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1.
Econ Hum Biol ; 53: 101351, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38306727

RESUMO

This paper contributes to the literature on the impact of the COVID-19 outbreak on mental health by providing novel evidence of its interaction with labor market conditions and the long-term persistence of these effects. We run four waves of a large-scale representative survey in Spain between April 2020 and April 2022, and benchmark our data against a decade of pre-pandemic information. We document an increase in the share of individuals reporting depressive feelings from 16% prior to the pandemic to 46% in April 2020. We show that this effect is more pronounced for women, younger individuals and those with unstable incomes. We apply machine learning techniques, mediation analysis and event studies to document the role of the labor market as an important driver of these effects. Our results are crucial for the design of targeted policies that proof useful in overcoming the long lasting consequences of the pandemic.


Assuntos
COVID-19 , Depressão , Saúde Mental , Humanos , COVID-19/epidemiologia , COVID-19/psicologia , Feminino , Masculino , Espanha/epidemiologia , Adulto , Pessoa de Meia-Idade , Depressão/epidemiologia , Pandemias , Renda/estatística & dados numéricos , SARS-CoV-2 , Fatores Etários , Fatores Sexuais , Adulto Jovem , Aprendizado de Máquina , Idoso , Fatores Socioeconômicos
2.
J Clin Med ; 13(4)2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38398395

RESUMO

Laparoscopy offers numerous advantages over open procedures, minimizing trauma, reducing pain, accelerating recovery, and shortening hospital stays. Despite other technical advancements, pneumoperitoneum insufflation has received little attention, barely evolving since its inception. We explore the impact of pneumoperitoneum on patient outcomes and advocate for a minimally invasive approach that prioritizes peritoneal homeostasis. The nonlinear relationship between intra-abdominal pressure (IAP) and intra-abdominal volume (IAV) is discussed, emphasizing IAP titration to balance physiological effects and surgical workspace. Maintaining IAP below 10 mmHg is generally recommended, but factors such as patient positioning and surgical complexity must be considered. The depth of neuromuscular blockade (NMB) is explored as another variable affecting laparoscopic conditions. While deep NMB appears favorable for surgical stillness, achieving a balance between IAP and NMB depth is crucial. Temperature and humidity management during pneumoperitoneum are crucial for patient safety and optical field quality. Despite the debate over the significance of temperature drop, humidification and the warming of insufflated gas offer benefits in peritoneal homeostasis and visual clarity. In conclusion, there is potential for a paradigm shift in pneumoperitoneum management, with dynamic IAP adjustments and careful control of insufflated gas temperature and humidity to preserve peritoneal homeostasis and improve patient outcomes in minimally invasive surgery.

3.
Int J Mol Sci ; 25(2)2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38256003

RESUMO

Eosinophilic esophagitis (EoE) is a chronic, progressive, type 2 inflammatory disease with increasing global prevalence. An eosinophil-predominant inflammation that permeates the epithelium and deeper esophageal layers characterizes the disease. Several cytokines, mainly derived from inflammatory T-helper 2 (Th2) cells and epithelial cells, are involved in perpetuating inflammatory responses by increasing surface permeability and promoting tissue remodeling characterized by epithelial-mesenchymal transition (EMT) and collagen deposition. This leads to esophageal strictures and narrow caliber esophagi, which are proportional a patient's age and untreated disease length. Pathophysiological mechanisms leading to EoE have been described in recent years, and transforming growth factor beta (TGF)-beta have been involved in fibrotic phenomena in EoE. However, evidence on the dependence of these phenomena on TGF-beta is scarce and contradictory. This review provides state-of-the art knowledge on intimate mechanisms of esophageal fibrosis in EoE and its clinical consequences.


