Gastric outlet obstruction (GOO) is usually associated with a poor prognosis and a significant decrease in a patient's quality of life. Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) using ...lumen-apposing metal stents (LAMS) has emerged as a safe and effective palliation procedure for GOO in patients that are unfit for surgery. Without an exclusive gold-standard technique for EUS-GE, we aimed to compare the currently available ones in this systematic review and meta-analysis, the first on this subspecialty.
A comprehensive search from multiple electronic databases was performed. The search had a particular emphasis on the techniques used in performing EUS-GE. We identified all the studies in which EUS-GE was performed as palliation for GOO from its inception to the current date. The outcomes analyzed were the following: technical and clinical success, total and severe adverse events (AEs), procedure duration, and length of hospital stay (LOHS).
Twenty studies involving 863 patients were the basis of this statistical analysis. Patients underwent the following techniques: direct gastroenterostomy (DGE) (n=718), balloon-assisted gastroenterostomy (BAGE) (n=27), and endoscopic ultrasound (EUS)-guided double-balloon-occluded gastrojejunostomy bypass (n=118). In comparison to balloon-assisted techniques, DGE had a lower rate of AEs, -0.121 (95% CI -0.191 to -0.051 p=0.001); and LOHS for the DGE group, -2.684 (95% CI -1.031 to -4.337 p=0.001). The other analyzed outcomes presented no statistically significant differences. On a sub-analysis, BAGE showed a lower rate of AEs than EUS-guided double-balloon-occluded gastrojejunostomy bypass, -0.196 (95% CI -0.061 to -0.331 p=0.004).
EUS-GE is a safe and effective procedure for palliating GOO. When correctly administered, any of the analyzed techniques may be used to palliate GOO with similar technical and clinical outcomes. DGE had significantly lower rates of AEs and LOHS, which can be inferred as a safer procedure. These results should be interpreted cautiously due to the limited few studies that are available and accessible. Therefore, further well-designed, randomized clinical studies on the topic are warranted to compare the different techniques from more sources.
Detrimental biopsychosocial effects of the COVID-19 pandemic on populations have been established worldwide. Despite research indicating that the transition to parenthood is a vulnerable period for ...maternal and paternal health, an in-depth examination of the specific challenges the pandemic poses for new mothers and fathers is still lacking. Using a mixed-method design, we investigated individual and relational well-being of women and men who were expecting their first child during the first months of the COVID-19 pandemic in Portugal and its associations with contextual, individual, and relational factors. Adults older than 18 (
= 316, 198 women) from early pregnancy to 6-months postpartum completed a cross-sectional online survey assessing sociodemographic, individual (depression, anxiety, perceived stress), and relational (dyadic adjustment, perceived social support) self-report measures. From those, 99 participants (64 women) responded to an open-ended question and reported perceived changes in their couple's relationship due to the pandemic. Men responding during strict lockdown measures reported significantly higher levels of perceived stress relative to those men who were not under lockdown. Overall, women reported higher levels of depression and greater social support than men. Qualitative analyses resulted in two main themes: Individual Changes and Relational Changes. These themes aggregate personal concerns and experiences (e.g., worsening of mental health, uncertainty about the future, lack of freedom) interrelated with relational issues (e.g., increased togetherness, avoidance of physical contact, and increased availability for parenthood during lockdown). The prevalence of negative effects (58.6%) exceeded the described positive effects (28.3%), and 13.1% described both positive and negative effects of the pandemic. Current findings offer grounds for important evidence-based strategies to mitigate the potential adverse effects of the current pandemic on new mothers' and fathers' individual and relational well-being.
