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1.
Eur J Pediatr ; 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38730194

RESUMEN

To evaluate the influence of early nutritional intake on the growth pattern of very preterm infants. This was an observational study including 109 newborns (< 32 weeks gestational age). Perinatal morbidities, nutritional therapy (first four weeks of life), and weight, length, and head circumference (HC) growth at term-equivalent age were evaluated. Growth restriction was defined as a difference > 1.2 SD between the birth and term age measurements. Growth restriction at term-equivalent age: 52.3% (weight), 42.9% (length), and 22% (HC). Morbidities were positively correlated with nutrition therapy and negatively correlated with the total energy provision: protein ratio. The duration of parenteral nutrition, the time to reach full enteral feedings, and the total energy provision: protein ratio were significantly correlated. Nutrient intake influenced weight, length, and HC growth, and cumulative energy deficit was significantly associated with HC growth restriction.   Conclusion: Perinatal morbidities interfere with nutritional therapy and early nutrient intake, leading to insufficient energy and energy provision: protein ratio for growth. What is Known: • The intake of macronutrients early in life, mainly protein, is important for the optimal growth of pretem infants. • The severity of morbidities and low gestational ages impact the nutritional management of preterm infants. What is New: • The number of morbidities, reflecting the severity of the neonatal clinical course, had a detrimental effect on the nutritional therapy and nutrients intake. • The inadequate energy provision per gram of protein ratio was significantly associated with growth restriction in all growth measures at the second week of life, persisting for head circumference up to the fourth week, highlighting the importance of its measurement, as it could be a precocious sign of development risk.

2.
J Psychiatr Res ; 175: 144-152, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38733929

RESUMEN

Symptom provocation paradigms are paramount to understand a heterogeneous disorder as obsessive-compulsive disorder (OCD). The main aim of our work was to develop and validate an open-access set of OCD-related images comprising three main subtypes: washing, checking, and symmetry. Twenty-six OCD patients and 25 controls provided valence and arousal ratings for a set of OCD-related, aversive, and neutral images. Linear mixed model analyses were used to estimate the main effects of group, image category, and group-image category interaction in image ratings. All main effects were found to be significant for both arousal and valence ratings, except for the group in arousal ratings. Path analysis confirmed our hypothesis that the OCI-R subscales influenced the subjective ratings of the corresponding image categories, particularly among patients. Independent samples t-tests were performed for each OCD picture to compose the set. Arousal demonstrated a greater capacity to distinguish controls and patients, thus sustaining our choice of using these ratings for the final Braga Obsessive-Compulsive Image Set (BOCIS). Our study demonstrated that the stimuli of the BOCIS reliably portray OCD-like triggers for washing, checking and symmetry subtypes. Its open-access availability will facilitate significant progress in both clinical and research settings.

3.
Int J Mol Sci ; 25(9)2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38732233

RESUMEN

Donepezil (DNPZ) is a cholinesterase inhibitor used for the management of Alzheimer's disease (AD) and is dependent on membrane transporters such as ABCG2 to actively cross brain barriers and reach its target site of action in the brain. Located in the brain ventricles, the choroid plexus (CP) forms an interface between the cerebrospinal fluid (CSF) and the bloodstream, known as the blood-CSF barrier (BCSFB). Historically, the BCSFB has received little attention as a potential pathway for drug delivery to the central nervous system (CNS). Nonetheless, this barrier is presently viewed as a dynamic transport interface that limits the traffic of molecules into and out of the CNS through the presence of membrane transporters, with parallel activity with the BBB. The localization and expression of drug transporters in brain barriers represent a huge obstacle for drug delivery to the brain and a major challenge for the development of therapeutic approaches to CNS disorders. The widespread interest in understanding how circadian clocks modulate many processes that define drug delivery in order to predict the variability in drug safety and efficacy is the next bridge to improve effective treatment. In this context, this study aims at characterizing the circadian expression of ABCG2 and DNPZ circadian transport profile using an in vitro model of the BCSFB. We found that ABCG2 displays a circadian pattern and DNPZ is transported in a circadian way across this barrier. This study will strongly impact on the capacity to modulate the BCSFB in order to control the penetration of DNPZ into the brain and improve therapeutic strategies for the treatment of AD according to the time of the day.


