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1.
Int Immunol ; 36(3): 111-128, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38066638

RESUMO

Nurr1 is a member of the orphan nuclear receptor family NR4A (nuclear receptor subfamily 4 group A) that modulates inflammation in several cell lineages, both positively and negatively. Macrophages are key regulators of inflammatory responses, yet information about the role of Nurr1 in human macrophages is scarce. Here we examined Nurr1 expression and activity in steady state and activated human macrophages. Pro- and anti-inflammatory macrophages were generated in vitro by culture of blood monocytes with granulocyte/macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF), respectively. Nurr1 expression was predominant in macrophages with the pro-inflammatory phenotype. Nurr1 activation with the agonists 1,1-bis(3'-indolyl)-1-(p-chlorophenyl) methane (C-DIM12) or isoxazolo-pyridinone 7e (IP7e) did not globally modify the polarization status of pro-inflammatory macrophages, but they decreased their production of TNF, IL-1ß, IL-6, IL-8, IL-12 p40, CCL2, IFN-ß, and reactive oxygen species, with variable potencies. Conversely, Nurr1 deficient macrophages increased the expression of transcripts encoding inflammatory mediators, particularly that of IL6, IFNB1, and CCL2. Mechanistically, endogenous Nurr1 interacted with NF-κB p65 in basal conditions and upon lipopolysaccharide (LPS)-mediated activation. C-DIM12 stabilized those complexes in cells exposed to LPS and concurrently decreased NF-κB transcriptional activity and p65 nuclear translocation. Expression of high levels of Nurr1 was associated with a subset of dermal macrophages that display enhanced levels of TNF and lower expression of the anti-inflammatory marker CD163L1 in skin lesions from patients with bullous pemphigoid (BP), a chronic inflammatory autoimmune blistering disorder. These results suggest that Nurr1 expression is linked with the pro-inflammatory phenotype of human macrophages, both in vivo and in vitro, where it may constitute a brake to attenuate the synthesis of inflammatory mediators.


Assuntos
Fator Estimulador de Colônias de Macrófagos , NF-kappa B , Humanos , NF-kappa B/metabolismo , Fator Estimulador de Colônias de Macrófagos/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/genética , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Anti-Inflamatórios/metabolismo
2.
Artigo em Inglês | MEDLINE | ID: mdl-38643312

RESUMO

INTRODUCTION: Cancer-associated thrombosis (CAT) is a significant concern among patients with malignant diseases, leading to increased mortality. While current guidelines recommend primary thromboprophylaxis for venous thromboembolism (VTE) in medium-to-high-risk outpatients, this practice remains controversial. A better understanding of primary thromboprophylaxis is crucial, yet there is a lack of Real-World Evidence (RWE) in Portugal. AIMS: This RWE study aimed to elucidate primary thromboprophylaxis practices among cancer outpatients in Portugal. METHODS: A five-year observational multicentric study in eight Portuguese health institutions enrolled 124 adult cancer outpatients under primary thromboprophylaxis for VTE. The endpoints were CAT, bleeding, cancer progression and death. RESULTS: High thrombotic risk tumours were prevalent, with 57% (71) of the patients presenting with pancreatic and gastric cancers. Regarding primary thromboprophylaxis, 55% (68) received Low-Molecular-Weight Heparin (LMWH). VTE was presented in 11% (14) of the patients and major bleeding in 2% (2). Vascular compression, elevated D-dimer and previous VTE were significantly associated with VTE occurrence under primary thromboprophylaxis. The Onkotev model was shown to be the best risk assessment model (RAM) in this population (p = 0.007). CAT patients exhibited a lower progression-free survival than non-CAT patients (p = 0.021), while thrombosis did not influence overall survival (p = 0.542). CONCLUSION: Primary thromboprophylaxis in medium-to-high-risk cancer outpatients is a safe and effective practice in real-world settings. This study is the first Portuguese RWE on primary thromboprophylaxis, highlighting evidence for improving prophylactic strategies in this population.

