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1.
Cell ; 181(7): 1547-1565.e15, 2020 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-32492405

RESUMO

Homeostasis of neural firing properties is important in stabilizing neuronal circuitry, but how such plasticity might depend on alternative splicing is not known. Here we report that chronic inactivity homeostatically increases action potential duration by changing alternative splicing of BK channels; this requires nuclear export of the splicing factor Nova-2. Inactivity and Nova-2 relocation were connected by a novel synapto-nuclear signaling pathway that surprisingly invoked mechanisms akin to Hebbian plasticity: Ca2+-permeable AMPA receptor upregulation, L-type Ca2+ channel activation, enhanced spine Ca2+ transients, nuclear translocation of a CaM shuttle, and nuclear CaMKIV activation. These findings not only uncover commonalities between homeostatic and Hebbian plasticity but also connect homeostatic regulation of synaptic transmission and neuronal excitability. The signaling cascade provides a full-loop mechanism for a classic autoregulatory feedback loop proposed ∼25 years ago. Each element of the loop has been implicated previously in neuropsychiatric disease.


Assuntos
Canais de Potássio Ativados por Cálcio de Condutância Alta/metabolismo , Potenciação de Longa Duração/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Proteínas de Ligação a RNA/metabolismo , Potenciais de Ação/fisiologia , Processamento Alternativo/genética , Processamento Alternativo/fisiologia , Animais , Proteína Quinase Tipo 1 Dependente de Cálcio-Calmodulina/metabolismo , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Feminino , Células HEK293 , Homeostase/fisiologia , Humanos , Canais de Potássio Ativados por Cálcio de Condutância Alta/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso/fisiologia , Antígeno Neuro-Oncológico Ventral , Plasticidade Neuronal/fisiologia , Neurônios/metabolismo , Proteínas de Ligação a RNA/fisiologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Sinapses/metabolismo , Transmissão Sináptica/fisiologia
2.
Cell ; 169(5): 836-848.e15, 2017 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-28525754

RESUMO

Myriad experiences produce transient memory, yet, contingent on the internal state of the organism and the saliency of the experience, only some memories persist over time. How experience and internal state influence the duration of memory at the molecular level remains unknown. A self-assembled aggregated state of Drosophila Orb2A protein is required specifically for long-lasting memory. We report that in the adult fly brain the mRNA encoding Orb2A protein exists in an unspliced non-protein-coding form. The convergence of experience and internal drive transiently increases the spliced protein-coding Orb2A mRNA. A screen identified pasilla, the fly ortholog of mammalian Nova-1/2, as a mediator of Orb2A mRNA processing. A single-nucleotide substitution in the intronic region that reduces Pasilla binding and intron removal selectively impairs long-term memory. We posit that pasilla-mediated processing of unspliced Orb2A mRNA integrates experience and internal state to control Orb2A protein abundance and long-term memory formation.


Assuntos
Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Íntrons , Memória de Longo Prazo , Ribonucleoproteínas/metabolismo , Fatores de Transcrição/genética , Fatores de Poliadenilação e Clivagem de mRNA/genética , Animais , Sequência de Bases , Comportamento Animal , Encéfalo/metabolismo , Condicionamento Psicológico , Proteínas de Drosophila/química , Drosophila melanogaster/genética , Aprendizagem , Modelos Animais , Motivação , Mutação , Isoformas de Proteínas/metabolismo , Splicing de RNA , Fatores de Transcrição/química , Fatores de Transcrição/metabolismo , Fatores de Poliadenilação e Clivagem de mRNA/química , Fatores de Poliadenilação e Clivagem de mRNA/metabolismo
3.
Proc Natl Acad Sci U S A ; 121(10): e2314695121, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38416679

RESUMO

NOVA1 is a neuronal RNA-binding protein identified as the target antigen of a rare autoimmune disorder associated with cancer and neurological symptoms, termed paraneoplastic opsoclonus-myoclonus ataxia. Despite the strong association between NOVA1 and cancer, it has been unclear how NOVA1 function might contribute to cancer biology. In this study, we find that NOVA1 acts as an oncogenic factor in a GBM (glioblastoma multiforme) cell line established from a patient. Interestingly, NOVA1 and Argonaute (AGO) CLIP identified common 3' untranslated region (UTR) targets, which were down-regulated in NOVA1 knockdown GBM cells, indicating a transcriptome-wide intersection of NOVA1 and AGO-microRNA (miRNA) targets regulation. NOVA1 binding to 3'UTR targets stabilized transcripts including those encoding cholesterol homeostasis related proteins. Selective inhibition of NOVA1-RNA interactions with antisense oligonucleotides disrupted GBM cancer cell fitness. The precision of our GBM CLIP studies point to both mechanism and precise RNA sequence sites to selectively inhibit oncogenic NOVA1-RNA interactions. Taken together, we find that NOVA1 is commonly overexpressed in GBM, where it can antagonize AGO2-miRNA actions and consequently up-regulates cholesterol synthesis, promoting cell viability.


