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1.
J Crohns Colitis ; 18(1): 65-74, 2024 Jan 27.
Article in English | MEDLINE | ID: mdl-37522878

ABSTRACT

BACKGROUND: Both vedolizumab and ustekinumab are approved for the management of Crohn's disease [CD]. Data on which one would be the most beneficial option when anti-tumour necrosis factor [anti-TNF] agents fail are limited. AIMS: To compare the durability, effectiveness, and safety of vedolizumab and ustekinumab after anti-TNF failure or intolerance in CD. METHODS: CD patients from the ENEIDA registry who received vedolizumab or ustekinumab after anti-TNF failure or intolerance were included. Durability and effectiveness were evaluated in both the short and the long term. Effectiveness was defined according to the Harvey-Bradshaw index [HBI]. The safety profile was compared between the two treatments. The propensity score was calculated by the inverse probability weighting method to balance confounder factors. RESULTS: A total of 835 patients from 30 centres were included, 207 treated with vedolizumab and 628 with ustekinumab. Dose intensification was performed in 295 patients. Vedolizumab [vs ustekinumab] was associated with a higher risk of treatment discontinuation (hazard ratio [HR] 2.55, 95% confidence interval [CI]: 2.02-3.21), adjusted by corticosteroids at baseline [HR 1.27; 95% CI: 1.00-1.62], moderate-severe activity in HBI [HR 1.79; 95% CI: 1.20-2.48], and high levels of C-reactive protein at baseline [HR 1.06; 95% CI: 1.02-1.10]. The inverse probability weighting method confirmed these results. Clinical response, remission, and corticosteroid-free clinical remission were higher with ustekinumab than with vedolizumab. Both drugs had a low risk of adverse events with no differences between them. CONCLUSION: In CD patients who have failed anti-TNF agents, ustekinumab seems to be superior to vedolizumab in terms of durability and effectiveness in clinical practice. The safety profile is good and similar for both treatments.


Subject(s)
Antibodies, Monoclonal, Humanized , Crohn Disease , Ustekinumab , Humans , Ustekinumab/therapeutic use , Crohn Disease/drug therapy , Tumor Necrosis Factor Inhibitors/therapeutic use , Remission Induction , Tumor Necrosis Factor-alpha , Registries , Treatment Outcome , Retrospective Studies
2.
Rev. esp. quimioter ; 36(2): 160-168, abr. 2023. tab, graf
Article in English | IBECS | ID: ibc-217397

ABSTRACT

Background: Understanding the hospital impact of influenza requires enriching epidemiological surveillance registries with other sources of information. The aim of this study was to determine the validity of the Hospital Care Activity Record – Minimum Basic Data Set (RAE-CMBD) in the analysis of the outcomes of patients hospitalised with this infection. Methods: Observational and retrospective study of adults admitted with influenza in a tertiary hospital during the 2017/2018 and 2018/2019 seasons. We calculated the concordance of the RAE-CMBD with the influenza epidemiological surveillance registry (gold standard), as well as the main parameters of internal and external validity. Logistic regression models were used for risk adjustment of in-hospital mortality and length of stay. Results: A total of 907 (97.74%) unique matches were achieved, with high inter-observer agreement (ƙ=0.828). The RAE-CMBD showed a 79.87% sensitivity, 99.72% specificity, 86.71% positive predictive value and 99.54% negative predictive value. The risk-adjusted mortality ratio of patients with influenza was lower than that of patients without influenza: 0.667 (0.53-0.82) vs. 1.008 (0.98-1.04) and the risk-adjusted length of stay ratio was higher: 1.15 (1.12-1.18) vs. 1.00 (0.996-1.001). Conclusion: The RAE-CMBD is a valid source of information for the study of the impact of influenza on hospital care. The lower risk-adjusted mortality of patients admitted with influenza compared to other inpatients seems to point to the effectiveness of the main clinical and organisational measures adopted. (AU)