Recent studies from temperate lakes indicate that eutrophic systems tend to emit less carbon dioxide (CO2) and bury more organic carbon (OC) than oligotrophic ones, rendering them CO2 sinks in some ...cases. However, the scarcity of data from tropical systems is critical for a complete understanding of the interplay between eutrophication and aquatic carbon (C) fluxes in warm waters. We test the hypothesis that a warm eutrophic system is a source of both CO2 and CH4 to the atmosphere, and that atmospheric emissions are larger than the burial of OC in sediments. This hypothesis was based on the following assumptions: (i) OC mineralization rates are high in warm water systems, so that water column CO2 production overrides the high C uptake by primary producers, and (ii) increasing trophic status creates favorable conditions for CH4 production. We measured water-air and sediment-water CO2 fluxes, CH4 diffusion, ebullition and oxidation, net ecosystem production (NEP) and sediment OC burial during the dry season in a eutrophic reservoir in the semiarid northeastern Brazil. The reservoir was stratified during daytime and mixed during nighttime. In spite of the high rates of primary production (4858 ± 934 mg C m(-2) d(-1)), net heterotrophy was prevalent due to high ecosystem respiration (5209 ± 992 mg C m(-2) d(-1)). Consequently, the reservoir was a source of atmospheric CO2 (518 ± 182 mg C m(-2) d(-1)). In addition, the reservoir was a source of ebullitive (17 ± 10 mg C m(-2) d(-1)) and diffusive CH4 (11 ± 6 mg C m(-2) d(-1)). OC sedimentation was high (1162 mg C m(-2) d(-1)), but our results suggest that the majority of it is mineralized to CO2 (722 ± 182 mg C m(-2) d(-1)) rather than buried as OC (440 mg C m(-2) d(-1)). Although temporally resolved data would render our findings more conclusive, our results suggest that despite being a primary production and OC burial hotspot, the tropical eutrophic system studied here was a stronger CO2 and CH4 source than a C sink, mainly because of high rates of OC mineralization in the water column and sediments.
Cardiac glycosides, such as digoxin and digitoxin, are compounds that interact with Na+/K+‐ATPase to induce anti‐neoplastic effects; however, these cardiac glycosides have narrow therapeutic index. ...Thus, semi‐synthetic analogs of digitoxin with modifications in the sugar moiety has been shown to be an interesting approach to obtain more selective and more effective analogs than the parent natural product. Therefore, the aim of this study was to assess the cytotoxic potential of novel digitoxigenin derivatives, digitoxigenin‐α‐L‐rhamno‐pyranoside (1) and digitoxigenin‐α‐L‐amiceto‐pyranoside (2), in cervical carcinoma cells (HeLa) and human diploid lung fibroblasts (Wi‐26‐VA4). In addition, we studied the anticancer mechanisms of action of these compounds by comparing its cytotoxic effects with the potential to modulate the activity of three P‐type ATPases; Na+/K+‐ATPase, sarco/endoplasmic reticulum Ca2+‐ATPase (SERCA), and plasma membrane Ca2+‐ATPase (PMCA). Briefly, the results showed that compounds 1 and 2 were more cytotoxic and selectivity for HeLa tumor cells than the nontumor cells Wi‐26‐VA4. While the anticancer cytotoxicity in HeLa cells involves the modulation of Na+/K+‐ATPase, PMCA and SERCA, the modulation of these P‐type ATPases was completely absent in Wi‐26‐VA4 cells, which suggest the importance of their role in the cytotoxic effect of compounds 1 and 2 in HeLa cells. Furthermore, the compound 2 inhibited directly erythrocyte ghosts PMCA and both compounds were more cytotoxic than digitoxin in HeLa cells. These results provide a better understanding of the mode of action of the synthetic cardiac glycosides and highlights 1 and 2 as potential anticancer agents.
Chagas disease, which is caused by the protozoan Trypanosoma cruzi, is endemic to Latin America and mainly affects low-income populations. Chemotherapy is based on two nitrocompounds, but their ...reduced efficacy encourages the continuous search for alternative drugs. Our group has characterised the trypanocidal effect of naphthoquinones and their derivatives, with naphthoimidazoles derived from β-lapachone (N1, N2 and N3) being the most active in vitro.
