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1.
Cell Rep ; 43(4): 114091, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38607914

RESUMO

Nitric oxide (NO) is a gasotransmitter required in a broad range of mechanisms controlling plant development and stress conditions. However, little is known about the specific role of this signaling molecule during lipid storage in the seeds. Here, we show that NO is accumulated in developing embryos and regulates the fatty acid profile through the stabilization of the basic/leucine zipper transcription factor bZIP67. NO and nitro-linolenic acid target and accumulate bZIP67 to induce the downstream expression of FAD3 desaturase, which is misregulated in a non-nitrosylable version of the protein. Moreover, the post-translational modification of bZIP67 is reversible by the trans-denitrosylation activity of peroxiredoxin IIE and defines a feedback mechanism for bZIP67 redox regulation. These findings provide a molecular framework to control the seed fatty acid profile caused by NO, and evidence of the in vivo functionality of nitro-fatty acids during plant developmental signaling.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Fatores de Transcrição de Zíper de Leucina Básica , Ácidos Graxos , Óxido Nítrico , Peroxirredoxinas , Ácidos Graxos/metabolismo , Proteínas de Arabidopsis/metabolismo , Peroxirredoxinas/metabolismo , Arabidopsis/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética , Óxido Nítrico/metabolismo , Regulação da Expressão Gênica de Plantas , Sementes/metabolismo , Metabolismo dos Lipídeos , Processamento de Proteína Pós-Traducional
3.
Cir. pediátr ; 37(2): 79-83, Abr. 2024. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-232270

RESUMO

Introducción: Existen numerosas alternativas en lo que respecta alos cuidados postoperatorios en la cirugía de hipospadias. El objetivo deeste estudio es evaluar la situación actual de estos cuidados en nuestromedio y revisar la evidencia existente al respecto para cirujanos pediátricos que realizan este tipo de intervenciones. Material y métodos: Hemos elaborado y distribuido una encuestaque recoge los principales puntos en el cuidado postoperatorio del hipospadias dirigida a cirujanos pediátricos. Se ha realizado revisión dela evidencia actual publicada al respecto en la especialidad.Resultados: Hemos obtenido un total de 46 respuestas. El 100% delos cirujanos dejan algún tipo de sonda o stent y más del 80% están deacuerdo en retirarlo tras 5 o 7 días. El 87,8% de los encuestados utilizael doble pañal, pero solo el 65,2% da alta precoz en el postoperatorio.Un 60,9% pauta profilaxis antibiótica mientras dure el sondaje y un34,8% antibioterapia a dosis plenas. Discusión: Existe consenso general respecto a la tutorización de lauretroplastia y el uso de apósito compresivo entre los cirujanos pediátricos encuestados. Se detectan más discrepancias en el uso de antibioterapia y el alta precoz. La evidencia actual y la práctica a nivel internacional apunta hacia el uso de la sonda a doble pañal con alta precozy la limitación del uso de antibióticos postoperatorios. En ausencia declara evidencia que favorezca un tipo de cuidado u otro, la experienciadel paciente podría ser utilizada para elegir el mejor protocolo postoperatorio individualizado.(AU)


Introduction: There are many alternatives available regarding postoperative care in hypospadias surgery. The objective of this study wasto assess the current care situation in our environment and to review theevidence available for pediatric surgeons who conduct this procedure. Materials and methods. A survey regarding the main aspects ofhypospadias postoperative care was created and distributed to pediatricsurgeons. In addition, the evidence currently published in this field wasreviewed. Results: A total of 46 replies were achieved. 100% of the surgeonsleave in place a probe or stent, and more than 80% remove it after 5 or7 days. 87.8% of the respondents use a double diaper, but only 65.2%discharge patients early in the postoperative period. 60.9% prescribeantibiotic prophylaxis for as long as the probe remains in place, and34.8% use full-dose antibiotic therapy. Discussion: There was a general consensus regarding urethroplastyguiding and the use of compression dressings among the pediatric surgeons surveyed. However, more discrepancies were found in the use ofantibiotic therapy and early discharge. The currently available evidenceand international practice suggest using a probe with double diaperand early discharge, with postoperative antibiotics being limited. Inthe absence of clear evidence for a specific care type, the patient’sexperience could be used to choose the best postoperative protocol onan individual basis.(AU)


