Mapping the cellular biogeography of human bone marrow niches using single-cell transcriptomics and proteomic imaging.

Non-hematopoietic cells are essential contributors to hematopoiesis. However, heterogeneity and spatial organization of these cells in human bone marrow remain largely uncharacterized. We used single-cell RNA sequencing (scRNA-seq) to profile 29,325 non-hematopoietic cells and discovered nine transcriptionally distinct subtypes. We simultaneously profiled 53,417 hematopoietic cells and predicted their interactions with non-hematopoietic subsets. We employed co-detection by indexing (CODEX) to spatially profile over 1.2 million cells. We integrated scRNA-seq and CODEX data to link predicted cellular signaling with spatial proximity. Our analysis revealed a hyperoxygenated arterio-endosteal neighborhood for early myelopoiesis, and an adipocytic localization for early hematopoietic stem and progenitor cells (HSPCs). We used our CODEX atlas to annotate new images and uncovered mesenchymal stromal cell (MSC) expansion and spatial neighborhoods co-enriched for leukemic blasts and MSCs in acute myeloid leukemia (AML) patient samples. This spatially resolved, multiomic atlas of human bone marrow provides a reference for investigation of cellular interactions that drive hematopoiesis.

Assessment of fall-back MRLs for revoked CXLs previously implemented in the EU legislation and review of the JMPR evaluation of the toxicological data related to pyrasulfotole, pyraziflumid, spiropidion and tetraniliprole.

In accordance with Article 43 of Regulation (EC) 396/2005, EFSA received a request from the European Commission to propose fall-back maximum residue levels (MRLs) for recently revoked Codex MRLs that have been previously implemented in the EU legislation. Overall, MRLs for 12 a.s. are concerned, i.e. chlormequat, diazinon, bifenthrin, fludioxonil, indoxacarb, difenoconazole, famoxadone, azoxystrobin, mandipropamid, emamectin benzoate, flutriafol and afidopyropen. In addition, EFSA was requested to evaluate the toxicological data assessed by JMPR related to pyrasulfotole, pyraziflumid, spiropidion and tetraniliprole. These are active substances have not been assessed previously at EU level. The assessment should allow to take a decision, if the CXLs adopted for these four a.s. can be implemented in the EU MRL legislation.

Identifying the Spatial Architecture That Restricts the Proximity of CD8+ T Cells to Tumor Cells in Pancreatic Ductal Adenocarcinoma.

The anti-tumor function of CD8+ T cells is dependent on their proximity to tumor cells. Current studies have focused on the infiltration level of CD8+ T cells in the tumor microenvironment, while further spatial information, such as spatial localization and inter-cellular communication, have not been defined. In this study, co-detection by indexing (CODEX) was designed to characterize PDAC tissue regions with seven protein markers in order to identify the spatial architecture that regulates CD8+ T cells in human pancreatic ductal adenocarcinoma (PDAC). The cellular neighborhood algorithm was used to identify a total of six conserved and distinct cellular neighborhoods. Among these, one unique spatial architecture of CD8+ T and CD4+ T cell-enriched neighborhoods enriched the majority of CD8+ T cells, but heralded a poor prognosis. The proximity analysis revealed that the CD8+ T cells in this spatial architecture were significantly closer to themselves and the CD4+ T cells than to the tumor cells. Collectively, we identified a unique spatial architecture that restricted the proximity of CD8+ T cells to tumor cells in the tumor microenvironment, indicating a novel immune evasion mechanism of pancreatic ductal adenocarcinoma in a topologically regulated manner and providing new insights into the biology of PDAC.

Heavy Metal Bioaccumulation in Peruvian Food and Medicinal Products.

