Species limits and introgression in Pimelodus from the Magdalena-Cauca River basin.

Low morphological differentiation among taxa hampers their appropriate identification, basic biological studies and promotion of any conservation effort. Aiming to provide the first insight into the evolution and speciation among north-western South American members of Pimelodus, this study tested the hypothesis that Pimelodus yuma, Pimelodus grosskopfii and Pimelodus crypticus represent three independently evolving species and explored signals of interspecific hybridisation. The outcomes based on mitochondrial (cox1) and nuclear (RADseq, microsatellites and rag2) markers combined with coalescence-based and allele-frequency methods confirmed that each studied species represents an independently evolving unit. Contrary to expectations, P. yuma was found as a sister clade of P. blochii, while P. crypticus (formerly confused with P. blochii) was phylogenetically closer to P. grosskopfii. We also found strong evidence of ancient introgression (0.66-3.32 mya) between the non-sibling species P. yuma and P. grosskopfii, breaking the absence of interbreeding and the independent evolutionary trajectory among north-western South American Pimelodus during their diversification history, a pre-requisite to define species limits. However, there were non-significant values of current gene flow between them, supporting the hypothesis of full isolation.

Depression and Anxiety after Stroke in Young Adult Filipinos.

BACKGROUND AND OBJECTIVES: Young adult patients may suffer from poststroke depression (PSD) and anxiety. Few studies have evaluated these important psychiatric conditions that may lead to adverse outcomes in young adults. We aimed to determine the prevalence of PSD and anxiety as well as to identify their predictors in a population of young Filipino adults (18-49 years old). METHODS: We performed a cross-sectional epidemiologic study in the largest tertiary hospital in the Philippines. The study involved the administration of a structured survey tool and review of medical records. The Hospital Anxiety and Depression Score - Pilipino version (HADS-P) was used to screen for anxiety and depression. Multivariable logistic regression analysis was performed to determine significant socio-economic and clinical risk factors of PSD and anxiety. RESULTS: 114 young adult stroke patients were included. The prevalence of depression was 20.2% while that of anxiety was 34.2%. Significant predictors of PSD were the presence of anxiety (OR 1.84; CI 1.05-3.22), lower mRS scores (mRS 3-5 OR 5.52; 95% CI 1.09-8.03) and diabetes (OR 2.09; 95% CI 1.67-6.26). Meanwhile, significant predictors of poststroke anxiety included depression (OR 7.5; 95% CI 5.02-21.94) and dependency (Barthel Index scores 95-100; OR 0.94; 95% CI 0.89-0.99). Relationship status, educational attainment, stroke subtype and location were not found to be significant predictors of PSD and anxiety. CONCLUSION: A significant proportion of young adults suffered from depression and anxiety after stroke. Clinicians should be aware of these psychiatric conditions that influence outcomes and quality of life of young adults with stroke.

Non-Traumatic Intracerebral Hematoma in the Young: Findings from a Tertiary Hospital in the Philippines.

BACKGROUND: There is geographic variability in the clinical profile and outcomes of non-traumatic intracerebral hematoma (ICH) in the young, and data for the Philippines is lacking. We aimed to describe this in a cohort from the Philippines, and identify predictors of mortality. METHODS: We performed a retrospective study of all patients aged 19-49 years with radiographic evidence of non-traumatic ICH admitted in our institution over five years. Data on demographics, risk factors, imaging, etiologies, surgical management, in-hospital mortality, and discharge functional outcomes were collected. Multivariate logistic regression analysis was done to determine factors predictive of mortality. RESULTS: A total of 185 patients were included, which had a mean age of 40.98 years and a male predilection (71.9%). The most common hematoma location was subcortical, but it was lobar for the subgroup of patients aged 19-29 years. Overall, the most common etiology was hypertension (73.0%), especially in patients aged 40-49. Conversely, the incidence of vascular lesions and thrombocytopenia was higher in patients aged 19-29. Surgery was done in 7.0% of patients. The rates of mortality and favorable functional outcome at discharge were 8.7% and 35.1%, respectively. Younger age (p = 0.004), higher NIHSS score on admission (p=0.01), higher capillary blood glucose on admission (p=0.02), and intraventricular extension of hematoma (p = 0.01) predicted mortality. CONCLUSIONS: In the Philippines, the most common etiology of ICH in young patients was hypertension, while aneurysms and AVM's were the most common etiology in the subgroup aged 19 - 29 years. Independent predictors of mortality were identified.

