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1.
Food Funct ; 15(14): 7669-7680, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38961720

RESUMO

The rates of overweight and obesity around the world have increased in past years. The body's adipose tissue stimulates the antioxidant and oxidation imbalance capacity at the cellular level. This scenario favors an inflammatory low-grade systemic condition starting with insulin resistance, which in turn may involve diabetes mellitus type 2 and cognitive decline afterward. Neurological diseases have been correlated to senile age diseases over time. This scenario calls for a change in the incidence of obesity in the younger generation. An unhealthy dietary consumption together with sedentary habits might lead to poor gut absorption of nutrients. Several plants and foods have bioactive compounds that can reduce or inhibit radical scavengers, reactive oxygen species, and metal ion complexes that threaten the cerebral defense system. The bitter acids from hops (Humulus lupulus L.) have been demonstrated to have promising effects on lipid and carbohydrate metabolism improvement, reducing inflammatory responses through alpha acids, beta acids, and analogs action. Therefore, the current study aimed to investigate the bioactivity of hop bitter acids in obese and lean mice. For that, a dry hop extract (DHE) was obtained by applying carbon dioxide as the fluid of supercritical extraction. Afterward, seventy-eight male mice of the C57BL/6J strain were weighed and randomly distributed into six groups of 13 animals each according to the diet offered: (NO) normolipidic diet, (NO1) normolipidic diet containing 0.35% alpha acids, (NO2) normolipidic diet containing 3.5% alpha acids, (HP) hyperlipidic diet, (HP1) hyperlipidic diet containing 0.35% alpha acids, and (HP2) hyperlipidic diet containing 3.5% alpha acids. After applying the glycemic tolerance and insulin tolerance tests, a better stabilization of glycemia levels and weight gain among those animals fed with DHE (NO2 and HP2) were observed in comparison to the obese control group (HP) (p < 0.05). There was also an amelioration of antioxidant capacity observed by checking the enzymatic profile by SOD and an apparent mitigation of brain degeneration by checking GSK3ß and p-IRS1 proteins expression (p < 0.05). The y-maze cognitive test applied to highlight possible obesity-harmful animal brains did not indicate a statistical difference between the groups. Although the weekly dietary intake between the obese HP2 group (33.32 ± 4.11, p < 0.05) and control HP (42.3 ± 5.88, p < 0.05) was different. The bioactive compounds present in DHE have demonstrated relevant effects on glycemic control, insulin signaling, and the consequent modulatory action of the obesity-related markers with the brain's inflammatory progression.


Assuntos
Disfunção Cognitiva , Modelos Animais de Doenças , Humulus , Camundongos Endogâmicos C57BL , Obesidade , Extratos Vegetais , Humulus/química , Animais , Obesidade/metabolismo , Obesidade/tratamento farmacológico , Masculino , Extratos Vegetais/farmacologia , Camundongos , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Glicemia/metabolismo , Antioxidantes/farmacologia , Humanos , Resistência à Insulina
2.
Nat Metab ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951660

RESUMO

As the microbiome field moves from descriptive and associative research to mechanistic and interventional studies, being able to account for all confounding variables in the experimental design, which includes the maternal effect1, cage effect2, facility differences3, as well as laboratory and sample handling protocols4, is critical for interpretability of results. Despite significant procedural and bioinformatic improvements, unexplained variability and lack of replicability still occur. One underexplored factor is that the microbiome is dynamic and exhibits diurnal oscillations that can change microbiome composition5-7. In this retrospective analysis of 16S amplicon sequencing studies in male mice, we show that sample collection time affects the conclusions drawn from microbiome studies and its effect size is larger than those of a daily experimental intervention or dietary changes. The timing of divergence of the microbiome composition between experimental and control groups is unique to each experiment. Sample collection times as short as only 4 hours apart can lead to vastly different conclusions. Lack of consistency in the time of sample collection may explain poor cross-study replicability in microbiome research. The impact of diurnal rhythms on the outcomes and study design of other fields is unknown but likely significant.