Assuntos
Humanos , Masculino , Feminino , Cuidados Pós-Operatórios , Hipospadia , Doenças do Recém-Nascido , Cateteres Urinários , Antibioticoprofilaxia , Pediatria , Cirurgia Geral , Inquéritos e Questionários
4.
Orphanet J Rare Dis ; 19(1): 85, 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38402381

RESUMO

BACKGROUND: Neurofibromatosis type 1 (NF1) is one of the most common RASopathies predisposing affected patients to melanic lesions and benign tumors. NF1 is associated with considerable esthetic and functional burden negatively affecting the patient's quality of life (QoL). This study aims to assess the clinical features of NF1 patients and evaluate their impact on QoL. We identified NF1 patients from a public health database of a region in Spain. All patients underwent clinical and ophthalmological evaluation for NF1 features. We measured QoL using the Spanish version of the Skindex-29. RESULTS: Forty patients fulfilled the NF1 National Institute of Health criteria when we recruited patients. The median age was 42.00 years (IQR 26.5 -53.75). The median total Skindex-29 score was 12.3 (IQR 5.9-22.4); (emotion: 15.0, IQR 5.0-37.5; symptoms 8.9, IQR 0.0-17.9 and functioning 8.3; IQR 0.5-18.3). Women and NF1 patients with lower educational levels were associated with poorer QoL scores. We identified itching and sleep troubles to influence NF1 patients' QoL negatively. CONCLUSION: NF1 considerably influences the psychological well-being of NF1 patients. We observed that female and low-educated patients scored higher on the emotional dimension of the Skindex-29 and could, therefore, be more at risk of depression. We also pointed out some "minor symptoms" that negatively impact NF1 patients' QoL such, as itching and sleep troubles which doctors could treat if sought by doctors.


Assuntos
Neurofibromatose 1 , Humanos , Feminino , Adulto , Neurofibromatose 1/patologia , Qualidade de Vida/psicologia , Inquéritos e Questionários , Emoções , Prurido/complicações
5.
Psychol Med ; 54(3): 620-630, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37667630

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) has serious physiological and psychological consequences. The long-term (>12 weeks post-infection) impact of COVID-19 on mental health, specifically in older adults, is unclear. We longitudinally assessed the association of COVID-19 with depression symptomatology in community-dwelling older adults with metabolic syndrome within the framework of the PREDIMED-Plus cohort. METHODS: Participants (n = 5486) aged 55-75 years were included in this longitudinal cohort. COVID-19 status (positive/negative) determined by tests (e.g. polymerase chain reaction severe acute respiratory syndrome coronavirus 2, IgG) was confirmed via event adjudication (410 cases). Pre- and post-COVID-19 depressive symptomatology was ascertained from annual assessments conducted using a validated 21-item Spanish Beck Depression Inventory-II (BDI-II). Multivariable linear and logistic regression models assessed the association between COVID-19 and depression symptomatology. RESULTS: COVID-19 in older adults was associated with higher post-COVID-19 BDI-II scores measured at a median (interquartile range) of 29 (15-40) weeks post-infection [fully adjusted ß = 0.65 points, 95% confidence interval (CI) 0.15-1.15; p = 0.011]. This association was particularly prominent in women (ß = 1.38 points, 95% CI 0.44-2.33, p = 0.004). COVID-19 was associated with 62% increased odds of elevated depression risk (BDI-II ≥ 14) post-COVID-19 when adjusted for confounders (odds ratio; 95% CI 1.13-2.30, p = 0.008). CONCLUSIONS: COVID-19 was associated with long-term depression risk in older adults with overweight/obesity and metabolic syndrome, particularly in women. Thus, long-term evaluations of the impact of COVID-19 on mental health and preventive public health initiatives are warranted in older adults.