Human Oocyte-Derived Methylation Differences Persist in the Placenta Revealing Widespread Transient Imprinting.

Thousands of regions in gametes have opposing methylation profiles that are largely resolved during the post-fertilization epigenetic reprogramming. However some specific sequences associated with imprinted loci survive this demethylation process. Here we present the data describing the fate of germline-derived methylation in humans. With the exception of a few known paternally methylated germline differentially methylated regions (DMRs) associated with known imprinted domains, we demonstrate that sperm-derived methylation is reprogrammed by the blastocyst stage of development. In contrast a large number of oocyte-derived methylation differences survive to the blastocyst stage and uniquely persist as transiently methylated DMRs only in the placenta. Furthermore, we demonstrate that this phenomenon is exclusive to primates, since no placenta-specific maternal methylation was observed in mouse. Utilizing single cell RNA-seq datasets from human preimplantation embryos we show that following embryonic genome activation the maternally methylated transient DMRs can orchestrate imprinted expression. However despite showing widespread imprinted expression of genes in placenta, allele-specific transcriptional profiling revealed that not all placenta-specific DMRs coordinate imprinted expression and that this maternal methylation may be absent in a minority of samples, suggestive of polymorphic imprinted methylation.

Phenolic Profile, Antioxidant and Anti-Proliferative Activities of Methanolic Extracts from Asclepias linaria Cav. Leaves.

Asclepias linaria Cav. (Apocynaceae) is a shrubby plant endemic of Mexico which has been used in traditional medicine. However, the bioactive potential of this plant remains unexplored. In this study, the phenolic composition, antioxidant, and cytotoxic activities of A. linaria leaves were determined. In order to estimate the phenolic composition of the leaves, the total phenolic, flavonoid, and condensed tannins contents were determined. Furthermore, the antioxidant activity was measured by the scavenging activity of the 2,2-diphenyl-1-picrylhydrazyl (DPPH•) and 2,2'-azino-bis[3-ethylbenzothiazoline-6-sulphonic acid] (ABTS•+) radicals and the total antioxidant capacity. The phenolic compounds identified in the A. linaria leaves by ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS) include phenolic acids, such as p-coumaric and ferulic acid, as well as flavonoids, such as rutin and quercetin. The leaves' extracts of A. linaria showed a high scavenging activity of DPPH• and ABTS•+ radicals (IC50 0.12 ± 0.001 and 0.51 ± 0.003 µg/mL, respectively), high total antioxidant capacity values (99.77 ± 4.32 mg of ascorbic acid equivalents/g of dry tissue), and had a cytotoxic effect against K562 and HL60 hematologic neoplasia cells lines, but no toxicity towards the normal mononuclear cell line was observed. These results highlight the potential of A. linaria and could be considered as a possible alternative source of anticancer compounds.

The transcription factor MEF2A fine-tunes gene expression in the atrial and ventricular chambers of the adult heart.

The distinct morphological and functional properties of the cardiac chambers arise from an elaborate developmental program involving cell lineage determination, morphogenesis, and dynamic spatiotemporal gene expression patterns. Although a number of transcription factors have been identified for proper gene regulation in the chambers, the complete transcriptional network that controls these patterns remains poorly defined. Previous studies have implicated the MEF2C transcription factor in the regulation of chamber-restricted enhancers. To better understand the mechanisms of MEF2-mediated regional gene regulation in the heart, we took advantage of MEF2A knock-out (KO) mice, a model that displays a predominantly ventricular chamber phenotype. Transcriptomic analysis of atrial and ventricular tissue from adult MEF2A KO hearts revealed a striking difference in chamber gene expression, with a larger proportion of dysregulated genes in the atrial chambers. Canonical pathway analysis of genes preferentially dysregulated in the atria and ventricles revealed distinct MEF2A-dependent cellular processes in each cardiac chamber. In the atria, MEF2A regulated genes involved in fibrosis and adhesion, whereas in the ventricles, it controlled inflammation and endocytosis. Finally, analysis of transcription factor-binding site motifs of differentially dysregulated genes uncovered distinct MEF2A co-regulators for the atrial and ventricular gene sets, and a subset of these was found to cooperate with MEF2A. In conclusion, our results suggest a mechanism in which MEF2 transcriptional activity is differentially recruited to fine-tune gene expression levels in each cardiac chamber. This regulatory mechanism ensures optimal output of these gene products for proper physiological function of the atrial and ventricular chambers.