Assuntos
Glioblastoma , MicroRNAs , Humanos , Glioblastoma/genética , Glioblastoma/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , MicroRNAs/genética , Homeostase/genética , Colesterol , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Antígeno Neuro-Oncológico Ventral
4.
Annu Rev Nutr ; 44(1): 383-404, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39207876

RESUMO

Our aim was to conduct an umbrella review of evidence from meta-analyses of observational studies investigating the link between sugar-sweetened beverage consumption and human health outcomes. Using predefined evidence classification criteria, we evaluated evidence from 47 meta-analyses encompassing 22,055,269 individuals. Overall, 79% of these analyses indicated direct associations between greater sugar-sweetened beverage consumption and higher risks of adverse health outcomes. Convincing evidence (class I) supported direct associations between sugar-sweetened beverage consumption and risks of depression, cardiovascular disease, nephrolithiasis, type 2 diabetes mellitus, and higher uric acid concentrations. Highly suggestive evidence (class II) supported associations with risks of nonalcoholic fatty liver disease and dental caries. Out of the remaining 40 meta-analyses, 29 were graded as suggestive or weak in the strength of evidence (classes III and IV), and 11 showed no evidence (class V). These findings inform and provide support for population-based and public health strategies aimed at reducing sugary drink consumption for improved health.


Assuntos
Bebidas Adoçadas com Açúcar , Humanos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Cárie Dentária/epidemiologia , Cárie Dentária/prevenção & controle , Cárie Dentária/etiologia , Depressão/epidemiologia , Depressão/etiologia , Depressão/prevenção & controle , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/prevenção & controle , Metanálise como Assunto , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Estudos Observacionais como Assunto , Bebidas Adoçadas com Açúcar/efeitos adversos , Bebidas Adoçadas com Açúcar/estatística & dados numéricos
5.
Diabetologia ; 67(10): 2225-2235, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39001935

RESUMO

AIMS/HYPOTHESIS: Understanding the impact of the overall construct of ultra-processed foods on diabetes risk can inform dietary approaches to diabetes prevention. In this study, we aimed to evaluate the association between ultra-processed food consumption and risk of diabetes in a community-based cohort of middle-aged adults in the USA. We hypothesised that a higher intake of ultra-processed foods is associated with a higher risk of incident diabetes. METHODS: The study included 13,172 participants without diabetes at baseline (1987-1989) in the Atherosclerosis Risk in Communities (ARIC) study. Dietary intake was assessed with a 66-item semiquantitative food frequency questionnaire, and foods were categorised by processing level using the Nova classification system. Ultra-processed food was analysed categorically (quartiles of energy-adjusted intake) and continuously (per one additional serving/day). We used Cox regression to evaluate the association of ultra-processed food intake with risk of diabetes with adjustment for sociodemographic characteristics, total energy intake, health behaviours and clinical factors. RESULTS: Over a median follow-up of 21 years, there were 4539 cases of incident diabetes. Participants in the highest quartile of ultra-processed food intake (8.4 servings/day on average) had a significantly higher risk of diabetes (HR 1.13; 95% CI 1.03, 1.23) compared with participants in the lowest quartile of intake after adjustment for sociodemographic, lifestyle and clinical factors. Each additional serving of ultra-processed food consumed daily was associated with a 2% higher risk of diabetes (HR 1.02; 95% CI 1.00, 1.04). Highest quartile consumption of certain ultra-processed food groups, including sugar- and artificially sweetened beverages, ultra-processed meats and sugary snacks, was associated with a 29%, 21% and 16% higher risk of diabetes, respectively, compared with the lowest quartile. CONCLUSIONS/INTERPRETATION: We found that a higher intake of ultra-processed food was associated with higher risk of incident diabetes, particularly sugar- and artificially sweetened beverages, ultra-processed meats and sugary snacks. Our findings suggest interventions reducing ultra-processed food consumption and specific food groups may be an effective strategy for diabetes prevention.