Asunto(s)
Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Barrera Hematoencefálica , Donepezilo , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/metabolismo , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/genética , Barrera Hematoencefálica/metabolismo , Animales , Humanos , Encéfalo/metabolismo , Inhibidores de la Colinesterasa/farmacocinética , Inhibidores de la Colinesterasa/farmacología , Transporte Biológico , Plexo Coroideo/metabolismo , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Ratones , Ritmo Circadiano , Proteínas de Neoplasias
4.
Br J Pharmacol ; 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38773354

RESUMEN

BACKGROUND AND PURPOSE: The ryanodine receptor 2 (RyR2) is present in both the heart and kidneys, and plays a crucial role in maintaining intracellular Ca2+ homeostasis in cells in these organs. This study aimed to investigate the impact of M201-A on RyR2, as well as studying its effects on cardiac and renal functions in preclinical and clinical studies. EXPERIMENTAL APPROACH: Following the administration of M201-A (1,4-benzothiazepine-1-oxide derivative), we monitored diastolic Ca2+ leak via RyR2 and intracellular Ca2+ concentration in isolated rat cardiomyocytes and in cardiac and renal function in animals. In a clinical study, M201-A was administered intravenously at doses of 0.2 and 0.4 mg·kg-1 once daily for 20 min for four consecutive days in healthy males, with the assessment of haemodynamic responses. KEY RESULTS: In rat heart cells, M201-A effectively inhibited spontaneous diastolic Ca2+ leakage through RyR2 and exhibited positive lusi-inotropic effects on the rat heart. Additionally, it enhanced natriuresis and improved renal function in dogs. In human clinical studies, when administered intravenously, M201-A demonstrated an increase in natriuresis, glomerular filtration rate and creatinine clearance, while maintaining acceptable levels of drug safety and tolerability. CONCLUSIONS AND IMPLICATIONS: The novel drug M201-A inhibited diastolic Ca2+ leak via RyR2, improved cardiac lusi-inotropic effects in rats, and enhanced natriuresis and renal function in humans. These findings suggest that this drug may offer a potential new treatment option for chronic kidney disease and heart failure.

5.
Rev Col Bras Cir ; 51: e20243600, 2024.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-38716913

RESUMEN

INTRODUCTION: In 2020, the world suffered a major impact from the COVID-19 pandemic, especially due to the high transmissibility of the virus. It is a disease that predominates with respiratory manifestations, but there is involvement of the gastrointestinal tract, causing symptoms ranging from mild to more severe. Highlighting gastrointestinal bleeding, it is a symptom resulting from the involvement of the SARS-CoV-2 virus described by several reports and case series. METHODS: through an integrative literature review, of a qualitative nature, works that corresponded to the eligibility criteria were selected, totaling 16 articles included in this review. RESULTS: of the patients who manifested gastrointestinal symptoms associated with the disease, common comorbidities and clinical manifestations were identified, in addition to therapies used to treat the infection, which were predisposing factors for the development of gastrointestinal bleeding. CONCLUSION: The presence of gastrointestinal bleeding in patients with COVID-19 is established in the literature, since the pathophysiological mechanisms of the disease directly affect the GIT. Early recognition of symptoms and suspicion of gastrointestinal involvement allows better management of patients and complications.