3.
J Am Nutr Assoc ; : 1-7, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958672

RESUMO

OBJECTIVE: To investigate the acute effects of ingesting a beverage containing guarana (Paullinia cupana) seed powder on performance during field tests related to physical capacities that are determinants of soccer performance, such as lower limb power, sprint, agility, and the capacity to carry out intermittent exercise. METHODS: The study was conducted using a randomized, crossover, and counterbalanced design, with a beverage containing guarana or placebo administered in a double-blind manner. Twenty-seven under-17 soccer players of a professional soccer club performed a battery of tests 60 min after the ingestion of guarana (3 g of the fruit seed powder) or placebo. Trials were performed with a 7-day washout period. The battery of tests included a countermovement jump test, sprints of 10 and 20 m, an Illinois agility test, and a Yo-Yo Intermittent Recovery Test level 1 (YYIR1). RESULTS: Guarana ingestion did not improve countermovement jump, sprints, or agility (p > 0.05). However, guarana ingestion increased the distance covered in the YYIR1, compared with placebo ingestion (p = 0.01). CONCLUSION: Acute ingestion of guarana improves the capacity to perform intermittent exercise in soccer players but seems to be ineffective to improve lower limb power, sprint, and agility.

4.
Am J Med Genet A ; : e63802, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38924610

RESUMO

Low-pass whole genome sequencing (LP-WGS) has been applied as alternative method to detect copy number variants (CNVs) in the clinical setting. Compared with chromosomal microarray analysis (CMA), the sequencing-based approach provides a similar resolution of CNV detection at a lower cost. In this study, we assessed the efficiency and reliability of LP-WGS as a more affordable alternative to CMA. A total of 1363 patients with unexplained neurodevelopmental delay/intellectual disability, autism spectrum disorders, and/or multiple congenital anomalies were enrolled. Those patients were referred from 15 nonprofit organizations and university centers located in different states in Brazil. The analysis of LP-WGS at 1x coverage (>50kb) revealed a positive testing result in 22% of the cases (304/1363), in which 219 and 85 correspond to pathogenic/likely pathogenic (P/LP) CNVs and variants of uncertain significance (VUS), respectively. The 16% (219/1363) diagnostic yield observed in our cohort is comparable to the 15%-20% reported for CMA in the literature. The use of commercial software, as demonstrated in this study, simplifies the implementation of the test in clinical settings. Particularly for countries like Brazil, where the cost of CMA presents a substantial barrier to most of the population, LP-WGS emerges as a cost-effective alternative for investigating copy number changes in cytogenetics.

5.
Early Hum Dev ; 195: 106069, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38924944

RESUMO

INTRODUCTION: The low attendance of families in child developmental follow-up programs for at-risk preterm children is a challenge in Brazil. OBJECTIVE: This study evaluates the feasibility of implementing a developmental follow-up program for Brazilian preterm infants in a hybrid format. METHODS: This is an observational, prospective cohort study, involving preterm infants. Longitudinal developmental test results, the participation frequency in the program, and the number of referrals to early intervention programs were used to assess feasibility. The General Movements (GMs) assessment, Alberta Infant Motor Scale (AIMS) and, Survey of Wellbeing of Young Children (SWYC) Milestones were administered via telehealth. The Bayley-III was administered in-person. RESULTS: Thirty-four preterm infants attended the follow-up until 12 months of corrected age and 18 (52.9 %) concluded all follow-up assessments. Twenty-six (76.5 %) attended all assessments via telehealth, and 26 (76.5 %) attended the in-person assessment. Eighteen (52.9 %) infants showed at least one altered result in development tests. Infants exhibiting abnormal results in the GMs assessment, motor developmental delay according to the AIMS, or developmental delay based on Balley-III were promptly referred to early intervention services. CONCLUSION: This study demonstrated high participation rate and low dropout in a developmental follow-up program employing a hybrid format. The substantial number of identified infants with developmental delay emphasizes the importance of timely detection of motor delays to referral to early intervention services.