Assuntos
Fast Foods , Humanos , Pessoa de Meia-Idade , Masculino , Feminino , Estudos Prospectivos , Fast Foods/efeitos adversos , Fatores de Risco , Diabetes Mellitus/epidemiologia , Manipulação de Alimentos , Ingestão de Energia , Estudos de Coortes , Dieta , Alimento Processado
6.
Artigo em Inglês | MEDLINE | ID: mdl-38759823

RESUMO

BACKGROUND & AIMS: Ultra-processed foods (UPFs) may have a negative impact on bowel habits. We aimed to assess the association between UPF and unprocessed or minimally processed food (MPF) intake and bowel habits among adults in the United States (U.S.). METHODS: We performed a cross-sectional study using data from the National Health and Nutrition Examination Survey (2005-2010). We used two 24-hour dietary recalls and, based on the Nova classification, calculated intakes of UPFs and MPFs. Constipation and diarrhea were defined using the Bristol Stool Form Scale and stool frequency. We performed survey-weighted logistic regression and substitution analysis to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Among 12,716 U.S. adults, there were 1290 cases of constipation and 1067 cases of diarrhea. Median UPF and MPF intakes were 26.5% and 66.2% of total grams per day, respectively. Greater UPF consumption (in % gram/d) was associated with higher odds of constipation (adjusted OR [aORQ4 vs Q1], 2.20; 95% CI, 1.76-2.74) (Ptrend < .001) but not diarrhea (aORQ4 vs Q1, 0.82; 95% CI, 0.62-1.09) (Ptrend = .12). Increased MPF consumption was associated with lower odds of constipation (aORQ4 vs Q1, 0.46; 95% CI, 0.370-0.57) (Ptrend < .001). Associations with constipation were attenuated after adjusting for diet quality (aORQ4 vs Q1, UPF, 1.53; MPF, 0.69). Substituting 10% of UPF intake with an equivalent proportion of MPFs was associated with lower odds of constipation (aOR, 0.90; 95% CI, 0.87-0.93). CONCLUSIONS: UPF intake was associated with higher odds of constipation, whereas the odds were lower with greater MPF consumption. The effect of food processing on bowel habits was independent of diet quality.

7.
J Nutr ; 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39128546

RESUMO

BACKGROUND: Interest in plant-based eating has increased alongside increased variety and availability of highly processed plant-based meat and dairy alternatives. The impact of the shifting commercial landscape and public interest in plant-based eating on dietary intake is unknown. OBJECTIVES: To examine trends in the consumption and composition of plant-based diets in the United States adults. METHODS: Serial cross-sectional data from the National Health and Nutrition Examination Survey were used to assess trends in the proportion of United States adults aged ≥20 y consuming a plant-based diet (defined as ≥50% total protein from plants on a 24-h dietary recall) from 1999-2000 to 2017-March 2020 (n = 51,698). Trends in processing level (percentage energy intake from ultraprocessed foods) and diet quality [Healthy Eating Index (HEI)-2020 scores] were assessed in the subset of adults consuming plant-based diets (n = 8327). RESULTS: The proportion of United States adults consuming plant-based diets increased from 14.4% (95% CI: 12.9%, 16.0%) to 17.2% (95% confidence interval [CI]: 15.5%, 19.1%; P = 0.005 for trend). In all survey cycles, ultraprocessed foods accounted for the majority of energy intake, and ultraprocessed food intake in plant-based diets did not significantly change over time [50.7% kcal (95% CI: 47.3%, 54.1%) in 1999-2000 compared with 52.7% kcal (95% CI: 49.7%, 55.6%) in 2017-March 2020; P for trend = 0.34]. The quality of plant-based diets, measured by HEI-2020 scores, improved from 52.1 (95% CI: 49.7, 54.6) to 55.8 (95% CI: 54.1, 57.5; P for trend <0.001). CONCLUSIONS: Between 1999 and March 2020, the proportion of United States adults consuming a plant-based diet increased. Among people consuming plant-based diets, ultraprocessed foods contributed most to energy intake and there was no sustained change in intake over time. The mean diet quality was low but improved modestly.