Asunto(s)
COVID-19 , Hemorragia Gastrointestinal , Humanos , COVID-19/complicaciones , Hemorragia Gastrointestinal/etiología , SARS-CoV-2 , Factores de Riesgo
6.
Br J Nutr ; : 1-35, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38772907

RESUMEN

This cross-sectional study aims to describe and compare energy, nutrient intake, and food consumption according to eating location and by age groups using data from the National Food, Nutrition and Physical Activity Survey (IAN-AF 2015/2016). Dietary intake was estimated by two non-consecutive days of food diaries (children)/24-hour recalls (other age groups) and four eating location categories were defined according to the proportion of meals consumed at out of home locations: Home (at least 80% of meals at home), Other Homes, School or Work and Restaurants and Other Places. The majority of meals (69.1%) were consumed at home. Meals were also often taken at school by children and adolescents, and in restaurants and similar outlets by adults and elderly. Children and adolescents in the School or Work category ate more fruit, vegetables and pulses and cereals and starchy tubers, whereas adults in this category ate more red and processed meats, sugar sweetened beverages and sweets. Compared to Home category, Restaurants and Other Places was associated with worse diet adequacies among children (ß=-1.0; 95%CI=-2.0, -0.04), adolescents: (ß=-2.4; 95%CI=-3.2, -1.5) and adults (ß=-1.3; 95%CI=-1.6, -1.0) reflecting higher intakes of energy, fat, trans and saturated fatty acids, and sodium. The elderly consumed more free sugars and fat when eating out of home in general. Overall, findings reflect important variation in nutrient profiles by eating location, with meals taken at school or work contributing to higher consumption of nutrient-dense foods and those taken in restaurants and other similar settings implying higher consumption of energy-dense foods.

7.
Heliyon ; 10(7): e28241, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38560242

RESUMEN

Background: Family-Centered Care (FCC) is an approach to healthcare planning, delivery and evaluation, based on beneficial partnerships between health professionals, patients and families. FCC may be particularly relevant for families with children with intellectual disability (ID), given their needs of continuum care. Objective: To identify which components of the FCC are practiced and which health outcomes are considered effective in families with children with ID. Method: A systematic review guided by the PRISMA STATEMENT 2020 approach and the STROBE reporting guidelines was performed on specific databases through the EBSCOhost Web platform: MEDLINE with Full Text, CINAHL PLUS with Full Text, Academic Search Complete and Psychology and Behavioral Sciences Collection. Peer-reviewed articles published in English or Portuguese languages from 2018 to September 2023 were retrieved. Methodological quality was established using the Quality Assessment Tool for Observational, Cohort and Cross-Sectional Studies - NHLBI, NIH. Results: Ten studies met the eligibility criteria and were synthetized. The results revealed nine components, reflecting the way FCC was developed: shared decision-making; family education; respect for culture; family engagement; recognition of the family's needs, characteristics and interests; specialized care support; social and emotional support; family functionality; and family seen as a unit. The health outcomes demonstrate effective gains in improving children's health through family satisfaction with health services. Also achieved psychological and social benefits, with improved family well-being and quality of life, favoring family empowerment. Conclusions: The evidence suggests that FCC components involves an effective partnership between the family and health professionals as the main key in developing care plans, as well as the experience that the family unit brings to the delivery of care. FCC approach include all family members as decision-makers, providing emotional, physical and instrumental levels of support. Health outcomes emerged in three strands; for children with ID, families and health services.

8.
J Taibah Univ Med Sci ; 19(3): 492-499, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38562915

RESUMEN

Objectives: This study analyzed the influence of 23 comorbidities on COVID-associated acute distress respiratory syndrome (CARDS) mortality in people with a history of diabetes mellitus. Methods: An observational, analytical, cross sectional study was utilized to investigate data from 6723 health services in Brazil, comprising 5433 people with diabetes. Adjusted logistic regression models for demographic factors such as age, sex, and race were used to analyze the association between CARDS mortality and comorbidities. Results: Persons with two (p < 0.001), three (p < 0.001), four (p < 0.001), and five (p < 0.001) simultaneous comorbidities had a higher chance of dying. We identified that diabetes patients who had concomitant metabolic diseases (p = 0.019), neurological disorders (p < 0.001), or were smokers (p < 0.001) had a higher predicted mortality risk based on CADRS. Conclusion: The number of comorbidities plays a determining role in CARDS mortality in people with diabetes, especially those who suffer from smoking and neurological diseases simultaneously.