Impact of chronic hepatitis C on mortality in cirrhotic patients admitted to intensive-care unit.

BACKGROUND: Cirrhosis and severe sepsis are factors associated with increased mortality in intensive care unit (ICU), but chronic hepatitis C (CHC) has been less studied in ICU. The aim of this study was to analyze the impact of CHC on the mortality of cirrhotic patients admitted to ICU according to severe sepsis and decompensated cirrhosis. METHODS: We carried out a retrospective study based on CHC-cirrhotic patients (CHC-group) admitted to ICU (n = 1138) and recorded in the Spanish Minimum Basic Data Set (2005-2010). A control-group (randomly selected cirrhotic patients without HIV, HBV, or HCV infections) was also included (n = 4127). The primary outcome variable was ICU mortality. The cumulative mortality rate on days 7, 30, and 90 in patients admitted to the ICUs was calculated by dividing the number of deaths by the number of patients admitted to the ICU. The adjusted hazard ratio (aHR) for death in the ICU was estimated through a semi-parametric Bayesian model of competing risk. RESULTS: The CHC-group had a higher cumulative incidence of severe sepsis than the control-group in compensated cirrhosis (37.4 vs. 31.1%; p = 0.024), but no differences between the CHC-group and the control-group in decompensated cirrhosis were found. Moreover, a higher cumulative incidence of severe sepsis was associated with decompensated cirrhosis compared to compensated cirrhosis in the control-group (40.1 vs. 31.1%; p < 0.001) whereas this was not observed in the CHC group (38.1 vs. 37.4%; p = 0.872). The CHC-group had higher cumulative mortality than the control-group by days 7 (47 vs. 41.3%; p < 0.001), 30 (78.5 vs. 73.5%; p < 0.001), and 90 (96.3 vs. 95.9%; p < 0.001). In a competitive risk model, the CHC-group had a higher risk of dying if the ICU course was complicated by severe sepsis (adjusted hazard ratio (aHR) = 1.19; p = 0.003), but no significant values in patients with absence of severe sepsis were found (aHR = 1.09; p= 0.068). When patients were stratified by cirrhosis stage and severe sepsis, CHC patients with compensated cirrhosis had the higher risk of death if they had severe sepsis (aHR = 1.35; p = 0.002). Moreover, the survival was low in patients with decompensated cirrhosis and severe sepsis but we did not find significant differences between CHC-group and control-group. CONCLUSIONS: CHC was associated with an increased risk of death in cirrhotic patients admitted to ICUs, particularly in patients with compensated cirrhosis and severe sepsis.

Advancement of an Infra-Red Technique for Whole-Field Concentration Measurements in Fluidized Beds.

For a better understanding and description of the mass transport phenomena in dense multiphase gas-solids systems such as fluidized bed reactors, detailed and quantitative experimental data on the concentration profiles is required, which demands advanced non-invasive concentration monitoring techniques with a high spatial and temporal resolution. A novel technique based on the selective detection of a gas component in a gas mixture using infra-red properties has been further developed. The first stage development was carried out using a very small sapphire reactor and CO2 as tracer gas. Although the measuring principle was demonstrated, the real application was hindered by the small reactor dimensions related to the high costs and difficult handling of large sapphire plates. In this study, a new system has been developed, that allows working at much larger scales and yet with higher resolution. In the new system, propane is used as tracer gas and quartz as reactor material. In this study, a thorough optimization and calibration of the technique is presented which is subsequently applied for whole-field measurements with high temporal resolution. The developed technique allows the use of a relatively inexpensive configuration for the measurement of detailed concentration fields and can be applied to a large variety of important chemical engineering topics.

Mortality of patients infected with HIV in the intensive care unit (2005 through 2010): significant role of chronic hepatitis C and severe sepsis.