Objetivos: Conocer el impacto hospitalario de la gripe requiere enriquecer los registros de vigilancia epidemiológicos con otras fuentes de información. El objetivo de este estudio fue determinar la validez del Registro de Actividad de Atención Especializada – Conjunto Mínimo Básico de Datos (RAE-CMBD) en el análisis de los resultados asistenciales de los pacientes hospitalizados con esta infección. Métodos: Estudio observacional retrospectivo de los adultos ingresados con gripe en un hospital terciario durante las temporadas 2017/2018 y 2018/2019. Se calculó la concor-dancia del RAE-CMBD con el registro de vigilancia epidemiológica de gripe (estándar de referencia), así como los principales parámetros de validez interna y externa. Se utilizaron modelos de regresión logística para el ajuste por riesgo de la mortalidad intrahospitalaria y duración de la estancia. Resultados: Se lograron 907 (97,74%) emparejamientos únicos, con una concordancia interobservadores elevada (ƙ=0,828). El RAE-CMBD mostró una sensibilidad del 79,87%, especificidad del 99,72%, valor predictivo positivo del 86,71% y negativo del 99,54%. La razón de mortalidad ajustada por riesgo de los pacientes con gripe fue menor que la de los pacientes sin gripe: 0,667 (0,53–0,82) vs. 1,008 (0,98–1,04) y la razón de duración de la estancia ajustada por riesgo, mayor: 1,15 (1,12–1,18) vs. 1,00 (0,996–1,001). Conclusiones: El RAE-CMBD es una fuente de información válida para el estudio del impacto de la gripe en la atención hospitalaria. La menor mortalidad ajustada por riesgo de los pacientes ingresados con gripe respecto de los demás ingresados, parece apuntar a la efectividad de las principales medidas clínicas y organizativas adoptadas. (AU)


Subject(s)
Humans , Male , Female , Middle Aged , Aged , Aged, 80 and over , Influenza, Human , Hospitalization , Epidemiological Monitoring , Retrospective Studies , Infection Control , Vaccination
3.
Toxins (Basel) ; 13(11)2021 11 19.
Article in English | MEDLINE | ID: mdl-34822600

ABSTRACT

The genus Brachycephalus is a fascinating group of miniaturized anurans from the Brazilian Atlantic Forest, comprising the conspicuous, brightly colored pumpkin-toadlets and the cryptic flea-toads. Pumpkin-toadlets are known to contain tetrodotoxins and therefore, their bright colors may perform an aposematic function. Previous studies based on a limited number of mitochondrial and nuclear-encoded markers supported the existence of two clades containing species of pumpkin-toadlet phenotype, but deep nodes remained largely unresolved or conflicting between data sets. We use new RNAseq data of 17 individuals from nine Brachycephalus species to infer their evolutionary relationships from a phylogenomic perspective. Analyses of almost 5300 nuclear-encoded ortholog protein-coding genes and full mitochondrial genomes confirmed the existence of two separate pumpkin-toadlet clades, suggesting the convergent evolution (or multiple reversals) of the bufoniform morphology, conspicuous coloration, and probably toxicity. In addition, the study of the mitochondrial gene order revealed that three species (B. hermogenesi, B. pitanga, and B. rotenbergae) display translocations of different tRNAs (NCY and CYA) from the WANCY tRNA cluster to a position between the genes ATP6 and COIII, showing a new mitochondrial gene order arrangement for vertebrates. The newly clarified phylogeny suggests that Brachycephalus has the potential to become a promising model taxon to understand the evolution of coloration, body plan and toxicity. Given that toxicity information is available for only few species of Brachycephalus, without data for any flea-toad species, we also emphasize the need for a wider screening of toxicity across species, together with more in-depth functional and ecological study of their phenotypes.


Subject(s)
Anura/physiology , Skin Pigmentation/physiology , Transcriptome , Animals , Anura/genetics , Brazil , Forests , Genome, Mitochondrial , Phenotype , Phylogeny , Skin Pigmentation/genetics
4.
J Clin Med ; 10(19)2021 Sep 26.
Article in English | MEDLINE | ID: mdl-34640421

ABSTRACT

BACKGROUND: The impact of biologics on the risk of postoperative complications (PC) in inflammatory bowel disease (IBD) is still an ongoing debate. This lack of evidence is more relevant for ustekinumab and vedolizumab. AIMS: To evaluate the impact of biologics on the risk of PC. METHODS: A retrospective study was performed in 37 centres. Patients treated with biologics within 12 weeks before surgery were considered "exposed". The impact of the exposure on the risk of 30-day PC and the risk of infections was assessed by logistic regression and propensity score-matched analysis. RESULTS: A total of 1535 surgeries were performed on 1370 patients. Of them, 711 surgeries were conducted in the exposed cohort (584 anti-TNF, 58 vedolizumab and 69 ustekinumab). In the multivariate analysis, male gender (OR: 1.5; 95% CI: 1.2-2.0), urgent surgery (OR: 1.6; 95% CI: 1.2-2.2), laparotomy approach (OR: 1.5; 95% CI: 1.1-1.9) and severe anaemia (OR: 1.8; 95% CI: 1.3-2.6) had higher risk of PC, while academic hospitals had significantly lower risk. Exposure to biologics (either anti-TNF, vedolizumab or ustekinumab) did not increase the risk of PC (OR: 1.2; 95% CI: 0.97-1.58), although it could be a risk factor for postoperative infections (OR 1.5; 95% CI: 1.03-2.27). CONCLUSIONS: Preoperative administration of biologics does not seem to be a risk factor for overall PC, although it may be so for postoperative infections.