9.
J Surg Case Rep ; 2024(4): rjae188, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38572284

RESUMEN

The treatment of recurrent ovarian cancer has been based on systemic therapy. The role of secondary cytoreductive surgery has been addressed recently in several trials. Imaging plays a key role in helping the surgical team to decide which patients will have resectable disease and benefit from surgery. The role of staging laparoscopy and several imaging and clinical scores has been extensively debated in the field. In other surgical fields there have been reports of using 3D imaging software and 3D printed models to help surgeons better plan the surgical approach. To the best of our knowledge, we report the first case of a patient with recurrent ovarian cancer undergoing 3D modeling before secondary cytoreductive surgery. The 3D modeling was of most value to evaluate the extension of the disease in our patient who underwent a successful secondary cytoreductive surgery and is currently free of the disease.

10.
bioRxiv ; 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38617230

RESUMEN

Parkinson's disease (PD) is characterized by the degeneration of dopaminergic nigrostriatal inputs, which causes striatal network dysfunction and leads to pronounced motor deficits. Recent evidence highlights astrocytes as a potential local source of striatal network modulation. However, it remains unknown how dopamine loss affects striatal astrocyte activity and whether astrocyte activity regulates behavioral deficits in PD. We addressed these questions by performing astrocyte-specific calcium recordings and manipulations using in vivo fiber photometry and chemogenetics. We find that locomotion elicits astrocyte calcium activity over a slower timescale than neurons. Unilateral dopamine depletion reduced locomotion-related astrocyte responses. Chemogenetic activation facilitated astrocyte activity, and improved asymmetrical motor deficits and open field exploratory behavior in dopamine lesioned mice. Together, our results establish a novel role for functional striatal astrocyte signaling in modulating motor function in PD and highlight non-neuronal targets for potential PD therapeutics.

11.
World J Gastroenterol ; 30(11): 1545-1555, 2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38617446

RESUMEN

BACKGROUND: The gluten-free diet (GFD) has limitations, and there is intense research in the development of adjuvant therapies. AIM: To examine the effects of orally administered Aspergillus niger prolyl endopeptidase protease (AN-PEP) on inadvertent gluten exposure and symptom prevention in adult celiac disease (CeD) patients following their usual GFD. METHODS: This was an exploratory, double-blind, randomized, placebo-controlled trial that enrolled CeD patients on a long-term GFD. After a 4-wk run-in period, patients were randomized to 4 wk of two AN-PEP capsules (GliadinX; AVI Research, LLC, United States) at each of three meals per day or placebo. Outcome endpoints were: (1) Average weekly stool gluten immunogenic peptides (GIP) between the run-in and end of treatments and between AN-PEP and placebo; (2) celiac symptom index (CSI); (3) CeD-specific serology; and (4) quality of life. Stool samples were collected for GIP testing by ELISA every Tuesday and Friday during run-ins and treatments. RESULTS: Forty patients were randomized for the intention-to-treat analysis, and three were excluded from the per-protocol assessment. Overall, 628/640 (98.1%) stool samples were collected. GIP was undetectable (< 0.08 µg/g) in 65.6% of samples, and no differences between treatment arms were detected. Only 0.5% of samples had GIP concentrations sufficiently high (> 0.32 µg/g) to potentially cause mucosal damage. Median GIP concentration in the AN-PEP arm was 44.7% lower than in the run-in period. One-third of patients exhibiting GIP > 0.08 µg/g during run-in had lower or undetectable GIP after AN-PEP treatment. Compared with the run- in period, the proportion of symptomatic patients (CSI > 38) in the AN-PEP arm was significantly lower (P < 0.03). AN-PEP did not result in changes in specific serologies. CONCLUSION: This exploratory study conducted in a real-life setting revealed high adherence to the GFD. The AN-PEP treatment did not significantly reduce the overall GIP stool concentration. However, given the observation of a significantly lower prevalence of patients with severe symptoms in the AN-PEP arm, further clinical research is warranted.


