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BACKGROUND: Salmonellosis is a major cause of morbidity and mortality and one of the most frequent etiologies of diarrhea in the world. Mortality due to Salmonellosis in Latin America still poorly understood, and there is a lack of studies that evaluate resistance and clinical manifestations. The aims of this study were to characterize patients infected with Salmonella spp. seen in a university hospital in Colombia between 2012 and 2021, to evaluate trends in antibiotic resistance and to determine the proportion of overall mortality and related factors. METHODS: Retrospective observational study. All patients with microbiological diagnosis of Salmonella spp. were included. The sociodemographic, clinical and microbiological characteristics were described, and the proportion of antibiotic resistant isolates per year was estimated. The prevalence of mortality according to age groups was calculated. Log binomial regression models were used to establish factors associated with mortality. RESULTS: Five hundred twenty-two patients were analyzed. Salmonellosis accounted for 0.01% of all medical consultations. The median age was 16 years old. The most common clinical presentation was gastroenteric syndrome (77.1%) and symptoms included diarrhea (79.1%), fever (66.7%), abdominal pain (39.6%) and vomiting (35.2%). Of the Salmonella spp. isolates, 78.2% were not classified, 19.1% corresponded to non-typhoidal Salmonella and 2.7% to Salmonella typhi. Mortality occurs in 4.02% of the patients and was higher in patients with hematologic malignancy (11.6%). When analyzing by age group, the proportion of deaths was 2.8% in patients aged 15 years or younger, while in those older than 15 years it was 5.4%. Factors associated to mortality where bacteremia (aPR = 3.41 CI95%: 1.08-10.76) and to require treatment in the ICU (aPR = 8.13 CI95%: 1.82-37.76). In the last 10 years there has been a steady increase in resistance rates to ciprofloxacin, ampicillin, ampicillin/sulbactam and ceftriaxone, reaching rates above 60% in recent years. CONCLUSIONS: Despite improved availability of antibiotics for the treatment of salmonellosis in the past decades, mortality due to salmonellosis continues occurring in children and adults, mainly in patients with hematological malignancies and bacteremia. Antibiotic resistance rates have increased significantly over the last 10 years. Public health strategies for the control of this disease should be strengthened, especially in vulnerable populations.
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Bacteriemia , Infecções por Salmonella , Adolescente , Adulto , Criança , Humanos , Ampicilina/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Estudos de Coortes , Diarreia/microbiologia , Hospitais Universitários , Salmonella , Infecções por Salmonella/tratamento farmacológico , Infecções por Salmonella/epidemiologia , Infecções por Salmonella/microbiologia , América do Sul , Estudos RetrospectivosRESUMO
Social isolation can be a consequence of acquired brain injury (ABI). Few studies have examined the relationship between social isolation and mental health after ABI. In this cross-sectional and case-control study, we compared 51 ABI survivors and 51 matched healthy controls on measures of social isolation (network size, social support and loneliness) mental health and mental health problems. We explored the relationship between structural, functional and subjective components of social isolation and examined whether they were associated with mental health outcomes. No group differences were found on size of the network and perceived social support. The ABI group exhibited marginally higher levels of loneliness. The ABI group presented higher levels of depression, lower levels of quality of life and emotional wellbeing. In both groups, perception of social support was inversely related to subjective experience of loneliness. The relationship between network size and loneliness was only significant in the ABI group. Only loneliness significantly predicted quality of life, emotional wellbeing, depression and anxiety in people with brain injury. The relationship between social isolation variables in ABI is discussed, as well as the theoretical and clinical implications of focusing on loneliness to improve mental health after brain injury.