Assuntos
Esofagite Eosinofílica , Humanos , Citocinas , Células Epiteliais , Transição Epitelial-Mesenquimal , Epitélio
4.
J Clin Med ; 13(2)2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38256451

RESUMO

Prone positioning (PP) represents a therapeutic intervention with the proven capacity of ameliorating gas exchanges and ventilatory mechanics indicated in acute respiratory distress syndrome (ARDS). When PP is selectively applied to moderate-severe cases of ARDS, it sensitively affects clinical outcomes, including mortality. After the COVID-19 outbreak, clinical application of PP peaked worldwide and was applied in 60% of treated cases, according to large reports. Research on this topic has revealed many physiological underpinnings of PP, focusing on regional ventilation redistribution and the reduction of parenchymal stress and strain. However, there is a lack of evidence on biomarkers behavior in different phases and phenotypes of ARDS. Patients response to PP are, to date, decided on PaO2/FiO2 ratio improvement, whereas scarce data exist on biomarker tracking during PP. The purpose of this review is to explore current evidence on the clinical relevance of biomarkers in the setting of moderate-severe ARDS of different etiologies (i.e., COVID and non-COVID-related ARDS). Moreover, this review focuses on how PP may modulate biomarkers and which biomarkers may have a role in outcome prediction in ARDS patients.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38284792

RESUMO

BACKGROUND: Swallowed topical corticosteroids (tC) are common therapy for patients with eosinophilic esophagitis (EoE). Widely heterogeneous results have occurred due to their active ingredients, formulations and doses. OBJECTIVE: To assess the effectiveness of topical corticosteroid therapy for EoE in real-world practice. METHODS: Cross-sectional study analysis of the multicentre EoE CONNECT registry. Clinical remission was defined as a decrease of ≥50% in dysphagia symptom scores; histological remission was defined as a peak eosinophil count below 15 per high-power field. The effectiveness in achieving clinico-histological remission (CHR) was compared for the main tC formulations. RESULTS: Overall, data on 1456 prescriptions of tC in monotherapy used in 866 individual patients were assessed. Of those, 904 prescriptions with data on formulation were employed for the induction of remission; 234 reduced a previously effective dose for maintenance. Fluticasone propionate formulations dominated the first-line treatment, while budesonide was more common in later therapies. A swallowed nasal drop suspension was the most common formulation of fluticasone propionate. Doses ≥0.8 mg/day provided a 65% CHR rate and were superior to lower doses. Oral viscous solution prepared by a pharmacist was the most common prescription of budesonide; 4 mg/day provided no benefit over 2 mg/day (CHR rated being 72% and 80%, respectively). A multivariate analysis revealed budesonide orodispersible tablets as the most effective therapy (OR 18.9, p < 0.001); use of higher doses (OR 4.3, p = 0.03) and lower symptom scores (OR 0.9, p = 0.01) were also determinants of effectiveness. CONCLUSION: Reduced symptom severity, use of high doses, and use of budesonide orodispersible tablets particularly were all independent predictors of tC effectiveness.

6.
Nutrients ; 15(21)2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37960160

RESUMO

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a common concomitant condition in patients with inflammatory bowel disease (IBD). We aim to assess the magnitude of this association. METHODS: We searched MEDLINE, EMBASE and Scopus libraries for the period up to February 2023 to identify studies reporting cohorts of IBD patients in which NALFLD was evaluated. RESULTS: Eighty-nine studies were analyzed. The overall prevalence of NAFLD was 24.4% (95%CI, 19.3-29.8) in IBD, 20.2% (18.3-22.3) in Crohn's disease and 18.5% (16.4-20.8) for ulcerative colitis. Higher prevalence was found in male compared to female patients, in full papers compared to abstracts, and in cross-sectional studies compared to prospective and retrospective ones. The prevalence of NAFLD in IBD has increased in studies published from 2015 onwards: 23.2% (21.5-24.9) vs. 17.8% (13.2-22.9). Diagnostic methods for NAFLD determined prevalence figures, being highest in patients assessed by controlled attenuation parameter (38.8%; 33.1-44.7) compared to ultrasonography (28.5%; 23.1-34.2) or other methods. The overall prevalence of fibrosis was 16.7% (12.2-21.7) but varied greatly according to the measurement method. CONCLUSION: One-quarter of patients with IBD might present with NAFLD worldwide. This proportion was higher in recent studies and in those that used current diagnostic methods.