6.
Microb Ecol ; 87(1): 88, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38943017

RESUMO

Plastic pollution poses a worldwide environmental challenge, affecting wildlife and human health. Assessing the biodegradation capabilities of natural microbiomes in environments contaminated with microplastics is crucial for mitigating the effects of plastic pollution. In this work, we evaluated the potential of landfill leachate (LL) and estuarine sediments (ES) to biodegrade polyethylene (PE), polyethylene terephthalate (PET), and polycaprolactone (PCL), under aerobic, anaerobic, thermophilic, and mesophilic conditions. PCL underwent extensive aerobic biodegradation with LL (99 ± 7%) and ES (78 ± 3%) within 50-60 days. Under anaerobic conditions, LL degraded 87 ± 19% of PCL in 60 days, whereas ES showed minimal biodegradation (3 ± 0.3%). PE and PET showed no notable degradation. Metataxonomics results (16S rRNA sequencing) revealed the presence of highly abundant thermophilic microorganisms assigned to Coprothermobacter sp. (6.8% and 28% relative abundance in anaerobic and aerobic incubations, respectively). Coprothermobacter spp. contain genes encoding two enzymes, an esterase and a thermostable monoacylglycerol lipase, that can potentially catalyze PCL hydrolysis. These results suggest that Coprothermobacter sp. may be pivotal in landfill leachate microbiomes for thermophilic PCL biodegradation across varying conditions. The anaerobic microbial community was dominated by hydrogenotrophic methanogens assigned to Methanothermobacter sp. (21%), pointing at possible syntrophic interactions with Coprothermobacter sp. (a H2-producer) during PCL biodegradation. In the aerobic experiments, fungi dominated the eukaryotic microbial community (e.g., Exophiala (41%), Penicillium (17%), and Mucor (18%)), suggesting that aerobic PCL biodegradation by LL involves collaboration between fungi and bacteria. Our findings bring insights on the microbial communities and microbial interactions mediating plastic biodegradation, offering valuable perspectives for plastic pollution mitigation.


Assuntos
Bactérias , Biodegradação Ambiental , Microbiota , Microplásticos , Instalações de Eliminação de Resíduos , Microplásticos/metabolismo , Bactérias/classificação , Bactérias/metabolismo , Bactérias/genética , Bactérias/isolamento & purificação , Poluentes Químicos da Água/metabolismo , Poliésteres/metabolismo , Sedimentos Geológicos/microbiologia , RNA Ribossômico 16S/genética , Estuários , Polietileno/metabolismo , Polietilenotereftalatos/metabolismo
7.
Sci Rep ; 14(1): 14815, 2024 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937573

RESUMO

The association of postpartum cardiac reverse remodeling (RR) with urinary proteome, particularly in pregnant women with cardiovascular (CV) risk factors who show long-term increased risk of cardiovascular disease and mortality is unknown. We aim to profile the urinary proteome in pregnant women with/without CV risk factors to identify proteins associated with postpartum RR. Our study included a prospective cohort of 32 healthy and 27 obese and/or hypertensive and/or diabetic pregnant women who underwent transthoracic echocardiography, pulse-wave-velocity, and urine collection at the 3rd trimester and 6 months postpartum. Shotgun HPLC-MS/MS profiled proteins. Generalized linear mixed-effects models were used to identify associations between urinary proteins and left ventricle mass (LVM), a surrogate of RR. An increase in arterial stiffness was documented from 3rd trimester to 6 months after delivery, being significantly elevated in women with CV risk factors. In addition, the presence of at least one CV risk factor was associated with worse LVM RR. We identified 6 and 11 proteins associated with high and low LVM regression, respectively. These proteins were functionally linked with insulin-like growth factor (IGF) transport and uptake regulation by IGF binding-proteins, platelet activation, signaling and aggregation and the immune system's activity. The concentration of IGF-1 in urine samples was associated with low LVM regression after delivery. Urinary proteome showed a predicting potential for identifying pregnant women with incomplete postpartum RR.


