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The developmental regulator SOX9 is linked to cancer progression mainly as a result of its role in the regulation of cancer stem cells (CSCs). However, its activity in the differentiated cells that constitute the heterogeneous tumor bulk has not been extensively studied. In this work, we addressed this aspect in gastric cancer, glioblastoma and pancreatic adenocarcinoma. SOX9 silencing studies revealed that SOX9 is required for cancer cell survival, proliferation and evasion of senescence in vitro and tumor growth in vivo. Gain of-SOX9 function showed that high levels of SOX9 promote tumor cell proliferation in vitro and in vivo. Mechanistically, the modulation of SOX9 changed the expression of the transcriptional repressor BMI1 in the same direction in the three types of cancer, and the expression of the tumor suppressor p21 CIP in the opposite direction. In agreement with this, SOX9 expression positively correlated with BMI1 levels and inversely with p21 CIP in clinical samples of the different cancers. Moreover, BMI1 re-establishment in SOX9-silenced tumor cells restored cell viability and proliferation as well as decreased p21 CIP in vitro and tumor growth in vivo. These results indicate that BMI1 is a critical effector of the pro-tumoral activity of SOX9 in tumor bulk cells through the repression of p21 CIP . Our results highlight the relevance of the SOX9-BMI1-p21 CIP axis in tumor progression, shedding novel opportunities for therapeutic development.

Introduction: Type 2 diabetes mellitus (T2DM) is characterized by chronic inflammation, in which different types of immune cells participate, such as TH17 cells and Treg cells. The aim of this study was to determine the relationship between Treg and Th17 in patients with different times of T2DM progression., Material and Methods: Nineteen control subjects and 40 patients with T2DM were included. T2DM patients were classified into two groups: the first group consisted of twenty patients with less than10 years of disease progression (T2DM < 10), and the second group included 20 patients with a disease progression of 10 years or more (T2DM ≥ 10). Additionally, an analysis was performed according to the metabolic control, depending on HbA1c levels. The peripheral blood ratio of both Th17 and Treg cells was measured by standard flow cytometry protocols., Results: No significant difference was found in Th17 cells of patients with T2DM < 10 or T2DM ≥ 10 and controls. With respect to CD4+CD25+FoxP3+ and CD4+CD25h Treg cells, a significant decrease was observed in patients with T2DM ≥ 10, mainly in patients with poor or moderate metabolic control. Statistical analysis performed in all patients with T2DM revealed a decrease in three cell subsets as well a negative correlation between Th17 cells and total cholesterol, CD4+CD25h cells with glucose and HbA1c levels, while a positive correlation was observed between CD4+CD25h cells and BMI., Conclusions: A decrease on both Treg and Th17 cell subsets in T2DM patients was observed suggesting that the metabolic decontrol and the progression time of T2DM could modify the proportions of Th17 and Treg cells., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Termedia.)

Background: It is known that late surgical reconstruction of the anterior cruciate ligament (ACL) is associated with a medial meniscal (MM) tears. However, the association between factors relating to sports and work activities and joint instability, has not been examined in non-athletic subjects., Objective: To compare sports and work activities and other factors associated with MM tears, in subjects with ACL rupture., Method: A case-control design study, of patients with ACL injury, 140 cases and 140 controls with and without a rupture of MM respectively, were included. Sociodemographic factors, sports and work activities were compared., Results: The independent factors associated with MM ruptures were continuing sports activities after injury (odds ratio [OR]: 3.6; 95% confidence interval [95% CI]: 1.7-7.9), joint instability (OR: 2.2; 95% CI: 1.8-2.6), time between injury and surgical intervention (time of evolution) (OR: 1.003; 95% CI: 1.0-1.01) and age (OR: 1.1; 95% CI: 1.03-1.1)., Conclusions: Intense activities of daily life such as continuing sports activities, after an ACL injury in non-athletic factory workers subjects, without previous training, as well as, age, joint instability and surgical delay are risk factors for rupture of MM., (Copyright: © 2020 Permanyer.)

Drought is now recognized as the abiotic stress that causes most problems in agriculture, mainly due to the strong water demand from intensive culture and the effects of climate change, especially in arid/semi-arid areas. When plants suffer from water deficit (WD), a plethora of negative physiological alterations such as cell turgor loss, reduction of CO 2 net assimilation rate, oxidative stress damage, and nutritional imbalances, among others, can lead to a decrease in the yield production and loss of commercial quality. Nutritional imbalances in plants grown under drought stress occur by decreasing water uptake and leaf transpiration, combined by alteration of nutrient uptake and long-distance transport processes. Plants try to counteract these effects by activating drought resistance mechanisms. Correct accumulation of salts and water constitutes an important portion of these mechanisms, in particular of those related to the cell osmotic adjustment and function of stomata. In recent years, molecular insights into the regulation of K + , Cl - , and water transport under drought have been gained. Therefore, this article brings an update on this topic. Moreover, agronomical practices that ameliorate drought symptoms of crops by improving nutrient homeostasis will also be presented., (Copyright © 2019 Nieves-Cordones, García-Sánchez, Pérez-Pérez, Colmenero-Flores, Rubio and Rosales.)

Telomeres are considered potential anti-cancer targets. Most studies have focused on telomerase inhibition, but this strategy has largely failed in clinical trials. Direct disruption of the shelterin complex through TRF1 inhibition can block tumorigenesis in cancer mouse models by a mechanism that involves DNA damage induction and reduction of proliferation and stemness. Any anti-cancer target, however, must fulfill the requisite of not showing deleterious effects in healthy tissues. Here, we show that Trf1 genetic deletion in wild-type and cancer-prone p53- and Ink4Arf-deficient mice does not affect organismal viability and only induces mild phenotypes like decreased body weight and hair graying or hair loss, the skin being the most affected tissue. Importantly, we found that Trf1 is essential for tumorigenesis in p53- and Ink4Arf-deficient mice, as we did not find a single tumor originating from Trf1-deleted cells. These findings indicate a therapeutic window for targeting Trf1 in cancer treatment., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Coral reefs are the most diverse habitats in the marine realm. Their productivity, structural complexity, and biodiversity critically depend on ecosystem services provided by corals that are threatened because of climate change effects-in particular, ocean warming and acidification. The coral holobiont is composed of the coral animal host, endosymbiotic dinoflagellates, associated viruses, bacteria, and other microeukaryotes. In particular, the mandatory photosymbiosis with microalgae of the family Symbiodiniaceae and its consequences on the evolution, physiology, and stress resilience of the coral holobiont have yet to be fully elucidated. The functioning of the holobiont as a whole is largely unknown, although bacteria and viruses are presumed to play roles in metabolic interactions, immunity, and stress tolerance. In the context of climate change and anthropogenic threats on coral reef ecosystems, the Tara Pacific project aims to provide a baseline of the "-omics" complexity of the coral holobiont and its ecosystem across the Pacific Ocean and for various oceanographically distinct defined areas. Inspired by the previous Tara Oceans expeditions, the Tara Pacific expedition (2016-2018) has applied a pan-ecosystemic approach on coral reefs throughout the Pacific Ocean, drawing an east-west transect from Panama to Papua New Guinea and a south-north transect from Australia to Japan, sampling corals throughout 32 island systems with local replicates. Tara Pacific has developed and applied state-of-the-art technologies in very-high-throughput genetic sequencing and molecular analysis to reveal the entire microbial and chemical diversity as well as functional traits associated with coral holobionts, together with various measures on environmental forcing. This ambitious project aims at revealing a massive amount of novel biodiversity, shedding light on the complex links between genomes, transcriptomes, metabolomes, organisms, and ecosystem functions in coral reefs and providing a reference of the biological state of modern coral reefs in the Anthropocene., Competing Interests: The authors have declared that no competing interests exist.