INTRODUCTION: The combination antiretroviral therapy (cART) has led to decreased opportunistic infections and hospital admissions in human immunodeficiency virus (HIV)-infected patients, but the intensive care unit (ICU) admission rate remains constant (or even increased in some instances) during the cART era. Hepatitis C virus (HCV) infection is associated with an increased risk for hospital admission and/or mortality (particularly those related to severe liver disease) compared with the general population. The aim of this study was to assess the mortality among HIV-infected patients in ICU, and to evaluate the impact of HIV/HCV coinfection and severe sepsis on ICU mortality. METHODS: We carried out a retrospective study based on patients admitted to ICU who were recorded in the Minimum Basic Data Set (2005 through 2010) in Spain. HIV-infected patients (All-HIV-group (n = 1,891)) were divided into two groups: HIV-monoinfected patients (HIV group (n = 1,191)) and HIV/HCV-coinfected patients (HIV/HCV group (n = 700)). A control group (HIV(-)/HCV(-)) was also included (n = 7,496). RESULTS: All-HIV group had higher frequencies of severe sepsis (57.7% versus 39.4%; P < 0.001) than did the control group. Overall, ICU mortality in patients with severe sepsis was much more frequent than that in patients without severe sepsis (other causes) at days 30 and 90 in HIV-infected patients and the control group (P < 0.001). Moreover, the all-HIV group in the presence or absence of severe sepsis had a higher percentage of death than did the control group at days 7 (P < 0.001), 30 (P < 0.001) and 90 (P < 0.001). Besides, the HIV/HCV group had a higher percentage of death, both in patients with severe sepsis and in patients without severe sepsis compared with the HIV group at days 7 (P < 0.001) and 30 (P < 0.001), whereas no differences were found at day 90. In a bayesian competing-risk model, the HIV/HCV group had a higher mortality risk (adjusted hazard ratio (aHR) = 1.44 (95% CI = 1.30 to 1.59) and aHR = 1.57 (95% CI = 1.38 to 1.78) for patients with and without severe sepsis, respectively). CONCLUSIONS: HIV infection was related to a higher frequency of severe sepsis and death among patients admitted to the ICU. Besides, HIV/HCV coinfection contributed to an increased risk of death in both the presence and the absence of severe sepsis.

Methylene blue biosorption by pericarp of corn, alfalfa, and agave bagasse wastes.

The presence of dyes in effluent is a matter of concern due to their toxicologic and aesthetical effects. In this research, locally available agro-industrial wastes (Zea mays pericarp, ZMP; Agave tequilana bagasse, ATB; and Medicago sativa waste, MSW) were used as alternative low-cost adsorbents for the removal of methylene blue (MB) from aqueous solutions. The adsorbents were characterized physically and chemically by Fourier transform infrared, scanning electron microscopy, potentiometric titrations, and N2 physisorption. MB adsorption experiments were carried out in batch systems and experimental data were used to calculate the adsorption isotherm model parameters (Langmuir, Freundlich, and Temkin) and the adsorption kinetic model parameters (pseudo-first- and pseudo-second-order models). MB-loaded biosorbents were desorbed with deionized water, ethanol (10% and 50% v/v), hydrochloric acid (0.01 and 0.05 N), and sodium hydroxide (0.1 N) at room temperature, and the best eluent was used in various adsorption-desorption cycles. The selected agricultural wastes can be considered as promising adsorbents for dye uptake from water since they exhibit considerable MB adsorption capacity (MSW 202.6 mg g(-1), ATB 156.2mg g(-1), and ZMP 110.9mg g(-1)), but it is lower than that reported for activated carbon; however, the biosorbents show higher adsorption rate than powdered activated carbon. Furthermore, the adsorbents can be economically regenerated with HCl solutions and reused for seven adsorption-desorption cycles.

Low-performance diagnosis of covered anaerobic lagoons as a waste management strategy in the intensive dairy industry.

Covered anaerobic lagoons (CALs) are Latin America's main livestock waste treatment systems. Mexico has 680 CALs that present low biogas yields (0.05 m3 m-3 digester d-1) and low COD removal rates (< 60%). This work focused on diagnosing CAL´s low performance in dairy farms by determining and analyzing operational parameters. Seven CALs located in the main dairy basin of Mexico were analyzed. The sampling areas for each CAL were the supernatant, the active zone, settled sludge, and digester inlet and outlet. The variation of the process parameter values corroborated that CALs appeared stratified and not working as expected. The sludge zone, comprising 50-58% of total solids content and 1-15% of total CALs volume, showed an elemental compounds content suitable for organic fertilizer (340, 48, and 5 kg t-1 of C, N, and S, respectively). However, this zone contained, at least, 85% of the slowly hydrolysable material; the methanogenic potential was less than 87 mL CH4 g VS-1, and the C/N ratio ranged from 4.9 to 17, outside of the optimal range. The biogas produced did not exceed 60% of methane content and more than 3000 ppm of H2S. The sludge zone significantly influences the lagoon's dynamics since it is a nutrient sink. Furthermore, the lack of agitation is the leading cause for the low energy yield and the low removal of organic matter rate. This work provides valuable information to address the operational problems within the CALs improving our understanding that shall allow proposing reactivation alternatives.