Assuntos
Período Pós-Parto , Proteoma , Remodelação Ventricular , Humanos , Feminino , Gravidez , Adulto , Proteoma/análise , Período Pós-Parto/urina , Estudos Prospectivos , Biomarcadores/urina , Rigidez Vascular , Ecocardiografia , Fatores de Risco
8.
Braz J Phys Ther ; 28(4): 101090, 2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38943740

RESUMO

BACKGROUND: Functional capacity impairment is a crucial consequence of chronic obstructive pulmonary disease (COPD). Although it can be identified with simple tests, such as the sit-to-stand tests, its prevalence, relation with disease severity, and the characteristics of people presenting this impairment remain unknown. OBJECTIVE: To explore the functional capacity of people with COPD. METHODS: A cross-sectional study with people with COPD and age-/sex-matched healthy controls was conducted. Functional capacity was assessed with the 5-repetitions (5-STS) and the 1-minute (1-minSTS) sit-to-stand tests. People with COPD were grouped according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classifications. Comparisons between people with COPD and healthy controls, and among GOLD groups were established. Associations between symptoms, muscle strength, quality of life, and measures of functional capacity were explored. RESULTS: 302 people with COPD [79% male; mean (SD) 68 (10) years old] and 304 healthy controls [75% male; 66 (9) years old] were included. 23% of people with COPD presented impairment in the 5-STS and 33% in the 1-minSTS. People with COPD from all GOLD classifications presented significantly lower functional capacity than healthy controls (5-STS: COPD median [1st quartile; 3rd quartile] 8.4 [6.7; 10.6] versus healthy 7.4 [6.2; 9.3] s; 1-minSTS: COPD 27 [21; 35] vs healthy 35 [29; 43] reps). Correlations with symptoms, muscle strength, and quality of life were mostly weak (5-STS: rs [-0.34; 0.33]; 1-minSTS: rs [-0.47; 0.40]). CONCLUSION: People with COPD have decreased functional capacity independently of their GOLD classifications. The prevalence of functional impairment is 23-33%. Because impaired functional capacity is a treatable trait not accurately reflected by other outcomes, comprehensive assessment and management is needed.

9.
Aesthetic Plast Surg ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831064

RESUMO

INTRODUCTION: Hand aging is a prevalent concern characterized by the atrophy of local soft tissues and increased visibility of vessels and tendons. Hyaluronic acid (HA) and calcium hydroxyapatite (CaHA) are well-established treatments for addressing this issue. While hybrid filler containing HA and CaHA has been proposed for facial rejuvenation, studies investigating its efficacy for hand rejuvenation are lacking. OBJECTIVE: This study aims to assess the safety and efficacy of a premixed hybrid filler containing calcium hydroxyapatite (CaHA) and hyaluronic acid (HA) for hand rejuvenation. METHODS: A prospective, double-blind, controlled trial was conducted. The control arm (CA) received conventional subdermal treatment with CaHA at a 1:1 dilution. The intervention arm (IA) underwent hybrid treatment, consisting of CaHA at a 1:1 dilution combined with 1 ml of low-density HA. Evaluation was performed subjectively using the Global Aesthetic Improvement Scale (GAIS) and the Manchester Hand Grading System (MHGS), and objectively using cutometry, corneometry, and ultrasound. RESULTS: Both the CA and the IA exhibited high rates of patient satisfaction and satisfaction as assessed by blinded evaluators. Although numerical superiority was observed in the IA, no statistical difference was found between the two groups. Significant improvements in hydration, elasticity, and skin thickness were observed in both arms, with no discernible difference between them. Greater ultrasound echogenicity was noted in the IA, which, as indicated by existing literature, may suggest enhanced biostimulation. No adverse effects were reported in either arm. CONCLUSION: Premixed filler containing HA and CaHA for hand rejuvenation appears to be a safe and effective approach. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