Chloride (Cl - ) has traditionally been considered a micronutrient largely excluded by plants due to its ubiquity and abundance in nature, its antagonism with nitrate (NO 3 - ), and its toxicity when accumulated at high concentrations. In recent years, there has been a paradigm shift in this regard since Cl - has gone from being considered a harmful ion, accidentally absorbed through NO 3 - transporters, to being considered a beneficial macronutrient whose transport is finely regulated by plants. As a beneficial macronutrient, Cl - determines increased fresh and dry biomass, greater leaf expansion, increased elongation of leaf and root cells, improved water relations, higher mesophyll diffusion to CO 2 , and better water- and nitrogen-use efficiency. While optimal growth of plants requires the synchronic supply of both Cl - and NO 3 - molecules, the NO 3 - /Cl - plant selectivity varies between species and varieties, and in the same plant it can be modified by environmental cues such as water deficit or salinity. Recently, new genes encoding transporters mediating Cl - influx ( ZmNPF6.4 and ZmNPF6.6 ), Cl - efflux ( AtSLAH3 and AtSLAH1 ), and Cl - compartmentalization ( AtDTX33 , AtDTX35 , AtALMT4, and GsCLC2 ) have been identified and characterized. These transporters have proven to be highly relevant for nutrition, long-distance transport and compartmentalization of Cl - , as well as for cell turgor regulation and stress tolerance in plants.

An interferometer with a minimum of optical hardware is employed to measure invasiveness the size of biological samples. Nowadays, there are several techniques in microscopy that render high quality resolved images. For instance, consider optical microscopy that has been around for over a century and has since developed in different configurations such as: bright and dark field, phase contrast, confocal, polarized, and so on. However, only a few of these use interferometry to retrieve not only the sample's amplitude but also its phase. An interesting example of the latter is digital holography which normally uses a Mach Zehnder interferometer setup. In the research work reported here a transmission digital holographic interferometer designed with a simple and minimal optical hardware, that avoids the drawback of the small field of view present in classical optical microscopic systems, is used to measure the microscopic dimensions of pollen grains. This optical configuration can be manipulated to magnify and project the image of a semitransparent sample over a neutral phase screen. The use of a collimated beam through the sample prevents geometrical distortions for high magnification values. The measurements using this novel configuration have been validated using a standard precision pattern displacement specimen with certified dimensions. As proof of principle, microscopically characterized pollen grains are placed in the transmission set up in order to estimate their dimensions from the interferometrically retrieved optical phase. Results match and thus show a relation between the sample's size and the optical phase magnitude.

Chloride (Cl - ) has been recently described as a beneficial macronutrient, playing specific roles in promoting plant growth and water-use efficiency (WUE). However, it is still unclear how Cl - could be beneficial, especially in comparison with nitrate (NO 3 - ), an essential source of nitrogen that shares with Cl - similar physical and osmotic properties, as well as common transport mechanisms. In tobacco plants, macronutrient levels of Cl - specifically reduce stomatal conductance (g s ) without a concomitant reduction in the net photosynthesis rate (A N ). As stomata-mediated water loss through transpiration is inherent in the need of C 3 plants to capture CO 2 , simultaneous increase in photosynthesis and WUE is of great relevance to achieve a sustainable increase in C 3 crop productivity. Our results showed that Cl - -mediated stimulation of larger leaf cells leads to a reduction in stomatal density, which in turn reduces g s and water consumption. Conversely, Cl - improves mesophyll diffusion conductance to CO 2 (g m ) and photosynthetic performance due to a higher surface area of chloroplasts exposed to the intercellular airspace of mesophyll cells, possibly as a consequence of the stimulation of chloroplast biogenesis. A key finding of this study is the simultaneous improvement of A N and WUE due to macronutrient Cl - nutrition. This work identifies relevant and specific functions in which Cl - participates as a beneficial macronutrient for higher plants, uncovering a sustainable approach to improve crop yield., (© 2019 The Authors The Plant Journal © 2019 John Wiley & Sons Ltd.)

Liver ischemia and reperfusion injury (IRI) remains a serious clinical problem affecting liver transplantation outcomes. IRI causes up to 10% of early organ failure and predisposes to chronic rejection. Cyclooxygenase-2 (COX-2) is involved in different liver diseases, but the significance of COX-2 in IRI is a matter of controversy. This study was designed to elucidate the role of COX-2 induction in hepatocytes against liver IRI. In the present work, hepatocyte-specific COX-2 transgenic mice (hCOX-2-Tg) and their wild-type (Wt) littermates were subjected to IRI. hCOX-2-Tg mice exhibited lower grades of necrosis and inflammation than Wt mice, in part by reduced hepatic recruitment and infiltration of neutrophils, with a concomitant decrease in serum levels of proinflammatory cytokines. Moreover, hCOX-2-Tg mice showed a significant attenuation of the IRI-induced increase in oxidative stress and hepatic apoptosis, an increase in autophagic flux, and a decrease in endoplasmic reticulum stress compared to Wt mice. Interestingly, ischemic preconditioning of Wt mice resembles the beneficial effects observed in hCOX-2-Tg mice against IRI due to a preconditioning-derived increase in endogenous COX-2, which is mainly localized in hepatocytes. Furthermore, measurement of prostaglandin E 2 (PGE 2 ) levels in plasma from patients who underwent liver transplantation revealed a significantly positive correlation of PGE 2 levels and graft function and an inverse correlation with the time of ischemia. Conclusion: These data support the view of a protective effect of hepatic COX-2 induction and the consequent rise of derived prostaglandins against IRI., (© 2018 by the American Association for the Study of Liver Diseases.)

Chloroquine (CQ) is an old antimalarial drug currently being investigated for its anti-tumor properties. As chloroquine has been shown to inhibits several potassium channels, we decided to study its effect on the tumor-related Kv10.1 channel by using patch-clamp electrophysiology and cell migration assays. We found that chloroquine inhibited Kv10.1 channels transiently expressed in HEK-293 cells in a concentration- and voltage-dependent manner acting from the cytoplasmic side of the plasma membrane. Chloroquine also inhibited the outward potassium currents from MDA-MB-231 cells, which are mainly carried through Kv10.1 channels as was confirmed using astemizole. Additionally, chloroquine decreased MDA-MB-231 cell migration in the in vitro scratch wound healing assay. In conclusion, our data suggest that chloroquine decreases MDA-MB-231 cell migration by inhibiting Kv10.1 channels. The inhibition of Kv10.1 channels could represent another mechanism of the antitumoral action of chloroquine, besides autophagy inhibition and tumor vessel normalization., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Previous studies have shown that accumulation of advanced glycation end products (AGEs) can be the cause of diabetic nephropathy (DN) in diabetic patients. Dihydrochalcone 3'- O -β-d-glucopyranosyl α,4,2',4',6'-pentahydroxy⁻dihydrochalcone ( 1 ) is a powerful antiglycation compound previously isolated from Eysenhardtia polystachya . The aim was to investigate whether ( 1 ) was able to protect against diabetic nephropathy in streptozotocin (STZ)-induced diabetic mice, which displayed renal dysfunction markers such as body weight, creatinine, uric acid, serum urea, total urinary protein, and urea nitrogen in the blood (BUN). In addition, pathological changes were evaluated including glycated hemoglobin (HbA1c), advanced glycation end products (AGEs) in the kidney, as well as in circulation level and pro-inflammatory markers ICAM-1 levels in diabetic mice. After 5 weeks, these elevated markers of dihydrochalcone treatment (25, 50 and 100 mg/kg) were significantly ( p < 0.05) attenuated. In addition, they ameliorate the indices of renal inflammation as indicated by ICAM-1 markers. The kidney and circulatory AGEs levels in diabetic mice were significantly ( p < 0.05) attenuated by ( 1 ) treatment. Histological analysis of kidney tissues showed an important recovery in its structure compared with the diabetic group. It was found that the compound ( 1 ) attenuated the renal damage in diabetic mice by inhibiting AGEs formation.

