Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA.

Circulating tumour DNA (ctDNA) can be used to detect and profile residual tumour cells persisting after curative intent therapy1. The study of large patient cohorts incorporating longitudinal plasma sampling and extended follow-up is required to determine the role of ctDNA as a phylogenetic biomarker of relapse in early-stage non-small-cell lung cancer (NSCLC). Here we developed ctDNA methods tracking a median of 200 mutations identified in resected NSCLC tissue across 1,069 plasma samples collected from 197 patients enrolled in the TRACERx study2. A lack of preoperative ctDNA detection distinguished biologically indolent lung adenocarcinoma with good clinical outcome. Postoperative plasma analyses were interpreted within the context of standard-of-care radiological surveillance and administration of cytotoxic adjuvant therapy. Landmark analyses of plasma samples collected within 120 days after surgery revealed ctDNA detection in 25% of patients, including 49% of all patients who experienced clinical relapse; 3 to 6 monthly ctDNA surveillance identified impending disease relapse in an additional 20% of landmark-negative patients. We developed a bioinformatic tool (ECLIPSE) for non-invasive tracking of subclonal architecture at low ctDNA levels. ECLIPSE identified patients with polyclonal metastatic dissemination, which was associated with a poor clinical outcome. By measuring subclone cancer cell fractions in preoperative plasma, we found that subclones seeding future metastases were significantly more expanded compared with non-metastatic subclones. Our findings will support (neo)adjuvant trial advances and provide insights into the process of metastatic dissemination using low-ctDNA-level liquid biopsy.

Evolution of the Major Components of Innate Immunity in Animals.

Innate immunity is present in all animals. In this review, we explore the main conserved mechanisms of recognition and innate immune responses among animals. In this sense, we discuss the receptors, critical for binding to pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs); the downstream signaling proteins; and transcription factors that govern immune responses. We also highlight conserved inflammatory mediators that are induced after the recognition of DAMPs and PAMPs. At last, we discuss the mechanisms that are involved in the regulation and/or generation of reactive oxygen species (ROS), influencing immune responses, like heme-oxygenases (HOs).

Effects of front-of-package nutrition labelling systems on objective understanding and purchase intention in Panama: results from a multi-arm parallel-group randomised controlled trial.

OBJECTIVE: To assess the effect of different front-of-package (FOPL) schemes on the objective understanding of the nutritional content and intention to purchase products, in Panama. DESIGN: Single-blinded multi-arm parallel-group randomised controlled trial. SETTING: Supermarkets across Panama. Participants were exposed to two-dimensional images of 15 mock-up products presented at random and balanced orders. Participants assigned to the intervention groups were exposed to mock-ups featuring one FOPL scheme: black octagonal warning labels (OWL), traffic-light labelling (TFL), or guideline daily amounts (GDA). Control group was not exposed to any FOPL scheme. PARTICIPANTS: Adult supermarket shoppers (n=1200). Participants were blinded to group assignment. RESULTS: Similar number of participants were randomised to and analysed in each group: OWL (n=300), TFL (n=300), GDA (n=300), and control (n=300). The odds for choosing to purchase the least harmful or none of the options more often was the highest in the OWL group. Compared to the control group, two times higher in the OWL group (OR 2·13, 95% confidence interval 1·60-2·84), and 57% higher in the TFL (1·57, 1·40-2·56), with no changes in the GDA (0·97, 0·73-1·29). OWL also resulted in the highest odds for correctly identifying the least harmful option, and for correctly identifying a product with excessive amounts of sugars, sodium and/or saturated fats. CONCLUSIONS: OWL performed best in helping shoppers to correctly identify when a product contained excessive amounts of nutrients of concern, to correctly identify the least harmful option, and to decide to purchase the least harmful or none of the options, more often.

Double peroxidase and histone acetyltransferase AgTip60 maintain innate immune memory in primed mosquitoes.