8.
J Nutr ; 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39299474

RESUMO

BACKGROUND: There is a need to understand the underlying biological mechanisms through which ultra-processed foods negatively affect health. Proteomics offers a valuable tool with which to examine different aspects of ultra-processed foods and their impact on health. OBJECTIVES: The aim of this study was to identify protein biomarkers of usual ultra-processed food consumption and assess their relation to the incidence of coronary heart disease (CHD), chronic kidney disease (CKD), and all-cause mortality risk. METHODS: A total of 9361 participants from the Atherosclerosis Risk in Communities visit 3 (1993-1995) were included. Dietary intake was assessed using a 66-item food-frequency questionnaire and the processing levels were categorized on the basis of the Nova classification. Plasma proteins were detected using an aptamer-based proteomic assay. We used multivariable linear regressions to examine the association between ultra-processed food and proteins, and Cox proportional hazard models to identify associations between ultra-processed food-related proteins and health outcomes. Models extensively controlled for sociodemographic characteristics, health behaviors, and clinical factors. RESULTS: Eight proteins (6 positive, 2 negative) were identified as significantly associated with ultra-processed food consumption. Over a median follow-up of 22 y, there were 1276, 3084, and 5127 cases of CHD, CKD, and death, respectively. Three, 5, and 3 ultra-processed food-related proteins were associated with each outcome, respectively. One protein (ß-glucuronidase) was significantly associated with a higher risk of all 3 outcomes, and 3 proteins (receptor-type tyrosine-protein phosphatase U, C-C motif chemokine 25, and twisted gastrulation protein homolog 1) were associated with a higher risk of 2 outcomes. CONCLUSIONS: We identified a panel of protein biomarkers that were significantly associated with ultra-processed food consumption. These proteins may be considered potential biomarkers for ultra-processed food intake and may elucidate the biological processes through which ultra-processed foods impact health outcomes.

9.
J Nutr ; 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38735573

RESUMO

OBJECTIVE: This study aimed to investigate the association between consumption of ultra-processed foods (UPFs) and leucocyte telomere length (LTL). METHODS: This cross-sectional study utilized data from the UK Biobank, including a total of 64,690 participants. LTL was measured using Q-PCR with natural logarithmic conversion and Z-score normalization. Dietary data were collected through a 24-hour recall questionnaire from 2009 to 2010. UPFs were identified using the Nova food classification and analyzed as either a continuous or categorical variable respectively. Multiple linear regression models were employed to analyze the association between UPF consumption and LTL. RESULTS: The included participants had an average age of 56.26 years, of whom 55.2% were female. After adjusting for sociodemographic, lifestyle-related and anthropometric variables, LTL exhibited a decrease of 0.005 (95% CI: -0.007, -0.002) with one UPF serving/day increase. Compared to participants consuming ≤ 3.5 servings/day, those consuming 3.5 to < 6, 6 to ≤ 8 and > 8 servings/day showed a shortening of LTL by 0.025 (95% CI: -0.047, -0.004), 0.034 (95% CI: -0.055, -0.012) and 0.038 (95% CI: -0.062, -0.015), respectively (P for trend = 0.001). Subgroup analyses by UPF subclasses revealed that consumption of ready-to-eat/heated food (ß = -0.008, 95% CI: -0.014, -0.002), beans and potatoes (ß = -0.024, 95% CI: -0.039, -0.009), animal-based products (ß = -0.011, 95% CI: -0.019, -0.004), artificial sugar (ß = -0.014, 95% CI: -0.025, -0.004), and beverages (ß = -0.005, 95% CI: -0.009, -0.001) showed negative associations with LTL. Conversely, breakfast cereals (ß = 0.020, 95% CI: 0.004, 0.036) and vegetarian alternatives (ß = 0.057, 95% CI: 0.027, 0.086) showed positive correlations with LTL. CONCLUSIONS: Our study found that a higher consumption of total UPFs was associated with a shorter LTL. However, some subclass UPFs may be associated with longer LTL, depending on their nutritional composition.

10.
Crit Rev Food Sci Nutr ; : 1-9, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38363072

RESUMO

Recently, ultra-processed foods received a lot of attention, but also criticism. Our aim was to provide an overview of the existing evidence of ultra-processed food consumption on human health. We conducted a systematic search in four databases until January 5th, 2024. Systematic reviews with meta-analyses on ultra-processed food consumption as defined by the NOVA classification system were included. The certainty of evidence was evaluated by the GRADE approach. We identified 16 publications. Moderate certainty of evidence was found for all-cause mortality (Summary Risk Ratio per 50 g: 1.02; 95% confidence Interval (CI): 1.01, 1.03), cardiovascular disease incidence and mortality (per 50 g/d: 1.04; 95% CI: 1.02, 1.06, and 1.05; 95% CI: 1.01, 1.08), type 2 diabetes incidence (per 10%: 1.12; 95% CI: 1.10, 1.13) and colorectal cancer (per 10%: 1.04; 95% CI: 1.01, 1.07). For several outcomes such as inflammatory bowel diseases, obesity, metabolic syndrome, nonalcoholic fatty liver disease, mental health as well as nutrient quality, similar estimates were observed, but certainty of evidence was limited. Discussing the NOVA concept, it remains unclear whether the processing of foods leads to increased health risks or if ultra-processed food consumption is only a measure for poor diet quality.