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Lesões Encefálicas , Solidão , Humanos , Solidão/psicologia , Saúde Mental , Qualidade de Vida , Estudos Transversais , Estudos de Casos e Controles , Isolamento Social/psicologia , Apoio Social , Lesões Encefálicas/complicações , Lesões Encefálicas/psicologiaRESUMO
Herein we report the synthesis of covalently functionalized carbon nano-onions (CNOs) via a reductive approach using unprecedented alkali-metal CNO intercalation compounds. For the first time, an in situ Raman study of the controlled intercalation process with potassium has been carried out revealing a Fano resonance in highly doped CNOs. The intercalation was further confirmed by electron energy loss spectroscopy and X-ray diffraction. Moreover, the experimental results have been rationalized with DFT calculations. Covalently functionalized CNO derivatives were synthesized by using phenyl iodide and n-hexyl iodide as electrophiles in model nucleophilic substitution reactions. The functionalized CNOs were exhaustively characterized by statistical Raman spectroscopy, thermogravimetric analysis coupled with gas chromatography and mass spectrometry, dynamic light scattering, UV-vis, and ATR-FTIR spectroscopies. This work provides important insights into the understanding of the basic principles of reductive CNOs functionalization and will pave the way for the use of CNOs in a wide range of potential applications, such as energy storage, photovoltaics, or molecular electronics.
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Two series of 2,5-di(butoxy)phenyleneethynylenes, one halogenated (nPEC4-X; n=2, 3, or 4) and the other boron-dipyrromethene (BODIPY) terminated (nPEC4-By; n=3, 4, or 5; By=BODIPY), were synthesized monodirectionally by the step-by-step approach and the molecular structure was corroborated by NMR spectroscopy (1 H, 13 C-DEPTQ-135, COSY, HSQC, HMBC, 11 B, 19 F) and MALDI-TOF mass spectrometry. The multiplicity and J-coupling constants of 1 H, 11 B, and 19 F/11 Bâ NMR signals revealed, in the nPEC4-By series, that the phenyl in the meso position of BODIPY becomes electronically part of the conjugation of the phenyleneethynylene chain, whereas BODIPY is electronically isolated. The photophysical, electrochemical, and theoretical studies confirm this finding because the properties of nPEC4-By are comparable to those of the nPEC4-X oligomers and BODIPY, indicating negligible electron communication between BODIPY and the nPEC4 moieties. Nevertheless, energy transfer (ET) from nPEC4 to BODIPY was rationalized by spectroscopy and theoretical calculations. Its yield decreases with the nPEC4 conjugation length, according to the increase in distance between the two chromophores, resulting in dual emission for the longest oligomer in which ET is quenched.
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Single-walled carbon nanotubes (SWCNTs) can be doped with potassium, similar to graphite, leading to intercalation compounds. These binary systems exhibit a clear metallic character. However, the entire picture of how electron doping (e-doping) modifies the SWCNTs' vibrational spectra as a function of their diameter, chirality, and metallicity is still elusive. Herein, we present a detailed study of the intercalation and solid state reduction of metallic and semiconducting enriched HiPco SWCNTs. We performed a combined experimental and theoretical study of the evolution of their Raman response with potassium exposure, focusing specifically on their radial breathing mode (RBM). We found the charge donated from the potassium atoms occupies antibonding π orbitals of the SWCNTs, weakening their C-C bonds, and reducing the RBM frequency. This RBM downshift with increasing doping level is quasi-linear with a steplike behavior when the Fermi level crosses a van Hove singularity for semiconducting species. Moreover, this weakening of the C-C bonds is greater with decreasing curvature, or increasing diameter. Overall, this suggests the RBM downshift with e-doping is proportional to both the SWCNT's integrated density of states (DOS) ϱ(ε) and diameter d. We have provided a precise and complete description of the complex electron doping mechanism in SWCNTs up to a charge density of -18 me/C, far beyond that achievable by standard gate voltage studies, not being the highest doping possible, but high enough to track the effects of doping in SWCNTs based on their excitation energy, diameter, band gap energy, chiral angle, and metallicity. This work is highly relevant to tuning the electronic properties of SWCNTs for applications in nanoelectronics, plasmonics, and thermoelectricity.
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Surface enhanced Raman spectroscopy (SERS) measurements are conventionally performed using assemblies of metal nanostructures on a macro- to micro-sized substrate or by dispersing colloidal metal nanoparticles directly onto the sample of interest. Despite intense use, these methods allow neither the removal of the nanoparticles after a measurement nor a defined confinement of the SERS measurement position. So far, tip enhanced Raman spectroscopy is still the key technique in this regard but not adequate for various samples mainly due to diminished signal enhancement compared to other techniques, poor device fabrication reproducibility, and cumbersome experimental setup requirements. Here, we demonstrate that a rational combination of only four gold nanoparticles (AuNPs) on a DNA origami template, and single silicon nanowires (SiNWs) yield functional optical amplifier nanoprobes for SERS. These nanoscale SERS devices offer a spatial resolution below the diffraction limit of light and still a high electric field intensity enhancement factor ( EF) of about 105 despite of miniaturization.