Immune priming in Anopheles gambiae is mediated by the systemic release of a hemocyte differentiation factor (HDF), a complex of lipoxin A4 bound to Evokin, a lipid carrier. HDF increases the proportion of circulating granulocytes and enhances mosquito cellular immunity. Here, we show that Evokin is present in hemocytes and fat-body cells, and messenger RNA (mRNA) expression increases significantly after immune priming. The double peroxidase (DBLOX) enzyme, present in insects but not in vertebrates, is essential for HDF synthesis. DBLOX is highly expressed in oenocytes in the fat-body tissue, and these cells increase in number in primed mosquitoes. We provide direct evidence that the histone acetyltransferase AgTip60 (AGAP001539) is also essential for a sustained increase in oenocyte numbers, HDF synthesis, and immune priming. We propose that oenocytes may function as a population of cells that are reprogrammed, and orchestrate and maintain a broad, systemic, and long-lasting state of enhanced immune surveillance in primed mosquitoes.

Understanding the experiences of lung cancer patients during the COVID-19 pandemic: a qualitative interview study.

PURPOSE: The study explores experiences of lung cancer patients during COVID-19 and considers how changes to care delivery and personal lives affected patient needs. METHODS: Semi-structured telephone interviews were conducted to explore experiences of lung cancer patients during COVID-19. Interviews were audio-recorded, transcribed verbatim and analysed thematically. Interview participants were purposively selected based on age, gender, treatment status, timing of diagnosis (pre/post first COVID-19 lockdown) from a sample of lung cancer patients (any histological subtype/any cancer stage/any point in treatment) who had completed a questionnaire exploring how participants' lives were impacted by the pandemic and their thoughts on clinical care and remote communication. RESULTS: Thirty lung cancer patients who participated in the questionnaire study were approached and participated in an interview. Three themes were identified: (1) Adapting to new modes of communication (focusing on experiences of remote communication); (2) Experience of care delivery during the pandemic (describing how all aspects of care delivery had been affected); (3) Impact of the COVID-19 pandemic on quality of life (QOL) (focus on the psychological impact and feeling of reduced support). Themes 1 and 2 are heavily interlinked and both had bearing on patients' QOL experience. CONCLUSION: Lung cancer patients were impacted psychologically by changes to care delivery and changes in their personal life. The findings highlight some benefits to remote consultations but the stage of the treatment pathway and illness trajectory should be considered when determining if this is appropriate. Participants felt support from peers, family and friends was limited during the pandemic.

Endoparasites of the Iberian wolf (Canis lupus signatus) and mesocarnivores in Central Portugal.

At the end of the nineteenth century, massive population declines were observed in carnivores due to the emergence of infectious diseases. This study aims to investigate, by means of coprological analysis, the prevalence and intensity of the parasites that infect the endangered Iberian wolf Canis lupus signatus and two mesocarnivores (the red fox Vulpes vulpes and the stone marten Martes foina) in Central Portugal. In total, 67.2% of the samples screened were infected; Toxascaris leonina (40.6%) was the parasite with the highest prevalence, followed by Ancylostomatidae and Eimeria spp. (28.1%). Eimeria spp. was found in stone marten with the highest infection rate (37,800 OPG), followed by T. leonina (10,100 EPG) in a red fox sample. Moderate to high levels of parasitic infections were identified in 73.3% of red foxes from the western area. Our results highlight the possibility of cross-infection among these carnivore species and cross-contamination in the wildlife-livestock-human interface.

BASIDIN as a New Protein Effector of the Phytopathogen Causing Witche's Broom Disease in Cocoa.

The fungus Moniliophthora perniciosa secretes protein effectors that manipulate the physiology of the host plant, but few effectors of this fungus have had their functions confirmed. We performed functional characterization of a promising candidate effector of M. perniciosa. The inoculation of rBASIDIN at 4 µmol L-1 in the mesophyll of leaflets of Solanum lycopersicum caused symptoms of shriveling within 6 h without the presence of necrosis. However, when sprayed on the plant at a concentration of 11 µmol L-1, it caused wilting symptoms only 2 h after application, followed by necrosis and cell death at 48 h. rBASIDIN applied to Theobroma cacao leaves at the same concentration caused milder symptoms. rBASIDIN caused hydrogen peroxide production in leaf tissue, damaging the leaf membrane and negatively affecting the photosynthetic rate of Solanum lycopersicum plants. Phylogenetic analysis indicated that BASIDIN has orthologs in other phytopathogenic basidiomycetes. Analysis of the transcripts revealed that BASIDIN and its orthologs are expressed in different fungal species, suggesting that this protein is differentially regulated in these basidiomycetes. Therefore, the results of applying BASIDIN allow the inference that it is an effector of the fungus M. perniciosa, with a strong potential to interfere in the defense system of the host plant.