11.
Br J Nutr ; 131(9): 1619-1632, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38220223

RESUMO

UK front of package labelling (FOPL) informs consumers on the nutrient content of food. However, FOPL does not consider food processing, and with the UK government being urged to act on ultra-processed food (UPF), whether UPF should be added to FOPL is unclear. This study compared food and drink in the UK National Diet and Nutrition Survey (NDNS) Intake24 database based on FOPL, nutrient content and NOVA classification, to understand whether UPF are covered by dietary recommendations for foods high in fat, salt and sugar. NDNS items were coded into minimally processed food (MPF), processed culinary ingredients, processed food and UPF according to the NOVA classification and FOPL traffic lights. UPF contained greater energy, fat, saturated fat (SF), total sugar (TS) and salt than MPF. UPF had a greater odds of containing red FOPL and an unhealthier overall FOPL score (OR:4·59 (95 % CI: 3·79, 5·57); OR:7·0 (95 % CI: 6·1, 8·2), respectively) and lower odds of containing green FOPL (OR:0·05 (95 % CI: 0·03, 0·10)), compared with MPFs. For items with no red FOPL, UPF still contained greater energy, fat, SF, TS and salt than MPF. However, several UPF have healthier FOPL scores. UPF had an unhealthier nutritional profile and FOPL score than MPF. For items with no red FOPL, UPF still had an unhealthier profile than MPF, with a higher energy density. Importantly, not all UPF were unhealthy according to FOPL. These results indicate partial overlap between FOPL, nutrient content and NOVA classification of UK food and drink products, with implications for UK food and drink labelling.


Assuntos
Fast Foods , Manipulação de Alimentos , Rotulagem de Alimentos , Inquéritos Nutricionais , Valor Nutritivo , Reino Unido , Humanos , Fast Foods/classificação , Fast Foods/análise , Dieta , Nutrientes/análise , Política Nutricional , Gorduras na Dieta/análise
12.
Br J Nutr ; 131(8): 1461-1472, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38174358

RESUMO

The study evaluated the association between ultra-processed foods (UPF) and nutrient intake and identified the socio-demographic characteristics associated with UPF consumption among a nationally representative sample of middle-older adults. Dietary assessment was collected in 2013 using a validated FFQ. The Nova system was used to classify food and drinks into UPF. The percentage of dietary energy from UPF was calculated and used throughout the analyses, and average nutrient intake across quintiles of UPF was evaluated. The determinants associated with the dietary caloric contribution of UPF intake were investigated using linear regression models. A cross-sectional analysis of a nationally representative study of Americans over the age of 50, the Health and Retirement Study, was conducted. The analysis included 6220 participants. The mean age was 65 (se 0·28) years, with 55 % being female. UPF intake accounted for 51 % (se 0·25) of total intake. An increase in the percentage of (%UPF) consumption was correlated with an increase in calories, carbohydrates, saturated fat and sugar, and a decrease in fibre, vitamins and minerals. %UPF intake was inversely associated with being Hispanic, higher income, physical activity, vegetarian diet and Mediterranean diet but positively associated with very low food insecurity. UPF represented half of the calories consumed. A higher %UPF intake was associated with a lower nutrient profile, suggesting decreasing %UPF intake as a strategy to improve the nutritional quality of middle-older adults. A few socio-demographic factors were associated with %UPF, which would help in planning strategies to reduce UPF consumption.


Assuntos
Fast Foods , Alimento Processado , Humanos , Feminino , Idoso , Masculino , Estudos Transversais , Manipulação de Alimentos , Dieta , Ingestão de Energia
13.
Curr Oncol Rep ; 26(3): 221-235, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38319507

RESUMO

PURPOSE OF REVIEW: The eastern provinces of Canada exhibit a heightened prevalence and mortality rate of lung cancer compared to their western counterparts. While established risk factors for lung cancer exist in Canada, there remains ambiguity regarding the underlying provincial and territorial trends. This review aims to identify and analyze potential contributors to healthcare inequality, guiding policymakers towards a strategic and sustainable approach at the provincial level. RECENT FINDINGS: Existing studies emphasize the significant roles played by socio-economic and environmental factors in influencing lung cancer disparities across Canadian provinces. However, a noticeable research gap persists, particularly in systematically examining the factors that amplify geographical disparities in lung cancer incidence and mortality rates within Canada. This review underscores the disparities in lung cancer prevalence and mortality rates between eastern and western Canadian provinces. While socio-economic and environmental factors have been identified as influential, there is an evident need for further research to comprehensively understand and address the underlying contributors to these geographical discrepancies.