To better query regional sources of metal(loid) exposure in an under-communicated region, available scientific literature from 50 national universities (undergraduate and graduate theses and dissertations), peer-reviewed journals, and reports published in Spanish and English were synthesized with a focus on metal(loid) bioaccumulation in Peruvian food and medicinal products utilized locally. The study considered 16 metal(loid)s that are known to exert toxic impacts on humans (Hg, Al, Sb, As, Ba, Be, Cd, Cr, Sn, Ni, Ag, Pb, Se, Tl, Ti, and U). A total of 1907 individual analyses contained within 231 scientific publications largely conducted by Peruvian universities were analyzed. These analyses encompassed 239 reported species classified into five main food/medicinal groups-plants, fish, macroinvertebrates and mollusks, mammals, and "others" category. Our benchmark for comparison was the World Health Organization (Codex Alimentarius) standards. The organisms most frequently investigated included plants such as asparagus, corn, cacao, and rice; fish varieties like trout, tuna, and catfish; macroinvertebrates and mollusks including crab and shrimp; mammals such as alpaca, cow, chicken eggs, and milk; and other categories represented by propolis, honey, lichen, and edible frog. Bioaccumulation-related research increased from 2 to more than 25 publications per year between 2006 and 2022. The results indicate that Peruvian food and natural medicinal products can have dangerous levels of metal(loid)s, which can cause health problems for consumers. Many common and uncommon food/medicinal products and harmful metals identified in this analysis are not regulated on the WHO's advisory lists, suggesting the urgent need for stronger regulations to ensure public safety. In general, Cd and Pb are the metals that violated WHO standards the most, although commonly non-WHO regulated metals such as Hg, Al, As, Cr, and Ni are also a concern. Metal concentrations found in Peru are on many occasions much higher than what has been reported elsewhere. We conclude that determining the safety of food/medicinal products is challenging due to varying metal concentrations that are influenced not only by metal type but also geographical location. Given the scarcity of research findings in many regions of Peru, urgent attention is required to address this critical knowledge gap and implement effective regulatory measures to protect public health.

Unveiling Macrophage Heterogeneity and Their Spatial Distribution Using Multiplexed Tissue Imaging.

Macrophages display a high degree of phenotypic diversity and plasticity, which is influenced by their location within the tissue microenvironment. Co-Detection by Indexing (CODEX), a multiplexed imaging technique, allows the simultaneous detection of multiple membrane and cellular markers that enable the accurate identification of tissue-resident hematopoietic and non-hematopoietic cells, while conferring spatial information at a single-cell level. Here we describe the use of CODEX to visualize the phenotypic and spatial heterogeneity of murine tissue-resident macrophages in several organs, and a pipeline to characterize their cellular microenvironments and interactions.

Impact of smart phone use on adolescence health in India.

Smart phone use is on the rise globally, which may have an impact on people's health. The second-largest country in terms of mobile phone usage is India. However, there aren't many studies that have been done in India to evaluate its health impacts. Therefore, it is of interest to assess the effectiveness of codex on the impact of smart phone use on various dimensions of health status among adolescence. The pre-test mean score for knowledge regarding the impact of smart phones on physical health was 1.92, while the post-test mean score was 3.75. The pre-test and post-test standard deviations were 0.91 and 0.93, respectively, and the mean deviation score was the 't'-value that was 11.000 and Significant at the p<0.001*** level. The research was conducted in higher secondary school, and 60 students participated. The research design was a pre-experimental design; a self-administered questionnaire was used to assess the knowledge of Students on the Impact of mobile phone use on various dimensions of health. Most people, on average, spend 3 hours and 15 minutes on their phones each day. As adolescents are engaged in smartphone use, it disturbs their sleep patterns, adversely impacting their short-term memory.

T cell-mediated curation and restructuring of tumor tissue coordinates an effective immune response.

