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1.
J Clin Microbiol ; : e0010324, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38785446

RESUMEN

The monkeypox virus (MPXV) outbreak, primarily endemic to Africa, has spread globally, with Brazil reporting the second-highest number of cases. The emergence of MPXV in non-endemic areas has raised concerns, particularly due to the co-circulation of other exanthematous viruses such as varicella-zoster virus (VZV) and molluscum contagiosum virus (MOCV). To perform an accurate differential diagnosis of MPXV during the ongoing outbreak in Minas Gerais, Brazil, a 5PLEX qPCR assay targeting orthopoxviruses (OPV), VZV, and MOCV was used to retrospectively analyze all clinical samples that tested negative for MPXV in the initial screening conducted at Funed. In summary, our study analyzed 1,175 clinical samples received from patients suspected of MPXV infection and found a positivity rate of 33.8% (397 samples) for MPXV using the non-variola qPCR assay. Testing the 778 MPXV-negative clinical samples using the 5PLEX qPCR assay revealed that 174 clinical samples (22.36%) tested positive for VZV. MOCV DNA was detected in 13 and other OPV in 3 clinical samples. The sequencing of randomly selected amplified clinical samples confirmed the initial molecular diagnosis. Analysis of patient profiles revealed a significant difference in the median age between groups testing positive for MPXV and VZV and a male predominance in MPXV cases. The geographic distribution of positive cases was concentrated in the most populous mesoregions of Minas Gerais state. This study highlights the challenges posed by emerging infectious diseases. It emphasizes the importance of epidemiological surveillance and accurate diagnosis in enabling timely responses for public health policies and appropriate medical care. IMPORTANCE: Brazil ranks second in the number of cases during the global monkeypox epidemic. The study, conducted in Minas Gerais, the second most populous state in Brazil with over 20 million inhabitants, utilized differential diagnostics, revealing a significant number of positive cases for other exanthematous viruses and emphasizing the need for accurate diagnoses. During the study, we were able to assess the co-circulation of other viruses alongside monkeypox, including varicella-zoster virus, molluscum contagiosum virus, and other orthopoxviruses. The significance of the research is underscored by the concentration of positive cases in populous areas, highlighting the challenges posed by emerging infectious diseases. This demographic context further amplifies the importance of the research in guiding public health policies and medical interventions, given the substantial population at risk. The study not only addresses a global concern but also holds critical implications for a state with such a large population and geographic expanse within Brazil. Overall, the study emphasizes the pivotal role of surveillance and precise diagnosis in guiding effective public health responses and ensuring appropriate medical interventions.

2.
Int J Mol Sci ; 25(10)2024 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-38791565

RESUMEN

Currently, approximately 70% of new cases of Chagas disease (CD) in Brazil are attributed to oral transmission, particularly through foods such as açaí, bacaba, and sugarcane juice, primarily in the northern and northeastern regions of the country. This underscores the imperative need to control the spread of the disease. The methods utilized to conduct quality control for food associated with outbreaks and to assess the potential for the oral transmission of CD through consuming açaí primarily rely on isolating the parasite or inoculating food into experimental animals, restricting the analyses to major research centers. While there are existing studies in the literature on the detection and quantification of T. cruzi DNA in açaí, the evaluation of parasites' viability using molecular methods in this type of sample and differentiating between live and dead parasites in açaí pulp remain challenging. Consequently, we developed a molecular methodology based on RT-qPCR for detecting and quantifying viable T. cruzi in açaí pulp samples. This protocol enables the stabilization and preservation of nucleic acids in açaí, along with incorporating an exogenous internal amplification control. The standardization of the RNA extraction method involved a simple and reproducible approach, coupled with a one-step RT-qPCR assay. The assay underwent validation with various T. cruzi DTUs and demonstrated sensitivity in detecting up to 0.1 viable parasite equivalents/mL in açaí samples. Furthermore, we investigated the effectiveness of a bleaching method in eliminating viable parasites in açaí samples contaminated with T. cruzi by comparing the detection of DNA versus RNA. Finally, we validated this methodology using açaí pulp samples positive for T. cruzi DNA, which were collected in a municipality with a history of oral CD outbreaks (Coari-AM). This validation involved comparing the detection and quantification of total versus viable T. cruzi. Collectively, our findings demonstrate the feasibility of this methodology in detecting viable forms of T. cruzi in açaí pulp samples, emerging as a crucial tool for monitoring oral outbreaks of Chagas disease resulting from açaí consumption.