Assuntos
COVID-19 , Síndrome Metabólica , Humanos , Feminino , Idoso , COVID-19/epidemiologia , Depressão/psicologia , Síndrome Metabólica/epidemiologia , Sobrepeso/epidemiologia , Obesidade/epidemiologia
6.
Nat Commun ; 14(1): 8368, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38114471

RESUMO

NEMO is a ubiquitin-binding protein which regulates canonical NF-κB pathway activation in innate immune signaling, cell death regulation and host-pathogen interactions. Here we identify an NF-κB-independent function of NEMO in proteostasis regulation by promoting autophagosomal clearance of protein aggregates. NEMO-deficient cells accumulate misfolded proteins upon proteotoxic stress and are vulnerable to proteostasis challenges. Moreover, a patient with a mutation in the NEMO-encoding IKBKG gene resulting in defective binding of NEMO to linear ubiquitin chains, developed a widespread mixed brain proteinopathy, including α-synuclein, tau and TDP-43 pathology. NEMO amplifies linear ubiquitylation at α-synuclein aggregates and promotes the local concentration of p62 into foci. In vitro, NEMO lowers the threshold concentrations required for ubiquitin-dependent phase transition of p62. In summary, NEMO reshapes the aggregate surface for efficient autophagosomal clearance by providing a mobile phase at the aggregate interphase favoring co-condensation with p62.


Assuntos
Quinase I-kappa B , NF-kappa B , Humanos , NF-kappa B/metabolismo , Quinase I-kappa B/genética , Quinase I-kappa B/metabolismo , alfa-Sinucleína/genética , Ubiquitina/metabolismo , Autofagia/genética
7.
Pathogens ; 12(11)2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-38003835

RESUMO

Co-infections are a poorly understood aspect of tick-borne diseases. In the United States alone, nineteen different tick-borne pathogens have been identified. The majority of these agents are transmitted by only two tick species, Ixodes scapularis and Amblyomma americanum. Surveillance studies have demonstrated the presence of multiple pathogens in individual ticks suggesting a risk of polymicrobial transmission to humans. However, relatively few studies have explored this relationship and its impact on human disease. One of the key factors for this deficiency are the intrinsic limitations associated with molecular and serologic assays employed for the diagnosis of tick-borne diseases. Limitations in the sensitivity, specificity and most importantly, the capacity for inclusion of multiple agents within a single assay represent the primary challenges for the accurate detection of polymicrobial tick-borne infections. This review will focus on outlining these limitations and discuss potential solutions for the enhanced diagnosis of tick-borne co-infections.

8.
Tob Induc Dis ; 21: 157, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38034128

RESUMO

INTRODUCTION: The role of cigarette smoking on breast cancer risk remains controversial, due to its dual carcinogenic-antiestrogenic action. METHODS: In the population-based multi-case-control study (MCC-Spain), we collected epidemiological and clinical information for 1733 breast cancer cases and 1903 controls, including smoking exposure. The association with breast cancer, overall, by pathological subtype and menopausal status, was assessed using logistic and multinomial regression models. RESULTS: Smokers had higher risk of premenopausal breast cancer, particularly if they had smoked ≥30 years (AOR=1.75; 95% CI: 1.04-2.94), although most estimates did not achieve statistical significance. In contrast, among postmenopausal women, smoking was associated with lower risk of breast cancer, mainly in overweight and obese women. The strongest risk reductions were observed among postmenopausal women who had stopped smoking ≥10 years before cancer diagnosis, particularly for HER2+ tumors (AOR=0.28; 95% CI: 0.11-0.68); p for heterogeneity = 0.040). Also, those who had smoked <10 pack-years (AOR=0.68; 95% CI: 0.47-0.98) or 10-25 pack-years (AOR=0.62; 95% CI: 0.42-0.92) during their lifetime were at a reduced risk of all breast cancer subtypes (p for heterogeneity: 0.405 and 0.475, respectively); however, women who had smoked more than 25 pack-years showed no reduced risk. CONCLUSIONS: Menopausal status plays a key role in the relationship between tobacco and breast cancer for all cancer subtypes. While smoking seems to increase the risk in premenopausal woman, it might be associated to lower risk of breast cancer among postmenopausal women with excess weight.