Asunto(s)
Aspergillus niger , Aspergillus , Enfermedad Celíaca , Adulto , Humanos , Enfermedad Celíaca/diagnóstico , Dieta Sin Gluten , Glútenes , Prolil Oligopeptidasas , Calidad de Vida
12.
Nutr Health ; : 2601060241248716, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38650585

RESUMEN

Aim: To assess the effect of cashew nut flour on the hematological parameters of children living with HIV-AIDS. Method: A 32-week randomized, blind clinical trial conducted at a specialized outpatient clinic. Children aged 2-12 years were allocated to intervention groups (IGs) (n = 11) receiving 12 g/day of cashew nut flour and control groups (CGs) (n = 9) receiving 12 g/day of carboxymethyl cellulose. Parameters of erythrocytes, leukocytes, platelets, and lipid profiles were evaluated. Results: In the IG, the elevation and reduction of leukocyte and lipid profile biomarkers, respectively, were not statistically significant (p > 0.05). A clinically and statistically significant increase in mean corpuscular hemoglobin concentration was observed in the CG (p = 0.018), with a large effect size (Cohen's d = 0.9). There were no statistically significant changes in platelet counts among participants (p = 0.18). The effect size for white blood cell count, low-density lipoprotein cholesterol, very low-density lipoprotein, and triglycerides was moderate in the IG compared to the CG. Conclusion: Cashew nut flour supplementation may increase levels of leukocytes and lipid profile parameters in children living with HIV. Brazilian Clinical Trials Registry (REBEC): U1111.1276.6591.

13.
BMJ Open ; 14(4): e076064, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38594182

RESUMEN

INTRODUCTION: The paediatric population represents a quarter of the world's population, and like adult patients, they have also suffered immeasurably from the SARS-CoV-2 pandemic. Immunisation is an effective strategy for reducing the number of COVID-19 cases. With the advancements in vaccination for younger age groups, parents or guardians have raised doubts and questions about adverse effects and the number of doses required. Therefore, systematic reviews focusing on this population are needed to consolidate evidence that can help in decision-making and clinical practice. This protocol aims to assess the safety of COVID-19 vaccines in paediatric patients and evaluate the correlation between the number of vaccine doses and side effects. METHODS AND ANALYSIS: We will search the PubMed, ClinicalTrials.gov, Web of Science, Embase, CINAHL, Latin American and Caribbean Health Sciences Literature, Scopus and Cochrane databases for randomised and quasi-randomised clinical trials that list the adverse effects of the COVID-19 vaccine and assess its correlation with the number of doses, without any language restrictions. Two reviewers will select the studies according to the inclusion and exclusion criteria, extract data and asses for risk of bias using the Cochrane risk-of-bias tool. The Review Software Manager (RevMan V.5.4.1) will be used to synthesise the data. We will use the Working Group's Grading of Recommendations Assessment, Development and Evaluations to grade the strength of the evidence of the results. ETHICS AND DISSEMINATION: Formal ethical approval is not required as no primary data are collected. This systematic review will be disseminated through a peer-reviewed publication. PROSPERO REGISTRATION NUMBER: CRD42023390077.