Asunto(s)
Enfermedad de Chagas , Trypanosoma cruzi , Trypanosoma cruzi/genética , Trypanosoma cruzi/aislamiento & purificación , Enfermedad de Chagas/epidemiología , Enfermedad de Chagas/parasitología , Enfermedad de Chagas/transmisión , Enfermedad de Chagas/diagnóstico , Animales , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Euterpe , Brasil/epidemiología , Humanos , ADN Protozoario/genética
3.
Front Psychiatry ; 15: 1303007, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38686124

RESUMEN

Objective: Our objective was to check if the ICD-10 operational criteria application changes non-operational, prototype-based diagnoses obtained in a real-life scenario. Methods: Psychiatry residents applied the diagnostic criteria of the ICD-10 as a "diagnostic test" to five outpatient patients they were already following who had a prototype-based diagnosis. Tests were used to ascertain whether changes in opinion were significant and if any of the diagnostic groups were more prone to change than others. The present paper is part of the study with UTN U1111-1260-1212. Results: Seventeen residents reviewed their last five case files, retrieving 85 diagnostic pairs of non-operational-based vs. operational-based diagnoses. The Stuart-Maxwell test did not indicate a significant opinion change (χ2 = 5.25, p = 0.39; power = 0.94) besides 30% of diagnostic changes. Despite not being statistically significant, 20.2% of all evaluations resulted in a change that would affect treatment choices. Using ICD-10 operational criteria slightly increased the number of observed diagnoses, but probably without clinical relevance. None of the non-operational diagnoses have a higher tendency to change with operational criteria application (χ2 = 11.6, p = 0.07). The female gender was associated with a higher diagnostic change tendency. Conclusion: Applying ICD-10 operational criteria as a diagnostic test does not induce a statistically significant diagnostic opinion change in residents and no diagnostic group seems more sensible to diagnostic change. Gender-related differences in diagnostic opinion changes might be evidence of sunk cost bias. Although not statistically significant, using operational criteria after diagnostic elaboration might help to deal with subjects without adequate treatment response.

4.
Clin Oral Investig ; 28(2): 122, 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38286954

RESUMEN

OBJECTIVES: To evaluate the temporomandibular joint (TMJ), condylar and mandibular movements in obstructive sleep apnea (OSA) patients treated with mandibular advancement device (MAD) and to identify the influence of these anatomic factors on upper airway (UA) volume and polysomnographic outcomes after treatment. MATERIALS AND METHODS: Twenty OSA patients were prospectively treated with MAD. Clinical examinations, cone-beam computed tomography, and polysomnography were performed before MAD treatment and after achieving therapeutic protrusion. Polysomnographic variables and three-dimensional measurements of the TMJ, mandible, and upper airway were statistically analyzed. RESULTS: Condylar rotation, anterior translation, and anterior mandibular displacement were directly correlated with total UA volume, while vertical mandibular translation was inversely correlated with the volume of the inferior oropharynx. MAD treatment resulted in an increase in the volume and area of the superior oropharynx. There was no statistically significant correlation between condylar rotation and translation and polysomnographic variables. With MAD, there was a significant increase in vertical dimension, changes in condylar position (rotation and translation), and mandibular displacement. The central and medial lengths of the articular eminence were inversely correlated with condylar rotation and translation, respectively. The lateral length of the eminence was directly correlated with condylar translation, and the lateral height was directly correlated with condylar rotation and translation. CONCLUSION: Condylar and mandibular movements influenced UA volume. The articular eminence played a role in the amount of condylar rotation and translation. CLINICAL RELEVANCE: Individualized anatomical evaluation of the TMJ proves to be important in the therapy of OSA with MAD.