Assuntos
Neoplasias Pulmonares , Humanos , Canadá/epidemiologia , Neoplasias Pulmonares/epidemiologia , Fatores de Risco , Incidência , Disparidades em Assistência à Saúde
14.
Mol Biol Rep ; 51(1): 233, 2024 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-38282049

RESUMO

Dravet syndrome is a severe form of epilepsy characterised by recurrent seizures and cognitive impairment. It is mainly caused by variant in the SCN1A gene in 90% of cases, which codes for the α subunit of the voltage-gated sodium channel. In this study, we present one suspected case of Dravet syndrome in Moroccan child that underwent exome analysis and were confirmed by Sanger sequencing. The variant was identified in the SCN1A gene, and is a new variant that has never been described in the literature. The variant was found de nova in our case, indicating that it was not inherited from the parents. The variant, SCN1A c.965-2A>G p.(?), is located at the splice site and results in an unknown modification of the protein. This variant is considered pathogenic on the basis of previous studies. These results contribute to our knowledge of the SCN1A gene mutations associated with Dravet syndrome and underline the importance of genetic analysis in the diagnosis and confirmation of this disorder. Further studies are needed to better understand the functional consequences of this variant and its implications for therapeutic strategies in Dravet syndrome.


Assuntos
Epilepsias Mioclônicas , Epilepsia , Criança , Humanos , Epilepsias Mioclônicas/genética , Epilepsias Mioclônicas/diagnóstico , Canal de Sódio Disparado por Voltagem NAV1.1/genética , Epilepsia/genética , Mutação/genética , Análise de Sequência , Convulsões
15.
Eur J Nutr ; 63(2): 377-396, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37989797

RESUMO

PURPOSE: To investigate the role of adiposity in the associations between ultra-processed food (UPF) consumption and head and neck cancer (HNC) and oesophageal adenocarcinoma (OAC) in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: Our study included 450,111 EPIC participants. We used Cox regressions to investigate the associations between the consumption of UPFs and HNC and OAC risk. A mediation analysis was performed to assess the role of body mass index (BMI) and waist-to-hip ratio (WHR) in these associations. In sensitivity analyses, we investigated accidental death as a negative control outcome. RESULTS: During a mean follow-up of 14.13 ± 3.98 years, 910 and 215 participants developed HNC and OAC, respectively. A 10% g/d higher consumption of UPFs was associated with an increased risk of HNC (hazard ratio [HR] = 1.23, 95% confidence interval [CI] 1.14-1.34) and OAC (HR = 1.24, 95% CI 1.05-1.47). WHR mediated 5% (95% CI 3-10%) of the association between the consumption of UPFs and HNC risk, while BMI and WHR, respectively, mediated 13% (95% CI 6-53%) and 15% (95% CI 8-72%) of the association between the consumption of UPFs and OAC risk. UPF consumption was positively associated with accidental death in the negative control analysis. CONCLUSIONS: We reaffirmed that higher UPF consumption is associated with greater risk of HNC and OAC in EPIC. The proportion mediated via adiposity was small. Further research is required to investigate other mechanisms that may be at play (if there is indeed any causal effect of UPF consumption on these cancers).


Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Neoplasias de Cabeça e Pescoço , Humanos , Adiposidade , Estudos Prospectivos , Alimento Processado , Análise de Mediação , Obesidade , Adenocarcinoma/epidemiologia , Adenocarcinoma/etiologia , Fast Foods/efeitos adversos , Dieta , Manipulação de Alimentos
16.
Eur J Nutr ; 63(6): 2367-2378, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38809325