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DNA/química , Ouro/química , Nanopartículas Metálicas/química , Nanofios/química , Silício/química , Análise Espectral Raman/métodos , Azul de Metileno/análise , Modelos Moleculares , Propriedades de SuperfícieRESUMO
TAR DNA-binding protein 43 (TDP-43) is a hallmark of some neurodegenerative disorders, such as frontotemporal lobar degeneration and amyotrophic lateral sclerosis. TDP-43-related pathology is characterized by its abnormally phosphorylated and ubiquitinated aggregates. It is involved in many aspects of RNA processing, including mRNA splicing, transport, and translation. However, its exact physiological function and role in mechanisms that lead to neuronal degeneration remain elusive. Transgenic rats that were characterized by TDP-43 depletion in neurons exhibited enhancement of the acquisition of fear memory. At the cellular level, TDP-43-depleted neurons exhibited a decrease in the short-term plasticity of intrinsic neuronal excitability. The induction of long-term potentiation in the CA3-CA1 areas of the hippocampus resulted in more stable synaptic enhancement. At the molecular level, the protein levels of an unedited (R) FLOP variant of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) GluR1 and GluR2/3 subunits decreased in the hippocampus. Alterations of FLOP/FLIP subunit composition affected AMPAR kinetics, reflected by cyclothiazide-dependent slowing of the decay time of AMPAR-mediated miniature excitatory postsynaptic currents. These findings suggest that TDP-43 may regulate activity-dependent neuronal plasticity, possibly by regulating the splicing of genes that are responsible for fast synaptic transmission and membrane potential.
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Proteínas de Ligação a DNA/metabolismo , Hipocampo/metabolismo , Memória/fisiologia , Plasticidade Neuronal/fisiologia , Neurônios/metabolismo , Animais , Proteínas de Ligação a DNA/genética , Espinhas Dendríticas/metabolismo , Ratos , Ratos Transgênicos , Receptores de AMPA/metabolismo , Transmissão Sináptica/fisiologiaRESUMO
A cup of coffee is the final product of a complex chain of operations. Wet postharvest processing of coffee is one of these operations, which involves a fermentation that inevitably has to be performed on-farm. During wet coffee processing, the interplay between microbial activities and endogenous bean metabolism results in a specific flavor precursor profile of the green coffee beans. Yet, how specific microbial communities and the changing chemical compositions of the beans determine the flavor of a cup of coffee remains underappreciated. Through a multiphasic approach, the establishment of the microbial communities, as well as their prevalence during wet processing of Coffea arabica, was followed at an experimental farm in Ecuador. Also, the metabolites produced by the microorganisms and those of the coffee bean metabolism were monitored to determine their influence on the green coffee bean metabolite profile over time. The results indicated that lactic acid bacteria were prevalent well before the onset of fermentation and that the fermentation duration entailed shifts in their communities. The fermentation duration also affected the compositions of the beans, so that longer-fermented coffee had more notes that are preferred by consumers. As a consequence, researchers and coffee growers should be aware that the flavor of a cup of coffee is determined before as well as during on-farm processing and that under the right conditions, longer fermentation times can be favorable, although the opposite is often believed.IMPORTANCE Coffee needs to undergo a long chain of events to transform from coffee cherries to a beverage. The coffee postharvest processing is one of the key phases that convert the freshly harvested cherries into green coffee beans before roasting and brewing. Among multiple existing processing methods, the wet processing has been usually applied for Arabica coffee and produces decent quality of both green coffee beans and the cup of coffee. In the present case study, wet processing was followed by a multiphasic approach through both microbiological and metabolomic analyses. The impacts of each processing step, especially the fermentation duration, were studied in detail. Distinct changes in microbial ecosystems, processing waters, coffee beans, and sensory quality of the brews were found. Thus, through fine-tuning of the parameters in each step, the microbial diversity and endogenous bean metabolism can be altered during coffee postharvest processing and hence provide potential to improve coffee quality.