Antigen-specific T cells traffic to, are influenced by, and create unique cellular microenvironments. Here we characterize these microenvironments over time with multiplexed imaging in a melanoma model of adoptive T cell therapy and human patients with melanoma treated with checkpoint inhibitor therapy. Multicellular neighborhood analysis reveals dynamic immune cell infiltration and inflamed tumor cell neighborhoods associated with CD8+ T cells. T cell-focused analysis indicates T cells are found along a continuum of neighborhoods that reflect the progressive steps coordinating the anti-tumor immune response. More effective anti-tumor immune responses are characterized by inflamed tumor-T cell neighborhoods, flanked by dense immune infiltration neighborhoods. Conversely, ineffective T cell therapies express anti-inflammatory cytokines, resulting in regulatory neighborhoods, spatially disrupting productive T cell-immune and -tumor interactions. Our study provides in situ mechanistic insights into temporal tumor microenvironment changes, cell interactions critical for response, and spatial correlates of immunotherapy outcomes, informing cellular therapy evaluation and engineering.

Overpromoted and underregulated: National binding legal measures related to commercially produced complementary foods in seven Southeast Asian countries are not fully aligned with available guidance.

The market for commercially produced complementary foods (CPCF) is rapidly expanding in Southeast Asia; however, the existence and content of mandatory national policies, standards and legislation (binding legal measures) for CPCF in the region is unclear. To assess the status of national binding legal measures for CPCF in Southeast Asia, a legal and policy desk review was conducted in seven countries (Cambodia, Laos People's Democratic Republic, Indonesia, Malaysia, Philippines, Thailand and Viet Nam). The alignment of the national binding legal measures relevant to CPCF was assessed against guidance on CPCF nutrient composition and labelling requirements provided by Codex Alimentarius and the World Health Organization (WHO). Each of the seven countries had at least two national binding legal measures related to the nutrient composition or labelling of CPCF; however, there was limited alignment with the guidance from Codex and WHO. No country was fully aligned with the three CPCF-specific Codex standards/guidelines and only one country was in full alignment with the recommendations related to the protection of breastfeeding from the 'WHO Guidance on ending the inappropriate promotion of foods for infants and young children'. The findings of the review indicate that the existing national binding legal measures are insufficient to ensure that the CPCF sold as suitable for older infants and young children are nutritionally adequate and labelled in a responsible manner that does not mislead caregivers. Improved and enforced national binding legal measures for CPCF, in alignment with global guidance, are required to ensure that countries protect, promote and support optimal nutrition for children 6-36 months of age.

Model-based evaluation of spatiotemporal data reduction methods with unknown ground truth through optimal visualization and interpretability metrics.

Optimizing and benchmarking data reduction methods for dynamic or spatial visualization and interpretation (DSVI) face challenges due to many factors, including data complexity, lack of ground truth, time-dependent metrics, dimensionality bias and different visual mappings of the same data. Current studies often focus on independent static visualization or interpretability metrics that require ground truth. To overcome this limitation, we propose the MIBCOVIS framework, a comprehensive and interpretable benchmarking and computational approach. MIBCOVIS enhances the visualization and interpretability of high-dimensional data without relying on ground truth by integrating five robust metrics, including a novel time-ordered Markov-based structural metric, into a semi-supervised hierarchical Bayesian model. The framework assesses method accuracy and considers interaction effects among metric features. We apply MIBCOVIS using linear and nonlinear dimensionality reduction methods to evaluate optimal DSVI for four distinct dynamic and spatial biological processes captured by three single-cell data modalities: CyTOF, scRNA-seq and CODEX. These data vary in complexity based on feature dimensionality, unknown cell types and dynamic or spatial differences. Unlike traditional single-summary score approaches, MIBCOVIS compares accuracy distributions across methods. Our findings underscore the joint evaluation of visualization and interpretability, rather than relying on separate metrics. We reveal that prioritizing average performance can obscure method feature performance. Additionally, we explore the impact of data complexity on visualization and interpretability. Specifically, we provide optimal parameters and features and recommend methods, like the optimized variational contractive autoencoder, for targeted DSVI for various data complexities. MIBCOVIS shows promise for evaluating dynamic single-cell atlases and spatiotemporal data reduction models.