Asunto(s)
Avance Mandibular , Apnea Obstructiva del Sueño , Humanos , Ferulas Oclusales , Mandíbula/diagnóstico por imagen , Apnea Obstructiva del Sueño/diagnóstico por imagen , Apnea Obstructiva del Sueño/terapia , Apnea Obstructiva del Sueño/etiología , Articulación Temporomandibular , Tomografía Computarizada de Haz Cónico , Resultado del Tratamiento
5.
Dermatology ; 240(1): 132-141, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38035549

RESUMEN

INTRODUCTION: Although the dermoscopic features of facial lentiginous melanomas (LM), including lentigo maligna and lentigo maligna melanoma, have been extensively studied, the literature about those located on the scalp is scarce. This study aims to describe the dermoscopic features of scalp LM and assess the diagnostic accuracy of dermoscopy to discriminate them from equivocal benign pigmented macules. METHODS: Consecutive cases of scalp LM and histopathology-proven benign but clinically equivocal pigmented macules (actinic keratoses, solar lentigos, seborrhoeic keratoses, and lichen planus-like keratoses) from four referral centres were included. Dermoscopic features were analysed by two blinded experts. The diagnostic performance of a predictive model was assessed. RESULTS: 56 LM and 44 controls were included. Multiple features previously described for facial and extrafacial LM were frequently identified in both groups. Expert's sensitivity to diagnose scalp LM was 76.8% (63.6-87.0) and 78.6% (65.6-88.4), with specificity of 54.5% (38.9-69.6) and 56.8% (41.0-71.7), and fair agreement (kappa coefficient 0.248). The strongest independent predictors of malignancy were (OR, 95% CI) chaos of colour (15.43, 1.48-160.3), pigmented reticular lines (14.96, 1.68-132.9), increased density of vascular network (3.45, 1.09-10.92), and perifollicular grey circles (2.89, 0.96-8.67). The predictive model achieved 85.7% (73.8-93.6) sensitivity, 61.4% (45.5-75.6) specificity, and 81.5 (73.0-90.0) area under curve to discriminate benign and malignant lesions. A diagnostic flowchart was proposed, which should improve the diagnostic performance of dermoscopy. CONCLUSION: Both facial and extrafacial dermoscopic patterns can be identified in scalp LM, with considerable overlap with benign pigmented macules, leading to low specificity and interobserver agreement on dermoscopy.


Asunto(s)
Neoplasias Faciales , Peca Melanótica de Hutchinson , Queratosis Actínica , Melanoma , Neoplasias Cutáneas , Humanos , Melanoma/diagnóstico por imagen , Melanoma/patología , Peca Melanótica de Hutchinson/diagnóstico por imagen , Peca Melanótica de Hutchinson/patología , Neoplasias Cutáneas/diagnóstico por imagen , Neoplasias Cutáneas/patología , Cuero Cabelludo/patología , Dermoscopía , Neoplasias Faciales/patología , Queratosis Actínica/patología , Estudios de Casos y Controles , Estudios Retrospectivos , Diagnóstico Diferencial
6.
Rev Bras Enferm ; 76Suppl 4(Suppl 4): e20230108, 2023.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-38088713

RESUMEN

OBJECTIVES: to analyze the influence of sociodemographic and clinical variables, as well as the surgical checklist adherence score, on the occurrence of surgical site infection among patients undergoing myocardial revascularization. METHODS: an observational, longitudinal, retrospective study was conducted at a university hospital, involving 266 medical records of patients who underwent myocardial revascularization surgery. Instruments containing sociodemographic, clinical, and infection-related variables were used, along with the Perioperative Surgical Safety Checklist. Descriptive, bivariate, and logistic regression analyses were employed. RESULTS: surgical site infection occurred in 89 (33.5%) patients. There was a statistically significant association between body temperature outside the range of 36 degrees Celsius to 36.5 degrees Celsius (p=0.01), the presence of invasive devices (p=0.05), surgical procedures with the anticipation of critical events (p<0.001), and the occurrence of infection. CONCLUSIONS: body temperature, the presence of invasive devices, and surgical procedures with the anticipation of critical events were significant factors contributing to an increased risk of infection.