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Bactérias/metabolismo , Coffea/microbiologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Coffea/química , Coffea/metabolismo , Café/química , Equador , Fermentação , Aromatizantes/química , Aromatizantes/metabolismo , Manipulação de Alimentos , Humanos , Metabolômica , Microbiota , Sementes/química , Sementes/metabolismo , Sementes/microbiologiaRESUMO
Male breast cancer is a rare disease that is still poorly understood. It is mainly classified by immunohistochemistry as a luminal disease. In this study, we assess for the first time the correlation between molecular subtypes based on a validated six-marker immunohistochemical panel and PAM50 signature in male breast cancer, and the subsequent clinical outcome of these different subtypes. We collected 67 surgical specimens of invasive male breast cancer from four different Spanish pathology laboratories. Immunohistochemical staining for the six-marker panel was performed on tissue microarrays. PAM50 subtypes were determined in a research-use-only nCounter Analysis System. We explored the association of immunohistochemical and PAM50 subtypes. Overall survival and disease-free survival were analyzed in the different subtypes of each classification. The distribution of tumor molecular subtypes according PAM50 was: 60% luminal B, 30% luminal A and 10% human epidermal growth factor receptor 2 (Her2) enriched. Only one Her2-enriched tumor was also positive by immunohistochemistry and was treated with trastuzumab. None of the tumors were basal-like. Using immunohistochemical surrogates, 51% of the tumors were luminal B, 44% luminal A, 4% triple-negative and 1% Her2-positive. The clinicopathological characteristics did not differ significantly between immunohistochemical and PAM50 subtypes. We found a significant worse overall survival in Her2-enriched compared with luminal tumors. Male breast cancer seems to be mainly a genomic luminal disease with a predominance of the luminal B subtype. In addition, we found a proportion of patients with Her2-negative by immunohistochemistry but Her2-enriched profile by PAM50 tumors with a worse outcome compared with luminal subtypes that may benefit from anti-Her2 therapies.
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Neoplasias da Mama Masculina/metabolismo , Carcinoma Ductal de Mama/metabolismo , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Neoplasias da Mama Masculina/patologia , Carcinoma Ductal de Mama/patologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto JovemRESUMO
BACKGROUND: Post-traumatic stress disorder (PTSD) and obesity are highly prevalent in adolescents. Emerging findings from our laboratory and others are consistent with the novel hypothesis that obese individuals may be predisposed to developing PTSD. Given that aberrant fear responses are pivotal in the pathogenesis of PTSD, the objective of this study was to determine the impact of an obesogenic Western-like high-fat diet (WD) on neural substrates associated with fear. METHODS: Adolescent Lewis rats (nâ¯=â¯72) were fed with either the experimental WD (41.4% kcal from fat) or the control diet. The fear-potentiated startle paradigm was used to determine sustained and phasic fear responses. Diffusion tensor imaging metrics and T2 relaxation times were used to determine the structural integrity of the fear circuitry including the medial prefrontal cortex (mPFC) and the basolateral complex of the amygdala (BLA). RESULTS: The rats that consumed the WD exhibited attenuated fear learning and fear extinction. These behavioral impairments were associated with oversaturation of the fear circuitry and astrogliosis. The BLA T2 relaxation times were significantly decreased in the WD rats relative to the controls. We found elevated fractional anisotropy in the mPFC of the rats that consumed the WD. We show that consumption of a WD may lead to long-lasting damage to components of the fear circuitry. CONCLUSIONS: Our findings demonstrate that consumption of an obesogenic diet during adolescence has a profound impact in the maturation of the fear neurocircuitry. The implications of this research are significant as they identify potential biomarkers of risk for psychopathology in the growing obese population.