10.
JAMA Netw Open ; 6(10): e2337994, 2023 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-37851444

RESUMO

Importance: Strategies targeting body composition may help prevent chronic diseases in persons with excess weight, but randomized clinical trials evaluating lifestyle interventions have rarely reported effects on directly quantified body composition. Objective: To evaluate the effects of a lifestyle weight-loss intervention on changes in overall and regional body composition. Design, Setting, and Participants: The ongoing Prevención con Dieta Mediterránea-Plus (PREDIMED-Plus) randomized clinical trial is designed to test the effect of the intervention on cardiovascular disease prevention after 8 years of follow-up. The trial is being conducted in 23 Spanish research centers and includes men and women (age 55-75 years) with body mass index between 27 and 40 and metabolic syndrome. The trial reported herein is an interim subgroup analysis of the intermediate outcome body composition after 3-year follow-up, and data analysis was conducted from February 1 to November 30, 2022. Of 6874 total PREDIMED-Plus participants, a subsample of 1521 individuals, coming from centers with access to a dual energy x-ray absorptiometry device, underwent body composition measurements at 3 time points. Intervention: Participants were randomly allocated to a multifactorial intervention based on an energy-reduced Mediterranean diet (MedDiet) and increased physical activity (PA) or to a control group based on usual care, with advice to follow an ad libitum MedDiet, but no physical activity promotion. Main Outcomes and Measures: The outcomes (continuous) were 3-year changes in total fat and lean mass (expressed as percentages of body mass) and visceral fat (in grams), tested using multivariable linear mixed-effects models. Clinical relevance of changes in body components (dichotomous) was assessed based on 5% or more improvements in baseline values, using logistic regression. Main analyses were performed in the evaluable population (completers only) and in sensitivity analyses, multiple imputation was performed to include data of participants lost to follow-up (intention-to-treat analyses). Results: A total of 1521 individuals were included (mean [SD] age, 65.3 [5.0] years; 52.1% men). In comparison with the control group (n=761), participants in the intervention arm (n=760) showed greater reductions in the percentage of total fat (between group differences after 1-year, -0.94% [95% CI, -1.19 to -0.69]; 3 years, -0.38% [95% CI, -0.64 to -0.12] and visceral fat storage after 1 year, -126 g [95% CI, -179 to -73.3 g]; 3 years, -70.4 g [95% CI, -126 to -15.2 g] and greater increases in the percentage of total lean mass at 1 year, 0.88% [95% CI, 0.63%-1.12%]; 3-years 0.34% [95% CI, 0.09%-0.60%]). The intervention group was more likely to show improvements of 5% or more in baseline body components (absolute risk reduction after 1 year, 13% for total fat mass, 11% for total lean mass, and 14% for visceral fat mass; after 3-years: 6% for total fat mass, 6% for total lean mass, and 8% for visceral fat mass). The number of participants needed to treat was between 12 and 17 to attain at least 1 individual with possibly clinically meaningful improvements in body composition. Conclusions and Relevance: The findings of this trial suggest a weight-loss lifestyle intervention based on an energy-reduced MedDiet and physical activity significantly reduced total and visceral fat and attenuated age-related losses of lean mass in older adults with overweight or obesity and metabolic syndrome. Continued follow-up is warranted to confirm the long-term consequences of these changes on cardiovascular clinical end points. Trial Registration: isrctn.org Identifier: ISRCTN89898870.


Assuntos
Doenças Cardiovasculares , Dieta Mediterrânea , Síndrome Metabólica , Masculino , Humanos , Feminino , Idoso , Pessoa de Meia-Idade , Doenças Cardiovasculares/prevenção & controle , Exercício Físico , Redução de Peso , Composição Corporal
11.
BMC Med ; 21(1): 390, 2023 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-37833678

