups, followed by lung histology. RESULTS: At the end of the exposure period, guinea pigs in the COPD group had higher respiratory frequency, while duty cycle (Ti/Ttot) was unaffected. There was a trend toward minute ventilation (MV) and expiratory flow at the mid-tidal volume (EF50) to be higher in the COPD group. Enhanced pause (Penh) was lower, while time of braking (TB) and time to PEF relative to Te (Rpef) were higher in the COPD group. All guinea pigs exposed to tobacco smoke developed emphysematous lesions in their lungs and gained less body weight than controls. CONCLUSIONS: In this COPD model, exposure to cigarette smoke produced changes in WBP characterized by a shallow breathing pattern with decreased Penh and a trend toward increasing EF50 (probably due to decreased elastic recoil), increased TB (suggesting dynamic laryngeal narrowing), and a trend of increasing MV (probably due to a higher metabolic rate). Many of these functional changes resemble those observed in patients with COPD and corroborate the suitability of this guinea pig model for the study of COPD.

Collagen-binding protein, Aegyptin, regulates probing time and blood feeding success in the dengue vector mosquito, Aedes aegypti.

Mosquito salivary glands have important roles in blood feeding and pathogen transmission. However, the biological relevance of many salivary components has yet to be determined. Aegyptin, a secreted salivary protein from Aedes aegypti, binds collagen and inhibits platelet aggregation and adhesion. We used a transgenic approach to study the relevance of Aegyptin in mosquito blood feeding. Aedes aegypti manipulated genetically to express gene-specific inverted-repeat RNA sequences exhibited significant reductions in Aegyptin mRNA accumulation (85-87%) and protein levels (>80-fold) in female mosquito salivary glands. Transgenic mosquitoes had longer probing times (78-300 s, P < 0.0001) when feeding on mice compared with controls (15-56 s), feeding success was reduced, and those feeding took smaller blood meals. However, no differences in feeding success or blood meal size were found in membrane feeding experiments using defibrinated human blood. Salivary gland extracts from transgenic mosquitoes failed to inhibit collagen-induced platelet aggregation in vitro. Reductions of Aegyptin did not affect salivary ADP-induced platelet aggregation inhibition or disturb anticlotting activities. Our results demonstrate the relevance of Aegyptin for A. aegypti blood feeding, providing further support for the hypothesis that platelet aggregation inhibition is a vital salivary function in blood feeding arthropods. It has been suggested that the multiple mosquito salivary components mediating platelet aggregation (i.e., Aegyptin, apyrase, D7) represent functional redundancy. Our findings do not support this hypothesis; instead, they indicate that multiple salivary components work synergistically and are necessary to achieve maximum blood feeding efficiency.

Factors influencing anthocyanin loss during nixtamalization of blue purple maize grain.

Blue purple maize grain loses a great amount of anthocyanins during the nixtamalization processing. The impact of the process factors on anthocyanins losses has not been studied in detail. The objectives of this work were to: (1) determine the step of the nixtamalization procedure where the greatest anthocyanin loss occurs and (2) study the effect of cooking time, alkali concentration, and sample size on anthocyanin losses (AL), and on the color of masa and tortilla from blue purple maize grain. Two cooking times were assayed (25 and 35 min), three alkali concentrations (0.5, 0.7, and 1.0% w/w), and two maize grain sample sizes (100 and 1000 g). Alkali concentration determines the time required to solubilize the maize grain pericarp, higher concentrations resulted in shorter maize grain pericarp solubilization times and this variable was related with AL. The greatest AL occurred during the grain cooking step, but an additional loss took place during the steeping of cooked grain. For the cooking time of 25 min, AL were of 38.3% during the cooking step, and 21.3% during the steeping of cooked grain. The cooking time had no effect (p > 0.05) on AL in masa and tortilla whereas alkali concentration and sample size significantly affected it. The greater the concentration and size, the higher the AL. The color of masa and tortilla were affected by cooking time and alkali concentration. Increasing alkali concentration during the nixtamalization procedure, reduced the brightness and chroma of masa and tortilla and made these products seem darker and dull.

Chromobacterium Csp_P reduces malaria and dengue infection in vector mosquitoes and has entomopathogenic and in vitro anti-pathogen activities.

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.

Bevacizumab and temozolomide versus temozolomide alone as neoadjuvant treatment in unresected glioblastoma: the GENOM 009 randomized phase II trial.

We sought to determine the impact of bevacizumab on reduction of tumor size prior to chemoradiotherapy in unresected glioblastoma patients. Patients were randomized 1:1 to receive temozolomide (TMZ arm) or temozolomide plus bevacizumab (TMZ + BEV arm). In both arms, neoadjuvant treatment was temozolomide (85 mg/m(2), days 1-21, two 28-day cycles), concurrent radiation plus temozolomide, and six cycles of adjuvant temozolomide. In the TMZ + BEV arm, bevacizumab (10 mg/kg) was added on days 1 and 15 of each neoadjuvant cycle and on days 1, 15 and 30 of concurrent treatment. The primary endpoint was investigator-assessed response to neoadjuvant treatment. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and the impact on outcome of MGMT methylation in tumor and serum. One hundred and two patients were included; 43 in the TMZ arm and 44 in the TMZ + BEV arm were evaluable for response. Results favored the TMZ + BEV arm in terms of objective response (3 [6.7 %] vs. 11 [22.9 %]; odds ratio 4.2; P = 0.04). PFS and OS were longer in the TMZ + BEV arm, though the difference did not reach statistical significance. MGMT methylation in tumor, but not in serum, was associated with outcome. More patients experienced toxicities in the TMZ + BEV than in the TMZ arm (P = 0.06). The combination of bevacizumab plus temozolomide is more active than temozolomide alone and may well confer benefit in terms of tumor shrinkage in unresected patients albeit at the expense of greater toxicity.

Leishmania major telomerase TERT protein has a nuclear/mitochondrial eclipsed distribution that is affected by oxidative stress.

In its canonical role the reverse transcriptase telomerase recovers the telomeric repeats that are lost during DNA replication. Other locations and activities have been recently described for the telomerase protein subunit TERT in mammalian cells. In the present work, using biochemistry, molecular biology, and electron microscopy techniques, we found that in the human parasite Leishmania major, TERT (and telomerase activity) shared locations between the nuclear, mitochondrial, and cytoplasmic compartments. Also, some telomerase activity and TERT protein could be found in ∼ 100-nm nanovesicles. In the mitochondrial compartment, TERT appears to be mainly associated with the kinetoplast DNA. When Leishmania cells were exposed to H2O2, TERT changed its relative abundance and activity between the nuclear and mitochondrial compartments, with the majority of activity residing in the mitochondrion. Finally, overexpression of TERT in Leishmania transfected cells not only increased the parasitic cell growth rate but also increased their resistance to oxidative stress.