3.
Psychooncology ; 32(11): 1702-1709, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37749768

RESUMO

BACKGROUND: The first medical oncology appointment serves as a platform for patients to comprehend their diagnosis and prognostic implications of cancer. This study aimed to determine patients' communication preferences during their first medical oncology appointment and to assess the disparities between patients' preferences and perceptions. METHODS: A total of 169 cancer patients participated by completing the Communication in First Medical Oncology Appointment Questionnaire (C-FAQ), a two-section questionnaire designed to assess patients' preferences and perceptions regarding Content (information provided and its extent), Facilitation (timing and location of information delivery), and Support (emotional support) during their first medical oncology appointment. A comparative analysis was conducted to assess the variations between preferences and perceptions. RESULTS: Content emerged as the most significant dimension compared to Facilitation and Support. The physician's knowledge, honesty, and ability to provide clear information were considered the most important attributes. Patients evaluated most of their preferences as "very important". Patients' perception of the communication dimensions present during their appointment was below preferences for 11 items, indicating significant discrepancies in clinical practice. CONCLUSIONS: Patients highly valued their preferences concerning Content, Facilitation, and Support dimensions of communication. However, patient preferences were more prominently oriented towards the Content dimension. The discrepancies between preferences and perceptions should be viewed as an opportunity for enhancing communication skills through training.


Assuntos
Neoplasias , Relações Médico-Paciente , Humanos , Neoplasias/psicologia , Oncologia , Comunicação , Preferência do Paciente/psicologia
4.
Skin Res Technol ; 29(6): e13335, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37357666

RESUMO

OBJECTIVE: Cutaneous relief analysis is crucial in the development of new skincare products, as well as in the evaluation of dermatological treatments. The analysis can be performed by qualitative or quantitative methods. We propose a new algorithm to detect wrinkles and quantify skin roughness by image processing from a dermatoscope. METHODS: A clinical study was carried out with 33 research participants, and images were collected with the dermatoscope and PRIMOS equipment for wrinkle evaluation at two different times: Day 0 (D0) and 45 days (D45) after the use of a dermocosmetic product. Later, a new algorithm was developed to detect wrinkles in the acquired images by applying filters and image transformations that generate a segmented image highlighting the wrinkles. A roughness calculation method is proposed from the pixels belonging to wrinkles. RESULTS: Correlation between the values obtained by the PRIMOS equipment and the proposed system was verified. No correlation was found for data obtained at D0; however, there was correlation at time D45 by Spearman's similarity coefficient. By comparing roughness between times D0 and D45, the treatment was statistically significant for both PRIMOS and the proposed methodology data. CONCLUSION: The wrinkle detection algorithm, in addition to the roughness calculation, demonstrated a sensitivity comparable to the PRIMOS system in evaluating the effectiveness of the dermocosmetic treatment. SIGNIFICANCE: Considering the simplicity of the dermatoscope design compared to other established devices such as PRIMOS, the proposed system is promising as an alternative for dermatological evaluations.


Assuntos
Envelhecimento da Pele , Pele , Humanos , Pele/diagnóstico por imagem , Processamento de Imagem Assistida por Computador , Algoritmos
5.
Infancy ; 27(1): 159-180, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34582107

RESUMO

Infants born preterm (<37 gestational weeks, GW) are at increased risk for regulatory difficulties and insecure attachment. However, the association between infants' regulatory behavior patterns and their later attachment organization is understudied in the preterm population. We addressed this gap by utilizing a Portuguese sample of 202 mother-infant dyads. Specifically, we compared the regulatory behavior patterns of 74 infants born moderate-to-late preterm (MLPT, 32-36 GW) to those of 128 infants born full-term (FT, 37-42 GW) and evaluated the associations of these regulatory patterns with later attachment. Infants' regulatory behavior patterns (Social-Positive Oriented, Distressed-Inconsolable, or Self-Comfort Oriented) were evaluated in the Face-to-Face-Still-Face paradigm at 3 months, and their attachment organization (secure, insecure-avoidant, or insecure-ambivalent) was evaluated in the Strange Situation at 12 months corrected age. In both samples, the Social-Positive-Oriented regulatory pattern was associated with secure attachment; the Distressed-Inconsolable pattern with insecure-ambivalent attachment; and the Self-Comfort-Oriented pattern with insecure-avoidant attachment. However, compared to FT infants, infants born MLPT were more likely to exhibit a Self-Comfort-Oriented pattern and avoidant attachment. Most perinatal and demographic variables were not related to infant outcomes. However, infants with a higher 1-min Apgar were more likely to exhibit the Social-Positive-Oriented regulatory pattern and secure attachment.