Asunto(s)
COVID-19 , Vacunas , Adulto , Humanos , Niño , COVID-19/prevención & control , SARS-CoV-2 , Vacunas contra la COVID-19/efectos adversos , Vacunación , Proyectos de Investigación , Revisiones Sistemáticas como Asunto , Metaanálisis como Asunto
14.
Artículo en Inglés | MEDLINE | ID: mdl-38688175

RESUMEN

The present work aimed at the development and characterization of aroeira leaf flour (Schinus terebinthifolius Raddi), obtained by lyophilization and drying in an air circulation oven. The technological, physical, physico-chemical, morphological, functional, and microbiological aspects were analyzed. Physico-chemical analysis identified the following properties with values provided respectively for fresh leaves (FOin) and flours (FES and FLIO): low water activity (0.984, 0.370, 0.387 g/100 g), moisture (64.52, 5.37, 7.97 g /100 g), ash (2.69, 6.51, and 6.89 g/100 g), pH (0.89, 4.45, 4.48 g/100 g), lipids (0.84, 1.67, 5.23 g/100 g), protein (3.29, 8.23, 14.12 g/100 g), carbohydrates (17.02, 53.12, 33.02 g/100 g), ascorbic acid (19.70, 34.20, 36.90 mg/100 g). Sources of fiber from plant leaves and flours (11.64, 25.1, 32.89 g/100 g) showed increased levels of luminosity. For NMR, the presence of aliphatic and aromatic compounds with olefinic hydrogens and a derivative of gallic acid were detected. The most abundant minerals detected were potassium and calcium. Micrographs identified the presence of irregular, non-uniform, and sponge-like particles. The main sugars detected were: fructose, glucose, and maltose. Malic, succinic, citric, lactic, and formic acids were found. Fifteen phenolic compounds were identified in the samples, highlighting: kaempferol, catechin, and caffeic acid. The values ​​found for phenolics were (447, 716.66, 493.31 mg EAG/100 g), flavonoids (267.60, 267.60, 286.26 EC/100 g). Antioxidant activity was higher using the ABTS method rather than FRAP for analysis of FOin, FES, and FLIO. Since the flours of the aroeira leaf have an abundant matrix of nutrients with bioactive properties and antioxidant activity, they have a potential for technological and functional use when added to food.


Asunto(s)
Anacardiaceae , Harina , Hojas de la Planta , Hojas de la Planta/química , Anacardiaceae/química , Harina/análisis , Liofilización , Carbohidratos/análisis , Carbohidratos/química , Antioxidantes/análisis , Antioxidantes/química , Schinus
15.
Artículo en Inglés | MEDLINE | ID: mdl-38684174

RESUMEN

OBJECTIVES: Postoperative organ dysfunction is common after cardiac surgery, particularly when cardiopulmonary bypass (CPB) is used. The Sequential Organ Failure Assessment (SOFA) score is validated to predict morbidity and mortality in cardiac surgery. However, the impact of CPB duration on postoperative SOFA remains unclear. METHODS: This is a retrospective study. Categorical values are presented as percentages. The comparison of SOFA groups utilized the Kruskal-Wallis chi-squared test, complemented by ad hoc Dunn's test with Bonferroni correction. Multinomial logistics regressions were employed to evaluate the relationship between CPB time and SOFA. RESULTS: A total of 1032 patients were included. CPB time was independently associated with higher postoperative SOFA scores at 24 h. CPB time was significantly higher in patients with SOFA 4-5 (**P = 0.0022) or higher (***P < 0.001) when compared to SOFA 0-1. The percentage of patients with no/mild dysfunction decreased with longer periods of CPB, down to 0% for CPB time >180min (50% of the patients with >180m in of CPB presented SOFA ≥ 10). The same trend is observed for each of the SOFA variables, with higher impact in the cardiovascular and renal systems. Severe dysfunction occurs especially >200 min of CPB (cardiovascular system >100 min; other systems mainly >200 min). CONCLUSIONS: CPB time may predict the probability of postoperative SOFA categories. Patients with extended CPB durations exhibited higher SOFA scores (overall and for each variable) at 24 h, with higher proportion of moderate and severe dysfunction with increasing times of CPB.