Common and Trace Metals in Alzheimer's and Parkinson's Diseases.

Trace elements and metals play critical roles in the normal functioning of the central nervous system (CNS), and their dysregulation has been implicated in neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). In a healthy CNS, zinc, copper, iron, and manganese play vital roles as enzyme cofactors, supporting neurotransmission, cellular metabolism, and antioxidant defense. Imbalances in these trace elements can lead to oxidative stress, protein aggregation, and mitochondrial dysfunction, thereby contributing to neurodegeneration. In AD, copper and zinc imbalances are associated with amyloid-beta and tau pathology, impacting cognitive function. PD involves the disruption of iron and manganese levels, leading to oxidative damage and neuronal loss. Toxic metals, like lead and cadmium, impair synaptic transmission and exacerbate neuroinflammation, impacting CNS health. The role of aluminum in AD neurofibrillary tangle formation has also been noted. Understanding the roles of these elements in CNS health and disease might offer potential therapeutic targets for neurodegenerative disorders. The Codex Alimentarius standards concerning the mentioned metals in foods may be one of the key legal contributions to safeguarding public health. Further research is needed to fully comprehend these complex mechanisms and develop effective interventions.

Is the List of Ingredients a Source of Nutrition and Health Information in Food Labeling? A Scoping Review.

Nutrition labelling is any description intended to inform consumers about the nutritional properties of a food product and has focused primarily on nutrients. However, literature has shown that the nutritional quality of packaged foods is not limited to the amount of nutrients, considering that individuals do not consume only nutrients separately, but rather the entire food matrix. Therefore, to analyze the nutritional quality of a packaged food, it is necessary to read its ingredients. This scoping review aims to discuss (1) the list of ingredients as a source of health and nutrition information in food labelling; (2) opportunities to improve the nutrition labeling policies around the world. The study was carried out through a systematic search on Codex Alimentarius meeting reports. Results show that the list of ingredients is used as a source of nutritional and health information on food labelling; however, this label item is not considered in the regulatory field as a nutrition labelling requirement. It is suggested that nutrition labelling be discussed as a tool for food choices in the context of public health from a broader, consistent, convergent perspective, considering the list of ingredients as an item of nutrition labelling requirement to be included in public policies around the world.

GammaGateR: semi-automated marker gating for single-cell multiplexed imaging.

Motivation: Multiplexed immunofluorescence (mIF) is an emerging assay for multichannel protein imaging that can decipher cell-level spatial features in tissues. However, existing automated cell phenotyping methods, such as clustering, face challenges in achieving consistency across experiments and often require subjective evaluation. As a result, mIF analyses often revert to marker gating based on manual thresholding of raw imaging data. Results: To address the need for an evaluable semi-automated algorithm, we developed GammaGateR, an R package for interactive marker gating designed specifically for segmented cell-level data from mIF images. Based on a novel closed-form gamma mixture model, GammaGateR provides estimates of marker-positive cell proportions and soft clustering of marker-positive cells. The model incorporates user-specified constraints that provide a consistent but slide-specific model fit. We compared GammaGateR against the newest unsupervised approach for annotating mIF data, employing two colon datasets and one ovarian cancer dataset for the evaluation. We showed that GammaGateR produces highly similar results to a silver standard established through manual annotation. Furthermore, we demonstrated its effectiveness in identifying biological signals, achieved by mapping known spatial interactions between CD68 and MUC5AC cells in the colon and by accurately predicting survival in ovarian cancer patients using the phenotype probabilities as input for machine learning methods. GammaGateR is a highly efficient tool that can improve the replicability of marker gating results, while reducing the time of manual segmentation. Availability and Implementation: The R package is available at https://github.com/JiangmeiRubyXiong/GammaGateR.