Assuntos
Comportamento do Lactente , Relações Mãe-Filho , Afeto , Emoções , Feminino , Humanos , Lactente , Recém-Nascido , Mães , Gravidez
6.
Attach Hum Dev ; 23(6): 814-830, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-32363996

RESUMO

Prior research described three stable patterns of organized behavior employed by infants to manage stressful interactive situations with their mothers in the Face-to-Face Still-Face paradigm (FFSF) at 3 and 9 months postpartum.  The current longitudinal study expands this research by examining the extent to which these patterns predict infants' later attachment quality. For that purpose, 108 full-term infants and their mothers participated in the FFSF at 3 and 9 months, and in the Strange Situation at 12 months. Cross-tabulation analyses indicated a significant association between (1) the Social-positive oriented pattern and secure attachment, (2) the Distressed-inconsolable pattern and insecure-ambivalent attachment, and (3) the Self-comfort oriented pattern and insecure-avoidant attachment. Our results contribute to a growing body of studies suggesting that patterns of infants' regulatory behavior assessed during the FFSF during the first year, may be early developmental precursors of attachment patterns at 12 months.


Assuntos
Relações Mãe-Filho , Mães , Feminino , Humanos , Lactente , Comportamento do Lactente , Estudos Longitudinais , Apego ao Objeto
7.
COPD ; 17(5): 601-617, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32892650

RESUMO

COPD is a major cause of morbidity and mortality worldwide and carries a huge and growing economic and social burden. Telemedicine might allow the care of patients with limited access to health services and improve their self-management. During the COVID-19 pandemic, patient's safety represents one of the main reasons why we might use these tools to manage our patients. The authors conducted a literature search in MEDLINE database. The retrieval form of the Medical Subject Headings (Mesh) was ((Telemedicine OR Tele-rehabilitation OR Telemonitoring OR mHealth OR Ehealth OR Telehealth) AND COPD). We only included systematic reviews, reviews, meta-analysis, clinical trials and randomized-control trials, in the English language, with the selected search items in title or abstract, and published from January 1st 2015 to 31st May 2020 (n = 56). There was a positive tendency toward benefits in tele-rehabilitation, health-education and self-management, early detection of COPD exacerbations, psychosocial support and smoking cessation, but the heterogeneity of clinical trials and reviews limits the extent to which this value can be understood. Telemonitoring interventions and cost-effectiveness had contradictory results. The literature on teleconsultation was scarce during this period. The non-inferiority tendency of telemedicine programmes comparing to conventional COPD management seems an opportunity to deliver quality healthcare to COPD patients, with a guarantee of patient's safety, especially during the COVID-19 outbreak.


Assuntos
Betacoronavirus , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Doença Pulmonar Obstrutiva Crônica/terapia , Telemedicina/organização & administração , COVID-19 , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Humanos , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , SARS-CoV-2 , Autogestão
8.
Infancy ; 24(4): 501-525, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32677251

RESUMO

The current study addressed two aims: (1) to describe different patterns of infant regulatory behavior during the Face-to-Face Still-Face (FFSF) paradigm at 3 months of age and (2) to identify specific, independent predictors of these patterns from an a priori set of demographic, infant (e.g., temperament), and maternal (e.g., sensitivity) variables. Analyses were based on data collected for 121 mother-infant dyads assessed longitudinally in the newborn period and again at 3 months. In the newborn period, infants' neurobehavior was evaluated using the Neonatal Behavioral Assessment Scale (NBAS) and mothers reported on their caregiving confidence and their newborns' irritability and alertness. At 3 months, mothers reported on their infant's temperament, and mother-infant interactions were videotaped during free play and the FFSF. Three patterns of infant regulatory behavior were observed. The most common was a Social-Positive Oriented Pattern, followed by a Distressed-Inconsolable Pattern, and a Self-Comfort Oriented Pattern. Results of multinomial logistic regression indicated that categorical assignment was not associated with demographic or infant characteristics, but rather with dyadic regulatory processes in which maternal reparatory sensitivity played a crucial role.

