High Prevalence of Respiratory Muscle Weakness in Hospitalized Acute Heart Failure Elderly Patients

IntroductionRespiratory Muscle Weakness (RMW) has been defined when the maximum inspiratory pressure (MIP) is lower than 70% of the predictive value. The prevalence of RMW in chronic heart failure patients is 30 to 50%. So far there are no studies on the prevalence of RMW in acute heart failure (AHF) patients.ObjectivesEvaluate the prevalence of RMW in patients admitted because of AHF and the condition of respiratory muscle strength on discharge from the hospital.MethodsSixty-three patients had their MIP measured on two occasions: at the beginning of the hospital stay, after they had reached respiratory, hemodynamic and clinical stability and before discharge from the hospital. The apparatus and technique to measure MIP were adapted because of age-related limitations of the patients. Data on cardiac ejection fraction, ECG, brain natriuretic peptide (BNP) levels and on the use of noninvasive ventilation (NIV) were collected.ResultsThe mean age of the 63 patients under study was 75 years. On admission the mean ejection fraction was 33% (95% CI: 31–35) and the BNP hormone median value was 726.5 pg/ml (range: 217 to 2283 pg/ml); 65% of the patients used NIV. The median value of MIP measured after clinical stabilization was -52.7 cmH2O (range: -20 to -120 cmH₂O); 76% of the patients had MIP values below 70% of the predictive value. On discharge, after a median hospital stay of 11 days, the median MIP was -53.5 cmH₂O (range:-20 to -150 cmH₂O); 71% of the patients maintained their MIP values below 70% of the predictive value. The differences found were not statistically significant.ConclusionElderly patients admitted with AHF may present a high prevalence of RMW on admission; this condition may be maintained at similar levels on discharge in a large percentage of these patients, even after clinical stabilization of the heart condition.     

Early stages of divergence: phylogeography, climate modeling, and morphological differentiation in the South American lizard Liolaemus petrophilus (Squamata: Liolaemidae)

This study examines the phylogeographic structure within the Patagonian lizard Liolaemus petrophilus and tests for patterns of between-clade morphological divergence and sexual dimorphism, as well as demographic and niche changes associated with Pleistocene climate changes. We inferred intraspecific relationships, tested hypotheses for historical patterns of population expansion, and incorporated ecological niche modeling (ENM) with standard morphological and geometric morphometric analyses to examine between-clade divergence as indirect evidence for adaptation to different niches. The two inferred haploclades diverged during the early Pleistocene with the Southern clade depicting the genetic signature of a recent population increase associated with expanding niche envelope, whereas the Northern clade shows stable populations in a shrinking niche envelope. The combination of molecular evidence for postisolation demographic change and ENM, suggest that the two haploclades have responded differently to Pleistocene climatic events.     

Antileishmanial activity of a guaianolide from Tanacetum parthenium (L.) Schultz Bip

Leishmaniasis is one of the major infectious diseases affecting the poorest regions of the world. The present study evaluated the antileishmanial activity of a guaianolide purified from the hydroalcoholic extract of aerial parts of Tanacetum parthenium (L.) Schultz Bip. The isolated compound showed activity against the promastigote form of Leishmania amazonensis, with 50% inhibition (IC₅₀) of cell growth at a concentration of 2.6 μg/ml. For the intracellular amastigote form, this guaianolide reduced by 10% the survival index of parasites in macrophages when it was used at 20.0 μg/ml. The selective index (SI) ratio (CC₅₀ for J774G8 cells/IC₅₀ for protozoans) was 385, showing that it is more selective against the parasite than mammalian cells. Morphological alterations of protozoans treated with IC₅₀ included changes in size, shape, and structure (more than one nucleus and flagellum) under both light and scanning electron microscopies.     

Associations between a highly invasive species and native macrophytes differ across spatial scales

The association between invasive and native species varies across spatial scales and is affected by phylogenetic relatedness, but these issues have rarely been addressed in aquatic ecosystems. In this study, we used a non-native, highly invasive species of Poaceae (tropical signalgrass) to test the hypotheses that (i) tropical signalgrass success correlates negatively with success of most native species of macrophytes at fine spatial scales, but its success correlates positively or at random with natives at coarse spatial scales, and that (ii) tropical signalgrass is less associated with native species belonging to the family Poaceae than with species belonging to other families (Darwin’s naturalization hypothesis). We used a dataset obtained at fine (0.25 m²) and coarse (ca. 1,000 m²) scales. The presence/absence of all species was recorded at both scales, and their biomass was also measured at the fine scale. We tested the association between tropical signalgrass biomass and individual native species with logistic regressions at the fine scale, and using the T-score index between tropical signalgrass and each native species at both scales. The likelihood of the occurrence of six species (submersed and free-floating) was negatively affected by tropical signalgrass biomass at the fine scale. T-scores showed that three species were less associated with tropical signalgrass than expected by chance, but 22 species co-occurred more than expected by chance at the coarse scale. Associations between species of Poaceae and tropical signalgrass were null at the fine scale, but were positive or null at the coarse scale. In addition to showing that spatial scale affects the patterns of association among the non-native and individual native species, our results indicate that phylogeny did not explain associations between the invasive and native macrophytes, at both scales.     