The hydraulic traits of plants, or the efficiency of water transport throughout the plant hydraulic system, could help to anticipate the impact of climate change and improve crop productivity. However, the mechanisms explaining the role of hydraulic traits on plant photosynthesis and thus, plant growth and yield, are just beginning to emerge. We conducted an experiment to identify differences in growth patterns at leaf, root and whole plant level among four wild olive genotypes and to determine whether hydraulic traits may help to explain such differences through their effect on photosynthesis. We estimated the relative growth rate (RGR), and its components, leaf gas exchange and hydraulic traits both at the leaf and whole-plant level in the olive genotypes over a full year. Photosynthetic capacity parameters were also measured. We observed different responses to water stress in the RGRs of the genotypes studied being best explained by changes in the net CO 2 assimilation rate (NAR). Further, net photosynthesis, closely related to NAR, was mainly determined by hydraulic traits, both at leaf and whole-plant levels. This was mediated through the effects of hydraulic traits on stomatal conductance. We observed a decrease in leaf area: sapwood area and leaf area: root area ratios in water-stressed plants, which was more evident in the olive genotype Olea europaea subsp. guanchica (GUA8), whose RGR was less affected by water deficit than the other olive genotypes. In addition, at the leaf level, GUA8 water-stressed plants presented a better photosynthetic capacity due to a higher mesophyll conductance to CO 2 and a higher foliar N. We conclude that hydraulic allometry adjustments of whole plant and leaf physiological response were well coordinated, buffering the water stress experienced by GUA8 plants. In turn, this explained their higher relative growth rates compared to the rest of the genotypes under water-stress conditions.

Background: During pregnancy, the Zika virus (ZIKV) replicates in the placenta and central nervous system (CNS) of infected fetuses; nevertheless, the ability of ZIKV to replicate in other fetal tissues has not been extensively characterized., Methods: We researched whether dissemination of congenitally-acquired ZIKV outside the CNS exists by searching for the accumulation of the viral envelope protein, ZIKV ribonucleic acid (RNA), and infectious viral particles in different organs of a deceased newborn with Congenital Zika Syndrome. A real-time qualitative polymerase chain reaction (qPCR) was used to detect ZIKV RNA in the brain, thymus, lungs, kidneys, adrenal glands, spleen, liver, and small intestine. The same tissues were analyzed by indirect immunofluorescence and immunoperoxidase assays using the monoclonal antibody 4G2 to detect ZIKV envelope antigens. Isolation of infectious ZIKV in a cell culture was carried out using brain and kidney samples., Results: A postmortem, virological analysis of multiple organs, such as the kidneys (epithelial cells in the renal tubules), lungs (bronchial epithelia), thymus (epithelial cells inside the Hassall's corpuscles), and brain (neurons, ependymal cells, and macrophages) revealed the presence of ZIKV RNA and envelope antigens. Other tissues of the deceased newborn tested positive by qPCR for Epstein-Barr virus and human herpesvirus 6, including the brain cortex (Epstein-Barr) and the thymus, kidneys, and adrenal glands (human herpesvirus 6). The kidneys were identified as a significant niche for viral replication, given that infectious particles were successfully isolated from renal tissues., Conclusions: Our findings demonstrate the ability of congenitally-acquired ZIKV to produce disseminated infections and the viral tropism towards epithelial cells., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America.)

Honey bee plays the leading role in the pollination of many wild plants and crops, but it currently faces serious threats. Climate change is pointed out as one of the causes of the colony collapse disorder. Understanding the response of bees to the new climate change scenario is essential to face this challenge. Especially in the most sensitive bioclimatic zones, such as the Mediterranean areas. In this work, we remotely monitored the weight of the hives with an electronic device during a flowering period in the beekeeping seasons of 2016 and 2017, marked by extreme episodes of drought and high temperatures. We assessed bee colonies at the beginning, middle and at the end of the flowering as well, considering the adult bee population, bee brood, and pollen and honey reserves. The results showed that the flowering was reduced in three weeks in 2017 in comparison to 2016. In those years weight gain was 7.67 kg and 18.92 kg, respectively. The adverse conditions affected the evolution of the populations of bees and the reserves of honey and pollen in a meaningful way, increasing food stress for bees. It also affected the pollen spectrum and commercial characteristics of honey. Our results provide objective data about the effect of climate change on bees, but it also proved the relevant role of bees in the study of changes in the environment., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: For many years the abdominal region has been a reliable donor of abundant well-perfused tissue. The subdermal plexus constitutes an intricate network of microvessels that comprise the entire abdominal skin and allow for innumerable and redundant connections., Method: Using a retrospective cohort study, we considered the first 100 deep inferior epigastric perforator (DIEP) flaps performed for breast reconstruction in the High Specialty Medical Department #21 of the Mexican Institute of Social Security in Monterrey, Nuevo Leon, Mexico, from January 2010 until December 2015., Results: Of the 100 patients studied, 70 (70%) correspond to the group with abdominal scars and 30 (30%) to the group with no abdominal scars. Of the total patients, only one case of flap necrosis arose secondary to venous thrombosis (1%). This patient had no abdominal scars. The success of the flap was compared between groups using the Fisher exact test, obtaining p = 0.717., Conclusion: Abdominal scars do not represent a contraindication for breast reconstruction with DIEP flap even if perforator detection is performed only with hand held 8 MHz doppler., (Copyright: © 2019 Permanyer.)

MHCII in antigen-presenting cells (APCs) is a key regulator of adaptive immune responses. Expression of MHCII genes is controlled by the transcription coactivator CIITA, itself regulated through cell type-specific promoters. Here we show that the transcription factor NFAT5 is needed for expression of Ciita and MHCII in macrophages, but not in dendritic cells and other APCs. NFAT5-deficient macrophages showed defective activation of MHCII-dependent responses in CD4 + T lymphocytes and attenuated capacity to elicit graft rejection in vivo. Ultrasequencing analysis of NFAT5-immunoprecipitated chromatin uncovered an NFAT5-regulated region distally upstream of Ciita This region was required for CIITA and hence MHCII expression, exhibited NFAT5-dependent characteristics of active enhancers such as H3K27 acetylation marks, and required NFAT5 to interact with Ciita myeloid promoter I. Our results uncover an NFAT5-regulated mechanism that maintains CIITA and MHCII expression in macrophages and thus modulates their T lymphocyte priming capacity., (© 2018 Buxadé et al.)