16.
Cephalalgia ; 44(4): 3331024241247845, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38676534

RESUMEN

BACKGROUND: Cluster headache is a primary headache disorder characterized by bouts with circadian and circannual patterns. The CLOCK gene has a central role in regulating circadian rhythms. Here, we investigate the circannual CLOCK expression in a population of cluster headache patients in comparison to matched controls. METHODS: Patients with cluster headache were sampled two to four times over at least one year, both in or outside bouts, one week after each solstice and equinox. The expression of CLOCK was measured by quantitative real-time polymerase chain reaction (RT-PCR) in the peripheral blood. RESULTS: This study included 50 patients and 58 matched controls. Among the patient population, composed of 42/50 males (84%) with an average age of 44.6 years, 45/50 (90%) suffered from episodic cluster headache. Two to four samples were collected from each patient adding up to 161 samples, 36 (22.3%) of which were collected within a bout. CLOCK expression for cluster headache patients was considerably different from that of the control population in winter (p-value mean = 0.006283), spring (p-value mean = 0.000006) and summer (p-value mean = 0.000064), but not in autumn (p-value mean = 0.262272). For each season transition, the variations in CLOCK expression were more pronounced in the control group than in the cluster headache population. No statistically significant differences were found between bout and non-bout samples. No individual factors (age, sex, circadian chronotype, smoking and coffee habits or history of migraine) were related to CLOCK expression. CONCLUSIONS: We observed that CLOCK expression in cluster headache patients fluctuates less throughout the year than in the control population. Bout activity and lifestyle factors do not seem to influence CLOCK expression.


Asunto(s)
Proteínas CLOCK , Cefalalgia Histamínica , Humanos , Cefalalgia Histamínica/genética , Masculino , Femenino , Adulto , Proteínas CLOCK/genética , Proteínas CLOCK/biosíntesis , Persona de Mediana Edad , Ritmo Circadiano , Estaciones del Año
17.
Cell ; 187(9): 2269-2287.e16, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38608703

RESUMEN

Knudson's "two-hit" paradigm posits that carcinogenesis requires inactivation of both copies of an autosomal tumor suppressor gene. Here, we report that the glycolytic metabolite methylglyoxal (MGO) transiently bypasses Knudson's paradigm by inactivating the breast cancer suppressor protein BRCA2 to elicit a cancer-associated, mutational single-base substitution (SBS) signature in nonmalignant mammary cells or patient-derived organoids. Germline monoallelic BRCA2 mutations predispose to these changes. An analogous SBS signature, again without biallelic BRCA2 inactivation, accompanies MGO accumulation and DNA damage in Kras-driven, Brca2-mutant murine pancreatic cancers and human breast cancers. MGO triggers BRCA2 proteolysis, temporarily disabling BRCA2's tumor suppressive functions in DNA repair and replication, causing functional haploinsufficiency. Intermittent MGO exposure incites episodic SBS mutations without permanent BRCA2 inactivation. Thus, a metabolic mechanism wherein MGO-induced BRCA2 haploinsufficiency transiently bypasses Knudson's two-hit requirement could link glycolysis activation by oncogenes, metabolic disorders, or dietary challenges to mutational signatures implicated in cancer evolution.


Asunto(s)
Proteína BRCA2 , Neoplasias de la Mama , Glucólisis , Piruvaldehído , Animales , Proteína BRCA2/metabolismo , Proteína BRCA2/genética , Ratones , Humanos , Femenino , Piruvaldehído/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Haploinsuficiencia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Mutación , Daño del ADN , Reparación del ADN , Línea Celular Tumoral
18.
Rev Port Cardiol ; 2024 Apr 12.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-38615881

RESUMEN

Left bundle branch block (LBBB) is a frequent finding in patients with heart failure (HF), particularly in those with dilated cardiomyopathy (DCM). LBBB has been commonly described as a consequence of DCM development. However, a total recovery of left ventricular (LV) function after cardiac resynchronization therapy (CRT), observed in patients with LBBB and DCM, has led to increasing acknowledgement of LBBB-induced dilated cardiomyopathy (LBBB-iDCM) as a specific pathological entity. Its recognition has important clinical implications, as LBBB-iDCM patients may benefit from an early CRT strategy rather than medical HF therapy only. At present, there are no definitive diagnostic criteria enabling the universal identification of LBBB-iDCM, and no defined therapeutic approach in this subgroup of patients. This review compiles the main findings about LBBB-iDCM pathophysiology and the current proposed diagnostic criteria and therapeutic approach.