Desmoplastic stromal signatures predict patient outcomes in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second leading cause of cancer-related death. Hallmarks include desmoplasia with variable extracellular matrix (ECM) architecture and a complex microenvironment with spatially defined tumor, stromal, and immune populations. Nevertheless, the role of desmoplastic spatial organization in patient/tumor variability remains underexplored, which we elucidate using two technologies. First, we quantify ECM patterning in 437 patients, revealing architectures associated with disease-free and overall survival. Second, we spatially profile the cellular milieu of 78 specimens using codetection by indexing, identifying an axis of pro-inflammatory cell interactions predictive of poorer outcomes. We discover that clinical characteristics, including neoadjuvant chemotherapy status, tumor stage, and ECM architecture, correlate with differential stromal-immune organization, including fibroblast subtypes with distinct niches. Lastly, we define unified signatures that predict survival with areas under the receiver operating characteristic curve (AUCs) of 0.872-0.903, differentiating survivorship by 655 days. Overall, our findings establish matrix ultrastructural and cellular organizations of fibrosis linked to poorer outcomes.

Extended Spectrum ß-Lactamase-Producing Enterobacterales of Shrimp and Salmon Available for Purchase by Consumers in Canada-A Risk Profile Using the Codex Framework.

The extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales (ESBL-EB) encompass several important human pathogens and are found on the World Health Organization (WHO) priority pathogens list of antibiotic-resistant bacteria. They are a group of organisms which demonstrate resistance to third-generation cephalosporins (3GC) and their presence has been documented worldwide, including in aquaculture and the aquatic environment. This risk profile was developed following the Codex Guidelines for Risk Analysis of Foodborne Antimicrobial Resistance with the objectives of describing the current state of knowledge of ESBL-EB in relation to retail shrimp and salmon available to consumers in Canada, the primary aquacultured species consumed in Canada. The risk profile found that Enterobacterales and ESBL-EB have been found in multiple aquatic environments, as well as multiple host species and production levels. Although the information available did not permit the conclusion as to whether there is a human health risk related to ESBLs in Enterobacterales in salmon and shrimp available for consumption by Canadians, ESBL-EB in imported seafood available at the retail level in Canada have been found. Surveillance activities to detect ESBL-EB in seafood are needed; salmon and shrimp could be used in initial surveillance activities, representing domestic and imported products.

Tumor-associated macrophages trigger MAIT cell dysfunction at the HCC invasive margin.

Mucosal-associated invariant T (MAIT) cells represent an abundant innate-like T cell subtype in the human liver. MAIT cells are assigned crucial roles in regulating immunity and inflammation, yet their role in liver cancer remains elusive. Here, we present a MAIT cell-centered profiling of hepatocellular carcinoma (HCC) using scRNA-seq, flow cytometry, and co-detection by indexing (CODEX) imaging of paired patient samples. These analyses highlight the heterogeneity and dysfunctionality of MAIT cells in HCC and their defective capacity to infiltrate liver tumors. Machine-learning tools were used to dissect the spatial cellular interaction network within the MAIT cell neighborhood. Co-localization in the adjacent liver and interaction between niche-occupying CSF1R+PD-L1+ tumor-associated macrophages (TAMs) and MAIT cells was identified as a key regulatory element of MAIT cell dysfunction. Perturbation of this cell-cell interaction in ex vivo co-culture studies using patient samples and murine models reinvigorated MAIT cell cytotoxicity. These studies suggest that aPD-1/aPD-L1 therapies target MAIT cells in HCC patients.

Dietary fibre definition revisited - The case of low molecular weight carbohydrates.