Assuntos
Colite Ulcerativa , Doenças Inflamatórias Intestinais , Hepatopatia Gordurosa não Alcoólica , Feminino , Humanos , Masculino , Colite Ulcerativa/complicações , Colite Ulcerativa/epidemiologia , Estudos Transversais , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/epidemiologia , Cirrose Hepática/epidemiologia , Cirrose Hepática/complicações , Hepatopatia Gordurosa não Alcoólica/complicações , Prevalência , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco
7.
Int J Numer Method Biomed Eng ; 39(11): e3751, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38018384

RESUMO

When modeling complex fluid networks using one-dimensional (1D) approaches, boundary conditions can be imposed using zero-dimensional (0D) models. An application case is the modeling of the entire human circulation using closed-loop models. These models can be considered as a tool to investigate short-term transient and stationary hemodynamic responses to postural changes. The first shortcoming of existing 1D modeling methods in simulating these sudden maneuvers is their inability to deal with rapid variations in flow conditions, as they are limited to the subsonic case. On the other hand, numerical modeling of 0D models representing microvascular beds, venous valves or heart chambers is also currently modeled assuming subsonic flow conditions in 1D connecting vessels, failing when transonic and supersonic flow conditions appear. Therefore, if numerical simulation of sudden maneuvers is a goal in closed-loop models, it is necessary to reformulate the current methodologies used when coupling 0D and 1D models, allowing the correct handling of flow evolution for both subsonic and transonic conditions. This work focuses on the extension of the general methodology for the Junction Riemann Problem (JRP) when coupling 0D and 1D models. As an example of application, the short-term transient response to head-up tilt (HUT) from supine to upright position of a closed-loop model is shown, demonstrating the potential, capability and necessity of the presented numerical models when dealing with sudden maneuvers.


Assuntos
Hemodinâmica , Modelos Cardiovasculares , Humanos , Hemodinâmica/fisiologia , Coração/fisiologia , Simulação por Computador
8.
Dent Med Probl ; 60(3): 401-411, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37750479

RESUMO

BACKGROUND: Eating disorders (EDs) are considered a public health problem. Scientific research has focused on teenagers due to their higher prevalence in this population. However, other groups, such as university students, may be exposed to suffering from EDs due to their academic, social and personal characteristics. Identifying the magnitude of EDs and the associated characteristics may impact the generation of prevention strategies. OBJECTIVES: The aim of the present study was to establish the prevalence of the risk of EDs (anorexia nervosa (AN) and bulimia nervosa (BN)) and the associated factors in dental students at the University of Antioquia, Medellín, Colombia.. MATERIAL AND METHODS: A cross-sectional study was conducted on 278 students (76 males, 202 females) with the use of a Google-Forms survey. The validated Spanish version of the Eating Attitudes Test-26 (EAT-26) and the Sick, Control, One Stone, Fat, Food (SCOFF) questionnaire were used. Other recorded variables included sociodemographic data, coronavirus disease 2019 (COVID-19)-related factors, health, and social support (the Duke-11 profile). The bivariate analysis of the risk of EDs was conducted according to different variables (95% confidence interval (CI)), followed by the logistic regression models adjusting for different variables (adjusted prevalence ratio (aPR) and 95% CI). RESULTS: According to EAT-26, the risk of EDs was 27.6% (18.8-38.6) for males and 28.7% (22.9-35.3) for females. However, differences between males and females were higher when the SCOFF questionnaire was applied (males: 6.6% (2.8-14.5); females: 22.3% (17.1-28.5); p < 0.01). According to the SCOFF instrument, after adjusting for sociodemographic and health variables, women were more likely to report the symptoms of EDs (aPR: 2.20; 95% CI: 1.06-4.57). Women receiving information from social networks were more likely to report the symptoms of EDs (aPR: 1.85; 95% CI: 1.19-2.88). Multivariate models showed that women reporting poor self-rated health and some symptoms during the mandatory confinement caused by the COVID-19 pandemic were more likely to report the symptoms of EDs. CONCLUSIONS: A higher risk of EDs was found in dental students. Healthcare, psychological and/or psychiatric interviews, and educational/early prevention strategies are required.