The Effects of GCSF Primary Prophylaxis on Survival Outcomes and Toxicity in Patients with Advanced Non-Small Cell Lung Cancer on First-Line Chemoimmunotherapy: A Sub-Analysis of the Spinnaker Study.

GCSF prophylaxis is recommended in patients on chemotherapy with a >20% risk of febrile neutropenia and is to be considered if there is an intermediate risk of 10−20%. GCSF has been suggested as a possible adjunct to immunotherapy due to increased peripheral neutrophil recruitment and PD-L1 expression on neutrophils with GCSF use and greater tumour volume decrease with higher tumour GCSF expression. However, its potential to increase neutrophil counts and, thus, NLR values, could subsequently confer poorer prognoses on patients with advanced NSCLC. This analysis follows on from the retrospective multicentre observational cohort Spinnaker study on advanced NSCLC patients. The primary endpoints were OS and PFS. The secondary endpoints were the frequency and severity of AEs and irAEs. Patient information, including GCSF use and NLR values, was collected. A secondary comparison with matched follow-up duration was also undertaken. Three hundred and eight patients were included. Median OS was 13.4 months in patients given GCSF and 12.6 months in those not (p = 0.948). Median PFS was 7.3 months in patients given GCSF and 8.4 months in those not (p = 0.369). A total of 56% of patients receiving GCSF had Grade 1−2 AEs compared to 35% who did not receive GCSF (p = 0.004). Following an assessment with matched follow-up, 41% of patients given GCSF experienced Grade 1−2 irAEs compared to 23% of those not given GCSF (p = 0.023). GCSF prophylaxis use did not significantly affect overall or progression-free survival. Patients given GCSF prophylaxis were more likely to experience Grade 1−2 adverse effects and Grade 1−2 immunotherapy-related adverse effects.

International Survey on Frailty Assessment in Patients with Cancer.

BACKGROUND: Frailty negatively affects the outcomes of patients with cancer, and its assessment might vary widely in the real world. The objective of this study was to explore awareness and use of frailty screening tools among the ONCOassist healthcare professionals (HCPs) users. MATERIALS AND METHODS: We sent 2 emails with a cross-sectional 15-item survey in a 3-week interval between April and May 2021. Differences in the awareness and use of tools according to respondents' continents, country income, and job types were investigated. RESULTS: Seven hundred thirty-seven HCPs from 91 countries (81% physicians, 13% nurses, and 5% other HCPs) completed the survey. Three hundred and eighty-five (52%) reported assessing all or the majority of their patients; 518 (70%) at baseline and before starting a new treatment. Three hundred and four (43%) HCPs were aware of performance status (PS) scores only, 309 (42%) age/frailty/comorbidity (AFC) screening, and 102 (14%) chemotoxicity predictive tools. Five hundred and thirty-seven (73%) reported using tools; 423 (57%) just PS, 237 (32%) AFC, and 60 (8%) chemotoxicity ones. Reasons for tools non-use (485 responders) were awareness (70%), time constraints (28%), and uselessness (2%). There were significant differences in awareness and use of screening tools among different continents, country income, job types, and medical specialties (P < .001 for all comparisons). CONCLUSION: Among selected oncology HCPs, there is still a worldwide lack of knowledge and usage of frailty screening tools, which may differ according to their geography, country income, and education. Targeted initiatives to raise awareness and education are needed to implement frailty assessment in managing patients with cancer.

Open questions on the functional biology of the yolk granules during embryo development.

Biogenesis and consumption of the yolk are well-conserved aspects of the reproductive biology in oviparous species. Most egg-laying animals accumulate yolk proteins within the oocytes thus creating the source of nutrients and energy that will feed embryo development. Yolk accumulation drives the generation of a highly specialized oocyte cytoplasm with maternal mRNAs, ribosomes, mitochondria, and, mainly, a set of organelles collectively referred to as yolk granules (Ygs). Following fertilization, the Ygs are involved in regulated mechanisms of yolk degradation to fuel the anabolic metabolism of the growing embryo. Thus, yolk accumulation and degradation are essential processes that allow successful development in many species. Nevertheless, the molecular machinery and mechanisms dedicated to the programmed yolk mobilization throughout development are still enigmatic and remain mostly unexplored. Moreover, while the Ygs functional biology as a nutritional source for the embryo has been acknowledged, several reports have suggested that Ygs cargoes and functions go far beyond yolk storage. Evidence of the role of Ygs in gene expression, microbiota harboring, and paracrine signaling has been proposed. In this study, we summarize the current knowledge of the Ygs functional biology pointing to open questions and where further investigation is needed.