In the present work, the effects of N1, N2 and N3 on acutely infected mice were investigated.
in vivo activity of the compounds was assessed by parasitological, biochemical, histopathological, immunophenotypical, electrocardiographic (ECG) and behavioral analyses.
Naphthoimidazoles led to a decrease in parasitaemia (8 dpi) by reducing the number of bloodstream trypomastigotes by 25-50% but not by reducing mortality. N1 protected mice from heart injury (15 dpi) by decreasing inflammation. Bradycardia was also partially reversed after treatment with N1 and N2. Furthermore, the three compounds did not reverse hepatic and renal lesions or promote the improvement of other evaluated parameters.
N1 showed moderate trypanocidal and promising immunomodulatory activities, and its use in combination with benznidazole and/or anti-arrhythmic drugs as well as the efficacy of its alternative formulations must be investigated in the near future.
Candida albicans
is a human commensal fungus and the etiologic agent of nosocomial infections in immunocompromised individuals.
Candida
spp. is the most studied human fungal pathogen, and the ...mechanisms by which this fungus can evade the immune system affecting immunosuppressed individuals have been extensively studied. Most of these studies focus on different species of
Candida
, and there is much to be understood in virulence variability among lineages, specifically different
C. albicans
clinical isolates. To better understand the main mechanisms of its virulence variability modulated in
C. albicans
clinical isolates, we characterized L3881 lineage, which has been previously classified as hypovirulent, and SC5314 lineage, a virulent wild-type control, by using both
in vitro
and
in vivo
assays. Our findings demonstrated that L3881 presented higher capacity to avoid macrophage phagocytosis and higher resistance to oxidative stress than the wild type. These characteristics prevented higher mortality rates for L3881 in the animal model of candidiasis. Conversely, L3881 has been able to induce an upregulation of pro-inflammatory mediators both
in vitro
and
in vivo
. These results indicated that
in vitro
and
in vivo
functional characterizations are necessary for determination of virulence in different clinical isolates due to its modulation in the host–pathogen interactions.
Rhodoliths are free-living coralline algae (Rhodophyta, Corallinales) that are ecologically important for the functioning of marine environments. They form extensive beds distributed worldwide, ...providing a habitat and nursery for benthic organisms and space for fisheries, and are an important source of calcium carbonate. The Abrolhos Bank, off eastern Brazil, harbors the world's largest continuous rhodolith bed (of ∼21,000 km(2)) and has one of the largest marine CaCO3 deposits (producing 25 megatons of CaCO3 per year). Nevertheless, there is a lack of information about the microbial diversity, photosynthetic potential and ecological interactions within the rhodolith holobiont. Herein, we performed an ecophysiologic and metagenomic analysis of the Abrolhos rhodoliths to understand their microbial composition and functional components. Rhodoliths contained a specific microbiome that displayed a significant enrichment in aerobic ammonia-oxidizing betaproteobacteria and dissimilative sulfate-reducing deltaproteobacteria. We also observed a significant contribution of bacterial guilds (that is, photolithoautotrophs, anaerobic heterotrophs, sulfide oxidizers, anoxygenic phototrophs and methanogens) in the rhodolith metagenome, suggested to have important roles in biomineralization. The increased hits in aromatic compounds, fatty acid and secondary metabolism subsystems hint at an important chemically mediated interaction in which a functional job partition among eukaryal, archaeal and bacterial groups allows the rhodolith holobiont to thrive in the global ocean. High rates of photosynthesis were measured for Abrolhos rhodoliths (52.16 μmol carbon m(-2 )s(-1)), allowing the entire Abrolhos rhodolith bed to produce 5.65 × 10(5) tons C per day. This estimate illustrates the great importance of the Abrolhos rhodolith beds for dissolved carbon production in the South Atlantic Ocean.