RESUMO

PURPOSE: Consumption of ultra-processed foods (UPF) has increased despite potential adverse health effects. Recent studies showed an association between UPF consumption and some gastrointestinal disorders. We evaluated the association between UPF consumption and peptic ulcer disease (PUD) in a large Spanish cohort. METHODS: We conducted a prospective analysis of 18,066 participants in the SUN cohort, followed every two years. UPF was assessed at baseline and 10 years after. Cases of PUD were identified among participants reporting a physician-made diagnosis of PUD during follow-ups. Cases were only partially validated against medical records. Cox regression was used to assess the association between baseline UPF consumption and PUD risk. Based on previous findings and biological plausibility, socio-demographic and lifestyle variables, BMI, energy intake, Helicobacter pylori infection, gastrointestinal disorders, aspirin and analgesic use, and alcohol and coffee consumption were included as confounders.We fitted GEE with repeated dietary measurements at baseline and after 10 years of follow-up. Vanderweele's proposed E value was calculated to assess the sensitivity of observed associations to uncontrolled confounding. RESULTS: During a median follow-up of 12.2 years, we recorded 322 new PUD cases (1.56 cases/1000 person-years). Participants in the highest baseline tertile of UPF consumption had an increased PUD risk compared to participants in the lowest tertile (HR = 1.52, 95% CI: 1.15, 2.00, Ptrend=0.002). The E-values for the point estimate supported the observed association. The OR using repeated measurements of UPF intake was 1.39 (95% CI: 1.03, 1.87) when comparing extreme tertiles. CONCLUSION: The consumption of UPF is associated with an increased PUD risk.


Assuntos
Fast Foods , Úlcera Péptica , Humanos , Espanha/epidemiologia , Estudos Prospectivos , Feminino , Masculino , Úlcera Péptica/epidemiologia , Úlcera Péptica/etiologia , Pessoa de Meia-Idade , Incidência , Fast Foods/estatística & dados numéricos , Fast Foods/efeitos adversos , Adulto , Estudos de Coortes , Fatores de Risco , Dieta/estatística & dados numéricos , Dieta/métodos , Dieta/efeitos adversos , Seguimentos , Idoso , Manipulação de Alimentos/métodos , Alimento Processado
17.
Eur J Nutr ; 2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39180555

RESUMO

PURPOSE: Investigate the associations of ultra-processed foods (UPF) in healthful (hPDI) and unhealthful (uPDI) plant-based diets with all-cause mortality, greenhouse gas emissions (GHGE), and blue water consumption (BWC). METHODS: Analyses were based on 35,030 participants (20-70 years; 74% females) from the EPIC-NL cohort who were followed up from 1993 to 1997 through 2014. Plant-based diet indices (hPDI and uPDI) and UPF consumption were calculated from a validated FFQ, assessed at baseline. Cox proportional hazard and multiple linear regression models were used to estimate associations between combined quartiles of the PDI indices and UPF consumption. RESULTS: With lower hPDI and higher UPF diets as the reference, we observed the following. Risk estimates of all-cause mortality were 0.98 (95% CI: 0.83, 1.16) for lower UPF consumption, 0.86 (95% CI: 0.68, 1.08) for higher hPDI, and 0.78 (95% CI: 0.66, 0.89) for combined higher hPDI and lower UPF consumption. Results with the uPDI were inconclusive. Mean differences in GHGE and BWC were 1.4% (95% CI: 0.3, 2.4) and 1.6% (95% CI: -0.5, 3.7) for lower UPF consumption, -7.4% (95% CI: -8.6, -6.4) and 9.6% (95% CI: 7.2, 12.0) for higher hPDI, and - 6.8% (95% CI: -7.4, -6.1) and 13.1% (95% CI: 11.6, 14.8) for combined higher hPDI and lower UPF consumption. No apparent conflict between environmental impacts was observed for the uPDI; GHGE and BWC were lower for higher uPDI scores. CONCLUSION: Mortality risk and environmental impacts were mostly associated with the amount of plant-based foods and to a lesser extent UPF in the diet. Shifting to a more healthful plant-based diet could improve human health and reduce most aspects of environmental impact (GHGE, but not BWC) irrespective of UPF consumption.