9.
Proc Biol Sci ; 285(1870)2018 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-29321293

RESUMO

Variation in predation risk is a major driver of ecological and evolutionary change, and, in turn, of geographical variation in behaviour. While predation risk is rarely constant in natural populations, the extent to which variation in predation risk shapes individual behaviour in wild populations remains unclear. Here, we investigated individual differences in reproductive behaviour in 16 Trinidadian guppy populations and related it to the observed variation in predator biomass each population experienced. Our results show that high heterogeneity in predator biomass is linked to individual behavioural diversification. Increased within-population heterogeneity in predator biomass is also associated with behavioural polymorphism. Some individuals adjust the frequency of consensual mating behaviour in response to differences in sex ratio context, while others display constantly at elevated frequencies. This pattern is analogous to a 'live fast, die young' pace-of-life syndrome. Notably, both high and low mean differences in predator biomass led to a homogenization of individual frequency of consensual mating displays. Overall, our results demonstrate that individual behavioural variation is associated with heterogeneity in predator biomass, but not necessarily with changes in mean values of predator biomass. We suggest that heterogeneity in predator biomass is an informative predictor of adaptive responses to changes in biotic conditions.


Assuntos
Variação Biológica Individual , Poecilia/fisiologia , Comportamento Predatório/fisiologia , Comportamento Sexual Animal/fisiologia , Adaptação Psicológica , Animais , Evolução Biológica , Copulação , Masculino , Modelos Estatísticos , Razão de Masculinidade
10.
Glob Ecol Biogeogr ; 27(7): 760-786, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30147447

RESUMO

MOTIVATION: The BioTIME database contains raw data on species identities and abundances in ecological assemblages through time. These data enable users to calculate temporal trends in biodiversity within and amongst assemblages using a broad range of metrics. BioTIME is being developed as a community-led open-source database of biodiversity time series. Our goal is to accelerate and facilitate quantitative analysis of temporal patterns of biodiversity in the Anthropocene. MAIN TYPES OF VARIABLES INCLUDED: The database contains 8,777,413 species abundance records, from assemblages consistently sampled for a minimum of 2 years, which need not necessarily be consecutive. In addition, the database contains metadata relating to sampling methodology and contextual information about each record. SPATIAL LOCATION AND GRAIN: BioTIME is a global database of 547,161 unique sampling locations spanning the marine, freshwater and terrestrial realms. Grain size varies across datasets from 0.0000000158 km2 (158 cm2) to 100 km2 (1,000,000,000,000 cm2). TIME PERIOD AND GRAIN: BioTIME records span from 1874 to 2016. The minimal temporal grain across all datasets in BioTIME is a year. MAJOR TAXA AND LEVEL OF MEASUREMENT: BioTIME includes data from 44,440 species across the plant and animal kingdoms, ranging from plants, plankton and terrestrial invertebrates to small and large vertebrates. SOFTWARE FORMAT: .csv and .SQL.

12.
BMC Ecol ; 14: 18, 2014 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-24925225

RESUMO

BACKGROUND: The guppy (Poecilia reticulata) is a successful invasive species. It is also a species that mates multiply; previous studies have demonstrated that this strategy carries fitness benefits. Guppies are routinely introduced to tanks and troughs in regions outside their native range for mosquito-control purposes, and often spread beyond these initial confines into natural water bodies with negative ecological consequences. Here, using a mesocosm set up that resembles the containers into which single guppies are typically introduced for mosquito control, we ask whether singly-mated females are at a disadvantage, relative to multiply-mated females, when it comes to founding a population. Treatments were monitored for one year. RESULTS: A key finding was that mating history did not predict establishment success, which was 88% in both treatments. Furthermore, analysis of behavioural traits revealed that the descendants of singly-mated females retained antipredator behaviours, and that adult males showed no decrease in courtship vigour. Also, we detected no differences in behavioural variability between treatments. CONCLUSIONS: These results suggest that even when denied the option of multiple mating, singly-mated female guppies can produce viable populations, at least at the founder stage. This may prove to be a critical advantage in typical introduction scenarios where few individuals are released into enclosed water bodies before finding their way into natural ecosystems.