Assuntos
Transtornos da Alimentação e da Ingestão de Alimentos , Pandemias , Masculino , Adolescente , Humanos , Feminino , Estudos Transversais , Colômbia/epidemiologia , Estudantes de Odontologia , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia
9.
Front Psychol ; 14: 1150008, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37593647

RESUMO

Introduction: Employability is a crucial factor in managing to emerge and changing job demands. This study validates an expanded version of the Employability Appraisal Scale: EAS-60, as an instrument to identify and improve competencies for employability. Method: The EAS-60 was tested in a cross-sectional study in a Spanish population. An exploratory study was carried out using a sample of 188 workers, and the scale's structure was analyzed and confirmed in two Confirmatory Factor Analyses using a sample of 527 workers. Finally, reliability and validity were evaluated. Results: Exploratory and confirmatory analyses provide evidence supporting the multi-dimensional structure. The scale presents good psychometric properties and criteria for interpreting the scores. Discussion: The EAS-60 is a reliable and valid instrument. It allows Human Resource Managers to offer career plans at work that include specific actions of job socialization, training, improvement of specific skills, etc. Furthermore, employees can increase their employability and develop their professional careers.

11.
Cells ; 12(6)2023 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-36980184

RESUMO

Glioblastoma (GBM) is the most frequent primary malignant brain tumor and has a dismal prognosis. Unfortunately, despite the recent revolution of immune checkpoint inhibitors in many solid tumors, these have not shown a benefit in overall survival in GBM patients. Therefore, new potential treatment targets as well as diagnostic, prognostic, and/or predictive biomarkers are needed to improve outcomes in this population. The ß-galactoside binding protein Galectin-1 (Gal-1) is a protein with a wide range of pro-tumor functions such as proliferation, invasion, angiogenesis, and immune suppression. Here, we evaluated Gal-1 expression by immunohistochemistry in a homogenously treated cohort of GBM (the GLIOCAT project) and correlated its expression with clinical and molecular data. We observed that Gal-1 is a negative prognostic factor in GBM. Interestingly, we observed higher levels of Gal-1 expression in the mesenchymal/classical subtypes compared to the less aggressive proneural subtype. We also observed a Gal-1 expression correlation with immune suppressive signatures of CD4 T-cells and macrophages, as well as with several GBM established biomarkers, including SHC1, PD-L1, PAX2, MEOX2, YKL-40, TCIRG1, YWHAG, OLIG2, SOX2, Ki-67, and SOX11. Moreover, Gal-1 levels were significantly lower in grade 4 IDH-1 mutant astrocytomas, which have a better prognosis. Our results confirm the role of Gal-1 as a prognostic factor and also suggest its value as an immune-suppressive biomarker in GBM.


Assuntos
Astrocitoma , Glioblastoma , ATPases Vacuolares Próton-Translocadoras , Humanos , Galectina 1/genética , Galectina 1/metabolismo , Prognóstico , Glioblastoma/diagnóstico , Glioblastoma/genética , Glioblastoma/metabolismo , Astrocitoma/metabolismo , Biomarcadores , ATPases Vacuolares Próton-Translocadoras/metabolismo , Proteínas 14-3-3/metabolismo
12.
Int J Mol Sci ; 24(4)2023 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-36835081

RESUMO

Eosinophilic esophagitis (EoE) is a chronic, Th2-inflammatory disease of the esophagus that can severely affect food intake. Currently, diagnosis and assessing response to treatment of EoE is highly invasive and requires endoscopy with esophageal biopsies. Finding non-invasive and accurate biomarkers is important for improving patient well-being. Unfortunately, EoE is usually accompanied by other atopies, which make it difficult to identify specific biomarkers. Providing an update of circulating EoE biomarkers and concomitant atopies is therefore timely. This review summarizes the current knowledge in EoE blood biomarkers and two of its most common comorbidities, bronchial asthma (BA) and atopic dermatitis (AD), focusing on dysregulated proteins, metabolites, and RNAs. It also revises the current knowledge on extracellular vesicles (EVs) as non-invasive biomarkers for BA and AD, and concludes with the potential use of EVs as biomarkers in EoE.