18.
Nutr Neurosci ; 27(1): 42-54, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36989349

RESUMO

OBJECTIVES: To examine the association between high intakes of ultra-processed foods (UPF) and recurrence of depressive symptoms (DepS) in a Western non-Mediterranean country and its contribution to the overall diet-depression relationship. METHODS: Analyses were carried out on British participants from the Whitehall II cohort. Present analyses were restricted to white participants N = 4554 (74% men, mean age = 61; SD = 5.9). UPF consumption was estimated from a 127-item food frequency questionnaire using the NOVA classification, and cumulative average of UPF intakes (g/day) over 11 years of exposure (1991/1994-2002/2004) was computed. Recurrent DepS after measurement of UPF was defined as having two or more episodes of DepS (the Center for Epidemiologic Studies Depression Scale (CES-D) score ≥ 16 or antidepressants use) during four phases of follow-up (2002/2004-2015/2016). RESULTS: Over the follow-up, 588 (12.9%) cases of recurrent DepS were observed. After adjusting for socio-demographic factors, health behaviours and health status, participants in top quintile of UPF intakes [mean 33% of total daily intakes in grams] had 31% higher odds of recurrent DepS (odds ratio 1.31; 95% CI 1.04-1.64) compared to participants in the four lowest quintiles of UPF [mean 18.1% of total daily intakes in grams]. Additional analyses showed that associations between adherence to several diet quality measures and recurrent DepS were partially attenuated (17-27%) by UPF intakes. CONCLUSION: In this British population, high intakes of ultra-processed foods were associated with increased odds of recurrent depressive symptoms and contributed to the overall diet quality-depressive symptoms association.


Assuntos
Depressão , Alimento Processado , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , Estudos de Coortes , Depressão/epidemiologia , Fast Foods , Manipulação de Alimentos , Dieta
19.
Public Health Nutr ; 27(1): e112, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38557499

RESUMO

OBJECTIVE: This study aims to determine whether ultra-processed foods (UPFs) are being discussed in news media in Australia and whether this terminology, as described in the NOVA system, is being applied accurately. DESIGN: Interpretive content analysis of online and print media articles that mentioned UPFs from 2009 to 2023 in Australia. SETTING: Australia. PARTICIPANTS: Online and print media articles. RESULTS: A total of two hundred ninety-eight Australian media articles were captured. A substantial increase in the number of UPF articles was observed between 2017-2019 and 2021-2023. The UPF concept was inaccurately explained or defined in 32 % of the articles and was frequently used interchangeably with other descriptors, such as 'highly or heavily processed food', 'junk food', 'unhealthy food', 'packaged food' and 'discretionary food'. Most of the articles had a health focus; however, sustainability interest increased, particularly in the past 18 months. CONCLUSIONS: UPFs are increasingly being discussed in news media in Australia; however, the concept is still incorrectly presented in over a third of articles. This highlights the importance of improving the literacy about UPFs to ensure that messages are communicated in a way that is salient, accessible and accurate.


Assuntos
Manipulação de Alimentos , Meios de Comunicação de Massa , Humanos , Austrália , Alimentos , Fast Foods , Dieta
20.
Public Health Nutr ; 27(1): e180, 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39324345

RESUMO

OBJECTIVE: To characterise consumption of ultra-processed foods and drinks (UPF) across a range of socio-demographic characteristics of Canadians. DESIGN: Cross-sectional study. The national-level 2015 Canadian Community Health Survey-Nutrition provided data on all foods and drinks consumed on the previous day via a 24-hour dietary recall. All food items were classified according to the type of industrial processing using the NOVA system. Multivariable linear regression models examined associations between a range of socio-demographic characteristics and the mean energy contribution (% of total daily energy intake) from total UPF and UPF subgroups. SETTING: The ten Canadian provinces. PARTICIPANTS: Canadians aged 2 or older (n 20 103). RESULTS: UPF contributed, on average, nearly half (44·9 %) of total daily energy intake of Canadians. Children aged 6-12 and adolescents aged 13-18 consumed over half of total daily energy from UPF (adjusted means of 51·9 % and 50·7 %, respectively). Recent and long-term immigrants consumed a significantly lower share of energy from UPF (adjusted means of 42·2 % and 45·1 %, respectively) compared with non-immigrants (54·4 %), as did the food secure (42·8 %) v. those in moderately (48·1 %) or severely food-insecure households (50·8 %). More modest differences were observed for intake of total UPF and UPF subgroups by sex, education, income adequacy and region of residence. CONCLUSION: Levels of UPF consumption in 2015 in Canada were pervasive in all socio-demographic groups and highest among children and adolescents, non-immigrants and those living in food-insecure households. These findings can inform public health interventions to reduce UPF consumption and promote healthier diets in various socio-demographic groups.


Assuntos
Fast Foods , Fatores Socioeconômicos , Humanos , Canadá , Masculino , Feminino , Criança , Estudos Transversais , Adolescente , Adulto , Fast Foods/estatística & dados numéricos , Pré-Escolar , Adulto Jovem , Pessoa de Meia-Idade , Dieta/estatística & dados numéricos , Ingestão de Energia , Idoso , Manipulação de Alimentos , Inquéritos Nutricionais , Fatores Sociodemográficos , Alimento Processado
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