5.
iScience ; 24(9): 102987, 2021 Sep 24.
Article in English | MEDLINE | ID: mdl-34505005

ABSTRACT

Broadly neutralizing antibodies (bnAbs) against HIV-1 are frequently associated with the presence of autoreactivity/polyreactivity, a property that can limit their use as therapeutic agents. The bnAb 4E10, targeting the conserved Membrane proximal external region (MPER) of HIV-1, displays almost pan-neutralizing activity across globally circulating HIV-1 strains but exhibits nonspecific off-target interactions with lipid membranes. The hydrophobic apex of the third complementarity-determining region of the heavy chain (CDRH3) loop, which is essential for viral neutralization, critically contributes to this detrimental effect. Here, we have replaced the aromatic/hydrophobic residues from the apex of the CDRH3 of 4E10 with a single aromatic molecule through chemical modification to generate a variant that preserves the neutralization potency and breadth of 4E10 but with reduced autoreactivity. Collectively, our study suggests that the localized accumulation of aromaticity by chemical modification provides a pathway to ameliorate the adverse effects triggered by the CDRH3 of anti-HIV-1 MPER bnAbs.

6.
J Clin Med ; 11(1)2021 Dec 30.
Article in English | MEDLINE | ID: mdl-35011938

ABSTRACT

BACKGROUND: The evidence for the efficacy of glucocorticoids combined with tocilizumab (TCZ) in COVID-19 comes from observational studies or subgroup analysis. Our aim was to compare outcomes between hospitalized COVID-19 patients who received high-dose corticosteroid pulse therapy and TCZ and those who received TCZ. METHODS: A retrospective single-center study was performed on consecutive hospitalized patients with severe COVID-19 between 1 March and 23 April 2020. Patients treated with either TCZ (400-600 mg, one to two doses) and methylprednisolone pulses (MPD-TCZ group) or TCZ alone were analyzed for the occurrence of a combined endpoint of death and need for invasive mechanical ventilation during admission. The independence of both treatment groups was tested using machine learning classifiers, and relevant variables that were potentially different between the groups were measured through a mean decrease accuracy algorithm. RESULTS: An earlier date of admission was significantly associated with worse outcomes regardless of treatment type. Twenty patients died (27.0%) in the TCZ group, and 33 (44.6%) died or required intubation (n = 74), whereas in the MPD-TCZ group, 15 (11.0%) patients died and 29 (21.3%) patients reached the combined endpoint (n = 136; p = 0.006 and p < 0.001, respectively). Machine learning methodology using a random forest classifier confirmed significant differences between the treatment groups. CONCLUSIONS: MPD and TCZ improved outcomes (death and invasive mechanical ventilation) among hospitalized COVID-19 patients, but confounding variables such as the date of admission during the COVID-19 pandemic should be considered in observational studies.