Assuntos
Asma , Dermatite Atópica , Esofagite Eosinofílica , Vesículas Extracelulares , Humanos , Esofagite Eosinofílica/patologia , Biomarcadores/metabolismo , Vesículas Extracelulares/metabolismo
13.
Mar Drugs ; 21(2)2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36827105

RESUMO

Dinophysis acuminata and D. acuta, which follows it seasonally, are the main producers of lipophilic toxins in temperate coastal waters, including Southern Chile. Strains of the two species differ in their toxin profiles and impacts on shellfish resources. D. acuta is considered the major cause of diarrhetic shellfish poisoning (DSP) outbreaks in Southern Chile, but there is uncertainty about the toxicity of D. acuminata, and little information on microscale oceanographic conditions promoting their blooms. During the austral summer of 2020, intensive sampling was carried out in two northern Patagonian fjords, Puyuhuapi (PUY) and Pitipalena (PIT), sharing D. acuminata dominance and D. acuta near detection levels. Dinophysistoxin 1 (DTX 1) and pectenotoxin 2 (PTX 2) were present in all net tow samples but OA was not detected. Although differing in hydrodynamics and sampling dates, D. acuminata shared behavioural traits in the two fjords: cell maxima (>103 cells L-1) in the interface (S ~ 21) between the estuarine freshwater (EFW)) and saline water (ESW) layers; and phased-cell division (µ = 0.3-0.4 d-1) peaking after dawn, and abundance of ciliate prey. Niche analysis (Outlying Mean Index, OMI) of D. acuta with a high marginality and much lower tolerance than D. acuminata indicated an unfavourable physical environment for D. acuta (bloom failure). Comparison of toxin profiles and Dinophysis niches in three contrasting years in PUY-2020 (D. acuminata bloom), 2018 (exceptional bloom of D. acuta), and 2019 (bloom co-occurrence of the two species)-shed light on the vertical gradients which promote each species. The presence of FW (S < 11) and thermal inversion may be used to provide short-term forecasts of no risk of D. acuta blooms and OA occurrence, but D. acuminata associated with DTX 1 pose a risk of DSP events in North Patagonian fjords.


Assuntos
Dinoflagelados , Intoxicação por Frutos do Mar , Humanos , Toxinas Marinhas/análise , Estuários , Ácido Okadáico/análise
14.
Heliyon ; 9(1): e13097, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36747930

RESUMO

Envy is an important emotion that affects workers' behavior and performance. Instruments to measure envy are available, but new scales are needed for the analysis of work envy that include appraisals of challenge (benign envy) and threat (malicious envy). Based on Lazarus and Folkman's theory, the objective of this study is to develop and validate the Work Envy Appraisal Scale (WEAS) for Spanish workers. It had been carried out in two studies; in the first study, the scale was constructed and its dimensions were analyzed with a sample of 100 Spanish workers (sample 1). In the second study, the scale was validated and its psychometric properties were analyzed (sample 2, N = 219; sample 3, N = 532). The results of exploratory, confirmatory, and multigroup factor analysis showed good indices of fit for the two-factor structure. Moreover, the results showed adequate convergent and discriminant validity. Furthermore, our findings indicated that the scale is a reliable and valid instrument for measuring envy at work. This way of measuring envy at work (discerning its challenge and threat appraisal) makes it possible to find answers to some recurrent research questions (e.g. social desirability issues, the confusion of envy with other topics, etc.) and can facilitate reliable research on envy at work.

15.
Nat Commun ; 14(1): 746, 2023 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-36765091

RESUMO

A substantial proportion of cancer patients do not benefit from platinum-based chemotherapy (CT) due to the emergence of drug resistance. Here, we apply elemental imaging to the mapping of CT biodistribution after therapy in residual colorectal cancer and achieve a comprehensive analysis of the genetic program induced by oxaliplatin-based CT in the tumor microenvironment. We show that oxaliplatin is largely retained by cancer-associated fibroblasts (CAFs) long time after the treatment ceased. We determine that CT accumulation in CAFs intensifies TGF-beta activity, leading to the production of multiple factors enhancing cancer aggressiveness. We establish periostin as a stromal marker of chemotherapeutic activity intrinsically upregulated in consensus molecular subtype 4 (CMS4) tumors and highly expressed before and/or after treatment in patients unresponsive to therapy. Collectively, our study underscores the ability of CT-retaining CAFs to support cancer progression and resistance to treatment.