Rare Risk Variants Identification by Identity-by-Descent Mapping and Whole-Exome Sequencing Implicates Neuronal Development Pathways in Schizophrenia and Bipolar Disorder

Schizophrenia (SCZ) and bipolar disorder (BPD) are highly heritable disorders with an estimated co-heritability of 68%. Hundreds of common alleles have been implicated, but recently a role for rare, high-penetrant variants has been also suggested in both disorders. This study investigated a familial cohort of SCZ and BPD patients from a closed population sample, where the high recurrence of the disorders and the homogenous genetic background indicate a possible enrichment in rare risk alleles. A total of 230 subjects (161 cases, 22 unaffected relatives, and 47 controls) were genetically investigated through an innovative strategy that integrates identity-by-descent (IBD) mapping and whole-exome sequencing (WES). IBD analysis allowed to track high-risk haplotypes (IBD_risk) shared exclusively by multiple patients from different families and possibly carrying the most penetrant alleles. A total of 444 non-synonymous sequence variants, of which 137 disruptive, were identified in IBD_risk haplotypes by WES. Interestingly, gene sets previously implicated in SCZ (i.e., post-synaptic density (PSD) proteins, voltage-gated calcium channels (VGCCs), and fragile X mental retardation protein (FMRP) targets) were found significantly enriched in genes carrying IBD_risk variants. Further, IBD_risk variants were preferentially affecting genes involved in the extracellular matrix (ECM) biology and axon guidance processes which appeared to be functionally connected in the pathway-derived meta-network analysis. Results thus confirm rare risk variants as key factors in SCZ and BPD pathogenesis and highlight a role for the development of neuronal connectivity in the etiology of both disorders.     

<Emphasis Type="Italic">MBL2</Emphasis> gene polymorphisms in HHV-8 infection in people living with HIV/AIDS

Background

Host genetic factors such as MBL2 gene polymorphisms cause defects in the polymerization of MBL protein and result in a functional deficiency and/or in low serum levels that can influence susceptibility to various viral infections. The aim of this study was to estimate the frequency of alleles, genotypes and haplotypes related to -550, -221 and exon 1 polymorphisms of the MBL2 gene and investigate their association with HHV-8 in people living with HIV/AIDS (PLWHA), as well as the impacts on CD4 cell count and HIV viral load in HIV/HHV-8 coinfected and HIV monoinfected patients.

Results

A cross sectional study in PLWHA, with and without HHV-8 infection, exploring associations between different factors, was performed in the outpatient infectious and parasitic diseases clinic at a referral hospital. Genomic DNA extractions from leukocytes were performed using a commercial Wizard^® Genomic DNA Purification kit (Promega, Madison, WI). The promoter region (-550 and -221) was genotyped with the TaqMan system (Applied TaqMan Biosystems^® genotyping Assays), and the structural region (exon1) was genotyped with Express Sybr Greener Supermix kit (Invitrogen, USA). In total, 124 HIV/HHV-8 coinfected and 213 HIV monoinfected patients were analysed. Median TCD4 counts were significantly lower in HIV/HHV-8 coinfected patients, whereas the mean of the first and last viral load of HIV did not present significant difference. There was no difference in frequency between the LL, YY and AA genotypes between the HIV/HHV-8 coinfected or HIV monoinfected patients. However, in a multivariate analysis, coinfected patients with the intermediate expression haplotype of the MBL2 gene had an odds ratio of 3.1-fold (CI?=?1.2–7.6) of their last CD4 cell count being below 350 cells/mm³. Among the coinfected individuals, four developed KS and presented the intermediate expression MBL haplotype, with three being HYA/LXA and one being LYA/LYO.

Conclusions

Host genetic factors, such as -550, -221 and exon 1 polymorphisms, can be related to the may modify coinfections and/or to the development clinical manifestations caused by HHV-8, especially in HIV/HHV-8 coinfected patients who present the intermediate expression haplotypes of MBL.

     

A Livestock-Associated,Multidrug-Resistant,Methicillin-Resistant Staphylococcus aureus Clonal Complex 97 Lineage Spreading in Dairy Cattle and Pigs in Italy

Pandemic methicillin-resistant Staphylococcus aureus (MRSA) clonal complex 97 (CC97) lineages originated from livestock-to-human host jumps. In recent years, CC97 has become one of the major MRSA lineages detected in Italian farmed animals. The aim of this study was to characterize and analyze differences in MRSA and methicillin-susceptible S. aureus (MSSA) mainly of swine and bovine origins. Forty-seven CC97 isolates, 35 MRSA isolates, and 6 MSSA isolates from different Italian pig and cattle holdings; 5 pig MRSA isolates from Germany; and 1 human MSSA isolate from Spain were characterized by macrorestriction pulsed-field gel electrophoresis (PFGE) analysis, multilocus sequence typing (MLST), spa typing, staphylococcal cassette chromosome mec (SCCmec) typing, and antimicrobial resistance pattern analysis. Virulence and resistance genes were investigated by PCR and microarray analysis. Most of the isolates were of SCCmec type V (SCCmec V), except for two German MRSA isolates (SCCmec III). Five main clusters were identified by PFGE, with the German isolates (clusters I and II) showing 60.5% similarity with the Italian isolates, most of which (68.1%) grouped into cluster V. All CC97 isolates were Panton-Valentine leukocidin (PVL) negative, and a few (n = 7) tested positive for sak or scn. All MRSA isolates were multidrug resistant (MDR), and the main features were erm(B)- or erm(C)-mediated (n = 18) macrolide-lincosamide-streptogramin B resistance, vga(A)-mediated (n = 37) pleuromutilin resistance, fluoroquinolone resistance (n = 33), tet(K) in 32/37 tet(M)-positive isolates, and blaZ in almost all MRSA isolates. Few host-associated differences were detected among CC97 MRSA isolates: their extensive MDR nature in both pigs and dairy cattle may be a consequence of a spillback from pigs of a MRSA lineage that originated in cattle as MSSA and needs further investigation. Measures should be implemented at the farm level to prevent spillover to humans in intensive farming areas.