7.
Mol Phylogenet Evol ; 155: 106967, 2021 02.
Article in English | MEDLINE | ID: mdl-33031928

ABSTRACT

Hybridization can leave genealogical signatures in an organism's genome, originating from the parental lineages and persisting over time. This potentially confounds phylogenetic inference methods that aim to represent evolution as a strictly bifurcating tree. We apply a phylotranscriptomic approach to study the evolutionary history of, and test for inter-lineage introgression in the Salamandridae, a Holarctic salamanders group of interest in studies of toxicity and aposematism, courtship behavior, and molecular evolution. Although the relationships between the 21 currently recognized salamandrid genera have been the subject of numerous molecular phylogenetic studies, some branches have remained controversial and sometimes affected by discordances between mitochondrial vs. nuclear trees. To resolve the phylogeny of this family, and understand the source of mito-nuclear discordance, we generated new transcriptomic (RNAseq) data for 20 salamandrids and used these along with published data, including 28 mitochondrial genomes, to obtain a comprehensive nuclear and mitochondrial perspective on salamandrid evolution. Our final phylotranscriptomic data set included 5455 gene alignments for 40 species representing 17 of the 21 salamandrid genera. Using concatenation and species-tree phylogenetic methods, we find (1) Salamandrina sister to the clade of the "True Salamanders" (consisting of Chioglossa, Mertensiella, Lyciasalamandra, and Salamandra), (2) Ichthyosaura sister to the Near Eastern genera Neurergus and Ommatotriton, (3) Triturus sister to Lissotriton, and (4) Cynops paraphyletic with respect to Paramesotriton and Pachytriton. Combining introgression tests and phylogenetic networks, we find evidence for introgression among taxa within the clades of "Modern Asian Newts" and "Modern European Newts". However, we could not unambiguously identify the number, position, and direction of introgressive events. Combining evidence from nuclear gene analysis with the observed mito-nuclear phylogenetic discordances, we hypothesize a scenario with hybridization and mitochondrial capture among ancestral lineages of (1) Lissotriton into Ichthyosaura and (2) Triturus into Calotriton, plus introgression of nuclear genes from Triturus into Lissotriton. Furthermore, both mitochondrial capture and nuclear introgression may have occurred among lineages assigned to Cynops. More comprehensive genomic data will, in the future, allow testing this against alternative scenarios involving hybridization with other, extinct lineages of newts.


Subject(s)
Hybridization, Genetic , Phylogeny , Urodela/classification , Urodela/genetics , Animals , Cell Nucleus/genetics , DNA, Mitochondrial/genetics , Genome, Mitochondrial , Mitochondria/genetics , Transcriptome/genetics
8.
Cell Rep ; 32(7): 108037, 2020 08 18.
Article in English | MEDLINE | ID: mdl-32814041

ABSTRACT

The contribution of membrane interfacial interactions to recognition of membrane-embedded antigens by antibodies is currently unclear. This report demonstrates the optimization of this type of antibodies via chemical modification of regions near the membrane but not directly involved in the recognition of the epitope. Using the HIV-1 antibody 10E8 as a model, linear and polycyclic synthetic aromatic compounds are introduced at selected sites. Molecular dynamics simulations predict the favorable interactions of these synthetic compounds with the viral lipid membrane, where the epitope of the HIV-1 glycoprotein Env is located. Chemical modification of 10E8 with aromatic acetamides facilitates the productive and specific recognition of the native antigen, partially buried in the crowded environment of the viral membrane, resulting in a dramatic increase of its capacity to block viral infection. These observations support the harnessing of interfacial affinity through site-selective chemical modification to optimize the function of antibodies that target membrane-proximal epitopes.


Subject(s)
Antibodies, Neutralizing/immunology , Membrane Lipids/immunology , Humans
9.
Genes (Basel) ; 11(4)2020 Apr 07.
Article in English | MEDLINE | ID: mdl-32272804

ABSTRACT

In the original article, there was a mistake in Figure 5 as published. When summarizing the results in the scheme, the treatment groups were mixed, and so some of the symbols for morphological and gene expression traits were not in accordance with the results [...].

10.
Genes (Basel) ; 10(11)2019 10 31.
Article in English | MEDLINE | ID: mdl-31683677

ABSTRACT

Phenotypic plasticity and local adaptation via genetic change are two major mechanisms of response to dynamic environmental conditions. These mechanisms are not mutually exclusive, since genetic change can establish similar phenotypes to plasticity. This connection between both mechanisms raises the question of how much of the variation observed between species or populations is plastic and how much of it is genetic. In this study, we used a structured population of fire salamanders (Salamandra salamandra), in which two subpopulations differ in terms of physiology, genetics, mate-, and habitat preferences. Our goal was to identify candidate genes for differential habitat adaptation in this system, and to explore the degree of plasticity compared to local adaptation. We therefore performed a reciprocal transfer experiment of stream- and pond-originated salamander larvae and analyzed changes in morphology and transcriptomic profile (using species-specific microarrays). We observed that stream- and pond-originated individuals diverge in morphology and gene expression. For instance, pond-originated larvae have larger gills, likely to cope with oxygen-poor ponds. When transferred to streams, pond-originated larvae showed a high degree of plasticity, resembling the morphology and gene expression of stream-originated larvae (reversion); however the same was not found for stream-originated larvae when transferred to ponds, where the expression of genes related to reduction-oxidation processes was increased, possibly to cope with environmental stress. The lack of symmetrical responses between transplanted animals highlights the fact that the adaptations are not fully plastic and that some level of local adaptation has already occurred in this population. This study illuminates the process by which phenotypic plasticity allows local adaptation to new environments and its potential role in the pathway of incipient speciation.