RESUMO

BACKGROUND: Cross-sectionally, older age and obesity are associated with increased coronavirus disease-2019 (COVID-19) risk. We assessed the longitudinal associations of baseline and changes in adiposity parameters with COVID-19 incidence in older adults at high cardiovascular risk. METHODS: This analysis included 6874 men and women (aged 55-75 years) with overweight/obesity and metabolic syndrome in the PREDIMED-Plus lifestyle intervention trial for cardiovascular risk reduction. Body weight, body-mass-index (BMI), waist circumference, waist-to-height ratio (WHtR), and a body shape index (ABSI) were measured at baseline and annual follow-up visits. COVID-19 was ascertained by an independent Event Committee until 31 December 2021. Cox regression models were fitted to evaluate the risk of COVID-19 incidence based on baseline adiposity parameters measured 5-6 years before the pandemic and their changes at the visit prior to censoring. RESULTS: At the time of censoring, 653 incident COVID-19 cases occurred. Higher baseline body weight, BMI, waist circumference, and WHtR were associated with increased COVID-19 risk. During the follow-up, every unit increase in body weight (HRadj (95%CI): 1.01 (1.00, 1.03)) and BMI (HRadj: 1.04 (1.003, 1.08)) was associated with increased COVID-19 risk. CONCLUSIONS: In older adults with overweight/obesity, clinically significant weight loss may protect against COVID-19. TRIAL REGISTRATION: This study is registered at the International Standard Randomized Controlled Trial (ISRCT; http://www.isrctn.com/ISRCTN89898870 ).


Assuntos
COVID-19 , Síndrome Metabólica , Idoso , Feminino , Humanos , Masculino , Adiposidade , Índice de Massa Corporal , Peso Corporal , COVID-19/epidemiologia , COVID-19/complicações , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/complicações , Obesidade/complicações , Obesidade/epidemiologia , Obesidade/metabolismo , Sobrepeso/complicações , Sobrepeso/epidemiologia , Fatores de Risco , Circunferência da Cintura , Pessoa de Meia-Idade
12.
Nucleic Acids Res ; 51(19): 10719-10736, 2023 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-37713607

RESUMO

Artificial microRNAs (amiRNAs) are highly specific, 21-nucleotide (nt) small RNAs designed to silence target transcripts. In plants, their application as biotechnological tools for functional genomics or crop improvement is limited by the need of transgenically expressing long primary miRNA (pri-miRNA) precursors to produce the amiRNAs in vivo. Here, we analyzed the minimal structural and sequence requirements for producing effective amiRNAs from the widely used, 521-nt long AtMIR390a pri-miRNA from Arabidopsis thaliana. We functionally screened in Nicotiana benthamiana a large collection of constructs transiently expressing amiRNAs against endogenous genes and from artificially shortened MIR390-based precursors and concluded that highly effective and accurately processed amiRNAs can be produced from a chimeric precursor of only 89 nt. This minimal precursor was further validated in A. thaliana transgenic plants expressing amiRNAs against endogenous genes. Remarkably, minimal but not full-length precursors produce authentic amiRNAs and induce widespread gene silencing in N. benthamiana when expressed from an RNA virus, which can be applied into leaves by spraying infectious crude extracts. Our results reveal that the length of amiRNA precursors can be shortened without affecting silencing efficacy, and that viral vectors including minimal amiRNA precursors can be applied in a transgene-free manner to induce whole-plant gene silencing.


Assuntos
Arabidopsis , MicroRNAs , MicroRNAs/genética , Inativação Gênica , Plantas Geneticamente Modificadas/genética , Transgenes , Arabidopsis/genética
13.
Vaccines (Basel) ; 11(8)2023 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-37631950

RESUMO

Elderly care home residents are particularly vulnerable to COVID-19 due to immune-senescence, pre-existing medical conditions, and the risk of transmission from staff and visitors. This study aimed to describe the outcomes of a COVID-19 outbreak in a long-term care facility for elderly persons following the initial vaccination. A single-center, retrospective, observational design was used to analyze the variables associated with hospitalization and death rate by logistic regression. Adjusted odds ratios (aOR) and their 95% confidence intervals (CI) were calculated. Sixty-eight residents received the first dose of the COVID-19 vaccine. Despite being negative six days after vaccination, the performance of a second test 4 days later revealed 51 positives (75.0%) among residents and 18 among workers (56.3%). A total of 65 of the 68 residents (95.58%) had positive results with symptoms, whereas 34.9% required hospitalization, and 25.8% died. The best-fitting model to explain the distribution of cases reflects three points at the time of infection.. The time from vaccination to symptom onset explains the hospitalization and mortality rates since a day elapsed halves the risk of hospitalization (aOR = 0.57; CI = 0.38-0.75) and the risk of death by a quarter (aOR = 0.74; CI = 0.63-0.88). Nursing homes present an elevated risk of transmission and severity of SARS-CoV-2 infection. Although vaccination reduces the risk of hospitalization and death, extreme prevention and control measures are essential in these institutions despite the high vaccination coverage.