Background: Venous thromboembolism (VTE) has been studied in lower extremity fractures but little is known of its relation with upper extremity (UE) fractures. As an often overlooked but serious complication, VTE may compromise patient outcomes., Methods: Using data on inpatients (aged ≥ 18 years) at a level-I trauma center and patients in the National Surgical Quality Improvement Program database who sustained UE fractures (clavicle, humerus, or radius/ulna) and VTE in the same hospitalization between 2007 and 2014, the authors analyzed data on demographic characteristics, fracture type, VTE location (pulmonary embolism, lower extremity, or UE), VTE onset, polytrauma, operative or nonoperative management, comorbidities, and mortality., Results: Of 1984 inpatients with UE fractures at 1 instution, 9 experienced VTE on admission, and 17 (15 received thromboprophylaxis) experienced VTE during hospitalization, for an overall VTE rate of 1.3%. VTE occurred most often in patients with fractures of the proximal humerus (3.0%) followed by the clavicle (2.0%), midshaft humerus (1.9%), distal radius/ulna (0.95%), and distal humerus/elbow (0.36%) (p = 0.0035). There were no significant trends in the incidence of PE (p = 0.33) over the study period, but there was a sharp rise since 2011. In the national database, 42 of 11570 (0.36%) patients with UE fracture had VTE, with incidence by fracture location ranging from 0.14% (radius/ulna) to 0.98% (proximal humerus) (p = 0.00001). Predictors were chronic steroid use (odds ratio [OR] = 6.22, p = .030), inpatient status (OR = 4.09, p = .002), and totally disabled functional status (OR = 3.31, p = .021)., Conclusions: VTE incidence was highest following proximal humerus or clavicle fractures and are rarely associated with radius/ulna fractures. There may have been a rise in the incidence of PE since 2007, warranting further investigation.

Background: Use of methamphetamines (MA) and other stimulants have consistently been associated with HIV/STI risk globally. We evaluated a community mobilization intervention (Connect to Protect, C2P ® ) to prevent MA use among youth and reduce HIV risk behaviors through community structural changes., Design: A community-randomized trial in northern Thailand with matched districts randomized to C2P intervention or a standard voluntary counseling and testing (VCT) control. Intervention districts formed stakeholders' coalitions to plan tailored local prevention programs. Two independent random household samples of youth aged 14-24 were surveyed in 2009 and 2012. Lifetime and recent MA use was modeled with multilevel logistic regression., Results: Intervention initiatives included family-strengthening programs, school-based programs and opening a community drug treatment center. Control communities applied the government-led "war on drugs" approach in addition to youth and family programs. Baseline (N = 1077) and follow-up (N = 1225) samples included 47.5% females and 21.7% aged ≤16. Lifetime MA use in intervention districts reduced from 13.4% to 11.7% compared to reduction from 16.2% to 10.4% in the control districts (non-significant). In models, lifetime MA use was associated with: time (aOR = 0.6, 95%CI: 0.38-0.83), females (aOR = 0.2, 95%CI: 0.15-0.29), increasing age (aOR = 2.4, 95%CI: 1.40-4.20, ages 16-19; aOR = 3.5, 95%CI: 2.00-6.12, ages ≥20), and not being full-time students (aOR = 5.3, 95%CI: 3.77-7.37). Recent MA use showed similar results. Additionally, lifetime MA use was significantly associated with alcohol use, risky sexual behaviors and elevated depressive symptoms., Conclusions: Delay in developing and implementing specific prevention programs in the intervention districts slowed diffusion of the effect into the communities. Secular trends with contentious civil unrest and active drug-enforcement efforts in the control communities also contributed to the null intervention effect. Longer time and intensified efforts stressing a public health approach are needed to demonstrate the effectiveness of community mobilization in reducing substance use and HIV risk in this rural Thai community., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

In this study, honeybee colonies were monitored in a field study conducted on sunflowers grown from seeds treated with the systemic neonicotinoids thiamethoxam or clothianidin. This field trial was carried out in different representative growing areas in Spain over a beekeeping season. The health and development of the colonies was assessed by measuring factors that have a significant influence on their strength and overwintering ability. The parameters assessed were: colony strength (adult bees), brood development, amount of pollen and honey stores and presence and status of the queen. The concentration of residues (clothianidin and thiamethoxam) in samples of beebread and in adult bees was at the level of ng.g -1 ; in the ranges of 0.10-2.89 ng g -1 and 0.05-0.12 ng g -1 ; 0.10-0.37 ng g -1 and 0.01-0.05 ng g -1 , respectively. Multivariate models were applied to evaluate the interaction among factors. No significant differences were found between the honeybee colonies of the different treatment groups, either exposed or not to the neonicotinoids. The seasonal development of the colonies was affected by the environmental conditions which, together with the initial strength of the bee colonies and the characteristics of the plots, had a significant effect on the different variables studied., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Type 2 diabetes mellitus is characterized by insulin resistance in the liver. Insulin is not only involved in carbohydrate metabolism, it also regulates protein synthesis. This work describes the expression of proteins in the liver of a diabetic mouse and identifies the metabolic pathways involved. Twenty-week-old diabetic db/db mice were hepatectomized, after which proteins were separated by 2D-Polyacrylamide Gel Electrophoresis (2D-PAGE). Spots varying in intensity were analyzed using mass spectrometry, and biological function was assigned by the Database for Annotation, Visualization and Integrated Discovery (DAVID) software. A differential expression of 26 proteins was identified; among these were arginase-1, pyruvate carboxylase, peroxiredoxin-1, regucalcin, and sorbitol dehydrogenase. Bioinformatics analysis indicated that many of these proteins are mitochondrial and participate in metabolic pathways, such as the citrate cycle, the fructose and mannose metabolism, and glycolysis or gluconeogenesis. In addition, these proteins are related to oxidation⁻reduction reactions and molecular function of vitamin binding and amino acid metabolism. In conclusion, the proteomic profile of the liver of diabetic mouse db/db exhibited mainly alterations in the metabolism of carbohydrates and nitrogen. These differences illustrate the heterogeneity of diabetes in its different stages and under different conditions and highlights the need to improve treatments for this disease.

Here, we report for the first time the circulation of dengue virus type 1 (DENV-1) belonging to the lineage IV of genotype V (African American genotype) based on phylogenetic analysis of nucleotide sequences from 10 DENV-1-positive samples obtained in Mexico between 2012 and 2014. Our data revealed that the lineages III and IV of DENV-1 genotype V were found circulating during the same period, probably explaining the rise in the number of cases of severe dengue during that period.

Two trials with multiparous dairy cows were conducted. Experiment 1 tested the effects of increasing forage proportion in the diet (500, 600, and 700 g/kg DM) when a mixed sorghum (Sorghum bicolor) and jackbean (Cannavalia ensiformis) silage was used as forage. Experiment 2 studied the substitution of sorghum silage and soybean meal by jackbean silage or fresh cowpea (Vigna unguiculata) forage in the diet. All diets were iso-energetic and iso-proteic. In each experiment, 30 cows were used and separated into three groups. In experiment 1, there were no differences in dry matter intake (DMI), milk yield (MY), or apparent total tract digestibility (aTTd) among the three diets, but milk fat content increased with increasing forage proportion, even though the similar neutral detergent fiber of all diets. Nitrogen use efficiency was highest in the diet containing 600 g forage/kg DM, and some evidence was observed for a better profitability with this forage proportion. In experiment 2, feeding legumes increased DMI despite no effects on aTTd. Milk yield increased in line with DMI, with a larger increase for the fresh cowpea. Nitrogen use efficiency and milk composition were not affected by the diets. The increased MY and lower feed costs increased the economic benefits when feeding legumes, particularly when feeding fresh cowpea. Feeding fresh cowpea or jackbean silage to dairy cows appears to be an alternative to soybean as protein source, ideally at a forage proportions of 600 g/kg DM, without altering milk yield and quality and increasing the farm profitability.