Prognostic value of patient-reported outcome measures (PROMs) in adults with non-small cell Lung Cancer: a scoping review.

BACKGROUND: There is growing interest in the collection and use of patient-reported outcome measures (PROMs) to support clinical decision making in patients with non-small cell lung cancer (NSCLC). However, an overview of research into the prognostic value of PROMs is currently lacking. AIM: To explore to what extent, how, and how robustly the value of PROMs for prognostic prediction has been investigated in adults diagnosed with NSCLC. METHODS: We systematically searched Medline, Embase, CINAHL Plus and Scopus for English-language articles published from 2011 to 2021 that report prognostic factor study, prognostic model development or validation study. Example data charting forms from the Cochrane Prognosis Methods Group guided our data charting on study characteristics, PROMs as predictors, predicted outcomes, and statistical methods. Two reviewers independently charted the data and critically appraised studies using the QUality In Prognosis Studies (QUIPS) tool for prognostic factor studies, and the risk of bias assessment section of the Prediction model Risk Of Bias ASsessment Tool (PROBAST) for prognostic model studies. RESULTS: Our search yielded 2,769 unique titles of which we included 31 studies, reporting the results of 33 unique analyses and models. Out of the 17 PROMs used for prediction, the EORTC QLQ-C30 was most frequently used (16/33); 12/33 analyses used PROM subdomain scores instead of the overall scores. PROMs data was mostly collected at baseline (24/33) and predominantly used to predict survival (32/33) but seldom other clinical outcomes (1/33). Almost all prognostic factor studies (26/27) had moderate to high risk of bias and all four prognostic model development studies had high risk of bias. CONCLUSION: There is an emerging body of research into the value of PROMs as a prognostic factor for survival in people with NSCLC but the methodological quality of this research is poor with significant bias. This warrants more robust studies into the prognostic value of PROMs, in particular for predicting outcomes other than survival. This will enable further development of PROM-based prediction models to support clinical decision making in NSCLC.

Evaluating intake levels of nutrients linked to non-communicable diseases in Australia using the novel combination of food processing and nutrient profiling metrics of the PAHO Nutrient Profile Model.

PURPOSE: To investigate intake levels of nutrients linked to non-communicable diseases in Australia using the novel combination of food processing and nutrient profiling metrics of the PAHO Nutrient Profile Model. METHODS: Dietary intakes of 12,153 participants from the Australian Health Survey (2011-12) aged 2 + years were evaluated. Food items reported during a 24 h recall were classified using the NOVA system. The Pan-American Health Organization Nutrient Profile Model (PAHO NPM) was applied to identify processed and ultra-processed products with excessive content of critical nutrients. Differences in mean intakes and prevalence of excessive intakes of critical nutrients for groups of the population whose diets were made up of products with and without excessive content in critical nutrients were examined. RESULTS: The majority of Australians consumed daily at least three processed and ultra-processed products identified as excessive in critical nutrients according to the PAHO NPM. Individuals consuming these products had higher intakes of free sugars (ß = 8.9), total fats (ß = 11.0), saturated fats (ß = 4.6), trans fats (ß = 0.2), and sodium (ß = 1788 for adolescents and adults; ß = 1769 for children 5-10 years; ß = 1319 for children aged < 5 years) (p ≤ 0.001 for all nutrients) than individuals not consuming these foods. The prevalence of excessive intake of all critical nutrients also followed the same trend. CONCLUSION: The PAHO NPM has shown to be a relevant tool to predict intake levels of nutrients linked to non-communicable diseases in Australia and, therefore, could be used to inform policy actions aimed at increasing the healthiness of food environments.

Expenditures on sugar-sweetened beverages in Jamaica and its association with household budget allocation.