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Ansiedade/fisiopatologia , Dieta Hiperlipídica/psicologia , Medo/fisiologia , Envelhecimento/fisiologia , Tonsila do Cerebelo , Animais , Ansiedade/etiologia , Transtornos de Ansiedade , Encéfalo , Condicionamento Clássico , Dieta , Dieta Hiperlipídica/efeitos adversos , Extinção Psicológica/fisiologia , Aprendizagem , Masculino , Córtex Pré-Frontal , Ratos , Ratos Endogâmicos Lew , Reflexo de Sobressalto/fisiologia , Transtornos de Estresse Pós-Traumáticos/metabolismoRESUMO
The postharvest treatment and processing of fresh coffee cherries can impact the quality of the unroasted green coffee beans. In the present case study, freshly harvested Arabica coffee cherries were processed through two different wet and dry methods to monitor differences in the microbial community structure and in substrate and metabolite profiles. The changes were followed throughout the postharvest processing chain, from harvest to drying, by implementing up-to-date techniques, encompassing multiple-step metagenomic DNA extraction, high-throughput sequencing, and multiphasic metabolite target analysis. During wet processing, a cohort of lactic acid bacteria (i.e., Leuconostoc, Lactococcus, and Lactobacillus) was the most commonly identified microbial group, along with enterobacteria and yeasts (Pichia and Starmerella). Several of the metabolites associated with lactic acid bacterial metabolism (e.g., lactic acid, acetic acid, and mannitol) produced in the mucilage were also found in the endosperm. During dry processing, acetic acid bacteria (i.e., Acetobacter and Gluconobacter) were most abundant, along with Pichia and non-Pichia (Candida, Starmerella, and Saccharomycopsis) yeasts. Accumulation of associated metabolites (e.g., gluconic acid and sugar alcohols) took place in the drying outer layers of the coffee cherries. Consequently, both wet and dry processing methods significantly influenced the microbial community structures and hence the composition of the final green coffee beans. This systematic approach to dissecting the coffee ecosystem contributes to a deeper understanding of coffee processing and might constitute a state-of-the-art framework for the further analysis and subsequent control of this complex biotechnological process. IMPORTANCE: Coffee production is a long process, starting with the harvest of coffee cherries and the on-farm drying of their beans. In a later stage, the dried green coffee beans are roasted and ground in order to brew a cup of coffee. The on-farm, postharvest processing method applied can impact the quality of the green coffee beans. In the present case study, freshly harvested Arabica coffee cherries were processed through wet and dry processing in four distinct variations. The microorganisms present and the chemical profiles of the coffee beans were analyzed throughout the postharvest processing chain. The up-to-date techniques implemented facilitated the investigation of differences related to the method applied. For instance, different microbial groups were associated with wet and dry processing methods. Additionally, metabolites associated with the respective microorganisms accumulated on the final green coffee beans.
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Bactérias/metabolismo , Coffea/microbiologia , Manipulação de Alimentos , Fungos/metabolismo , Microbiota , Sementes/microbiologia , Ácido Acético/metabolismo , Acetobacter/isolamento & purificação , Bactérias/classificação , Bactérias/isolamento & purificação , Candida/isolamento & purificação , Dessecação , Endosperma/química , Endosperma/microbiologia , Enterobacteriaceae/isolamento & purificação , Fermentação , Fungos/isolamento & purificação , Ácido Láctico/metabolismo , Lactobacillus/isolamento & purificação , Lactobacillus/metabolismo , Manitol/metabolismo , Pichia/isolamento & purificação , Sementes/anatomia & histologia , Sementes/química , Leveduras/isolamento & purificaçãoRESUMO
To dispose of atomic oxygen, it is necessary the O2 activation; however, an energy barrier must be overcome to break the O-O bond. This work presents theoretical calculations of the O2 adsorption and dissociation on small pure Aun and Agm and bimetallic AunAgm (n + m ≤ 6) clusters using the density functional theory (DFT) and the zeroth-order regular approximation (ZORA) to explicitly include scalar relativistic effects. The most stable AunAgm clusters contain a higher concentration of Au with Ag atoms located in the center of the cluster. The O2 adsorption energy on pure and bimetallic clusters and the ensuing geometries depend on the spin multiplicity of the system. For a doublet multiplicity, O2 is adsorbed in a bridge configuration, whereas for a triplet only one O-metal bond is formed. The charge transfer from metal toward O2 occupies the σ*O-O antibonding natural bond orbital, which weakens the oxygen bond. The Au3 (2A) cluster presents the lowest activation energy to dissociate O2, whereas the opposite applies to the AuAg (3A) system. In the O2 activation, bimetallic clusters are not as active as pure Aun clusters due to the charge donated by Ag atoms being shared between O2 and Au atoms.