19.
Biomedicines ; 12(4)2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38672137

RESUMEN

Traumatic brain injury is one of the leading causes of morbidity and mortality worldwide and is one of the major public healthcare burdens in the US, with millions of patients suffering from the traumatic brain injury itself (approximately 1.6 million/year) or its repercussions (2-6 million patients with disabilities). The severity of traumatic brain injury can range from mild transient neurological dysfunction or impairment to severe profound disability that leaves patients completely non-functional. Indications for treatment differ based on the injury's severity, but one of the goals of early treatment is to prevent secondary brain injury. Hemodynamic stability, monitoring and treatment of intracranial pressure, maintenance of cerebral perfusion pressure, support of adequate oxygenation and ventilation, administration of hyperosmolar agents and/or sedatives, nutritional support, and seizure prophylaxis are the mainstays of medical treatment for severe traumatic brain injury. Surgical management options include decompressive craniectomy or cerebrospinal fluid drainage via the insertion of an external ventricular drain. Several emerging treatment modalities are being investigated, such as anti-excitotoxic agents, anti-ischemic and cerebral dysregulation agents, S100B protein, erythropoietin, endogenous neuroprotectors, anti-inflammatory agents, and stem cell and neuronal restoration agents, among others.

20.
Appetite ; 198: 107377, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38679064

RESUMEN

Most instruments measuring nutrition literacy evaluate theoretical knowledge, not necessarily reflecting skills relevant to food choices. We aimed to develop and validate a photograph-based instrument to assess nutrition literacy (NUTLY) among adults in Portugal. NUTLY assesses the ability to distinguish foods with different nutritional profiles; from each of several combinations of three photographs (two foods with similar contents and one with higher content) participants are asked to identify the food with the highest energy/sodium content. The NUTLY version with 79 combinations, obtained after experts/lay people evaluations, was applied to a sample representing different age, gender and education groups (n = 329). Dimensionality was evaluated through latent trait models. Combinations with negative or with positive small factor loadings were excluded after critical assessment. Internal consistency was measured using Cronbach's alpha and construct validity by comparing NUTLY scores with those obtained in the Medical Term Recognition Test and the Newest Vital Sign (NVS), and across education and training in nutrition/health groups. The cut-off to distinguish adequate/inadequate nutrition literacy was defined through ROC analysis using the Youden index criterion, after performing a Latent class analysis which identified a two-class model to have the best goodness of fit. Test-retest reliability was assessed after one month (n = 158). The final NUTLY scale was unidimensional and included 48 combinations (energy: 33; sodium: 15; α = 0.74). Mean scores (±standard deviation) were highest among nutritionists (39.9 ± 4.4), followed by health professionals (38.5 ± 4.1) and declined with decreasing education (p < 0.001). Those with adequate nutrition literacy according to NVS showed higher NUTLY scores (37.9 ± 4.3 vs. 33.9 ± 6.9, p < 0.001). Adequate nutrition literacy was defined as a NUTLY score≥35 (sensitivity: 89.3%; specificity: 93.7%). Test-retest reliability was high (ICC = 0.77). NUTLY is a valid and reliable nutrition literacy measurement tool.


Asunto(s)
Alfabetización en Salud , Fotograbar , Humanos , Femenino , Masculino , Adulto , Reproducibilidad de los Resultados , Portugal , Persona de Mediana Edad , Adulto Joven , Conocimientos, Actitudes y Práctica en Salud , Anciano , Encuestas y Cuestionarios/normas , Adolescente
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