BACKGROUND: Sugar-sweetened beverages (SSB) consumption is associated with overweight and obesity, which are important drivers for the increasing healthcare and other social costs. If expenditures on SSB decrease expenditures on other goods and services, such as education and healthcare, this "crowding-out" may have a lasting effect. The main objectives of this article are, first, to estimate the statistical association between the decision of spending in SSB and several households' sociodemographic characteristics; and second, to estimate the association between the decision of buying SSB and budget allocation across categories in Jamaica. METHODS: Using the Jamaican Household Expenditure Survey 2004-2005 a generalized ordered probit model was estimated to examine the association between socioeconomic variables and the decision to spend on SSB. Seemingly Unrelated Regression Equations (SURE) of all the expenditure groups (except the SSB group) were used to estimate the association between the decision of buying SSB and budget allocation on other goods and services. RESULTS: Expenditures on SSB are negatively affected by the size of the household and the area of residence (rural households spend more on SSB than urban ones), while having a larger proportion of children (15 or younger) and having a larger total budget is associated to more expenditures on SSB. Households with positive expenditure on SSB allocate significantly less budget to "Healthcare" and "Education", when compared to those who did not buy SSB. CONCLUSIONS: SSB expenditures may displace expenditures in necessary goods and services, which implies that decreasing the proportion of budget spent on SSB may have important present and future consequences on poorer households' human capital accumulation and future incomes.

Development and application of the TFA macrosimulation model: a case study of modelling the impact of trans fatty acid (TFA) elimination policies in Brazil.

INTRODUCTION: The consumption of trans-fatty acids (TFA) is directly associated with cardiovascular disease risk and is responsible for a significant health burden globally. The policy strategies for reducing TFA include limiting their content in foods and eliminating partially hydrogenated oils (PHO) in the market. This study aims to describe a comparative risk assessment macrosimulation model and to apply this tool to estimate the potential reductions in CVD mortality gained from the compared scenarios of TFA reduction/elimination in Brazil. METHODOLOGY: We developed and implemented a comparative risk assessment macrosimulation model estimates the potential CVD mortality reduction (coronary heart disease - CHD- and stroke) if TFA intake is reduced in diets. The TFA macrosimulation model estimates the change in the annual number of NCD deaths between baseline with current TFA consumption levels and alternate or counterfactual scenarios, such as considering different limits to TFA content in foods and the elimination of PHO in Brazil in 2018. The model incorporated additional outputs related to other impacts of TFA reduction on DPP, such as Years of Life Lost, Years of Productive Life Lost, and related economic impacts of premature deaths. RESULTS: In 2018, a 2% limit for TFA in the oils and fats and a 5% limit of TFAs for other foods could avert or postpone approximately 2,000 deaths (UI 95% 1,899-2,142) and save US$ 32.1 million savings in productivity losses to the economy associated to premature deaths. An intermediate scenario, applying a 2% limit of TFA in all food products In Brazil could prevent or postpone approximately 6,300 deaths (UI 95% 5,925-6,684) and the premature deaths prevented would represent US$ 100.2 million in economic saving. Finally, by banning PHO, approximately 10,500 deaths could be prevented or postponed (UI 95% 9,963 - 10,909), corresponding to US$ 166.7 million in savings to the economy because of premature deaths. CONCLUSION: The TFA macrosimulation model can efficiently compare different policy scenarios for trans fats reduction policies at the country level and proves that the elimination of PHOs from the food market in Brazil may significantly reduce the health burden of trans fatty acids in the country compared to other policy options. The model also represents a useful public health tool to support TFA reduction and elimination policies in other countries.

Building capacity in reducing population dietary sodium intake in the Americas.

Objective: To present some resources developed as part of the technical support of the Pan American Health Organization (PAHO) to Member States to reduce population dietary sodium intake, and to discuss the main challenges and opportunities to accelerate action toward sodium intake reduction in the Americas. Methods: Sources of information include a mapping of salt reduction policies conducted in 2019, reports from working group meetings, interviews conducted in 2020 and 2021 in seven countries, and technical documents developed around the Updated PAHO Regional Sodium Reduction Targets. Results: These tools show that, despite progress, challenges to succeed in this agenda persist. Priority given to sodium reduction is low in most countries, with insufficient resource allocation. There is a lack of intersectoral coordinated action, and a systemic approach to food systems is commonly missing. Surveillance mechanisms of sodium intake are insufficient, and industry interference in policy processes is commonly identified, undermining policy progress and success. There are also important regional opportunities to address these challenges. These include common ground for future collaborations by updating, strengthening, and complementing these existing tools, and technical and financial support for data generation. Conclusions: PAHO is committed to continue to support countries in the process of promoting, implementing, and monitoring cost-effective sodium reduction interventions. One key policy priority in this agenda is the adoption of the Updated PAHO Regional Sodium Reduction Targets with a mandatory approach, together with the comprehensive and complementary implementation of other strategies. Strong political will and commitment of countries will be critical to translate goals into concrete achievements in the Americas.