Asunto(s)
Revascularización Miocárdica , Infección de la Herida Quirúrgica , Humanos , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/etiología , Estudios Retrospectivos , Estudios Longitudinales , Factores de Riesgo
7.
Artículo en Inglés | MEDLINE | ID: mdl-38085328

RESUMEN

The use of Structured Diagnostic Assessments (SDAs) is a solution for unreliability in psychiatry and the gold standard for diagnosis. However, except for studies between the 50 s and 70 s, reliability without the use of Non-SDAs (NSDA) is seldom tested, especially in non-Western, Educated, Industrialized, Rich, and Democratic (WEIRD) countries. We aim to measure reliability between examiners with NSDAs for psychiatric disorders. We compared diagnostic agreement after clinician change, in an outpatient academic setting. We used inter-rater Kappa measuring 8 diagnostic groups: Depression (DD: F32, F33), Anxiety Related Disorders (ARD: F40-F49, F50-F59), Personality Disorders (PD: F60-F69), Bipolar Disorder (BD: F30, F31, F34.0, F38.1), Organic Mental Disorders (Org: F00-F09), Neurodevelopment Disorders (ND: F70-F99) and Schizophrenia Spectrum Disorders (SSD: F20-F29). Cohen's Kappa measured agreement between groups, and Baphkar's test assessed if any diagnostic group have a higher tendency to change after a new diagnostic assessment. We analyzed 739 reevaluation pairs, from 99 subjects who attended IPUB's outpatient clinic. Overall inter-rater Kappa was moderate, and none of the groups had a different tendency to change. NSDA evaluation was moderately reliable, but the lack of some prevalent hypothesis inside the pairs raised concerns about NSDA sensitivity to some diagnoses. Diagnostic momentum bias (that is, a tendency to keep the last diagnosis observed) may have inflated the observed agreement. This research was approved by IPUB's ethical committee, registered under the CAAE33603220.1.0000.5263, and the UTN-U1111-1260-1212.

8.
Lancet Digit Health ; 5(10): e679-e691, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37775188

RESUMEN

BACKGROUND: Diagnosis of skin cancer requires medical expertise, which is scarce. Mobile phone-powered artificial intelligence (AI) could aid diagnosis, but it is unclear how this technology performs in a clinical scenario. Our primary aim was to test in the clinic whether there was equivalence between AI algorithms and clinicians for the diagnosis and management of pigmented skin lesions. METHODS: In this multicentre, prospective, diagnostic, clinical trial, we included specialist and novice clinicians and patients from two tertiary referral centres in Australia and Austria. Specialists had a specialist medical qualification related to diagnosing and managing pigmented skin lesions, whereas novices were dermatology junior doctors or registrars in trainee positions who had experience in examining and managing these lesions. Eligible patients were aged 18-99 years and had a modified Fitzpatrick I-III skin type; those in the diagnostic trial were undergoing routine excision or biopsy of one or more suspicious pigmented skin lesions bigger than 3 mm in the longest diameter, and those in the management trial had baseline total-body photographs taken within 1-4 years. We used two mobile phone-powered AI instruments incorporating a simple optical attachment: a new 7-class AI algorithm and the International Skin Imaging Collaboration (ISIC) AI algorithm, which was previously tested in a large online reader study. The reference standard for excised lesions in the diagnostic trial was histopathological examination; in the management trial, the reference standard was a descending hierarchy based on histopathological examination, comparison of baseline total-body photographs, digital monitoring, and telediagnosis. The main outcome of this study was to compare the accuracy of expert and novice diagnostic and management decisions with the two AI instruments. Possible decisions in the management trial were dismissal, biopsy, or 3-month monitoring. Decisions to monitor were considered equivalent to dismissal (scenario A) or biopsy of malignant lesions (scenario B). The trial was registered at the Australian New Zealand Clinical Trials Registry ACTRN12620000695909 (Universal trial number U1111-1251-8995). FINDINGS: The diagnostic study included 172 suspicious pigmented lesions (84 malignant) from 124 patients and the management study included 5696 pigmented lesions (18 malignant) from the whole body of 66 high-risk patients. The diagnoses of the 7-class AI algorithm were equivalent to the specialists' diagnoses (absolute accuracy difference 1·2% [95% CI -6·9 to 9·2]) and significantly superior to the novices' ones (21·5% [13·1 to 30·0]). The diagnoses of the ISIC AI algorithm were significantly inferior to the specialists' diagnoses (-11·6% [-20·3 to -3·0]) but significantly superior to the novices' ones (8·7% [-0·5 to 18·0]). The best 7-class management AI was significantly inferior to specialists' management (absolute accuracy difference in correct management decision -0·5% [95% CI -0·7 to -0·2] in scenario A and -0·4% [-0·8 to -0·05] in scenario B). Compared with the novices' management, the 7-class management AI was significantly inferior (-0·4% [-0·6 to -0·2]) in scenario A but significantly superior (0·4% [0·0 to 0·9]) in scenario B. INTERPRETATION: The mobile phone-powered AI technology is simple, practical, and accurate for the diagnosis of suspicious pigmented skin cancer in patients presenting to a specialist setting, although its usage for management decisions requires more careful execution. An AI algorithm that was superior in experimental studies was significantly inferior to specialists in a real-world scenario, suggesting that caution is needed when extrapolating results of experimental studies to clinical practice. FUNDING: MetaOptima Technology.