11.
Food Funct ; 15(11): 5752-5784, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38753200

RESUMO

Brazil has a broad geographic biodiversity spread across its six different biomes. However, it has been suffering from the abusive exploitation of its resources, which poses a threat to the local fauna and flora. The Amazon and Atlantic Forest, for example, are birthplaces to rare and edible native species, such as bacaba (Oenocarpus bacaba, Arecaceae) and camu-camu (Myrciaria dubia, Myrtaceae), and cereja-do-Rio Grande (Eugenia involucrata, Myrtaceae) and grumixama (Eugenia brasiliensis, Myrtaceae), respectively. These plants produce fruits which are sources of macro and micronutrients, including sugars, dietary fibers, vitamins, minerals, and/or lipids. Nutritionally, their consumption have the ability to reach partially or totally the daily recommendations for adults of some nutrients. More recently, these fruits have also been exposed as interesting sources of minor bioactive compounds, such as carotenoids, terpenes, and/or polyphenols, the latter which include anthocyanins, phenolic acids, and tannins. Particularly, bacaba stands out for being a rich source of polyunsaturated fatty acids (around 22%, dry weight) and dietary fibers (6.5-21%, dry weight); camu-camu has very high contents of vitamin C (up to 5000 mg per 100 g of pulp, dry basis); and cereja-do-Rio-Grande and grumixama are abundant sources of anthocyanins. Although they are still underexplored, several in vitro and in vivo studies with different parts of the fruits, including the peel, seed, and pulp, indicate their health potential through anti-oxidative, anti-obesity, antihyperglycemic, antidyslipidemic, antimicrobial, and/or anticancer effects. All things considered, the focus of this research was to highlight the bioactive potential and health impact of native fruits from the Amazon and Atlantic Forest biomes.


Assuntos
Arecaceae , Florestas , Frutas , Myrtaceae , Frutas/química , Brasil , Humanos , Myrtaceae/química , Arecaceae/química , Eugenia/química , Compostos Fitoquímicos/análise , Antioxidantes/análise , Antioxidantes/farmacologia , Extratos Vegetais/química
13.
Food Res Int ; 184: 114241, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38609221

RESUMO

This review aimed to critically and comparatively analyze the physicochemical, proximate, nutritional, phytochemical composition, and bioactivities of araticum (Annona crassiflora Mart.) (AAc), a fruit from the Brazilian Cerrado. Additionally, the potential applications of this fruit in the food industry were reviewed. Data and information were collected from the Scopus, Web of Science, and Google Scholar databases. AAc, a fruit mainly studied in the Brazilian regions of Minas Gerais and Goiás, has well-documented physicochemical, proximate, and nutritional characteristics. It is rich in fiber, sugars, vitamins A and C, minerals, and oil, making it attractive to the food industry. However, there are research gaps, such as the impact of climatic conditions on the AAc chemical composition. Additional studies are needed, especially for the peel and seeds, and investigations of pre-treatments effect on the chemical composition are recommended. The application of AAc in food products is mainly limited to pulp, but there is potential for using peels and seeds. AAc is a rich source of phytochemical compounds with various biological properties, such as antioxidants, hepatoprotective, and antimicrobial activities. Future studies should explore other phytochemicals present in the fruit beyond phenolic compounds. The consumption of AAc can contribute to combating food insecurity malnutrition, and promoting the conservation of the Brazilian Cerrado.