Subject(s)
Acclimatization , Genetic Speciation , Transcriptome , Urodela/genetics , Animals , Ecosystem , Phenotype
11.
Genes (Basel) ; 10(10)2019 09 21.
Article in English | MEDLINE | ID: mdl-31546679

ABSTRACT

In the anuran family Dendrobatidae, aposematic species obtain their toxic or unpalatable alkaloids from dietary sources, a process known as sequestering. To understand how toxicity evolved in this family, it is paramount to elucidate the pathways of alkaloid processing (absorption, metabolism, and sequestering). Here, we used an exploratory skin gene expression experiment in which captive-bred dendrobatids were fed alkaloids. Most of these experiments were performed with Dendrobates tinctorius, but some trials were performed with D. auratus, D. leucomelas and Allobates femoralis to explore whether other dendrobatids would show similar patterns of gene expression. We found a consistent pattern of up-regulation of genes related to muscle and mitochondrial processes, probably due to the lack of mutations related to alkaloid resistance in these species. Considering conserved pathways of drug metabolism in vertebrates, we hypothesize alkaloid degradation is a physiological mechanism of resistance, which was evidenced by a strong upregulation of the immune system in D. tinctorius, and of complement C2 across the four species sampled. Probably related to this strong immune response, we found several skin keratins downregulated, which might be linked to a reduction of the cornified layer of the epidermis. Although not conclusive, our results offer candidate genes and testable hypotheses to elucidate alkaloid processing in poison frogs.


Subject(s)
Anura/genetics , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Pyridines/pharmacology , Sparteine/pharmacology , Transcriptome/drug effects , Animals , Bridged Bicyclo Compounds, Heterocyclic/pharmacokinetics , Gene Expression Regulation/drug effects , Pyridines/pharmacokinetics , Skin/metabolism , Sparteine/pharmacokinetics
12.
Nat Commun ; 10(1): 4077, 2019 09 09.
Article in English | MEDLINE | ID: mdl-31501432

ABSTRACT

Climatic conditions changing over time and space shape the evolution of organisms at multiple levels, including temperate lizards in the family Lacertidae. Here we reconstruct a dated phylogenetic tree of 262 lacertid species based on a supermatrix relying on novel phylogenomic datasets and fossil calibrations. Diversification of lacertids was accompanied by an increasing disparity among occupied bioclimatic niches, especially in the last 10 Ma, during a period of progressive global cooling. Temperate species also underwent a genome-wide slowdown in molecular substitution rates compared to tropical and desert-adapted lacertids. Evaporative water loss and preferred temperature are correlated with bioclimatic parameters, indicating physiological adaptations to climate. Tropical, but also some populations of cool-adapted species experience maximum temperatures close to their preferred temperatures. We hypothesize these species-specific physiological preferences may constitute a handicap to prevail under rapid global warming, and contribute to explaining local lizard extinctions in cool and humid climates.


Subject(s)
Environment , Genetic Variation , Genome , Lizards/genetics , Lizards/physiology , Temperature , Animals , Body Temperature Regulation/physiology , Climate , Evolution, Molecular , Phylogeny
13.
J Exp Zool B Mol Dev Evol ; 332(1-2): 26-35, 2019 01.
Article in English | MEDLINE | ID: mdl-30729684

ABSTRACT

Experimental work in the early 20th century showed that background albedo experienced by larvae of the fire salamander (Salamandra salamandra) induce a durable morphological modification of the postmetamorphic color pattern, which needed confirmation due to the controversies regarding Paul Kammerer's experiments. Such a carry-over effect would be relevant as the black and yellow pattern of the alkaloid-containing adult fire salamanders has been suggested to serve as an aposematic signal. Hence, we hypothesized that (a) adult coloration is conspicuous to potential predators under light conditions at night, given the nocturnal activity of this species, and (b) a condition affecting the salamander's coloration pattern would also affect its toxicity to maintain a quantitatively honest aposematic signal. To test the first hypothesis, we used spectrometry to model the vision of potential avian and snake predators and confirmed that fire salamander's black-and-yellow pattern is contrasting enough against the forest leaf litter to be considered conspicuous at night. To test the second hypothesis, we first confirmed the background carry-over effect on black and yellow proportions in the dorsal skin of experimentally reared fire salamanders, using a rigorous experimental design. Then, we calculated the conspicuousness and determined the alkaloid profiles of these individuals. We did not find a correlation between conspicuousness and toxicity at the intrapopulation level. Moreover, there was no background carry-over effect on the alkaloid profile. We discuss our results in a physiological, ecological, evolutionary, and historical context.