Low molecular weight (LMW) non-digestible carbohydrates (namely, oligosaccharides and inulin) are accepted as dietary fibre in many countries worldwide. The inclusion of oligosaccharides as dietary fibre was made optional within the Codex Alimentarius definition in 2009, which has caused great controversy. Inulin is accepted as dietary fibre by default, due to being a non-digestible carbohydrate polymer. Oligosaccharides and inulin occur naturally in numerous foods and are frequently incorporated into commonly consumed food products for a variety of purposes, such as to increase dietary fibre content. LMW non-digestible carbohydrates, due to their rapid fermentation in the proximal colon, may cause deleterious effects in individuals with functional bowel disorders (FBDs) and, as such, are excluded on the low FODMAP (fermentable oligosaccharides, disaccharides, and polyols) diet and similar protocols. Their addition to food products as dietary fibre allows the use of associated nutrition/health claims, causing a paradox for those with FBDs, which is further complicated by lack of clarity on food labelling. Therefore, this review aimed to discuss whether the inclusion of LMW non-digestible carbohydrates within the Codex definition of dietary fibre is warranted. This review provides justification for the exclusion of oligosaccharides and inulin from the Codex definition of dietary fibre. LMW non-digestible carbohydrates could, instead, be placed in their own category as prebiotics, recognised for their specific functional properties, or considered food additives, whereby they are not promoted for being beneficial for health. This would preserve the concept of dietary fibre being a universally beneficial dietary component for all individuals.

The Role of Multidimensional Indices for Mortality Prediction in Chronic Obstructive Pulmonary Disease.

(1) Background: Chronic obstructive pulmonary disease (COPD) is one of the most important respiratory diseases. It is characterised by a progressive course with individual differences in clinical presentation and prognosis. The use of multidimensional indices such as the BODE, eBODE, BODEX, CODEX, ADO, and Charlson Comorbidity Index has been proposed to predict the survival rate of COPD patients. However, there is limited research on the prognostic significance of these indices in predicting long-term survival rates in patients with COPD. The aim of this prospective cohort study was to investigate the prognostic value of the BODE, eBODE, BODEX, CODEX, ADO, COTE and Charlson Comorbidity Index in predicting 5- and 10-year survival in patients with COPD. (2) Methods: A total of 170 patients were included in the study and their clinical and functional characteristics of COPD progression, such as dyspnoea, body mass index and spirometry data, were evaluated. A Kaplan-Meier survival analysis was used to calculate 5- and 10-year survival rates. The predictive value of each index was assessed using Cox proportional hazards regression models. (3) Results: The 5-year survival rate was 62.35% and the 10-year survival rate was 34.70%. The BODE, eBODE, BODEX, CODEX, ADO, COTE and Charlson Comorbidity Index were all significantly associated with the 10-year survival rate of COPD patients (p < 0.05). The hazard ratios (HRs) for these indices were as follows: BODE (HR = 1.30, 95% confidence interval [CI] 1.21-1.39); eBODE (HR = 1.29, 95% CI 1.21-1.37); BODEX (HR = 1.48, 95% CI 1.35-1.63); CODEX (HR = 1.42, 95% CI 1.31-1.54); COTE (HR = 1.55, 95% CI 1.36-1.75); ADO (HR = 1.41, 95% CI 1.29-1.54); and Charlson Comorbidity Index (HR = 1.35, 95% CI 1.22-1.48). (4) Conclusions: The multidimensional indices are a useful clinical tool for assessing the course and prognosis of COPD. These indices can be used to identify patients at a high risk of mortality and guide the management of COPD patients.

Integrated Cytometry With Machine Learning Applied to High-Content Imaging of Human Kidney Tissue for In Situ Cell Classification and Neighborhood Analysis.