The wavelength-dependence of the complex refractive indices (RI) in the visible spectral range of secondary organic aerosols (SOA) are rarely studied, and the evolution of the RI with atmospheric aging is largely unknown. In this study, we applied a novel white light-broadband cavity enhanced spectroscopy to measure the changes in the RI (400-650 nm) of β-pinene and p-xylene SOA produced and aged in an oxidation flow reactor, simulating daytime aging under NO x -free conditions. It was found that these SOA are not absorbing in the visible range, and that the real part of the RI, n, shows a slight spectral dependence in the visible range. With increased OH exposure, n first increased and then decreased, possibly due to an increase in aerosol density and chemical mean polarizability for SOA produced at low OH exposures, and a decrease in chemical mean polarizability for SOA produced at high OH exposures, respectively. A simple radiative forcing calculation suggests that atmospheric aging can introduce more than 40% uncertainty due to the changes in the RI for aged SOA.

Pulmonary fibrosis is a fatal lung disease characterized by fibrotic foci and inflammatory infiltrates. Short telomeres can impair tissue regeneration and are found both in hereditary and sporadic cases. We show here that telomerase expression using AAV9 vectors shows therapeutic effects in a mouse model of pulmonary fibrosis owing to a low-dose bleomycin insult and short telomeres. AAV9 preferentially targets regenerative alveolar type II cells (ATII). AAV9- Tert -treated mice show improved lung function and lower inflammation and fibrosis at 1-3 weeks after viral treatment, and improvement or disappearance of the fibrosis at 8 weeks after treatment. AAV9- Tert treatment leads to longer telomeres and increased proliferation of ATII cells, as well as lower DNA damage, apoptosis, and senescence. Transcriptome analysis of ATII cells confirms downregulation of fibrosis and inflammation pathways. We provide a proof-of-principle that telomerase activation may represent an effective treatment for pulmonary fibrosis provoked or associated with short telomeres., Competing Interests: JP, PM, RS, ÁT, GG, JF, FB, MB No competing interests declared, MB is an employee for F. Hoffmann-La Roche Ltd, and the author declares no other competing financial interests, (© 2018, Povedano et al.)

Prostate cancer is diagnosed late in life, when co-morbidities are frequent. Among them, hypertension, hypercholesterolemia, diabetes or metabolic syndrome exhibit an elevated incidence. In turn, prostate cancer patients frequently undergo chronic pharmacological treatments that could alter disease initiation, progression and therapy response. Here we show that treatment with anti-cholesterolemic drugs, statins, at doses achieved in patients, enhance the pro-tumorigenic activity of obesogenic diets. In addition, the use of a mouse model of prostate cancer and human prostate cancer xenografts revealed that in vivo simvastatin administration alone increases prostate cancer aggressiveness. In vitro cell line systems supported the notion that this phenomenon occurs, at least in part, through the direct action on cancer cells of low doses of statins, in range of what is observed in human plasma. In sum, our results reveal a prostate cancer experimental system where statins exhibit an undesirable effect, and warrant further research to address the relevance and implications of this observation in human prostate cancer., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Cyclin O (encoded by CCNO ) is a member of the cyclin family with regulatory functions in ciliogenesis and apoptosis. Homozygous CCNO mutations have been identified in human patients with Reduced Generation of Multiple Motile Cilia (RGMC) and conditional inactivation of Ccno in the mouse recapitulates some of the pathologies associated with the human disease. These include defects in the development of motile cilia and hydrocephalus. To further investigate the functions of Ccno in vivo , we have generated a new mouse model characterized by the constitutive loss of Ccno in all tissues and followed a cohort during ageing. Ccno -/- mice were growth impaired and developed hydrocephalus with high penetrance. In addition, some Ccno +/- mice also developed hydrocephalus and affected Ccno -/- and Ccno +/- mice exhibited additional CNS defects including cortical thinning and hippocampal abnormalities. In addition to the CNS defects, both male and female Ccno -/- mice were infertile and female mice exhibited few motile cilia in the oviduct. Our results further establish CCNO as an important gene for normal development and suggest that heterozygous CCNO mutations could underlie hydrocephalus or diminished fertility in some human patients., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no conflict of interest.

Salp15, a salivary protein of Ixodes ticks, inhibits the activation of naïve CD4 T cells. Treatment with Salp15 results in the inhibition of early signaling events and the production of the autocrine growth factor, interleukin-2. The fate of the CD4 T cells activated in the presence of Salp15 or its long-term effects are, however, unknown. We now show that Salp15 binding to CD4 is persistent and induces a long-lasting immunomodulatory effect. The activity of Salp15 results in sustained diminished cross-antigenic antibody production even after interruption of the treatment with the protein. Transcriptionally, the salivary protein provokes an acute effect that includes known activation markers, such as Il2 or Cd44, and that fades over time. The long-term effects exerted by Salp15 do not involve the induction of either anergy traits nor increased populations of regulatory T cells. Similarly, the treatment with Salp15 does not result in B cell anergy or the generation of myeloid suppressor cells. However, Salp15 induces the increased expression of the ectoenzyme, CD73, in regulatory T cells and increased production of adenosine. Our study provides a profound characterization of the immunomodulatory activity of Salp15 and suggests that its long-term effects are due to the specific regulation of CD73.

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Purpose: To investigate survival outcomes of patients treated with concurrent cetuximab and radiotherapy for primary management of both HPV positive and negative OPSCC, and compare the results to traditional platinum-based therapy. We hypothesize that the use of cetuximab in the HPV positive OPSCC patients will result in inferior survival based on tumor biological differences., Study Design: A single institution retrospective analysis of 304 patients. The primary outcomes of interest were 1) overall survival and 2) relapse free survival. Pearson Chi-square tests were used to compare proportions between subgroups. One-way analysis of variance was used to compare the continuous variable age between subgroups. Kaplan-Meier method was used to produce survival curves, and comparisons between survival curves were made using the log-rank test. The survival functions comparing subgroups of chemotherapy were analyzed using semi-parametric (i.e. Cox proportional hazards models) and fully parametric regression with Weibull distributions. Multivariable models were adjusted for age at diagnosis, gender, race, chemotherapy, radiotherapy, and cancer stage., Results: In the multivariable analysis, the hazard ratio for cetuximab compared to cisplatin or carboplatin/paclitaxel was HR=0.77[95% CI = 0.67, 0.90] in the HPV - group, suggesting more favorable outcomes for the patients on cetuximab in this group. However, in the HPV + cohort, the hazard ratio was 1.88 [95% CI = 1.42, 2.50] for those patients treated with cetuximab vs platinum-based therapy., Conclusions: Our data suggest that cetuximab may have inferior outcomes in HPV-associated OPSCC compared to traditional platinum-based therapy., Competing Interests: CONFLICTS OF INTEREST There are no conflicts of interest to disclose.

Background: Substance use is common among men who have sex with men (MSM) worldwide, and epidemiologic data suggest that alcohol/substance-using MSM are at greater risk for HIV. However, there are scarce data on substance abuse treatment programs (SATPs) for substance-using MSM., Objectives: We examined proportions of substance use as well as SATP availability and use. We used multivariable regression models, controlling for potential confounders, to examine behavioral and demographic correlates of SATP availability and use., Methods: This is a cross-sectional study of a multi-region, online sample of substance-using MSM., Results: In this sample, 75% were substance-using MSM of whom 36% reported at-least-weekly use. Substance use was most prevalent among respondents from Eastern Europe/Central Asia (86%) and Latin America (79%). Among substance-using MSM, 96% and 33% reported alcohol intoxication and other substance use, respectively; 11% reported having high SATP availability; and 5% reported using SATPs. Controlling for global region of origin and age, high SATP availability was associated with high access to HIV risk-reduction education (aOR = 3.19; CI = 1.48-6.89), mental health services (aOR = 2.53; CI = 1.32-4.83), and medical care (aOR = 2.32; CI = 1.12-4.80); less than college-level education (aOR = 0.32; CI = 0.18-0.54); and higher comfort levels with providers (aOR = 1.75; CI = 1.30-2.37). Controlling for substance use frequency and personal income additionally, using SATPs was associated with higher levels of connection to the gay community (aOR = 2.76; CI = 1.22-6.22)., Conclusion: In this global sample of MSM, we found high alcohol intoxication and other substance use proportions. Few substance-using MSM report SATP availability, highlighting the need to develop novel substance use programs outside traditional treatment settings.