Subject(s)
Pigments, Biological , Salamandra/physiology , Skin Pigmentation , Alkaloids/metabolism , Animals , Birds , Larva , Predatory Behavior , Salamandra/growth & development
14.
J Exp Zool B Mol Dev Evol ; 330(2): 96-108, 2018 03.
Article in English | MEDLINE | ID: mdl-29504232

ABSTRACT

The postembryonic development of amphibians has been characterized as divided into three predominant periods, hereafter named primary developmental stages: premetamorphosis (PreM), prometamorphosis (ProM), metamorphic climax (Meta), and completion of metamorphosis (PostM), largely based on examination of anuran development. Here, we categorized the postembryonic development of larvae of a poisonous fire salamander (Salamandra salamandra) by integrating morphology and gene expression (transcriptomic) data. Morphological analysis revealed three distinct clusters suggestive of PreM, ProM, and Meta, which were confirmed in parallel by microarray-derived gene expression analysis. In total, 3,510 probes targeted transcripts differentially expressed between the clusters we identified. Genes upregulated in PreM related to organogenesis, and those upregulated in Meta underlie structural proteins and related to development of anatomical structures and pigmentation. Biosynthesis pathways of pigments (pteridines and melanin) were upregulated during late ProM and Meta. Gas chromatographic analysis of alkaloids indicated the onset of steroidal alkaloid biosynthesis at ProM. When comparing gene expression in the fire salamander to that in other amphibians-three anurans, Xenopus laevis, X. tropicalis, and Michrohyla fissipes, and one caudate, Ambystoma mexicanum- we identified genes with conserved expression patterns involved in basic metamorphic processes such as skin restructuring and tail fin resorption. Our results support that primary stages of postembryonic development in caudates are homologous to those of anurans, and offer a baseline for the study of the evolution of developmental modes.


Subject(s)
Gene Expression Profiling/veterinary , Urodela/growth & development , Urodela/genetics , Alkaloids/metabolism , Animals , Gene Expression Regulation, Developmental , Larva/genetics , Larva/growth & development
15.
J Mol Biol ; 429(8): 1213-1226, 2017 04 21.
Article in English | MEDLINE | ID: mdl-28300601

ABSTRACT

The exceptional breadth of broadly neutralizing antibodies (bNAbs) against the membrane-proximal external region (MPER) of the transmembrane protein gp41 makes this class of antibodies an ideal model to design HIV vaccines. From a practical point of view, however, the preparation of vaccines eliciting bNAbs is still a major roadblock that limits their clinical application. Fresh mechanistic insights are necessary to develop more effective strategies. In particular, the function of the unusually long complementarity-determining region three of the heavy chain (CDRH3) of 4E10, an anti-MPER bNAb, is an open question that fascinates researchers in the field. Residues comprising the apex region are dispensable for engagement of the epitope in solution; still, their single mutation profoundly impairs the neutralization capabilities of the antibody. Since this region is very hydrophobic, it has been proposed that the apex is essential for anchoring the antibody to the viral membrane where MPER resides. Herein, we have critically examined this idea using structural, biophysical, biochemical, and cell-based approaches. Our results demonstrate that the apex region is not just a "greasy" spot merely increasing the affinity of the antibody for the membrane. We demonstrate the three-dimensional engagement of the apex region of the CDRH3 with the conglomerate of gp41 epitope and membrane lipids as a means of effective binding and neutralization of the virus. This mechanism of recognition suggests a standard route of antibody ontogeny. Therefore, we need to focus our efforts on recreating a more realistic MPER/lipid immunogen in order to generate more effective anti-HIV-1 vaccines.