Assuntos
Annona , Indústria Alimentícia , Frutas , Sementes , Compostos Fitoquímicos
14.
Res Dev Disabil ; 149: 104742, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38678875

RESUMO

BACKGROUND: Autistic features and sensory processing difficulties and their phenotypic co-expression with alexithymia share a transdiagnostic vulnerability. In this work, we explored whether the current concept of broad autism phenotype rather translates altered sensory processing (non-specific to autism), meaning that the characteristics of altered sensory processing should be overexpressed among individuals with heightened vulnerability to sensory processing atypicalities (parents of children with sensorial processing disorder, or SPD parents) and individuals with heightened vulnerability to autistic traits (parents of children with autism spectrum disorders, or ASD parents). In addition, the association between altered sensory processing and alexithymia was inspected. METHOD: The Adolescent/Adult Sensory Profile, Autism Spectrum Quotient, and Toronto Alexithymia Scale were completed by 31 parents of children with ASD, 32 parents of children with SPD, and 52 parents of typically developed (TD) children. RESULTS: Extreme sensory patterns were overexpressed both in parents of children with SPD and parents of children with ASD when compared to parents of TD children. In addition, extreme sensory patterns were significantly associated with alexithymia scores. Specifically, sensory avoidance, low registration, and sensory sensitivity were positively correlated with alexithymia. No significant differences were found regarding the proportion of autistic traits and alexithymia between ASD and SPD groups of parents. CONCLUSIONS: These results challenge the specificity of broad autism phenotype and suggest a neurodevelopmental atypicity with roots in altered sensory and emotional processing.


Assuntos
Sintomas Afetivos , Transtorno do Espectro Autista , Pais , Humanos , Sintomas Afetivos/fisiopatologia , Sintomas Afetivos/psicologia , Transtorno do Espectro Autista/psicologia , Transtorno do Espectro Autista/fisiopatologia , Masculino , Feminino , Pais/psicologia , Criança , Adolescente , Adulto , Transtornos de Sensação/fisiopatologia , Transtornos de Sensação/psicologia , Estudos de Casos e Controles , Pessoa de Meia-Idade
15.
Microorganisms ; 12(4)2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38674664

RESUMO

The SARS-CoV-2 P.1 variant, responsible for an outbreak in Manaus, Brazil, is distinguished by 12 amino acid differences in the S protein, potentially increasing its ACE-2 affinity and immune evasion capability. We investigated the innate immune response of this variant compared to the original B.1 strain, particularly concerning cytokine production. Blood samples from three severe COVID-19 patients were analyzed post-infection with both strains. Results showed no significant difference in cytokine production of mononuclear cells and neutrophils for either variant. While B.1 had higher cytopathogenicity, neither showed viral replication in mononuclear cells. Structural analyses of the S protein highlighted physicochemical variations, which might be linked to the differences in infectivity between the strains. Our studies point to the increased infectivity of P.1 could stem from altered immunogenicity and receptor-binding affinity.

16.
Am J Physiol Heart Circ Physiol ; 326(5): H1193-H1203, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38334973

RESUMO

Pressure overload-induced hypertrophy compromises cardiac stretch-induced compliance (SIC) after acute volume overload (AVO). We hypothesized that SIC could be enhanced by physiological hypertrophy induced by pregnancy's chronic volume overload. This study evaluated SIC-cardiac adaptation in pregnant women with or without cardiovascular risk (CVR) factors. Thirty-seven women (1st trimester, 1stT) and a separate group of 31 (3rd trimester, 3rdT) women [healthy or with CVR factors (obesity and/or hypertension and/or with gestational diabetes)] underwent echocardiography determination of left ventricular end-diastolic volume (LVEDV) and E/e' before (T0), immediately after (T1), and 15 min after (T2; SIC) AVO induced by passive leg elevation. Blood samples for NT-proBNP quantification were collected before and after the AVO. Acute leg elevation significantly increased inferior vena cava diameter and stroke volume from T0 to T1 in both 1stT and 3rdT, confirming AVO. LVEDV and E/e' also increased immediately after AVO (T1) in both 1stT and 3rdT. SIC adaptation (T2, 15 min after AVO) significantly decreased E/e' in both trimesters, with additional expansion of LVEDV only in the 1stT. NT-pro-BNP increased slightly after AVO but only in the 1stT. CVR factors, but not parity or age, significantly impacted SIC cardiac adaptation. A distinct functional response to SIC was observed between 1stT and 3rdT, which was influenced by CVR factors. The LV of 3rdT pregnant women was hypertrophied, showing a structural limitation to dilate with AVO, whereas the lower LV filling pressure values suggest increased diastolic compliance.NEW & NOTEWORTHY The sudden increase of volume overload triggers an acute myocardial stretch characterized by an immediate rise in contractility by the Frank-Starling mechanism, followed by a progressive increase known as the slow force response. The present study is the first to characterize echocardiographically the stretch-induced compliance (SIC) mechanism in the context of physiological hypertrophy induced by pregnancy. A distinct functional adaptation to SIC was observed between first and third trimesters, which was influenced by cardiovascular risk factors.