Zika virus (ZIKV) is an emerging arthropod-borne flavivirus associated with severe congenital malformations and neurological complications. Although the ZIKV genome is well characterized, there is limited information regarding changes after cell isolation and culture adaptation. We isolated, and passaged in Vero cells, ZIKV from the serum of a symptomatic male patient and compared the viral genomes before and after culture. Single nucleotide polymorphisms were characteristic among serum-circulating genomes, while such diversity decreased after cell culture., (Copyright © 2017 Boukadida et al.)

Background: Neoadjuvant radiotherapy (NRT) enhances breast-conserving surgery outcomes, reducing local recurrence of breast cancer and increasing median survival. However, its effect on postoperative morbidity remains under-studied. We sought to assess the impact of NRT on 30-day postoperative morbidity after mastectomy., Methods: We analyzed data from women undergoing mastectomy (with or without immediate reconstruction) using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) 2005-2011 datasets. ACS-NSQIP is a prospective, risk-adjusted, outcomes-based registry. Data included demographic and perioperative factors. Outcomes studied included surgical site (wound and prosthesis/flap complications), systemic (cardiac, respiratory, neurological, urinary, and venous thromboembolism events), and overall morbidity. Logistic regression was used to estimate the unadjusted odds ratio (uOR) and adjusted odds ratio (aOR) between NRT and postoperative 30-day morbidity., Results: The study population included 77,902 women, of which 61,039 (78.4%) underwent mastectomy only and 16,863 (21.6%) underwent mastectomy with immediate breast reconstruction. NRT was administered to 266 (0.4%) mastectomy-only and 75 (0.4%) immediate breast reconstruction patients. In the mastectomy-only group, there were no significant differences in the rates of postoperative surgical site morbidity (aOR = 1.41; 95% confidence interval (CI): 0.76-2.63; P = 0.276), systemic morbidity (aOR = 0.72; 95% CI: 0.40-1.26; P = 0.252), and overall morbidity (aOR = 0.85; 95% CI: 0.54-1.33; P = 0.477) between NRT and control groups. Similarly, no significant differences were found for these three outcomes in the immediate breast reconstruction population. Statistical power for every comparison was >80%., Conclusions: This study suggests that NRT is not associated with significantly higher 30-day postoperative complications among breast cancer patients undergoing mastectomy with or without immediate breast reconstruction.

Following the performance of a superovulation protocol, multiple nodules were observed bilaterally in the uterine horns of 31 of 276 (11.2%) C57BL/6 J female mice aged 8.5 ± 0.6 (mean and standard error of mean) weeks. These lesions prevented embryo collection, and the uterine decidual reaction was suspected. Samples of pathological uteri (n = 20) and the normal genital tracts of donors treated with a similar superovulation protocol (control group, n = 10) were collected. Immunohistochemistry was performed to evaluate pancytokeratin, desmin, vimentin, progesterone receptor (PR), estrogen receptor α (ERα), Ki-67, cyclin D3 and c-Myc expression, as well as quantitative polymerase chain reaction to assess cyclin D3, Hoxa-10 and heparin-binding epidermal growth factor-like growth factor (HB-EGF) mRNA expression. The uterine decidual reaction presented a high degree of structural organization and specifically affected the antimesometrial region of the endometrium. The abnormal decidual cells were large polygonal cells that were frequently polyploid or binucleated and strongly positive for desmin. Immunohistochemistry showed higher Ki-67 proliferation index and higher expression of PR and cyclin D3 in decidual cells in the antimesometrial aspect of the endometrium, compared to nondecidualized endometrial stromal cells in the mesometrial aspect of affected uteri, and compared to endometrial stromal cells in healthy uteri. High expression of cyclin D3 and Hoxa-10 mRNA was also observed in uteri affected by the decidual reaction. These results suggest that PR overexpression in endometrial stromal cells, likely due to high progesterone levels, triggers cyclin D3 and Hoxa-10 overexpression, which may be involved in the pathological mechanisms of the mouse uterine decidual reaction.

Background: Medicaid and uninsured patients anecdotally incur higher cost and length of stay because of nonmedical, discharge-related factors. The purpose of this study was to investigate the association between primary payer and length of stay and cost, controlling for comorbidities and complications, in patients undergoing total laryngectomy., Methods: The sample included 4128 patients who underwent total laryngectomy in the 2005 to 2010 National Inpatient Sample (NIS). Patients were categorized into 4 subgroups based on payer status: Medicare, Medicaid, uninsured, and private insurance. Using multilevel modeling, we examined differences in length of stay and hospitalization costs., Results: The odds of being in the top quartile of length of stay increased for Medicaid patients by 41% (odds ratio [OR] = 1.41; 95% confidence interval [CI] = 1.03-1.92) compared with privately insured patients., Conclusion: After controlling for medical factors, Medicaid patients had increased lengths of stay. Overall costs were highest for those with public insurance, but no difference was seen for the adjusted cost. © 2016 Wiley Periodicals, Inc. Head Neck 39: 311-319, 2017., (© 2016 Wiley Periodicals, Inc.)

The burden of histoplasmosis has been poorly documented in most of the endemic areas for the disease, including Brazil. Also, modern non-culture-based diagnostic tests are often non-available in these regions. This was a prospective cohort study in HIV-infected patients with suspected disseminated disease evaluated with different diagnostic tests. Patients were enrolled in three referral medical centres in Porto Alegre, Brazil. Among 78 evaluated patients, disseminated histoplasmosis was confirmed in eight individuals (10.3%) by the means of classical (culture/histopathology) tests. Antigen detection in the urine was found to be more sensitive: IMMY ® ALPHA ELISA detected 13 positive cases (16.7%) and the in-house ELISA test developed by the Centers for Disease Prevention and Control (CDC) detected 14 (17.9%). IMMY ® and CDC tests provided concordant results in 96.2% of cases. This is the first study to compare the performance of the in-house CDC ELISA test with the IMMY ® commercial test for the diagnosis of histoplasmosis, and a high degree of concordance was observed. The study revealed that H. capsulatum is an important agent of disseminated disease in AIDS patients in Brazil, reinforcing the importance of making available modern diagnostic tests as well as safer antifungal agents for the treatment of histoplasmosis., (© 2016 Blackwell Verlag GmbH.)