Assuntos
Espécies Introduzidas , Poecilia/fisiologia , Reprodução/fisiologia , Comportamento Sexual Animal , Animais , Feminino , Masculino , Dinâmica Populacional
13.
Infant Behav Dev ; 75: 101930, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38461735

RESUMO

Infant regulatory behavior develops since birth and impacts their early social interactions. Infants differ in the relative coherence and incoherence of their cross-modal communicative signals during en-face infant-caregiver interactions. We expand this research by evaluating whether different infant regulatory patterns observed during the Face-to-Face Still-Face (FFSF) at 3 months are associated with the coherence or incoherence of infants' cross-modal communicative behaviors during en-face interactions or with multiple dimensions of mother-infant interactive behavior during free-play. Analyses were based on data collected from 100 mother-infant dyads from urban, working- and middle-class backgrounds in Portugal who were videotaped during the FFSF and free play at 3 months. Results confirm that infants' different regulatory behavior patterns in the FFSF at 3 months are associated with the coherence and incoherence of their cross-modal interactive behaviors and specific aspects of mother-infant interaction. Infants with a Social-Positive oriented regulatory pattern during the FFSF displayed more coherent and less incoherent communicative behaviors with their mothers and were more cooperative during free play. In turn, their mothers were more sensitive. Our findings support the perspective that infants' regulatory behavior strategies in the context of caregiver regulatory support and sensitivity are likely to increase dyadic correspondence and infant ability to engage with the world.


Assuntos
Comunicação , Comportamento do Lactente , Relações Mãe-Filho , Humanos , Relações Mãe-Filho/psicologia , Feminino , Lactente , Masculino , Comportamento do Lactente/psicologia , Comportamento do Lactente/fisiologia , Adulto , Mães/psicologia , Desenvolvimento Infantil/fisiologia , Jogos e Brinquedos/psicologia
14.
Mar Environ Res ; 194: 106321, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38159409

RESUMO

The dinoflagellates Protoceratium reticulatum and Lingulodinium polyedra are potential yessotoxin (YTX) producers, which have been associated with blooms responsible for economic, social, and ecological impacts around the world. They occur in Iberian waters, but in this region, little is known of their ecophysiology and toxin profiles. This study investigated the growth and toxin production of two strains of each species, from the Portuguese coast, at 15 °C, 19 °C, and 23 °C. Growth curves showed higher growth rates at 19 °C, for both species. YTX and three analogs (homo YTX; 45-OH YTX; 45-OH homo YTX) were investigated by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS), and the presence of other analogs was investigated by Liquid Chromatography-High-Resolution Mass Spectrometry (LC-HRMS). No evidence of toxin production was found in L. polyedra. By contrast, YTX and 45,55-diOH-YTX were detected in both strains of P. reticulatum. These results confirm P. reticulatum as a source of yessotoxins along the Portuguese coast and add to the observed high intraspecific variability on YTX production of both species, at a global scale.


Assuntos
Dinoflagellida , Toxinas Marinhas , Venenos de Moluscos , Oxocinas , Cromatografia Líquida , Toxinas Marinhas/análise , Temperatura , Portugal , Espectrometria de Massas em Tandem
15.
Early Hum Dev ; 189: 105943, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38241790

RESUMO

BACKGROUND: The impact of prematurity status on attachment quality remains indeterminate. Some studies found no differences between infants born preterm (PT) and infants born full-term (FT), while other investigations present opposite results. AIMS: We aim to contribute to this body of research by studying mother-infant interactive behaviors and quality of attachment in 3 independent samples: Full-Term (FT), Moderate-to-Late Preterm (MLPT) and Very-to-Extreme Preterm (VEPT). STUDY DESIGN: This is a longitudinal laboratory study conducted from 3 to 12 months of age (corrected-age in the case of infants born PT). SUBJECTS: The participants are 213 Portuguese infants (FT = 105; MLPT = 52; VEPT = 56) and their mothers. OUTCOME MEASURES: Mother-infant interactive behavior was observed in free-play at 3 and 9 months (corrected-age). Infant attachment was observed in Strange Situation at 12 months. RESULTS: Secure attachment is more prevalent in infants born FT, and ambivalent attachment is more prevalent in infants born VEPT. Infants with a secure attachment have higher gestational age and weight at birth. Infant and maternal interactive behavior quality is associated with attachment patterns and varies according to infant prematurity status. Last, the results indicate changes in maternal sensitivity and infant difficult behavior from 3 to 9 months of infant's age. CONCLUSIONS: Our findings indicate that prematurity status impacts attachment quality. Changes in maternal and infant behavior from 3 to 9 months suggest a period of rapid non-linear development, supporting a transactional multilayered approach to the study of mother-infant relationship.