Assuntos
Adaptação Fisiológica , Fatores de Risco de Doenças Cardíacas , Humanos , Feminino , Gravidez , Adulto , Função Ventricular Esquerda , Cardiomegalia/fisiopatologia , Cardiomegalia/diagnóstico por imagem , Cardiomegalia/etiologia , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Complicações Cardiovasculares na Gravidez/fisiopatologia , Complicações Cardiovasculares na Gravidez/diagnóstico por imagem , Complicações Cardiovasculares na Gravidez/sangue , Volume Sistólico , Terceiro Trimestre da Gravidez , Diabetes Gestacional/fisiopatologia , Complacência (Medida de Distensibilidade) , Primeiro Trimestre da Gravidez , Obesidade/fisiopatologia , Obesidade/complicações , Fatores de Risco
17.
Res Sq ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38410476

RESUMO

Clinical data revealed that KRAS mutant tumors, while initially sensitive to treatment, rapidly bypass KRAS dependence to acquire a drug-tolerant phenotype. However, the mechanisms underlying the transition from a drug-sensitive to a drug-tolerant state still elude us. Here, we show that global chromatin reorganization is a recurrent and specific feature of KRAS-dependent cells that tolerated KRAS silencing. We show that KRAS-dependent cells undergo G0/G1 cell cycle arrest after KRAS silencing, presenting a transcriptomic signature of quiescence. Proteomic analysis showed upregulated chromatin-associated proteins and transcription-associated biological processes. Accordingly, these cells shifted euchromatin/heterochromatin states, gained topologically associating domains, and altered the nanoscale physical organization of chromatin, more precisely by downregulating chromatin packing domains, a feature associated with the induction of quiescence. In addition, they also accumulated transcriptional alterations over time leading to a diversification of biological processes, linking chromatin alterations to transcriptional performance. Overall, our observations pinpoint a novel molecular mechanism of tolerance to KRAS oncogenic loss driven not by specific gene alterations but by global reorganization of genomic information, in which cells transition chromatin domain structure towards a more quiescent state and gain transcriptional reprogramming capacity.

18.
Int J Mol Sci ; 25(4)2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38396644

RESUMO

Germline variants in the FOXE1 transcription factor have been associated with thyroid ectopy, cleft palate (CP) and thyroid cancer (TC). Here, we aimed to clarify the role of FOXE1 in Portuguese families (F1 and F2) with members diagnosed with malignant struma ovarii (MSO), an ovarian teratoma with ectopic malignant thyroid tissue, papillary TC (PTC) and CP. Two rare germline heterozygous variants in the FOXE1 promoter were identified: F1) c.-522G>C, in the proband (MSO) and her mother (asymptomatic); F2) c.9C>T, in the proband (PTC), her sister and her mother (CP). Functional studies using rat normal thyroid (PCCL3) and human PTC (TPC-1) cells revealed that c.9C>T decreased FOXE1 promoter transcriptional activity in both cell models, while c.-522G>C led to opposing activities in the two models, when compared to the wild type. Immunohistochemistry and RT-qPCR analyses of patients' thyroid tumours revealed lower FOXE1 expression compared to adjacent normal and hyperplastic thyroid tissues. The patient with MSO also harboured a novel germline AXIN1 variant, presenting a loss of heterozygosity in its benign and malignant teratoma tissues and observable ß-catenin cytoplasmic accumulation. The sequencing of the F1 (MSO) and F2 (PTC) probands' tumours unveiled somatic BRAF and HRAS variants, respectively. Germline FOXE1 and AXIN1 variants might have a role in thyroid ectopy and cleft palate, which, together with MAPK pathway activation, may contribute to tumours' malignant transformation.