Asunto(s)
Teléfono Celular , Melanoma , Neoplasias Cutáneas , Humanos , Inteligencia Artificial , Australia , Melanoma/diagnóstico , Melanoma/patología , Estudios Prospectivos , Atención Secundaria de Salud , Sensibilidad y Especificidad , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patología
9.
Metabolites ; 13(8)2023 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-37623846

RESUMEN

Cardiovascular disease is a leading cause of death worldwide. Heart failure is a cardiovascular disease with high prevalence, morbidity, and mortality. Several natural compounds have been studied for attenuating pathological cardiac remodeling. Orange juice has been associated with cardiovascular disease prevention by attenuating oxidative stress. However, most studies have evaluated isolated phytochemicals rather than whole orange juice and usually under pathological conditions. In this study, we evaluated plasma metabolomics in healthy rats receiving Pera or Moro orange juice to identify possible metabolic pathways and their effects on the heart. METHODS: Sixty male Wistar rats were allocated into 3 groups: control (C), Pera orange juice (PO), and Moro orange juice (MO). PO and MO groups received Pera orange juice or Moro orange juice, respectively, and C received water with maltodextrin (100 g/L). Echocardiogram and euthanasia were performed after 4 weeks. Plasma metabolomic analysis was performed by high-resolution mass spectrometry. Type I collagen was evaluated in picrosirius red-stained slides and matrix metalloproteinase (MMP)-2 activity by zymography. MMP-9, tissue inhibitor of metalloproteinase (TIMP)-2, TIMP-4, type I collagen, and TNF-α protein expression were evaluated by Western blotting. RESULTS: We differentially identified three metabolites in PO (N-docosahexaenoyl-phenylalanine, diglyceride, and phosphatidylethanolamine) and six in MO (N-formylmaleamic acid, N2-acetyl-L-ornithine, casegravol isovalerate, abscisic alcohol 11-glucoside, cyclic phosphatidic acid, and torvoside C), compared to controls, which are recognized for their possible roles in cardiac remodeling, such as extracellular matrix regulation, inflammation, oxidative stress, and membrane integrity. Cardiac function, collagen level, MMP-2 activity, and MMP-9, TIMP-2, TIMP-4, type I collagen, and TNF-α protein expression did not differ between groups. CONCLUSION: Ingestion of Pera and Moro orange juice induces changes in plasma metabolites related to the regulation of extracellular matrix, inflammation, oxidative stress, and membrane integrity in healthy rats. Moro orange juice induces a larger number of differentially expressed metabolites than Pera orange juice. Alterations in plasma metabolomics induced by both orange juice are not associated with modifications in cardiac extracellular matrix components. Our results allow us to postulate that orange juice may have beneficial effects on pathological cardiac remodeling.