Assuntos
Recém-Nascido Prematuro , Relações Mãe-Filho , Humanos , Recém-Nascido , Lactente , Feminino , Comportamento Materno , Mães , Estudos Longitudinais
16.
Cureus ; 16(3): e56067, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38618397

RESUMO

Sinonasal (SN) malignancies are rare. Within SN adenocarcinomas, the most frequent are intestinal-type adenocarcinomas (ITACs). ITAC has been associated with wood and leather dust occupational exposure and TP53 mutations. Not much information is available regarding its characterization and treatment. The aim of this study is to characterize the clinicopathologic and prognostic factors of patients with sinonasal adenocarcinomas (SNACs) treated in our tertiary-level hospital. A retrospective, consecutive study including SNAC patients diagnosed between 2004-2023 was conducted. Clinicopathological data was collected, and p53 status was assessed in the tumor specimens. The association between p53 status and clinicopathological variables, as well as their impact on survival, was evaluated. In total, 35 were included, most of them having ITAC (91.4%) with papillary subtype (37.5%); the majority were subjected to occupational risk exposure (82.9%). Overexpression of p53 was identified in 48.6% of the tumors. Papillary and colonic subtypes were associated with higher median progression-free survival (mPFS) than mucinous and solid subtypes (mPFS 37 months, 95% CI, 20.0-54.0, vs. 9 months, 95% CI, 7.15-10.85, p=0.01); the former was also associated with higher median overall survival (mOS) (mOS 64 months, 95% CI, 37.18-90.81 vs. 14 months, 95% CI, 0-41.58, p=0.02). Histologic grade 1-2 and macroscopic complete resection were associated with higher PFS (PFS of five months of 90.9% vs. 33.3%, p=0.01; mPFS of 37 months, 95% CI, 4.93-69.07 vs. 10 months, 95% CI, 6.43-13.57, p=0.04, respectively). Disease recurrence with distant metastases was associated with lower OS (11 months, 95% CI, 6.1-15.9 vs. 53 months, 95% CI, 22.70-83.30, p=0.04). This study reinforces the importance of protective occupational measures. Future studies will be important to validate the best treatment strategy in the advanced stages of this disease and also to identify new prognostic and/or therapeutic target biomarkers in SNAC.

17.
medRxiv ; 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38605883

RESUMO

Objective: The Krebs cycle enzyme Aconitate Decarboxylase 1 (ACOD1) mediates itaconate synthesis in myeloid cells.. Previously, we reported that administration of 4-octyl itaconate abrogated lupus phenotype in mice. Here, we explore the role of the endogenous ACOD1/itaconate pathway in the development of murine lupus as well as their relevance in premature cardiovascular damage in SLE. Methods: We characterized Acod1 protein expression in bone marrow-derived macrophages and human monocyte-derived macrophages, following a TLR7 agonist (imiquimod, IMQ). Wild type and Acod1-/- mice were exposed to topical IMQ for 5 weeks to induce an SLE phenotype and immune dysregulation was quantified. Itaconate serum levels were quantified in SLE patients and associated to cardiometabolic parameters and disease activity. Results: ACOD1 was induced in mouse bone marrow-derived macrophages (BMDM) and human monocyte-derived macrophages following in vitro TLR7 stimulation. This induction was partially dependent on type I Interferon receptor signaling and specific intracellular pathways. In the IMQ-induced mouse model of lupus, ACOD1 knockout (Acod1-/-) displayed disruptions of the splenic architecture, increased serum anti-dsDNA and proinflammatory cytokine levels, enhanced kidney immune complex deposition and proteinuria, when compared to the IMQ-treated WT mice. Consistent with these results, Acod1-/- BMDM exposed to IMQ showed higher proinflammatory features in vitro. Itaconate levels were decreased in SLE serum compared to healthy control sera, in association with specific perturbed cardiometabolic parameters and subclinical vascular disease. Conclusion: These findings suggest that the ACOD1/itaconate pathway plays important immunomodulatory and vasculoprotective roles in SLE, supporting the potential therapeutic role of itaconate analogs in autoimmune diseases.