The human kidney is a complex organ with various cell types that are intricately organized to perform key physiological functions and maintain homeostasis. New imaging modalities, such as mesoscale and highly multiplexed fluorescence microscopy, are increasingly being applied to human kidney tissue to create single-cell resolution data sets that are both spatially large and multidimensional. These single-cell resolution high-content imaging data sets have great potential to uncover the complex spatial organization and cellular makeup of the human kidney. Tissue cytometry is a novel approach used for the quantitative analysis of imaging data; however, the scale and complexity of such data sets pose unique challenges for processing and analysis. We have developed the Volumetric Tissue Exploration and Analysis (VTEA) software, a unique tool that integrates image processing, segmentation, and interactive cytometry analysis into a single framework on desktop computers. Supported by an extensible and open-source framework, VTEA's integrated pipeline now includes enhanced analytical tools, such as machine learning, data visualization, and neighborhood analyses, for hyperdimensional large-scale imaging data sets. These novel capabilities enable the analysis of mesoscale 2- and 3-dimensional multiplexed human kidney imaging data sets (such as co-detection by indexing and 3-dimensional confocal multiplexed fluorescence imaging). We demonstrate the utility of this approach in identifying cell subtypes in the kidney on the basis of labels, spatial association, and their microenvironment or neighborhood membership. VTEA provides an integrated and intuitive approach to decipher the cellular and spatial complexity of the human kidney and complements other transcriptomics and epigenetic efforts to define the landscape of kidney cell types.

Once again on the Empress Zoe: Women, dermatology, cosmetics, and materia medica (medical matter) in the ancient world.

BACKGROUND: An article published in 2012 in the Journal of Cosmetic Dermatology discussed the historical sources presenting the Byzantine Empress Zoe Porphyrogenita as an expert in cosmetic and pharmacological remedies that could give their users a youthful appearance and a kind of eternal youth. However, it did not take into account a dermatological recipe attributed to Zoe which text transmission has preserved. AIMS: To examine some ingredients of Zoe's recipe from a historical medical point of view and contextualize the text in the tradition of ancient medical matter, physiology of aging, and gender pharmacological skills. METHODS: After contextualizing the recipe from the historical medical point of view, some of its ingredients have been analyzed in relation not only to their use in the most authoritative pharmacological and medical sources of antiquity but also to their symbolic meaning. RESULTS: The analysis of Zoe's dermatological recipe allowed to highlight: The links between cosmetics and medicine in Greek and Roman Antiquity. The reason why ancient sources dealing with medical matter attributed to certain substances and plants the power to save the human body from old age and decay. The consistency between the ingredients of Zoe's recipe and the humoral physiology by genders and by age of Hippocrates. The existence of a female tradition in pharmacological competence. CONCLUSION: Cosmetic dermatology of antiquity is the perfect point in which survival of the myth and rational pharmacology overlap.

Risk assessment supporting the establishment of a maximum residue limit for ractopamine in beef liver, applicable in the Arab Republic of Egypt.

In 2012, the Codex Alimentarius Commission adopted maximum residue limits (MRLs) for ractopamine in pig and cattle tissues. Egypt, a country that records a high consumption of beef liver, conducted a health risk assessment to estimate the risks associated with the adoption of Codex MRLs and the possible adoption of alternative values that may offer higher protection. Ractopamine was characterized based on previous assessments performed by international regulatory agencies, and an acceptable daily intake was set at 1 µg/kg bw for both chronic and acute ractopamine exposure. Beef liver consumption data for the Egyptian population were collected through a field survey (529 households, 1929 individuals). The standard body weight of 60 kg was used, as well as 70 kg, as a potentially more representative weight for the Egyptian population. Simulations showed that when the MRL for ractopamine in beef liver is set to 40 µg/kg (Codex MRL) or 20 µg/kg, the health-based guidance value of 1 µg/kg bw was not exceeded, as a result of chronic or acute exposure. An MRL of 20 µg/kg of ractopamine in beef liver was shown to provide optimum protection of Egyptian consumers, considering other potential sources of ractopamine intake and abnormally high consumption patterns, and was therefore recommended for adoption in Egypt. This study presents the inputs, model, and results of the probabilistic risk assessment that supported such recommendation. PRACTICAL APPLICATION: Residues of veterinary drugs, such as ractopamine, accumulate in animal tissues and may pose a risk to consumers. Establishing maximum residue limits (MRLs) will help importers by giving them the necessary visibility for commercial trade. It will also benefit Egyptian consumers, large consumers of beef liver, who will be better protected with a lower MRL than the internationally recommended one.