14.
Med. clín (Ed. impr.) ; 161(3): 107-109, ago. 2023. tab
Artigo em Espanhol | IBECS | ID: ibc-224005

RESUMO

Objetivo Analizar y describir la clasificación anatómica y etiológica, las características clínicas y epidemiológicas y los síntomas más frecuentes de los casos de uveítis en nuestra población. Pacientes y método Estudio observacional descriptivo, retrospectivo de los casos de uveítis atendidos en el Servicio de Oftalmología del Hospital Universitario Virgen del Rocío en el año 2021. Se estudiaron las características demográficas y clínicas. Resultados Se estudiaron 109 casos de uveítis, en 46 hombres y 63 mujeres, con una media de edad de 45,43±16,11 años. Los síntomas más frecuentes fueron dolor (74,31%), hiperemia (73,39%) y visión borrosa (65,14%). La clasificación anatómica más frecuente fue anterior (55,96%), seguida de panuveítis (18,35%), uveítis posterior (12,84%) e intermedia (7,34%). En cuanto a la etiología, la mayoría de las uveítis fueron idiopáticas (42,99%), seguidas de las no infecciosas (38,32%) y las infecciosas (18,69%). Conclusiones En el sur de España, las características de la uveítis son similares a las de otros estudios en países occidentales (AU)


Purpose Analyse and describe the anatomical and etiological classification, clinical and epidemiological characteristics and most frequent symptoms of uveitis cases in our population. Patients and method Descriptive, retrospective observational study of uveitis cases treated in the Ophthalmology Department of Virgen del Rocío University Hospital in 2021. The demographic and clinical characteristics were studied. Results A total of 109cases of uveitis were studied, 46 men and 63 women, with a mean age of 45.43±16.11 years. The most frequent symptoms were pain (74.31%), hyperemia (73.39%) and blurred vision (65.14%). The most frequent anatomical classification was anterior (55.96%), followed by panuveitis (18.35%), posterior (12.84%) and intermediate uveitis (7.34%). Regarding etiology, most uveitis were idiopathic (42.99%), followed by non-infectious (38.32%) and finally infectious (18.69%). Conclusions In southern España, the characteristics of uveitis are similar to other studies in Western countries (AU)


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Uveíte/diagnóstico , Uveíte/classificação , Estudos Retrospectivos , Uveíte/epidemiologia
15.
Global Health ; 19(1): 50, 2023 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-37443076

RESUMO

BACKGROUND: Metabolic syndrome (MetS) has become a growing risk factor of some non-communicable diseases. Increase of greenhouse gas emissions affects the planet. AIMS: To assess the association between MetS severity and amount of carbon dioxide (CO2) emitted in an adult population. DESIGN: Cross-sectional study (n = 6646; 55-76-year-old-men; 60-75-year-old-women with MetS). METHODS: Dietary habits were assessed using a pre-validated semi quantitative 143-item food frequency questionnaire. The amount of CO2 emitted due to the production of food consumed by person and day was calculated using a European database, and the severity of the MetS was calculated with the MetS Severity Score. RESULTS: Higher glycaemia levels were found in people with higher CO2 emissions. The risk of having high severe MetS was related to high CO2 emissions. CONCLUSIONS: Low CO2 emissions diet would help to reduce MetS severity. Advantages for both health and the environment were found following a more sustainable diet. TRIAL REGISTRATION: ISRCTN, ISRCTN89898870 . Registered 05 September 2013.