Human germ cell differentiation from fetal- and adult-derived induced pluripotent stem cells.

Historically, our understanding of molecular genetic aspects of human germ cell development has been limited, at least in part due to inaccessibility of early stages of human development to experimentation. However, the derivation of pluripotent stem cells may provide the necessary human genetic system to study germ cell development. In this study, we compared the potential of human induced pluripotent stem cells (iPSCs), derived from adult and fetal somatic cells to form primordial and meiotic germ cells, relative to human embryonic stem cells. We found that ∼5% of human iPSCs differentiated to primordial germ cells (PGCs) following induction with bone morphogenetic proteins. Furthermore, we observed that PGCs expressed green fluorescent protein from a germ cell-specific reporter and were enriched for the expression of endogenous germ cell-specific proteins and mRNAs. In response to the overexpression of intrinsic regulators, we also observed that iPSCs formed meiotic cells with extensive synaptonemal complexes and post-meiotic haploid cells with a similar pattern of ACROSIN staining as observed in human spermatids. These results indicate that human iPSCs derived from reprogramming of adult somatic cells can form germline cells. This system may provide a useful model for molecular genetic studies of human germline formation and pathology and a novel platform for clinical studies and potential therapeutical applications.

Divergent RNA-binding proteins, DAZL and VASA, induce meiotic progression in human germ cells derived in vitro.

Our understanding of human germ cell development is limited in large part due to inaccessibility of early human development to molecular genetic analysis. Pluripotent human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) have been shown to differentiate to cells of all three embryonic germ layers, as well as germ cells in vitro, and thus may provide a model for the study of the genetics and epigenetics of human germline. Here, we examined whether intrinsic germ cell translational, rather than transcriptional, factors might drive germline formation and/or differentiation from human pluripotent stem cells in vitro. We observed that, with overexpression of VASA (DDX4) and/or DAZL (Deleted in Azoospermia Like), both hESCs and iPSCs differentiated to primordial germ cells, and maturation and progression through meiosis was enhanced. These results demonstrate that evolutionarily unrelated and divergent RNA-binding proteins can promote meiotic progression of human-derived germ cells in vitro. These studies describe an in vitro model for exploring specifics of human meiosis, a process that is remarkably susceptible to errors that lead to different infertility-related diseases.

Single-cell multi-omic analysis profiles defective genome activation and epigenetic reprogramming associated with human pre-implantation embryo arrest.

During pre-implantation stages of mammalian development, maternally stored material promotes both the erasure of the sperm and oocyte epigenetic profiles and is responsible for concomitant genome activation. Here, we have utilized single-cell methylome and transcriptome sequencing (scM&T-seq) to quantify both mRNA expression and DNA methylation in oocytes and a developmental series of human embryos at single-cell resolution. We fully characterize embryonic genome activation and maternal transcript degradation and map key epigenetic reprogramming events in developmentally high-quality embryos. By comparing these signatures with early embryos that have undergone spontaneous cleavage-stage arrest, as determined by time-lapse imaging, we identify embryos that fail to appropriately activate their genomes or undergo epigenetic reprogramming. Our results indicate that a failure to successfully accomplish these essential milestones impedes the developmental potential of pre-implantation embryos and is likely to have important implications, similar to aneuploidy, for the success of assisted reproductive cycles.

Characterization of Cosmos sulphureus Cav. (Asteraceae): Phytochemical Screening, Antioxidant Activity and Chromatography Analysis.