Assuntos
Antineoplásicos , Fibroblastos Associados a Câncer , Neoplasias Colorretais , Humanos , Fibroblastos Associados a Câncer/patologia , Oxaliplatina/farmacologia , Distribuição Tecidual , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Microambiente Tumoral , Fibroblastos/patologia , Linhagem Celular Tumoral
16.
J Nutr ; 153(4): 1075-1088, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36842935

RESUMO

BACKGROUND: Early-life nutritional exposures may contribute to offspring epigenetic modifications. However, few studies have evaluated parental dietary quality effects on offspring DNA methylation (DNAm). OBJECTIVES: We aim to fill this gap by elucidating the influence of maternal and paternal whole-diet quality and inflammatory potential on offspring DNAm in the Lifeways Cross-generation cohort. METHODS: Families (n = 1124) were recruited around 16 weeks of gestation in the Republic of Ireland between 2001 and 2003. Maternal dietary intake during the first trimester and paternal diet during the 12 previous months were assessed with an FFQ. Parental dietary inflammatory potential and quality were determined using the energy-adjusted Dietary Inflammatory Index (E-DII), the Healthy Eating Index-2015 (HEI-2015), and the maternal DASH score. DNAm in the saliva of 246 children at age nine was measured using the Illumina Infinium HumanMethylationEPIC array. DNAm-derived biomarkers of aging, the Pediatric-Buccal-Epigenetic clock and DNAm estimator of telomere length, were calculated. Parental diet associations with the DNAm concentrations of 850K Cytosine-phosphate-guanine sites (CpG sites) and with DNAm-derived biomarkers of aging were examined using an epigenome-wide association study and linear regressions, respectively. RESULTS: Maternal HEI-2015 scores were inversely associated with DNAm at CpG site (cg21840035) located near the PLEKHM1 gene, whose functions involve regulation of bone development (ß = -0.0036, per 1 point increase in the score; P = 5.6 × 10-8). Higher paternal HEI-2015 score was related to lower methylation at CpG site (cg22431767), located near cell signaling gene LUZP1 (ß = -0.0022, per 1 point increase in the score, P = 4.1 × 10-8). There were no associations with parental E-DII and DASH scores, and no evidence of major effects on biomarkers of aging. CONCLUSIONS: Parental dietary quality in the prenatal period, evaluated by the HEI-2015, may influence offspring DNAm during childhood. Further research to improve our understanding of parental nutritional programming is warranted.


Assuntos
Metilação de DNA , Dieta , Gravidez , Feminino , Humanos , Criança , Epigênese Genética , Envelhecimento , Inflamação , Biomarcadores
17.
Sci Total Environ ; 865: 161288, 2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36587668

RESUMO

Harmful algal blooms (HABs) in southern Chile are a serious threat to public health, tourism, artisanal fisheries, and aquaculture in this region. Ichthyotoxic HAB species have recently become a major annual threat to the Chilean salmon farming industry, due to their severe economic impacts. In early austral autumn 2021, an intense bloom of the raphidophyte Heterosigma akashiwo was detected in Comau Fjord, Chilean Patagonia, resulting in a high mortality of farmed salmon (nearly 6000 tons of biomass) within 15 days. H. akashiwo cells were first detected at the head of the fjord on March 16, 2021 (up to 478 cells mL-1). On March 31, the cell density at the surface had reached a maximum of 2 × 105 cells mL-1, with intense brown spots visible on the water surface. Strong and persistent high-pressure anomalies over the southern tip of South America, consistent with the positive phase of the Southern Annular Mode (SAM), resulted in extremely dry conditions, high solar radiation, and strong southerly winds. A coupling of these features with the high water retention times inside the fjord can explain the spatial-temporal dynamics of this bloom event. Other factors, such as the internal local physical uplift process (favored by the north-to-south orientation of the fjord), salt-fingering events, and the uplift of subantarctic deep-water renewal, likely resulted in the injection of nutrients into the euphotic layer, which in turn could have promoted cell growth and thus high microalgal cell densities, such as reached by the bloom.