Objective: To evaluate whether an association exists between gonarthrosis and metabolic syndrome X (MS) as well as other potential risk factors., Method: Comparative cross-sectional study of 310 patients evaluated by pathology of knee grouped in patients with gonarthrosis and without it. Sociodemographic, anthropometric and laboratory data was obtained. Gonarthrosis was defined as a ≥ 2 score in Kellgren-Lawrence radiological scale, and MS was assessed using the International Diabetes Federation criteria. Odds ratio and logistic regression were used for bivariate and multivariate analysis respectively., Results: The prevalence of MS in patients who had gonarthrosis was 79.9%, statistically higher than in patients without gonarthrosis (p = 0.001). Other factors that had a statistically higher frequency in this group included diabetes mellitus (p = 0.02) and hypertension (p = 0.02). Multivariate analysis revealed MS had an association with a higher prevalence of gonarthrosis (p = 0.003), while high density lipoproteins (p = 0.02) was associated with a lower prevalence., Conclusions: MS and its related alterations are associated to gonarthrosis; their adequate control could prevent patients from developing the disease., (Copyright: © 2017 SecretarÍa de Salud)

Oncogenic mutations in the PI3K/AKT pathway are present in nearly half of human tumors. Nonetheless, inhibitory compounds of the pathway often induce pathway rebound and tumor resistance. We find that lung squamous cell carcinoma (SQCC), which accounts for ~20% of lung cancer, exhibits increased expression of the PI3K subunit PIK3R2, which is at low expression levels in normal tissues. We tested a new approach to interfere with PI3K/AKT pathway activation in lung SQCC. We generated tumor xenografts of SQCC cell lines and examined the consequences of targeting PIK3R2 expression. In tumors with high PIK3R2 expression, and independently of PIK3CA, KRAS, or PTEN mutations, PIK3R2 depletion induced lung SQCC xenograft regression without triggering PI3K/AKT pathway rebound. These results validate the use PIK3R2 interfering tools for the treatment of lung squamous cell carcinoma.

RAP1 is one of the components of shelterin, the capping complex at chromosome ends or telomeres, although its role in telomere length maintenance and protection has remained elusive. RAP1 also binds subtelomeric repeats and along chromosome arms, where it regulates gene expression and has been shown to function in metabolism control. Telomerase is the enzyme that elongates telomeres, and its deficiency causes a premature aging in humans and mice. We describe an unanticipated genetic interaction between RAP1 and telomerase. While RAP1 deficiency alone does not impact on mouse survival, mice lacking both RAP1 and telomerase show a progressively decreased survival with increasing mouse generations compared to telomerase single mutants. Telomere shortening is more pronounced in Rap1 -/- Terc -/- doubly deficient mice than in the single-mutant Terc -/- counterparts, leading to an earlier onset of telomere-induced DNA damage and degenerative pathologies. Telomerase deficiency abolishes obesity and liver steatohepatitis provoked by RAP1 deficiency. Using genomewide ChIP sequencing, we find that progressive telomere shortening owing to telomerase deficiency leads to re-localization of RAP1 from telomeres and subtelomeric regions to extratelomeric sites in a genomewide manner. These findings suggest that although in the presence of sufficient telomere reserve RAP1 is not a key factor for telomere maintenance and protection, it plays a crucial role in the context of telomerase deficiency, thus in agreement with its evolutionary conservation as a telomere component from yeast to humans., (© 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

Higher plants take up nutrients via the roots and load them into xylem vessels for translocation to the shoot. After uptake, anions have to be channeled toward the root xylem vessels. Thereby, xylem parenchyma and pericycle cells control the anion composition of the root-shoot xylem sap [1-6]. The fact that salt-tolerant genotypes possess lower xylem-sap Cl(-) contents compared to salt-sensitive genotypes [7-10] indicates that membrane transport proteins at the sites of xylem loading contribute to plant salinity tolerance via selective chloride exclusion. However, the molecular mechanism of xylem loading that lies behind the balance between NO3(-) and Cl(-) loading remains largely unknown. Here we identify two root anion channels in Arabidopsis, SLAH1 and SLAH3, that control the shoot NO3(-)/Cl(-) ratio. The AtSLAH1 gene is expressed in the root xylem-pole pericycle, where it co-localizes with AtSLAH3. Under high soil salinity, AtSLAH1 expression markedly declined and the chloride content of the xylem sap in AtSLAH1 loss-of-function mutants was half of the wild-type level only. SLAH3 anion channels are not active per se but require extracellular nitrate and phosphorylation by calcium-dependent kinases (CPKs) [11-13]. When co-expressed in Xenopus oocytes, however, the electrically silent SLAH1 subunit gates SLAH3 open even in the absence of nitrate- and calcium-dependent kinases. Apparently, SLAH1/SLAH3 heteromerization facilitates SLAH3-mediated chloride efflux from pericycle cells into the root xylem vessels. Our results indicate that under salt stress, plants adjust the distribution of NO3(-) and Cl(-) between root and shoot via differential expression and assembly of SLAH1/SLAH3 anion channel subunits., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Despite the promise of hematological parameters and blood chemistry in monitoring the health of marine fishes, baseline data is often lacking for small fishes that comprise central roles in marine food webs. This study establishes blood chemistry and hematological baseline parameters for the pinfish Lagodon rhomboides, a small marine teleost that is among the most dominant members of near-shore estuarine communities of the Atlantic Ocean and Gulf of Mexico. Given their prominence, pinfishes are an ideal candidate species to use as a model for monitoring changes across a wide range of near-shore marine communities. However, pinfishes exhibit substantial morphological differences associated with a preference for feeding in primarily sea-grass or sand dominated habitats, suggesting that differences in the foraging ecology of individuals could confound health assessments. Here we collect baseline data on the blood physiology of pinfish while assessing the relationship between blood parameters and measured aspects of feeding morphology using data collected from 37 individual fish. Our findings provide new baseline health data for this important near shore fish species and find no evidence for a strong linkage between blood physiology and either sex or measured aspects of feeding morphology. Comparing our hematological and biochemical data to published results from other marine teleost species suggests that analyses of trends in blood value variation correlated with major evolutionary transitions in ecology will shed new light on the physiological changes that underlie the successful diversification of fishes.

Arginine kinase (AK) (ATP: L-arginine phosphotransferase, E.C. 2.7.3.3) catalyzes the reversible transfer of ATP γ-phosphate group to L-arginine to synthetize phospho-arginine as a high-energy storage. Previous studies suggest additional roles for AK in cellular processes. Since AK is found only in invertebrates and it is homologous to creatine kinase from vertebrates, the objective of this work was to demonstrate nucleoside diphosphate kinase-like activity for shrimp AK. For this, AK from marine shrimp Litopenaeus vannamei (LvAK) was purified and its activity was assayed for phosphorylation of TDP using ATP as phosphate donor. Moreover, by using high-pressure liquid chromatography (HPLC) the phosphate transfer reaction was followed. Also, LvAK tryptophan fluorescence emission changes were detected by dTDP titration, suggesting that the hydrophobic environment of Trp 221, which is located in the top of the active site, is perturbed upon dTDP binding. The kinetic constants for both substrates Arg and dTDP were calculated by isothermal titration calorimetry (ITC). Besides, docking calculations suggested that dTDP could bind LvAK in the same cavity where ATP bind, and LvAK basic residues (Arg124, 126 and 309) stabilize the dTDP phosphate groups and the pyrimidine base interact with His284 and Ser122. These results suggest that LvAK bind and phosphorylate dTDP being ATP the phosphate donor, thus describing a novel alternate nucleoside diphosphate kinase-like activity for this enzyme.

Background: The structural characteristics of the fibula, strength, shape, length and limited donor site morbidity make it more suitable for reconstructing long bone defects larger than 6cm in the limbs., Material and Methods: A descriptive study was conducted using a non-probabilistic sample of consecutive cases undergoing on limb reconstruction with free fibular flap in the period from January 2010 to January 2015 in the Mexican Institute of Social Security No. 21, Monterrey Nuevo Leon., Results: The mean age of the ten cases included was 25 years, with the most common diagnosis being trauma in 4 patients, osteosarcoma in 2, followed by one congenital pseudoarthrosis of the tibia, one non-union fracture, and one gunshot wounds, respectively. The most common location was tibia, followed by humerus, radius, ulna and femur., Conclusions: This study has shown that the fibular free flap can be an excellent option for management of long bone defects, regardless of cause of the injury. One or more skin islands can be added for coverage in exposure of deep tissue and osteosynthesis material, thus preserving the septocutaneous perforators., (Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.)