Cosmos sulphureus Cav. (Asteraceae), and endemic plant of Mexico is used in herbal medicine. In this study, the phytochemical composition, phenolic content, and antioxidant activity of ethanolic and methanolic extracts from C. sulphureus leaves and flowers were determined. The phytochemical analysis showed the presence of compounds such as terpenoids, phenolic compounds, tannins, and flavonoids and the absence of alkaloids, saponins, glycosides, and anthraquinones. The experimental results showed that the extracts have high contents of phenolic, flavonoid, and condensed tannins contents. The phenolic compounds identified in the C. sulphureus extracts by high-performance thin-layer chromatography (HPTLC) include phenolic acids such as chlorogenic acid and caffeic acid as well flavonoids such as rutin and quercetin. The C. sulphureus extracts showed a relevant free radical scavenging activity, ferric-reducing antioxidant power, lipid peroxidation inhibition ability, and oxygen radical antioxidant capacity. This research highlights the phytochemical profile and antioxidant activity of phenolic compounds-rich extracts from C. sulphureus leaves and flowers.

Antifungal Activity of Rue Essential Oil and Commercial Chitosan on Native Corn Foliar Diseases.

Native corn in Cherán, Michoacán, southwestern Mexico, represents a high-impact economic, social, and religious support, although its yield is low due to fungal diseases. Fungicides are mainly used for their control, but the fungi involved create resistance. The aims of this study are to determine the incidence of foliar diseases in the field, isolate the causal fungi, evaluate the in vitro effect of the essential oil of rue (Ruta graveolens) on them, and identify the secondary metabolites. The essential oil was obtained using the steam distillation technique on fresh plants. Also used was an industrial-grade chitosan, and the commercial fungicide benomyl was used as a positive control. Rue essential oil was characterized by mass spectrometry with ultra-high-performance liquid chromatography with electrospray ionization (UHPLC-ESI). The highest incidence of disease was obtained for leaf rust (35%), followed by gray leaf spot (GLS) (24%) and leaf blight (19%). Rue essential oil inhibited 100% of the mycelial growth of Coniothyrium phyllachorae and 96% of the mycelium of Exseroilum turcicum. The benomyl fungicide effectively inhibited C. phyllachorae (86 to 91%), but not E. turcicum, with the opposite effect when using chitosan by inhibiting 89 to 90% of the latter's mycelial development. The majority compound of the essential oil of R. graveolens was 2-(3-phenylprop-2-enoyl)chromen-4-one; however, fatty acids were also detected: linoleic, palmitic, and retinoic acid.

The E-box binding factors Max/Mnt, MITF, and USF1 act coordinately with FoxO to regulate expression of proapoptotic and cell cycle control genes by phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase 3 signaling.

Phosphatidylinositol (PI) 3-kinase/Akt signaling plays a critical role in cell proliferation and survival, partly by regulation of FoxO transcription factors. Previous work using global expression profiling indicated that inhibition of PI 3-kinase in proliferating cells led to induction of genes that promote cell cycle arrest and apoptosis. The upstream regulatory regions of these genes had binding sites not only for FoxO, but also for Myc/Max transcription factors. In the present study, we have addressed the role of Myc family members and related E-box-binding proteins in the regulation of these genes. Chromatin immunoprecipitations and RNA interference indicated that transcription was repressed by Max-Mnt-Sin3a-histone deacetylase complexes in proliferating cells. Inhibition of PI 3-kinase led to a loss of Max/Mnt binding and transcriptional induction by MITF and USF1, as well as FoxO. Both MITF and USF1 were activated by glycogen synthase kinase (GSK) 3, with GSK3 phosphorylation sites on USF1 identified as the previously described activating site threonine 153 as well as serine 186. siRNA against MITF as well as against FoxO3a protected cells from apoptosis following PI 3-kinase inhibition. These results define a novel E-box-regulated network that functions coordinately with FoxO to regulate transcription of apoptotic and cell cycle regulatory genes downstream of PI 3-kinase/Akt/GSK3 signaling.

Influence of interleukin-28B single-nucleotide polymorphisms on progression to liver cirrhosis in human immunodeficiency virus-hepatitis C virus-coinfected patients receiving antiretroviral therapy.