Assuntos
Fissura Palatina , Cisto Dermoide , Fatores de Transcrição Forkhead , Neoplasias Ovarianas , Estruma Ovariano , Neoplasias da Glândula Tireoide , Animais , Feminino , Humanos , Ratos , Fissura Palatina/genética , Cisto Dermoide/genética , Fatores de Transcrição Forkhead/genética , Neoplasias Ovarianas/metabolismo , Estruma Ovariano/genética , Estruma Ovariano/metabolismo , Estruma Ovariano/patologia , Neoplasias da Glândula Tireoide/patologia
19.
Rheumatol Adv Pract ; 8(1): rkae013, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38384323

RESUMO

Objectives: To compare the prevalence of anxiety and depression in patients with GCA with that in the general population, using the Hospital Anxiety and Depression Scale (HADS), and to identify independent predictors of these psychiatric manifestations in patients with GCA. Methods: We conducted a cross-sectional study including all patients diagnosed with GCA followed during 1 year in a vasculitis outpatient clinic. The HADS and 36-item Short Form (SF-36) questionnaires were prospectively collected. Patients' HADS results were compared with an age- and gender-matched control group. HADS anxiety (HADS-A) and HADS depression (HADS-D) scores between 8 and 10 defined possible anxiety and depression and ≥11 defined probable anxiety and depression, respectively. Results: We included 72 patients and 288 controls. Compared with controls, patients with GCA had a statistically significant higher prevalence of HADS-A ≥8 (48.6% vs 26.4%), HADS-A ≥11 (30.6% vs 12.2%) and HADS-D ≥11 (33.3% vs 18.1%). GCA was an independent predictor of HADS-A ≥8 [odds ratio (OR) 3.3 (95% CI 1.9, 5.9)], HADS-A ≥11 [OR 3.8 (95% CI 2.0, 7.4)] and HADS-D ≥11 [OR 2.6 (95% CI 1.4, 4.7)]. Among patients with GCA, a negative correlation was observed between HADS-A/D and SF-36 mental health scores (r = -0.780 and r = -0.742, respectively). Glucocorticoid therapy was a predictor of HADS-A ≥8 [OR 10.4 (95% CI 1.2, 94.2)] and older age of HADS-D ≥8 [OR 1.2 (95% CI 1.1, 1.3)] and HADS-D ≥11 [OR 1.1 (95% CI 1.0, 1.2)]. Conclusions: Compared with the general population, patients with GCA have a higher prevalence of anxiety and depression and GCA is an independent predictor of these symptoms. Glucocorticoid treatment and older age are predictors of anxiety and depression, respectively, in patients with GCA.

20.
Cureus ; 16(1): e52867, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38406024

RESUMO

Membranous glomerulonephritis is the leading cause of nephrotic syndrome in non-diabetic Caucasian adults. For patients at risk of progressing to end-stage renal disease, immunosuppression, particularly rituximab, is the recommended treatment. While extremely rare, cases of cystoid macular edema associated with rituximab have been documented in the literature. In this report, we present the case of a 54-year-old male with membranous glomerulonephritis at a high risk of progressing to end-stage renal disease who experienced cystoid macular edema hours after receiving rituximab infusion. Following the discontinuation of the medication, the patient spontaneously recovered visual acuity without the need for any targeted therapy.

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