10.
Clin Nutr ESPEN ; 56: 9-12, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37344090

RESUMEN

BACKGROUND: This study aimed to evaluate the ability of the urea-to-albumin ratio (UAR) to predict mortality in critically ill coronavirus disease 2019 (COVID-19) patients. METHODS: This retrospective study included adult patients admitted with COVID-19 at two intensive care units (ICUs) at the University Hospital. Serum urea and albumin concentrations at ICU admission were used to calculate the UAR. All patients were followed up during hospitalization, and the ICU mortality rate was recorded. RESULTS: Two hundred and eleven patients were evaluated. The mean age was 57.8 ± 15.5 years, and 54% were male. Approximately 84.4% of patients were considered to be at nutritional risk by the NRS 2002, and the median UAR was 18.3 (10.5-34.8). The length of stay in the ICU was 10 (6-16) days, 38.4% of the patients required dialysis, and 64.9% died. Age, male sex, need of hemodialysis, lactate level, and inflammatory parameters were associated with higher mortality. Patients non-survivors had a higher UAR (23.7 [13.6-41.8] vs. 10.9 [8.5-16.8]; p < 0.001). The cutoff point with the best performance of UAR in the ROC curve for predicting mortality was ≥12.17 (AUC: 0.7201; CI 95%: 0.656-0.784). Additionally, the risk of mortality was 2.00-fold in the group of patients with UAR ≥12.17 (HR: 2.00 CI: 1.274-3.149; p = 0.003) and remained significant after adjusted analyzes (models 1 and 2). CONCLUSION: Our data suggest that a UAR ≥12.17 increased the risk of mortality by 2.00-fold in critically ill COVID-19 patients.


Asunto(s)
COVID-19 , Albúmina Sérica Humana , Urea , COVID-19/sangre , COVID-19/mortalidad , Urea/sangre , Humanos , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Unidades de Cuidados Intensivos , Pronóstico
12.
Front Mol Biosci ; 10: 1165132, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37101558

RESUMEN

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. Although many therapeutic options are available, several factors, including the presence of p53 mutations, impact tumor development and therapeutic resistance. TP53 is the second most frequently mutated gene in HCC, comprising more than 30% of cases. Mutations in p53 result in the formation of amyloid aggregates that promote tumor progression. The use of PRIMA-1, a small molecule capable of restoring p53, is a therapeutic strategy to pharmacologically target the amyloid state mutant p53. In this study, we characterize an HCC mutant p53 model for the study of p53 amyloid aggregation in HCC cell lines, from in silico analysis of p53 mutants to a 3D-cell culture model and demonstrate the unprecedented inhibition of Y220C mutant p53 aggregation by PRIMA-1. In addition, our data show beneficial effects of PRIMA-1 in several "gain of function" properties of mutant-p53 cancer cells, including migration, adhesion, proliferation, and drug resistance. We also demonstrate that the combination of PRIMA-1 and cisplatin is a promising approach for HCC therapy. Taken together, our data support the premise that targeting the amyloid-state of mutant p53 may be an attractive therapeutic approach for HCC, and highlight PRIMA-1 as a new candidate for combination therapy with cisplatin.

13.
Methods Cell Biol ; 175: 1-15, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36967137

RESUMEN

Primary cilia (PC) are sensory organelles that function as cellular antennas, transmitting signals between the extracellular and intracellular spaces in many vertebrate tissues. The cell generates and assembles PC through a highly regulated process called ciliogenesis. This complex process is involved in several physiological functions, including embryonic development, locomotion, cell cycle regulation or energetic homeostasis control. In general, when a cell finishes its cell division, the oldest centriole usually migrates to the plasma membrane and becomes a basal body that gives rise to the formation of a cilium. For this reason, the presence of cilia is incompatible with cell division, so when a cell is going to divide, the cilium and the basal body disappear. Ciliogenesis is triggered by various stimuli, all of them related to cell cycle blockade. This cell cycle, and ciliogenesis induction, can be observed by: (1) the influence of growth factors (lack of serum and consequent inability to promote cell cycle exit and increase the proportion of cells in G0); (2) pharmacological cell cycle inhibitors (staurosporine or etoposide); or (3) physiological cell cycle inhibition (excessive contact between neighboring cells). Evaluation of ciliogenesis induction is vitally important for the study of diseases related to ciliary dysfunction, called ciliopathies. That is why the use of correct protocols for inducing cilia formation and an accurate posterior visualization of the cilia after performing said protocols are essential parts in the study of these diseases. To facilitate this task, here we described detailed protocols to induce ciliogenesis in vitro and visualize PC by immunofluorescence microscopy in cultured cells.