BACKGROUND: Single-nucleotide polymorphisms (SNPs) near the IL28B gene have recently been associated with spontaneous hepatitis C virus (HCV) clearance and response to interferon-based therapies in patients with chronic hepatitis C. Because human immunodeficiency virus (HIV) coinfection appears to accelerate HCV-related liver fibrosis progression, any influence of IL28B SNP on the risk of developing cirrhosis might be more easily recognized in the coinfected population. METHODS: All HIV-HCV-coinfected patients who underwent hepatic elastography before initiating a course of pegylated interferon plus ribavirin therapy at 2 Spanish clinics were retrospectively identified. Liver cirrhosis was defined as >14.5 kPa by transient elastography. The IL28B rs12979860 SNP was examined in a blinded fashion. RESULTS: A total of 304 HIV-HCV-coinfected individuals were analyzed (mean age, 43 years; 80% were male; and 85% were receiving antiretroviral therapy), of whom 18% had cirrhosis. IL28B genotype distribution was as follows: CC, 46%; CT, 43%; and TT, 11%. Cirrhosis was more frequent in CC than CT/TT carriers (24% vs 13%; P = .01). Logistic regression analysis revealed that older age (odds ratio [OR], 1.05; 95% confidence interval [CI], 0.99-1.12]; P = .08), past alcohol abuse (OR, 1.97; 95% CI, 0.95-4.06; P = .07), and CC IL28B genotype (OR, 2.32; 95% CI, 1.22-4.41; P = .01) were predictors of cirrhosis. Interestingly, mean (SD) alanine aminotransferase (ALT) levels were greater (90 ± 53 vs 71 ± 33 IU/L;, P = .01) in IL28B CC than CT/TT carriers during the prior 4.8 ± 3.8 years. CONCLUSIONS: The IL28B rs12979860 CC genotype is associated with a higher prevalence of cirrhosis in HIV-HCV-coinfected patients than CT/TT genotypes, suggesting that IL28B CC carriers may experience a more rapid progression of HCV-related liver fibrosis, perhaps as result of increased liver inflammation. Thus, access to HCV treatment is of utmost importance in IL28B CC carriers, in whom treatment response is better and in whom progression to cirrhosis might occur more rapidly.

On the Potential of Gallium- and Indium-Based Liquid Metal Membranes for Hydrogen Separation.

The concept of liquid metal membranes for hydrogen separation, based on gallium or indium, was recently introduced as an alternative to conventional palladium-based membranes. The potential of this class of gas separation materials was mainly attributed to the promise of higher hydrogen diffusivity. The postulated improvements are only beneficial to the flux if diffusion through the membrane is the rate-determining step in the permeation sequence. Whilst this is a valid assumption for hydrogen transport through palladium-based membranes, the relatively low adsorption energy of hydrogen on both liquid metals suggests that other phenomena may be relevant. In the current study, a microkinetic modeling approach is used to enable simulations based on a five-step permeation mechanism. The calculation results show that for the liquid metal membranes, the flux is limited by the dissociative adsorption over a large temperature range, and that the membrane flux is expected to be orders of magnitude lower compared to the membrane flux through pure palladium membranes. Even when accounting for the lower cost of the liquid metals compared to palladium, the latter still outperforms both gallium and indium in all realistic scenarios, in part due to the practical difficulties associated with making liquid metal thin films.

Predictive Value of Hematologic Inflammatory Markers in Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND AND OBJECTIVE: Our study aimed to determine the ability of hematologic markers (neutrophil/lymphocyte ratio [NLR], platelet/lymphocyte ratio, and red cell distribution width [RDW]) in predicting delayed cerebral ischemia (DCI), modified Rankin Scale scores, and mortality in patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: A retrospective observational 6-year review of medical records was conducted to identify all consecutive patients with aSAH admitted to the largest training hospital in the Philippines. Univariable and multivariable regression analyses were performed to determine the association of the biomarkers with the respective outcomes. Receiver operating characteristic curves were used to detect overall predictive accuracy. RESULTS: A total of 222 patients with aSAH were included, of whom 11.71% developed DCI. Most patients with NLR ≥5.9 subsequently died (77 vs. 52%; P = 0.03). DCI was also associated with poor functional outcomes with higher modified Rankin Scale scores (3-6) on discharge (92% vs. 49%; P < 0.01), and longer duration of hospitalization (median, 20 vs. 13 days; P = 0.01). In receiver operating characteristic analyses, the value of RDW was predictive for DCI (area under the curve, 0.70; 95% confidence interval, 0.62-0.79; P < 0.01). The values of NLR (area under the curve, 0.67; 95% CI, 0.59-0.74) potentially predict functional outcome. RDW, NLR, and their combinations were poor discriminators of mortality. CONCLUSIONS: Our study showed that some hematologic parameters analyzed could be of potential value as prognostic biomarkers in patients with aSAH. Hematologic biomarkers are widely available and practical parameters that may be of considerable clinical value in aSAH management, especially in lower-middle-income countries such as the Philippines.