Interspecific differences in snake venom compositions can result from distinct regulatory mechanisms acting in each species. However, comparative analyses focusing on identifying regulatory elements ...and patterns that led to distinct venom composition are still scarce. Among venomous snakes, Bothrops cotiara and Bothrops fonsecai represent ideal models to complement our understanding of the regulatory mechanisms of venom production. These recently diverged species share a similar specialized diet, habitat, and natural history, but each presents a distinct venom phenotype. Here, we integrated data from the venom gland transcriptome and miRNome and the venom proteome of B. fonsecai and B. cotiara to better understand the regulatory mechanisms that may be acting to produce differing venom compositions. We detected not only the presence of similar toxin isoforms in both species but also distinct expression profiles of phospholipases A2 (PLA2) and some snake venom metalloproteinases (SVMPs) and snake venom serine proteinases (SVSPs) isoforms. We found evidence of modular expression regulation of several toxin isoforms implicated in venom divergence and observed correlated expression of several transcription factors. We did not find strong evidence for miRNAs shaping interspecific divergence of the venom phenotypes, but we identified a subset of toxin isoforms whose final expression may be fine-tuned by specific miRNAs. Sequence analysis on orthologous toxins showed a high rate of substitutions between PLA2s, which indicates that these toxins may be under strong positive selection or represent paralogous toxins in these species. Our results support other recent studies in suggesting that gene regulation is a principal mode of venom evolution across recent timescales, especially among species with conserved ecotypes.
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•Ni supported Ce0.9Sm0.1O2-δ nanowires with well-defined shape, size, and composition.•High surface and metallic area, oxygen vacancies, finely dispersed Ni particles.•Outstanding ...catalytic performance towards ethanol steam reforming.•High yields for hydrogen production and exceptional stability during 192 h of reaction.•Nanostructured catalysts displaying controlled and superior properties.
We reported herein the synthesis in high yields (>97%) of Ce0.9Sm0.1O2-δ nanowires displaying well-defined shape, size, and composition by a simple, fast, and low-cost two-step hydrothermal method. The Ce0.9Sm0.1O2-δ nanowires synthesis was followed by the wet impregnation of Ni without the utilization of any stabilizing agent. The Ni/Ce0.9Sm0.1O2-δ nanowires showed higher surface area, high concentration of oxygen vacancies at surface, and finely dispersed Ni particles with significantly higher metallic surface area as compared with catalysts prepared from commercial materials with similar compositions. Such unique and improved properties are reflected on the catalytic performance of the Ni/Ce0.9Sm0.1O2-δ nanowires towards ethanol steam reforming. The nanowires exhibited high yields for hydrogen production (∼60% of selectivity) and an exceptional stability with no loss of activity after 192 h of reaction at 550 °C. The reported results provide insights and can inspire high-yield production of nanostructured catalysts displaying controlled and superior properties that enable practical applications in heterogeneous catalysis.
Ontogenetic changes in venom composition have been described in
snakes, but only a few studies have attempted to identify the targeted paralogues or the molecular mechanisms involved in modifications ...of gene expression during ontogeny. In this study, we decoded
venom gland transcripts from six specimens of varying sizes and analyzed the variability in the composition of independent venom proteomes from 19 individuals. We identified 125 distinct putative toxin transcripts, and of these, 73 were detected in venom proteomes and only 10 were involved in the ontogenetic changes. Ontogenetic variability was linearly related to snake size and did not correspond to the maturation of the reproductive stage. Changes in the transcriptome were highly predictive of changes in the venom proteome. The basic myotoxic phospholipases A
(PLA
s) were the most abundant components in larger snakes, while in venoms from smaller snakes, PIII-class SVMPs were the major components. The snake venom metalloproteinases (SVMPs) identified corresponded to novel sequences and conferred higher pro-coagulant and hemorrhagic functions to the venom of small snakes. The mechanisms modulating venom variability are predominantly related to transcriptional events and may consist of an advantage of higher hematotoxicity and more efficient predatory function in the venom from small snakes.