Assuntos
Estuários , Microalgas , Animais , Mudança Climática , Proliferação Nociva de Algas , Salmão , Chile , Água
18.
Dig Liver Dis ; 55(3): 350-359, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36280437

RESUMO

BACKGROUND: Direct comparisons of childhood- and adulthood-onset eosinophilic esophagitis (EoE) are scarce. AIM: To compare disease characteristics, endoscopic and histological features, allergic concomitances and therapeutic choices across ages. METHODS: Cross-sectional analysis of the EoE CONNECT registry. RESULTS: The adulthood-onset cohort (those diagnosed at ≥18y) comprised 1044 patients and the childhood-onset cohort (patients diagnosed at <18 y), 254. Vomiting, nausea, chest and abdominal pain, weight loss, slow eating and food aversion were significantly more frequent in children; dysphagia, food bolus impaction and heartburn predominated in adults. A family history of EoE was present in 16% of pediatric and 8.2% of adult patients (p<0.001). Concomitant atopic diseases did not vary across ages. Median±IQR diagnostic delay (years) from symptom onset was higher in adults (2.7 ± 6.1) than in children (1 ± 2.1; p<0.001). Esophageal strictures and rings predominated in adults (p<0.001), who underwent esophageal dilation more commonly (p = 0.011). Inflammatory EoE phenotypes were more common in children (p = 0.001), who also presented higher eosinophil counts in biopsies (p = 0.015) and EREFS scores (p = 0.017). Despite PPI predominating as initial therapy in all cohorts, dietary therapy and swallowed topical corticosteroids were more frequently prescribed in children (p<0.001). CONCLUSIONS: Childhood-onset EoE has differential characteristics compared with adulthood-onset, but similar response to treatment.


Assuntos
Transtornos de Deglutição , Esofagite Eosinofílica , Humanos , Esofagite Eosinofílica/diagnóstico , Estudos Transversais , Diagnóstico Tardio , Transtornos de Deglutição/diagnóstico , Sistema de Registros
19.
Eur J Med Chem ; 246: 115003, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36493617

RESUMO

Since the identification of human choline kinase as a protein target against cancer progression, many compounds have been designed to inhibit its function and reduce the biosynthesis of phosphatidylcholine. Herein, we propose a series of bioisosteric inhibitors that are based on the introduction of sulphur and feature improved activity and lipophilic/hydrophilic balance. The evaluation of the inhibitory and of the antiproliferative properties of the PL (dithioethane) and FP (disulphide) libraries led to the identification of PL 48, PL 55 and PL 69 as the most active compounds of the series. Docking analysis using FLAP suggests that for hits to leads, binding mostly involves an interaction with the Mg2+ cofactor, or its destabilization. The most active compounds of the two series are capable of inducing apoptosis following the mitochondrial pathway and to significantly reduce the expression of anti-apoptotic proteins such as the Mcl-1. The fluorescence properties of the compounds of the PL library allowed the tracking of their mode of action, while PAINS (Pan Assays Interference Structures) filtration databases suggest the lack of any unspecific biological response.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Colina/metabolismo , Colina/farmacologia , Colina Quinase , Proliferação de Células , Antineoplásicos/química , Simulação de Acoplamento Molecular , Inibidores de Proteínas Quinases/farmacologia
20.
Cancers (Basel) ; 14(24)2022 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-36551619

RESUMO

Hypersialylation is a feature of pancreatic ductal adenocarcinoma (PDA) and it has been related to tumor malignancy and immune suppression. In this work, we have evaluated the potential of the sialyltransferase inhibitor, Ac53FaxNeu5Ac, to decrease tumor sialoglycans in PDA and to revert its malignant phenotype. Sialoglycans on PDA cells were evaluated by flow cytometry, and the functional impact of Ac53FaxNeu5Ac was assessed using E-selectin adhesion, migration, and invasion assays. PDA tumors were generated in syngeneic mice from KC cells and treated with Ac53FaxNeu5Ac to evaluate tumor growth, mice survival, and its impact on blocking sialic acid (SA) and on the tumor immune component. Ac53FaxNeu5Ac treatment on human PDA cells decreased α2,3-SA and sialyl-Lewisx, which resulted in a reduction in their E-selectin adhesion, and in their migratory and invasive capabilities. Subcutaneous murine tumors treated with Ac53FaxNeu5Ac reduced their volume, their SA expression, and modified their immune component, with an increase in CD8+ T-lymphocytes and NK cells. In conclusion, Ac53FaxNeu5Ac treatment weakened PDA cells' malignant phenotype, thereby reducing tumor growth while favoring anti-tumor immune surveillance. Altogether, these results show the positive impact of reducing SA expression by inhibiting cell sialyltransferases and open the way to use sialyltransferase inhibitors to target this dismal disease.

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