Assuntos
Síndrome Metabólica , Masculino , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/etiologia , Dióxido de Carbono , Estudos Transversais , Dieta/efeitos adversos , Fatores de Risco
16.
Biochem Pharmacol ; 214: 115681, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37429423

RESUMO

Although pharmacological treatment is the best option for most patients with advanced hepatocellular carcinoma (HCC), its success is very limited, partly due to reduced uptake and enhanced efflux of antitumor drugs. Here we have explored the usefulness of vectorizing drugs towards the organic anion transporting polypeptide 1B3 (OATP1B3) to enhance their efficacy against HCC cells. In silico studies (RNA-Seq data, 11 cohorts) and immunohistochemistry analyses revealed a marked interindividual variability, together with general downregulation but still expression of OATP1B3 in the plasma membrane of HCC cells. The measurement of mRNA variants in 20 HCC samples showed the almost absence of the cancer-type variant (Ct-OATP1B3) together with marked predominance of the liver-type variant (Lt-OATP1B3). In Lt-OATP1B3-expressing cells, the screening of 37 chemotherapeutical drugs and 17 tyrosine kinase receptors inhibitors (TKIs) revealed that 10 classical anticancer drugs and 12 TKIs were able to inhibit Lt-OATP1B3-mediated transport. Lt-OATP1B3-expressing cells were more sensitive than Mock parental cells (transduced with empty lentiviral vectors) to some Lt-OATP1B3 substrates (paclitaxel and the bile acid-cisplatin derivative Bamet-UD2), but not to cisplatin, which is not transported by Lt-OATP1B3. This enhanced response was abolished by competition with taurocholic acid, a known Lt-OATP1B3 substrate. Tumors subcutaneously generated in immunodeficient mice by Lt-OATP1B3-expressing HCC cells were more sensitive to Bamet-UD2 than those derived from Mock cells. In conclusion, Lt-OATP1B3 expression should be screened before deciding the use of anticancer drugs substrates of this carrier in the personalized treatment of HCC. Moreover, Lt-OATP1B3-mediated uptake must be considered when designing novel anti-HCC targeted drugs.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Transportadores de Ânions Orgânicos , Animais , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Cisplatino/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Transportadores de Ânions Orgânicos/metabolismo , Transportadores de Ânions Orgânicos Sódio-Independentes/metabolismo , Membro 1B3 da Família de Transportadores de Ânion Orgânico Carreador de Soluto/genética , Humanos
17.
Endocrinol Diabetes Nutr (Engl Ed) ; 70(7): 448-458, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37468414

RESUMO

BACKGROUND AND OBJECTIVE: The prevalence of type 2 diabetes (T2D) is high, it is increasing and its degree of control seems to be improvable with important social and health consequences. The objective of this study is to determine the regional differences in the degree of glycaemic control of T2D in Spain and its associated factors. MATERIAL AND METHODS: Cross-sectional, multicentre, observational study in patients with T2D between 18 and 85 years of age selected by consecutive sampling between 2014 and 2018. The population was divided into four regions: north, centre, Mediterranean and south-east. The main variable was the value of glycated haemoglobin (HbA1c). Sociodemographic and clinical variables, presence or absence of other risk factors and treatment were recorded. RESULTS: A total of 1587 patients with T2D were analysed, with a mean age of 65.93 years (standard deviation [SD] 10.14); 54.5% were men; the mean duration of T2D was 8.63 years (SD 6.64) and the mean HbA1c value was 7.05%. Of the total, 59.8% had an HbA1c value ≤ 7% (north 59.5%, centre 59.5%, Mediterranean 60.6% and south-east 59.8%; P=.99). The factors for poor control were: in the north, duration of T2D and being sedentary; in the centre, duration of T2D and having a low income; in the Mediterranean, duration of T2D; and in the south-east, duration of T2D and having a low level of education or income. Overall, 76.2% of the subjects had hypertension, 75.1% dyslipidaemia, and 51.7% obesity, with significant differences between regions only being observed in the case of dyslipidaemia (P<.001). CONCLUSIONS: No differences were observed in the degree of diabetes control in the different regions, with the percentage of patients needing intensification in their control being high in all of them. The factors associated with poor control were the duration of the disease, a low level of education or income, and a sedentary lifestyle.