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Black phosphorus intercalation compounds (BPICs) with alkali metals (namely: K and Na) have been synthesized in bulk by solid-state as well as vapor-phase reactions. By means of a combination of inâ situ X-ray diffraction, Raman spectroscopy, and DFT calculations the structural behavior of the BPICs at different intercalation stages has been demonstrated for the first time. Our results provide a glimpse into the very first steps of a new family of intercalation compounds, with a distinct behavior as compared to its graphite analogues (GICs), showing a remarkable structural complexity and a dynamic behavior.
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INTRODUCTION: Understanding the intricate dynamics between different waves of the COVID-19 pandemic and the corresponding variations in clinical outcomes is essential for informed public health decision-making. Comprehensive insights into these fluctuations can guide resource allocation, healthcare policies, and the development of effective interventions. This study aimed to compare the characteristics and clinical outcomes of COVID-19 at peak transmission points by including all patients attended during the first four pandemic waves in a referral center in Colombia. MATERIAL AND METHODS: In a prospective observational study of 2733 patients, clinical and demographic data were extracted from the Fundacion Valle de Lili's COVID-19 Registry, focusing on ICU admission, Invasive Mechanical Ventilation (IMV), length of hospital stay, and mortality. RESULTS: Our analysis unveiled substantial shifts in patient care patterns. Notably, the proportion of patients receiving glucocorticoid therapy and experiencing secondary infections exhibited a pronounced decrease across waves (p < 0.001). Remarkably, there was a significant reduction in ICU admissions (62.83% vs. 51.23% vs. 58.23% vs. 46.70 %, p < 0.001), Invasive Mechanical Ventilation (IMV) usage (39.25% vs. 32.22% vs. 31.22% vs. 21.55 %, p < 0.001), and Length of Hospital Stay (LOS) (9 vs. 8 vs. 8 vs. 8 days, p < 0.001) over the successive waves. Surprisingly, hospital mortality remained stable at approximately 18â20 % (p > 0.05). Notably, vaccination coverage with one or more doses surged from 0 % during the initial waves to 66.71 % in the fourth wave. CONCLUSIONS: Our findings emphasize the critical importance of adapting healthcare strategies to the evolving dynamics of the pandemic. The reduction in ICU admissions, IMV utilization, and LOS, coupled with the rise in vaccination rates, underscores the adaptability of healthcare systems. Hospital mortality's persistence may warrant further exploration of treatment strategies. These insights can inform public health responses, helping policymakers allocate resources effectively and tailor interventions to specific phases of the pandemic.
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COVID-19 , Unidades de Terapia Intensiva , Tempo de Internação , Respiração Artificial , Humanos , COVID-19/epidemiologia , Colômbia/epidemiologia , Masculino , Feminino , Estudos Prospectivos , Pessoa de Meia-Idade , Tempo de Internação/estatística & dados numéricos , Respiração Artificial/estatística & dados numéricos , Unidades de Terapia Intensiva/estatística & dados numéricos , Pandemias , Hospitalização/estatística & dados numéricos , Idoso , Adulto , Mortalidade Hospitalar , SARS-CoV-2 , Estudos de CoortesRESUMO
Childhood overweight/obesity is associated with stress-related psychopathology, yet the pathways connecting childhood obesity to stress susceptibility are poorly understood. We employed a systems biology approach with 62 adolescent Lewis rats fed a Western-like high-saturated fat diet (WD, 41% kcal from fat) or a control diet (CD, 13% kcal from fat). A subset of rats underwent a 31-day model of predator exposures and social instability (PSS). Effects were assessed using behavioral tests, DTI (diffusion tensor imaging), NODDI (neurite orientation dispersion and density imaging), 16S rRNA gene sequencing for gut microbiome profiling, hippocampal microglia analysis, and targeted gene methylation. Parallel experiments on human microglia cells (HMC3) examined how palmitic acid influences cortisol-related inflammatory responses. Rats exposed to WD and PSS exhibited deficits in sociability, increased fear/anxiety-like behaviors, food consumption, and body weight. WD/PSS altered hippocampal microstructure (subiculum, CA1, dentate gyrus), and microbiome analysis showed a reduced abundance of members of the phylum Firmicutes. WD/PSS synergistically promoted neuroinflammatory changes in hippocampal microglia, linked with microbiome shifts and altered Fkbp5 expression/methylation. In HMC3, palmitate disrupted cortisol responses, affecting morphology, phagocytic markers, and cytokine release, partially mediated by FKBP5. This study identifies gene-environment interactions that influence microglia biology and may contribute to the connection between childhood obesity and stress-related psychopathology later in life.