Asunto(s)
Cilios , Orgánulos , Cilios/metabolismo , Células Cultivadas , División Celular , Ciclo Celular , Centriolos/fisiología
14.
Cells ; 12(5)2023 03 04.
Artículo en Inglés | MEDLINE | ID: mdl-36899942

RESUMEN

The identification of Parkinson's disease (PD) biomarkers has become a main goal for the diagnosis of this neurodegenerative disorder. PD has not only been intrinsically related to neurological problems, but also to a series of alterations in peripheral metabolism. The purpose of this study was to identify metabolic changes in the liver in mouse models of PD with the scope of finding new peripheral biomarkers for PD diagnosis. To achieve this goal, we used mass spectrometry technology to determine the complete metabolomic profile of liver and striatal tissue samples from WT mice, 6-hydroxydopamine-treated mice (idiopathic model) and mice affected by the G2019S-LRRK2 mutation in LRRK2/PARK8 gene (genetic model). This analysis revealed that the metabolism of carbohydrates, nucleotides and nucleosides was similarly altered in the liver from the two PD mouse models. However, long-chain fatty acids, phosphatidylcholine and other related lipid metabolites were only altered in hepatocytes from G2019S-LRRK2 mice. In summary, these results reveal specific differences, mainly in lipid metabolism, between idiopathic and genetic PD models in peripheral tissues and open up new possibilities to better understand the etiology of this neurological disorder.


Asunto(s)
Enfermedad de Parkinson , Animales , Ratones , Biomarcadores , Modelos Animales de Enfermedad , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina/genética , Lipidómica , Hígado/metabolismo , Metabolómica , Enfermedad de Parkinson/metabolismo
15.
Clin Nutr ESPEN ; 54: 73-80, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36963901

RESUMEN

Cardiovascular diseases (CVD) are the major cause of global mortality, accounting for 31% of deaths worldwide. Healthy eating habits based on the consumption of bioactive molecules present in plant-based diets can contribute to the prevention of CVD. In this context, the consumption of common beans (Phaseolus vulgaris L.) is relevant. There are several species of beans, all of which provide proteins, carbohydrates, dietary fiber, vitamins, minerals, and phenolic compounds. More recently, the complexity of phytochemical components has expanded, including the role of antinutritional factors in nutrient bioavailability and immune responses. Experimental and clinical studies have shown that the consumption of beans results in less food consumption, control of body weight, and improvement of metabolic biochemical parameters. Thus, the consumption of beans is associated with a decrease in CVD risk factors. To date, there have been no interventional studies assessing CVD outcomes, such as hospitalization, infarction, and mortality, in the context of bean consumption. Furthermore, studies on the effect of bean consumption on metabolomics and intestinal microbiota are lacking. The purpose of this review is to explore the nutritional properties of beans and discuss the main effects of the consumption of beans on cardiovascular health. In conclusion, eating habits based on the consumption of bioactive molecules present in beans can contribute to the prevention of cardiovascular disease. Furthermore, there is a large gap in the literature regarding the consumption of beans associated with clinical outcomes, such as hospitalization and mortality.


Asunto(s)
Enfermedades Cardiovasculares , Phaseolus , Humanos , Enfermedades Cardiovasculares/prevención & control , Phaseolus/metabolismo , Minerales , Valor Nutritivo , Fibras de la Dieta
17.
Arch Gerontol Geriatr ; 106: 104870, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36442406