Assuntos
Diabetes Mellitus Tipo 2 , Dislipidemias , Masculino , Humanos , Idoso , Feminino , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobinas Glicadas , Controle Glicêmico , Espanha/epidemiologia , Estudos Transversais
18.
Rev Colomb Psiquiatr (Engl Ed) ; 52(2): 113-120, 2023.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-37453817

RESUMO

OBJECTIVE: To determine the factors associated with impostor syndrome in medical students from six regions of Peru. MATERIAL AND METHODS: A multicentre, cross-sectional study was conduced on students from first to the sixth year in six Peruvian regions. Sociodemographic, academic, and psychological characteristics were included through the Depression, Anxiety, and Stress Scale-21, the Rosenberg Self-Esteem Scale and the Clance Imposter Phenomenon Scale. Generalised linear models were performed using crude and adjusted estimated prevalence ratios. RESULTS: Of 2,231 medical students, 54.3% were female and 30.6% had the impostor phenomenon. An association was found between the PI and those who suffered from depression (aPR=1.51; 95%CI, 1.27-1.79), anxiety (aPR=2.25; 95%CI, 1.75-2.90), stress (aPR=1.37; 95%CI, 1.19-1.57), and being female (aPR=1.12; 95%CI, 1.01-1.26). CONCLUSIONS: Three out of 10 medical students suffer from PI; having some level of depression, anxiety, stress, being a woman, and/or attending the fourth academic year were predisposing factors for their development.


Assuntos
Estudantes de Medicina , Humanos , Feminino , Masculino , Estudantes de Medicina/psicologia , Peru/epidemiologia , Estudos Transversais , Transtornos de Ansiedade
19.
Arch. Soc. Esp. Oftalmol ; 98(7): 417-421, jul. 2023. ilus
Artigo em Espanhol | IBECS | ID: ibc-222990

RESUMO

Se presentan 3 casos de pacientes, con 66, 80 y 23años de edad, que presentaron una pérdida de visión unilateral. La tomografía de coherencia óptica (OCT) mostró edema macular junto con una lesión redondeada de pared hiperreflectiva y la angiografía con fluoresceína (AFG) de dos de ellos, dilataciones aneurismáticas perifoveales hiperfluorescentes con exudación. Ninguno de los casos mostró respuesta al tratamiento tras un año de seguimiento, diagnosticándose finalmente de complejo anómalo vascular exudativo perifoveal (PEVAC) (AU)


We present three cases of patients aged 66, 80 and 23, who presented unilateral vision loss. Optical coherence tomography (OCT) in all of them showed macular oedema and a rounded lesion with hyper-reflective wall, and fluorescein angiography (FAG) in two of them showed hyperfluorescent perifoveal aneurysmal dilations with exudation. None of the cases showed response to treatment after one year of follow-up, finally being diagnosed with perifoveal exudative vascular anomalous complex (PEVAC) (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto Jovem , Idoso , Idoso de 80 Anos ou mais , Exsudatos e Transudatos/diagnóstico por imagem , Edema Macular/diagnóstico por imagem , Malformações Vasculares/diagnóstico por imagem , Transtornos da Visão/diagnóstico por imagem , Cegueira , Angiofluoresceinografia , Tomografia de Coerência Óptica
20.
Arch Soc Esp Oftalmol (Engl Ed) ; 98(7): 417-421, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37285962

RESUMO

We present three cases of patients aged 66, 80 and 23, who presented unilateral vision loss. Optical coherence tomography (OCT) in all of them showed macular oedema and a rounded lesion with hyperreflective wall, and fluorescein angiography (FAG) in two of them showed hyperfluorescent perifoveal aneurysmal dilations with exudation. None of the cases showed response to treatment after one year of follow-up, finally being diagnosed with Perifoveal Exudative Vascular Anomalous Complex (PEVAC).


Assuntos
Edema Macular , Malformações Vasculares , Humanos , Exsudatos e Transudatos/diagnóstico por imagem , Angiofluoresceinografia/métodos , Transtornos da Visão
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