Evaluating progress and addressing actions to eliminate industrially produced trans-fatty acids in the Americas.

Objective: To evaluate the progress toward the 2023 target for the elimination of industrially produced trans-fatty acids (IP-TFA) in the Region of the Americas and to highlight the achievements of the four strategic lines of action from the Plan of Action for the Elimination of IP-TFA 2020-2025. Methods: A survey based on the World Health Organization (WHO) REPLACE package was used to collect data. The REPLACE package outlines six strategic action areas (Review, Promote, Legislate, Assess, Create, Enforce) to support the prompt, complete, and sustained elimination of IP-TFA from the food supply. Information was cross-checked and updated until December 2021. Results: Thirty countries in the Region responded to the survey between November 2019 and July 2020, an 85.7% response rate. As of December 2021, 21 additional indicators of the Regional Plan of Action were met, out of which, four consisted of new enactments of PAHO/WHO best practice policies for the elimination of IP-TFA by countries since baseline data was collected in 2018. This has resulted in a 63.0% increase in the proportion of the population in the Americas protected from consuming IP-TFA in 2021, compared to the baseline in 2018. Conclusion: Despite results showing progress in the Region, actions are needed to strengthen country capacity building and strategies to eliminate IP-TFA and fully achieve the 2023 goal.

Efficacy of different front-of-package labeling systems in changing purchase intention and product healthfulness perception for food products in Argentina.

Objectives: To identify the front-of-package scheme-Multiple Traffic Light (MTL), Nutri-Score (NS), and black octagon Warning System (WS)-most effective in reducing purchase intention and perceived product healthfulness of drinking yogurts, cookies and cheese spreads, and to assess the joint influence of nutrient claims on the effects. Methods: Randomized-controlled experiment. A within-subjects factorial design was used to evaluate the influence of three independent factors on perceived product healthfulness and purchase intention. A total of 704 adults in Argentina were shown three mock-up products and asked to indicate which product they would buy choosing between pairs of products from different categories and to rate product healthfulness on a 7-point Likert scale. Results: The WS was the most effective in reducing purchase intention in drinking yogurts (OR:0.16, 95%CI: 0.09;0.28), cookies (OR:0.10, 95%CI: 0.05;0.18) and cheese spreads (OR:0.10, 95%CI: 0.05;0.18), and the perception of healthfulness (WS Mean score 3,63 vs No label 4,24, p<0.001), regardless of the participants' gender, age, and level of education. NS was inefficacious in reducing product healthfulness perception, while MTL had significantly increased how healthful the product was perceived (p<0.001). Nutrient claims increased purchase intention and perception of healthfulness, thus reducing the effectiveness of front-of-package labels (p<0.001). Conclusions: In line with growing evidence, our findings support that WS perform better than NS and MTL in reducing purchase intention and healthfulness perception of products with excessive amounts of critical nutrients associated with the greatest burden of diseases. Front-of-package WS are expected to facilitate the population in Argentina to make healthier decisions.

[Processed and ultra-processed products and their relationship to quality of diet in childrenProdutos processados e ultraprocessados e sua relação com a qualidade da dieta em crianças]. / Productos procesados y ultraprocesados y su relación con la calidad de la dieta en niños.

Objective: Estimate the impact on quality in the early childhood diet (ages 2 to 4 years) in Uruguay, resulting from consumption of products containing excessive amounts of critical nutrients associated with noncommunicable diseases (NCDs) (free sugars, total fats, saturated fats, and sodium), according to the Pan American Health Organization (PAHO) Nutrient Profile Model. Methods: A 24-hour dietary recall survey was used with a representative sample of 401 participants from the 2018 Nutrition, Child Development, and Health Survey. The NOVA classification system was used to categorize foods according to the nature and purposes of the industrial processes they undergo. Foods were then analyzed using the PAHO Nutrient Profile Model, enabling identification of products with excessive amounts of these nutrients. Results: Fifty percent of children consumed three or more products with an excess of some of the nutrients linked to NCDs. About 9 out of 10 children consume products with an excess of at least one of the critical nutrients studied. Conclusion: Diets that do not contain ultra-processed and processed products with excess free sugars, total fats, saturated fats, or sodium were the best choice for children aged 2 to 4 years. Based on PAHO criteria, the consumption of products with excess critical nutrients (and of each additional gram of these products) significantly worsens diet quality, and impedes adherence to World Health Organization recommendations.