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At synaptic terminals, high voltage-activated Ca(v)2.1 and Ca(v)2.2 calcium channels have an essential and joint role in coupling the presynaptic action potential to neurotransmitter release. Here we show that membrane-tethered toxins allowed cell-autonomous blockade of each channel individually or simultaneously in mouse neurons in vivo. We report optimized constitutive, inducible and Cre recombinase-dependent lentiviral vectors encoding fluorescent recombinant toxins, and we also validated the toxin-based strategy in a transgenic mouse model. Toxins delivered by lentiviral vectors selectively inhibited the dopaminergic nigrostriatal pathway, and transgenic mice with targeted expression in nociceptive peripheral neurons displayed long-lasting suppression of chronic pain. Optimized tethered toxins are tools for cell-specific and temporal manipulation of ion channel-mediated activities in vivo, including blockade of neurotransmitter release.
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Bloqueadores dos Canais de Cálcio/farmacologia , Transmissão Sináptica/efeitos dos fármacos , ômega-Conotoxinas/farmacologia , Animais , Canais de Cálcio Tipo N/efeitos dos fármacos , Células Cultivadas , Dopamina/metabolismo , Humanos , Integrases/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Dor/prevenção & controle , Ratos , Ratos Wistar , ômega-Conotoxinas/metabolismoRESUMO
Mycotoxins are secondary metabolites produced by fungi occurring in food that are toxic to animals and humans. Early-life mycotoxins exposure has been linked to diverse pathologies. However, how maternal exposure to mycotoxins impacts on the intestinal barrier function of progeny has not been explored. Here, exposure of pregnant and lactating C57Bl/6J female mice to aflatoxin B1 (AFB1; 400 µg/kg body weight/day; 3 times a week) in gelatine pellets, from embryonic day (E)11.5 until weaning (postnatal day 21), led to gut immunological changes in progeny. The results showed an overall increase of lymphocyte number in intestine, a reduction of expression of epithelial genes related to microbial defence, as well as a decrease in cytokine production by intestinal type 2 innate lymphoid cells (ILC2). While susceptibility to chemically induced colitis was not worsened, immune alterations were associated with changes in gut microbiota and with a higher vulnerability to infection by the protozoan Eimeria vermiformis at early-life. Together these results show that maternal dietary exposure to AFB1 can dampen intestinal barrier homeostasis in offspring decreasing their capability to tackle intestinal pathogens. These data provide insights to understand AFB1 potential harmfulness in early-life health in the context of intestinal infections.
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Microbioma Gastrointestinal , Micotoxinas , Humanos , Gravidez , Camundongos , Feminino , Animais , Micotoxinas/toxicidade , Aflatoxina B1/toxicidade , Aflatoxina B1/metabolismo , Imunidade Inata , Exposição Dietética , Lactação , Linfócitos/metabolismoRESUMO
The co-occurrence of COVID-19 with endemic diseases is a public health concern that may affect patient prognosis and outcomes. The objective of this study was to describe the clinical characteristics of patients with dengue virus (DENV) and SARS-CoV-2 co-infections and compare their outcomes against those of COVID-19 patients without dengue. A cross-sectional study was conducted in patients with SARS-CoV-2 infection who attended a single center in Cali, Colombia, from March 2020 to March 2021. All patients who were tested by both real-time polymerase chain reaction for SARS-CoV-2 and IgM/NS1 for DENV were included. Dengue was diagnosed as having either an IgM- or an NS1- positive test. A total of 90 patients were included (72 with COVID-19 only and 18 with co-infection). Patients with co-infection had more dyspnea (61.1% versus 22.2%; P = 0.003) as well as higher oxygen desaturation (53.3% versus 13.4%; P = 0.002) and neutrophil-to-lymphocyte ratio (5.59 versus 3.84; P = 0.038) than patients with COVID-19 alone. The proportion of patients classified with moderate to severe COVID-19 was higher in the co-infection group (88.3% versus 47.8%; P = 0.002). Also, co-infection was associated with an increased need for mechanical ventilation (P = 0.06), intensive care unit (ICU) initial management (P = 0.02), and ICU admission during hospitalization (P = 0.04) compared with COVID-19 only. The ICU mortality rate was 66.6% in patients with co-infection versus 29.4% in patients infected with only SARS-CoV-2 (P < 0.05). The possibility of DENV and SARS-CoV2 co-infection occurred in the convergence of both epidemic waves. Co-infection was associated with worse clinical outcomes and higher mortality in ICU-admitted patients than in patients with the COVID-19 only.