Subject(s)
Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/metabolism , HIV Antibodies/chemistry , HIV Antibodies/metabolism , HIV Envelope Protein gp41/metabolism , HIV-1/immunology , Antibodies, Monoclonal/genetics , Broadly Neutralizing Antibodies , Cell Membrane/metabolism , Crystallography, X-Ray , Epitopes/chemistry , Epitopes/metabolism , HEK293 Cells , HIV Antibodies/genetics , HIV Envelope Protein gp41/chemistry , Humans , Lipid Bilayers , Tryptophan
16.
Mitochondrial DNA B Resour ; 2(2): 397-399, 2017 Jul 11.
Article in English | MEDLINE | ID: mdl-33473839

ABSTRACT

We reconstructed nearly complete mitogenomes for three species of poison frogs, Dendrobates auratus, D. leucomelas, and D. tinctorius, from RNAseq data. We recovered the 13 protein-coding genes, 22 tRNA genes (except tRNA-Val for D. leucomelas), and two rRNA genes for all three species, plus partial sequences of the control region. The order of genes agrees with that known from a previously sequenced D. auratus, being the most commonly found for neobatrachian frogs. Based on full-sibling comparisons we estimate the probable error rate of Illumina-RNAseq reconstructed mitogenomes of up to 0.15%.

17.
Microb Ecol ; 73(2): 455-465, 2017 02.
Article in English | MEDLINE | ID: mdl-27677894

ABSTRACT

Amphibian skin provides a habitat for bacterial communities in its mucus. Understanding the structure and function of this "mucosome" in the European fire salamander (Salamandra salamandra) is critical in the context of novel emerging pathogenic diseases. We compare the cutaneous bacterial communities of this species using amplicon-based sequencing of the 16S rRNA V4 region. Across 290 samples, over 4000 OTUs were identified, four of them consistently present in all samples. Larvae and post-metamorphs exhibited distinct cutaneous microbial communities. In adults, the parotoid gland surface had a community structure different from the head, dorsum, flanks and ventral side. Larvae from streams had higher phylogenetic diversity than those found in ponds. Their bacterial community structure also differed; species of Burkholderiaceae, Comamonadaceae, Methylophilaceae and Sphingomonadaceae were more abundant in pond larvae, possibly related to differences in factors like desiccation and decomposition rate in this environment. The observed differences in the cutaneous bacterial community among stages, body parts and habitats of fire salamanders suggest that both host and external factors shape these microbiota. We hypothesize that the variation in cutaneous bacterial communities might contribute to variation in pathogen susceptibility among individual salamanders.


Subject(s)
Bacteria/classification , Microbiota , Phylogeny , Skin/microbiology , Urodela/microbiology , Alkaloids , Animal Diseases/prevention & control , Animals , Bacteria/genetics , Bacteria/isolation & purification , Base Sequence , Biodiversity , Biological Control Agents , Classification , DNA, Bacterial , Environment , Germany , Larva/microbiology , Parotid Gland/microbiology , Poisons , Ponds/microbiology , RNA, Ribosomal, 16S/genetics , Sequence Analysis
18.
Rev. inf. cient ; 96(1)2017. tab
Article in Spanish | CUMED | ID: cum-68491

ABSTRACT

Se realizó un estudio descriptivo para evaluar la percepción del riesgo biológico que poseen los trabajadores en la central de esterilización del Hospital General Docente Dr Agostinho Neto en Guantánamo. El universo fue de 68 trabajadores y la muestra de 51. Las variables analizadas fueron grupo de edades, sexo, distribución según el área de trabajo y conocimientos, medidas de prevención de riesgo biológico. Entre los resultados obtenidos resaltan que la edad de 39-49 años fue la que más predominó, al igual que el sexo femenino, en el área sucia laboran los trabajadores mayormente expuestos con un total de 40 trabajadores para un 78 por ciento, los cuales no poseen el conocimiento necesario. El mayor número de trabajadores que laboran en áreas, su gran mayoría no cuentan con el conocimiento adecuado sobre riesgo biológico, y se propusieron medidas para la prevención del mismo. Se pretende hacer extensivo estas las medidas a todas las instalaciones con riesgo biológico de la institución(AU)


A descriptive study was carried out to evaluate the perception of the biological risk that the workers have in the sterilization center of the General Teaching Hospital Dr Agostinho Neto in Guantánamo. The universe was 68 workers and the sample of 51. The variables were analyzed: age, group, sex, distribution according to the area of work and knowledge, biological risk prevention measures. Among the results obtained, age 39-49 was the most prevalent and female gender, too. In the dirty area, the workers mostly exposed, with a total of 40 workers, for a total of 78 percent, who do not have the necessary knowledge. The greater numbers of workers working in areas, the great majority of them do not have adequate knowledge about biological risk, and proposed measures to prevent it. It is intended to extend these measures to all facilities with biological risk of the institution


Subject(s)
Humans , /prevention & control , Health Knowledge, Attitudes, Practice , Sterilization , Epidemiology, Descriptive
19.
Nat Commun ; 7: 13699, 2016 12 15.
Article in English | MEDLINE | ID: mdl-27976718