Reactive oxygen species (ROS) are constantly generated by cells and ROS-derived damage contributes to ageing. Protection against oxidative damage largely relies on the reductive power of NAPDH, whose levels are mostly determined by the enzyme glucose-6-phosphate dehydrogenase (G6PD). Here, we report a transgenic mouse model with moderate overexpression of human G6PD under its endogenous promoter. Importantly, G6PD-Tg mice have higher levels of NADPH, lower levels of ROS-derived damage, and better protection from ageing-associated functional decline, including extended median lifespan in females. The G6PD transgene has no effect on tumour development, even after combining with various tumour-prone genetic alterations. We conclude that a modest increase in G6PD activity is beneficial for healthspan through increased NADPH levels and protection from the deleterious effects of ROS.

Purpose: This study explored the effectiveness of simulated mouth models to improve identification and recording of dental restorations when compared to using traditional didactic instruction combined with 2-dimensional images. Simulation has been adopted into medical and dental education curriculum to improve both student learning and patient safety outcomes., Methods: A 2-sample, independent t-test analysis of data was conducted to compare graded dental recordings of dental hygiene students using simulated mouth models and dental hygiene students using 2-dimensional photographs. Evaluations from graded dental charts were analyzed and compared between groups of students using the simulated mouth models containing random placement of custom preventive and restorative materials and traditional 2-dimensional representations of didactically described conditions., Results: Results demonstrated a statistically significant (p≤0.0001) difference: for experimental group, students using the simulated mouth models to identify and record dental conditions had a mean of 86.73 and variance of 33.84. The control group students using traditional 2-dimensional images mean graded dental chart scores were 74.43 and variance was 14.25., Conclusion: Using modified simulation technology for dental charting identification may increase level of dental charting skill competency in first year dental hygiene students., (Copyright © 2016 The American Dental Hygienists’ Association.)

Objectives To identify measurable anatomical factors that may guide the surgical approach for posterior fossa selective vestibular neurectomy (SVN) and predict identification of the vestibulocochlear cleavage (VCC) plane. Study Design Dissection of fixed cadaveric heads through retrolabyrinthine and retrosigmoid-internal auditory canal (RSG-IAC) approaches with measurement of landmarks. Setting Cadaveric dissection model. Main Outcome Measures Area of the Trautmann triangle (TT) and the distance from the posterior semicircular canal to the anterior border of the sigmoid along the posterior Donaldson line (pDL). VCC planes from each approach were calculated and compared. Results Overall mean pDL was 8.53 mm (range: 5-11.5 mm); mean TT area was 124 mm(2) (range: 95-237 mm(2)). The VCC was identified in 63% of ears through the retrolabyrinthine (RVN) approach alone, whereas 37% of ears required the RSG-IAC approach. In ears requiring IAC dissection, the VCC was found within 1 to 2 mm distal to the porus. The pDL (p < 0.05) and area of TT (p < 0.05) were significantly larger in the RVN group compared with the RSG-IAC group. Conclusion Ears amenable to the RVN approach had a greater pDL and TT area. These anatomical measurements may have a role in surgical planning and the choice of approach for SVN.

Chloride (Cl(-)) is a micronutrient that accumulates to macronutrient levels since it is normally available in nature and actively taken up by higher plants. Besides a role as an unspecific cell osmoticum, no clear biological roles have been explicitly associated with Cl(-) when accumulated to macronutrient concentrations. To address this question, the glycophyte tobacco (Nicotiana tabacum L. var. Habana) has been treated with a basal nutrient solution supplemented with one of three salt combinations containing the same cationic balance: Cl(-)-based (CL), nitrate-based (N), and sulphate+phosphate-based (SP) treatments. Under non-saline conditions (up to 5 mM Cl(-)) and no water limitation, Cl(-) specifically stimulated higher leaf cell size and led to a moderate increase of plant fresh and dry biomass mainly due to higher shoot expansion. When applied in the 1-5 mM range, Cl(-) played specific roles in regulating leaf osmotic potential and turgor, allowing plants to improve leaf water balance parameters. In addition, Cl(-) also altered water relations at the whole-plant level through reduction of plant transpiration. This was a consequence of a lower stomatal conductance, which resulted in lower water loss and greater photosynthetic and integrated water-use efficiency. In contrast to Cl(-), these effects were not observed for essential anionic macronutrients such as nitrate, sulphate, and phosphate. We propose that the abundant uptake and accumulation of Cl(-) responds to adaptive functions improving water homeostasis in higher plants., (© The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.)

Regulatory T cells that express CD39 (CD39+ Treg) exhibit specific immunomodulatory properties. Ectonucleotidase CD39 hydrolyses ATP and ADP. ATP is a ligand of the P2X7 receptor and induces the shedding of CD62L and apoptosis. However, the role of ATP in CD39+ Treg cells has not been defined. Furthermore, NAD can activate the P2X7 receptor via ADP-ribosyltransferase (ART) enzymes and cause cell depletion in murine models. We evaluated the expression and function of P2X7 and ART1 in CD39+ Treg and CD39- Treg cells in the presence or absence of ATP and NAD. We isolated peripheral blood mononuclear cells from healthy subjects and purified CD4+ T cells, CD4+ CD25+ T cells and CD4+ CD25+ CD39+ T cells. P2X7 and ART1 expression was assessed by flow cytometry and real-time PCR. Our results showed low P2X7 expression on CD39+ Treg cells and higher levels of ART1 expression in CD4+ CD39+ T cells than the other subtypes studied. Neither shedding of CD62L nor cell death of CD39+ Treg or CD39- Treg cells was observed by 1mM ATP or 60μM NAD. In contrast, P2Xs receptor-dependent proliferation with 300μM ATP, was inhibited by NAD in the different cell types analysed. The NAD proliferation-inhibition was increased with P2Xs and A2a agonist and was reversed with P2Xs and A2a antagonist, therefore NAD inhibits P2Xs-dependent proliferation and A2a activation. In conclusion, our results suggest that the altered function and expression of P2X7 and ART1 in the human CD39+ Treg or CD39- Treg cells could participate in the resistance against cell death induced by ATP or NAD., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

Tight junctions (TJs) are highly specialized membrane domains involved in many important cellular processes such as the regulation of the passage of ions and macromolecules across the paracellular space and the establishment of cell polarity in epithelial cells. Over the past few years there has been increasing evidence that different components of the TJs can be hijacked by viruses in order to complete their infectious cycle. Viruses from at least nine different families of DNA and RNA viruses have been reported to use TJ proteins in their benefit. For example, TJ proteins such as JAM-A or some members of the claudin family of proteins are used by members of the Reoviridae family and hepatitis C virus as receptors or co-receptors during their entry into their host cells. Reovirus, in addition, takes advantage of the TJ protein Junction Adhesion Molecule-A (JAM-A) to achieve its hematogenous dissemination. Some other viruses are capable of regulating the expression or the localization of TJ proteins to induce cell transformation or to improve the efficiency of their exit process. This review encompasses the importance of TJs for viral entry, replication, dissemination, and egress, and makes a clear statement of the importance of studying these proteins to gain a better understanding of the replication strategies used by viruses that infect epithelial and/or endothelial cells.