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COVID-19 , Coinfecção , Vírus da Dengue , Dengue , Humanos , SARS-CoV-2 , COVID-19/epidemiologia , Vírus da Dengue/genética , Coinfecção/epidemiologia , Colômbia/epidemiologia , Estudos Transversais , RNA Viral , Dengue/complicações , Dengue/epidemiologia , Imunoglobulina MRESUMO
Optimizing the antibacterial properties of nanocomposites is a fundamental challenge for many biomedical applications. Here, we study how we may optimize the antibacterial activity of narrow-sized anisotropically flat silver nanoprisms (S-NPs) on graphene oxide (GO) against Escherichia coli. To do so, we transformed silver nanoparticles (AgNPs) into S-NPs and anchored them to GO via a facile and low-cost photochemical reduction method by varying the irradiation wavelength during the synthesis process in the visible range (440 to 650 nm and white light). We performed a physicochemical characterization of the resulting S-NP/GO nanocomposite using a combination of UV-vis spectroscopy, X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Our results reveal a synergistic effect between the silver nanoprism and the oxygen functional groups of the GO surface. The antibacterial activity of the S-NPs/GO nanocomposite shows a significantly higher 53% inhibition efficiency after being irradiated with a 540 nm wavelength light source, compared to AgNPs with a 1% inhibition efficiency, respectively. In so doing, we have demonstrated the utility of a low-cost photoreduction method to control the structural properties of silver nanoprism on GO and, in this way, enhance the antibacterial properties of the nanocomposite. These results should be of great interest in a wide range of biomedical applications and medical devices.
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Childhood obesity leads to hippocampal atrophy and altered cognition. However, the molecular mechanisms underlying these impairments are poorly understood. The neurotrophic factor neuregulin-1 (NRG1) and its cognate ErbB4 receptor play critical roles in hippocampal maturation and function. This study aimed to determine whether exogenous NRG1 administration reduces hippocampal abnormalities and neuroinflammation in rats exposed to an obesogenic Western-like diet (WD). Lewis rats were randomly divided into four groups (12 rats/group): (1) control diet+vehicle (CDV); (2) CD + NRG1 (CDN) (daily intraperitoneal injections: 5 µg/kg/day; between postnatal day, PND 21-PND 41); (3) WD + VEH (WDV); (4) WD + NRG1 (WDN). Neurobehavioral assessments were performed at PND 43-49. Brains were harvested for MRI and molecular analyses at PND 49. We found that NRG1 administration reduced hippocampal volume (7%) and attenuated hippocampal-dependent cued fear conditioning in CD rats (56%). NRG1 administration reduced PSD-95 protein expression (30%) and selectively reduced hippocampal cytokine levels (IL-33, GM-CSF, CCL-2, IFN-γ) while significantly impacting microglia morphology (increased span ratio and reduced circularity). WD rats exhibited reduced right hippocampal volume (7%), altered microglia morphology (reduced density and increased lacunarity), and increased levels of cytokines implicated in neuroinflammation (IL-1α, TNF-α, IL-6). Notably, NRG1 synergized with the WD to increase hippocampal ErbB4 phosphorylation and the tumor necrosis alpha converting enzyme (TACE/ADAM17) protein levels. Although the results did not provide sufficient evidence to conclude that exogenous NRG1 administration is beneficial to alleviate obesity-related outcomes in adolescent rats, we identified a potential novel interaction between obesogenic diet exposure and TACE/ADAM17-NRG1-ErbB4 signaling during hippocampal maturation. Our results indicate that supraoptimal ErbB4 activities may contribute to the abnormal hippocampal structure and cognitive vulnerabilities observed in obese individuals.