Objetivo: Estimar o efeito do consumo de produtos que contêm quantidades excessivas de nutrientes críticos associados a doenças não transmissíveis (DCNTs) ­ açúcares livres, gorduras totais, gorduras saturadas e sódio ­, de acordo com o modelo de perfil nutricional da Organização Pan-Americana da Saúde (OPAS), na qualidade da dieta da primeira infância uruguaia (crianças de 2 a 4 anos). Métodos: Um recordatório alimentar de 24 horas foi aplicado a uma amostra representativa de 401 participantes da Pesquisa de Nutrição, Desenvolvimento Infantil e Saúde de 2018. Foi utilizada a classificação proposta pelo sistema NOVA para categorizar os alimentos de acordo com sua natureza e os processos industriais a que são submetidos. A análise foi feita com base no modelo de perfil nutricional da OPAS, que possibilitou identificar os produtos com teor excessivo dos nutrientes supracitados. Resultados: Das crianças avaliadas, 50% consumiram três ou mais produtos com excesso de algum dos nutrientes vinculados às DCNT. Aproximadamente 9 em cada 10 crianças consomem produtos com excesso de pelo menos um dos nutrientes críticos estudados. Conclusão: As dietas que não contêm produtos ultraprocessados e processados com excesso de açúcares livres, gordura total, gordura saturada e sódio foram a melhor opção para crianças de 2 a 4 anos. A ingestão de produtos com excesso de nutrientes críticos segundo a OPAS (e cada grama adicional consumido desses produtos) piora significativamente a qualidade da dieta e impede o cumprimento das recomendações da Organização Mundial da Saúde.

Mitochondrial Epilepsy, a Challenge for Neurologists.

Primary mitochondrial diseases are relatively common inborn errors of energy metabolism, with a combined prevalence of 1 in 4300. These disorders typically affect tissues with high energy requirements, including the brain. Epilepsy affects >1% of the worldwide population, making it one of the most common neurological illnesses; it may be the presenting feature of a mitochondrial disease, but is often part of a multisystem clinical presentation. The major genetic causes of mitochondrial epilepsy are mutations in mitochondrial DNA and in the nuclear-encoded gene POLG. Treatment of mitochondrial epilepsy may be challenging, often representing a poor prognostic feature. This narrative review will cover the most recent advances in the field of mitochondrial epilepsy, from pathophysiology and genetic etiologies to phenotype and treatment options.

Enrolment of older adults with cancer in early phase clinical trials-an observational study on the experience in the north west of England.

INTRODUCTION: older patients represent the majority of cancer patients but are under-represented in trials, particularly early phase clinical trials (EPCTs). MATERIAL AND METHODS: observational retrospective study of patients referred for EPCTs (January-December 2018) at a specialist cancer centre in the UK. The primary aim was to analyse the successful enrolment into EPCTs according to age (<65/65+). The secondary aims were to identify enrolment obstacles and the outcomes of enrolled patients. Patient data were analysed at: referral; in-clinic assessment and after successful enrolment. Among patients assessed in clinic, a sample was defined by randomly matching the older cohort with the younger cohort (1:1) by tumour type. RESULTS: 555 patients were referred for EPCTs with a median age of 60 years, of whom 471 were assessed in new patient clinics (38% were 65+). From those assessed, a randomly tumour-matched sample of 318 patients (159 per age cohort) was selected. Older patients had a significantly higher comorbidity score measured by ACE-27 (P < 0.0001), lived closer to the hospital (P = 0.045) and were referred at a later point in their cancer management (P = 0.002). There was no difference in suitability for EPCTs according to age with overall 84% deemed suitable. For patients successfully enrolled into EPCTs, there was no difference between age cohorts (20.1 vs. 22.6% for younger and older, respectively; P = 0.675) and no significant differences in their safety and efficacy outcomes. DISCUSSION: older age did not affect the enrolment into EPCTs. However, the selected minority referred for EPCTs suggests a pre-selection upstream by primary oncologists.