18.
Presse Med ; 52(3): 104174, 2023 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-37778637

RESUMO

Bronchiectasis is a final common pathway of a wide variety of underlying conditions including infectious, autoimmune, allergic, genetic and inflammatory conditions. Patients experience a chronic disease with variable clinical symptoms and course, but most experience cough, sputum production and recurrent exacerbations. Symptoms of bronchiectasis lead to poor quality of life and exacerbations are the major driver of morbidity and mortality. Patients are often chronically infected with bacteria with the most common being Pseudomonas aeruginosa and Haemophilus influenzae. Treatment of bronchiectasis includes standardised testing to identify the underlying cause with targeted treatment if immune deficiency, allergic bronchopulmonary aspergillosis or non-tuberculous mycobacterial infection, for example, are identified. Airway clearance is the mainstay of therapy for patients with symptoms of cough and sputum production. Frequently exacerbating patients may benefit from long term antibiotic or mucoactive therapies. Bronchiectasis is a heterogeneous disease and increasingly precision medicine approaches are advocated to target treatments most appropriately and to limit the emergence of antimicrobial resistance.

19.
Acta Med Port ; 36(5): 358-360, 2023 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-36036725

RESUMO

Priapism may be a side effect of low-molecular-weight heparins, and its mechanism remains unknown. The authors present a clinical case of a 51-year-old male patient with oligodendroglioma. The patient presented ischemic priapism on the third month after starting tinzaparin, without other recent changes to his medication and he denied the use of other new medicines. The patient went through surgery and the erection was resolved but presented fibrosis of the cavernous body which left him with erectile dysfunction. Since this event, the patient is no longer receiving Heparin and has had no other episodes of priapism. The prompt recognition of this side effect may decrease its morbidity and consequent impact on the quality of life. More studies are needed to better understand its pathophysiology.


O priapismo pode ser um efeito adverso das heparinas de baixo peso molecular, cuja fisiopatologia não é totalmente compreendida. Os autores apresentam o caso de um doente, do sexo masculino, 51 anos, com diagnóstico de oligodendroglioma. O doente apresentou um episódio de priapismo, no terceiro mês sob tinzaparina, sem nenhuma outra alteração recente da sua medicação habitual e com consumo de outros medicamentos negado. Foi submetido a cirurgia, com resolução do priapismo, mas apresentou fibrose sequelar dos corpos cavernosos, com consequente disfunção eréctil. Desde então o doente não retomou heparina e não apresentou novos episódios de priapismo. Um célere reconhecimento do quadro pode contribuir para menores sequelas, com consequente diminuição da morbilidade e impacto na qualidade de vida. Mais investigação é necessária para aumentar o conhecimento sobre a fisiopatologia desta situação.


Assuntos
Disfunção Erétil , Priapismo , Humanos , Masculino , Pessoa de Meia-Idade , Priapismo/induzido quimicamente , Qualidade de Vida , Heparina de Baixo Peso Molecular/efeitos adversos
20.
Cureus ; 15(3): e35853, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37033504

RESUMO

We present the case of a 64-year-old woman with type 2 diabetes who was diagnosed with early-stage intrahepatic cholangiocarcinoma and underwent partial hepatectomy followed by adjuvant chemotherapy. The patient simultaneously developed skin lesions compatible with acanthosis nigricans (AN). Thirty-seven months after completing chemotherapy, the patient had a recurrence of extensive skin and mucosal lesions compatible with AN. A thoracic-abdominal-pelvic (TAP) CT showed a relapse with hepatic hilar adenopathy. Currently, she is under evaluation to undergo radical treatment. Malignancy is a rare cause of AN and skin lesions can arise before, during, or after the diagnosis. As a paraneoplastic syndrome, it is usually related to gastric adenocarcinoma, with cholangiocarcinoma being a rare entity in this setting. Although an uncommon manifestation, the malignant etiology should be considered among other prevalent causes, such as metabolic disorders, and establishing an association can lead to an early diagnosis and initiation of curative treatment.

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