ABSTRACT

Complex microbial communities inhabit vertebrate digestive systems but thorough understanding of the ecological dynamics and functions of host-associated microbiota within natural habitats is limited. We investigate the role of environmental conditions in shaping gut and skin microbiota under natural conditions by performing a field survey and reciprocal transfer experiments with salamander larvae inhabiting two distinct habitats (ponds and streams). We show that gut and skin microbiota are habitat-specific, demonstrating environmental factors mediate community structure. Reciprocal transfer reveals that gut microbiota, but not skin microbiota, responds differentially to environmental change. Stream-to-pond larvae shift their gut microbiota to that of pond-to-pond larvae, whereas pond-to-stream larvae change to a community structure distinct from both habitat controls. Predicted functions, however, match that of larvae from the destination habitats in both cases. Thus, microbial function can be matched without taxonomic coherence and gut microbiota appears to exhibit metagenomic plasticity.


Subject(s)
Ecosystem , Gastrointestinal Microbiome/genetics , Larva/microbiology , Ponds , RNA, Ribosomal, 16S/genetics , Rivers , Salamandra/microbiology , Skin/microbiology , Animals , Environment , Metagenome/genetics , Microbiota/genetics
20.
Farm. hosp ; 40(6): 514-528, nov.-dic. 2016. ilus
Article in English | IBECS | ID: ibc-158019

ABSTRACT

Purpose: To evaluate the effect of pharmacist interventions in the adaptation of pharmaceutical forms in elders institutionalized in nursing homes whose medicines are crushed, which may have a clinical relevance. Methods: Quasi-experimental, multicenter, transversal and prospective study carried out in 10 nursing homes. Subjects for whom drugs were being crushed were identified. Their treatments were reviewed in order to identify drugs that should not be crushed. In these cases, we proposed an alternative to the physician and we evaluated the degree of acceptance, its association to other variables and the pre-post adaptation index (tablets that can be crushed and capsules that can be opened/ total number of tablets and capsules before and after the intervention). Moreover, health professionals received a training course. Results: Medication was being crushed for 33% (618/1875) of residents (mean: 5 drugs susceptible of crushing). 220 pharmaceutical interventions were performed, mostly in extended release or gastro-resistant drugs (48% were accepted). Switch was the type of intervention more frequent (79%), mainly to immediate release forms or to a different drug. The adaptation index increased from 93% to 95% (p < 0.001). Satisfaction amongst health professionals was high. Conclusions: The pharmacist intervention improved the correct administration of drugs, thereby increasing safety and efficacy (AU)


Objetivo: Evaluar el efecto de la intervención del farmacéutico en la adecuación de formas farmacéuticas en ancianos institucionalizados en residencias de mayores a los que se les tritura la medicación y cuya alteración pueda tener relevancia clínica. Método: Estudio cuasiexperimental, multicéntrico, transversal y prospectivo de diseño antes-después en 10 residencias de mayores. Se identificaron los residentes a los que se les trituraba la medicación y se revisó su tratamiento para identificar los medicamentos que no se pueden triturar. Se comunicó al médico responsable la alternativa disponible y se evaluó el grado de aceptación, su asociación con otras variables medidas y el índice de adecuación pre-post, (comprimidos/cápsulas triturables respecto al total de comprimidos/cápsulas antes y después de la intervención). Se impartió además un curso formativo dirigido a los profesionales sanitarios. Resultados: Se trituraba la medicación al 33% (618/1.875) de los pacientes institucionalizados (media: 5 fármacos susceptibles de trituración). Se realizaron 220 intervenciones, mayoritariamente por tratarse de fármacos de liberación prolongada o gastrorresistentes, de las que se aceptaron el 48%. El tipo de intervención más frecuente fue el cambio (79%), mayoritariamente a formas de liberación inmediata o a otro principio activo. El índice de adecuación pasó del 93% al 95% (p < 0,001). La satisfacción de los profesionales con el curso fue elevada. Conclusiones: La intervención del farmacéutico ha mejorado la correcta administración de los medicamentos, aumentando con ello su seguridad y eficacia (AU)


Subject(s)
Humans , Aged , Aged, 80 and over , Pharmaceutical Services/methods , Dosage Forms/standards , Medication Therapy Management , Health of Institutionalized Elderly , Nursing Homes/statistics & numerical data , Administration, Oral , Solid Waste Grinding
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