RESUMEN

BACKGROUND: Frailty and ST-Elevation Myocardial Infarction (STEMI) share similar molecular pathways. Specific biomarkers, such as microRNAs (miRNAs), may provide insights into the molecular mechanisms that cause the relationship between frailty and STEMI. OBJECTIVE: Our aim was to identify and compare circulating miRNA levels between frail and non-frail older adults following STEMI and comprehend the regulatory miRNA-gene networks and pathways involved in this condition. METHODS: This exploratory study is a subanalysis of a larger observational study. In this study, we selected patients ≥ 65 years old, following STEMI, with pre-frail/frail (n=5) and non-frail (n=4) phenotype evaluated using the Clinical Frailty Scale and serum circulating miRNA levels were analyzed. RESULTS: Pre-frail/frail patients had greater serum levels of 53 miRNAs, compared with non-frail patients. Notably, miR-103a-3p, miR-598-3p, and miR-130a-3p were the top three significantly deregulated miRNAs predicted to modulate gene expression associated with aging. Additional computational analyses showed 7,420 predicted miRNA gene targets, which were regulated by at least two of the 53 identified miRNAs. Pathway enrichment analysis showed that axon guidance and MAPK signaling were among pathways regulated by miRNA target genes. CONCLUSIONS: These novel findings suggest a correlation between the identified miRNAs, target genes, and pathways in pre-frail and frail patients with myocardial infarction.


Asunto(s)
MicroARN Circulante , Fragilidad , Infarto del Miocardio con Elevación del ST , Humanos , MicroARN Circulante/sangre , MicroARN Circulante/metabolismo , Fragilidad/sangre , Fragilidad/diagnóstico , Fragilidad/metabolismo , Infarto del Miocardio con Elevación del ST/sangre , Infarto del Miocardio con Elevación del ST/diagnóstico , Infarto del Miocardio con Elevación del ST/metabolismo , Redes y Vías Metabólicas
18.
J Nephrol ; 36(3): 687-693, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36547774

RESUMEN

BACKGROUND: To assess the prevalence of frailty by the Clinical Frailty Scale (CFS) and the 5-item FRAIL scale and their association with hospitalization in hemodialysis (HD) patients. METHODS: This was a prospective observational study. We included patients of both genders ≥ 18 years old in HD treatment for at least 3 months. Demographic, clinical, and routine laboratory data were retrieved from the medical charts. Two different frailty assessment tools were used, the CFS and the FRAIL scale. Participants were followed up for 9 months and hospitalizations for all causes were evaluated. A Venn diagram was constructed to show the overlap of possible frailty and pre-frailty. Cox regression was used to identify the association between frailty and hospitalization. The significance level was 5%. RESULTS: A total of 137 subjects were included in the analysis. The median age was 61 (52-67) years and 60% were male. The hospitalization rate and mortality in 9 months were 22.6% and 7.29%, respectively. Regarding frailty, the overall prevalence was 13.8% assessed by CFS and 36.5% according to the FRAIL scale. In the Cox regression, frailty by FRAIL scale was associated with a 2.8-fold increase in the risk of hospitalization (OR = 2.880; 95% CI = 1.361-6.096; p = 0.006), but frailty assessed by the CFS was not associated with the need for hospitalization. CONCLUSION: In HD patients, the FRAIL scale proved to be an easy-to-apply tool, identifying a high prevalence of frailty and being a predictor of hospital admission.


Asunto(s)
Fragilidad , Humanos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Adolescente , Fragilidad/epidemiología , Anciano Frágil , Hospitalización , Estudios Prospectivos , Diálisis Renal
20.
ASAIO J ; 69(3): e121-e124, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-35696694

RESUMEN

Reverse cardiac remodeling may occur in some left ventricular assist device (LVAD) recipients. Although considered the standard therapy, surgical device explantation with repeat sternotomy might be undesirable or very high risk. On the other hand, there are few data reporting minimally invasive percutaneous LVAD deactivation. We describe a case of a man with LVAD malfunction due to driveline fracture and left ventricular (LV) function recovery who had a Heart Mate II deactivated with a percutaneous technique using a left atrial appendage occluder (LAAO) positioned inside the outflow cannula. To the best of our knowledge, this the first report of LVAD deactivation with the fully recapturable LAAO device. We propose that the use of a LAA occluder to obstruct HM II outflow cannula is feasible and safe.


Asunto(s)
Apéndice Atrial , Corazón Auxiliar , Masculino , Humanos , Corazón Auxiliar/efectos adversos , Cánula , Función Ventricular Izquierda/fisiología , Esternotomía
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