Capi-score: a quantitative algorithm for identifying disease patterns in nailfold videocapillaroscopy.

OBJECTIVES: The European Alliance of Associations for Rheumatology (EULAR) supports the use of nailfold videocapillaroscopy (NVC) to identify disease patterns (DPs) associated with systemic sclerosis (SSc) and Raynaud's phenomenon (RP). Recently, EULAR proposed an easy-to-manage procedure, a so-called Fast Track algorithm, to differentiate SSc from non-SSc patterns in NVC specimens. However, subjectivity among capillaroscopists remains a limitation. Our aim was to perform a software-based analysis of NVC peculiarities in a cohort of samples from SSc and RP patients and, subsequently, build a Fast Track-inspired algorithm to identify DPs without the constraint of interobserver variability. METHODS: NVCs were examined by 9 capillaroscopists. Those NVCs whose DPs were consensually agreed (≥2 out of 3 interobservers) were subsequently analysed with an in-house developed software. Each variable's results were grouped according to the consensually agreed DPs in order to identify useful hallmarks to categorise them. RESULTS: Eight-hundred and fifty-one NVCs (21 957 images) whose DPs had been consensually agreed were software-analysed. Appropriate cut-offs set in capillary density and percentage of abnormal and giant capillaries, tortuosities and hemorrhages allowed DP categorization and the development of the CAPI-Score algorithm. This consisted of 4 rules: Rule 1, SSc vs non-SSc, accuracy 0.88; Rules 2 and 3, SSc-early vs SSc-active vs SSc-late, accuracy 0.82; Rule 4, non-SSc normal vs non-SSc non-specific, accuracy 0.73. Accuracy improved when the analysis was limited to NVCs whose DPs had achieved full consensus among interobservers. CONCLUSIONS: The CAPI-Score algorithm may become a useful tool to assign DPs by overcoming the limitations of subjectivity.

Mechanisms of action of vitamin B1 (thiamine), B6 (pyridoxine), and B12 (cobalamin) in pain: a narrative review.

Pain is a complex sensory and emotional experience with nociceptive, nociplastic, and neuropathic components. An involvement of neurotropic B vitamins (B1 - thiamine, B6 - pyridoxine, and B12 - cyanocobalamin) as modulators of inflammation and pain has been long discussed. New evidence suggests their therapeutic potential in different pain conditions. In this review, we discuss the main role of neurotropic B vitamins on different nociceptive pathways in the nervous system and to describe their analgesic action mechanisms. The performed literature review showed that, through different mechanisms, these vitamins regulate several inflammatory and neural mediators in nociceptive and neuropathic pain. Some of these processes include aiming the activation of the descending pain modulatory system and in specific intracellular pathways, anti-inflammatory, antioxidative and nerve regenerative effects. Moreover, recent data shows the antinociceptive, antiallodynic, and anti-hyperalgesic effects of the combination of these vitamins, as well as their synergistic effects with known analgesics. Understanding how vitamins B1, B6, and B12 affect several nociceptive mechanisms can therefore be of significance in the treatment of various pain conditions.

Supplementation with liquid whey and ACIDAL® ML in drinking water affect gut pH and microflora and productive performance in laying hens.

1. As the use of antibiotics as growth promoters has been banned in many regions, there has been an on-going search for possible alternative compounds, such as prebiotics and organic acids. 2. This study was conducted to investigate the influence of liquid whey (LW) and organic acid (ACIDAL® ML) supplementation on performance, eggs characteristics, gut pH and health status in laying hens. 3. Seven hundred and fifty, Isa Brown chicks were randomly assigned to five treatments groups (n = 150) and each treatment had five replicates of 30 birds each. The birds were reared for 48 weeks. The treatments were administered in the drinking water at doses of: 250 ml/l of LW (Lacto25), 500 ml/l of LW (Lacto50) or 1 ml/l of ACIDAL® ML (Aci). A positive control group (T+) was treated with 500 mg/l of Tetracolivit (an antibiotic). The negative control group (T-) did not receive any treatment in the drinking water. 4. Administration of LW or ACIDAL® ML in the drinking water reduced (P < 0.05) the pH in the crop, proventriculus, ileum and caeca, as well as total coliform bacteria and E. coli, but increased Lactobacillus spp. in the ileum and caecum, compared to the negative control. 5. Oviposition was earlier in the birds in both the Lacto50 and Aci groups. The weight of birds at first lay and point of lay in the four treated groups was higher than those in negative control group. Furthermore, egg production was increased by 10.44% in birds receiving Lacto25, but the weight and quality traits were unaffected, while the egg shell ratio was higher in the Aci group compared to the other treatments. 6. The data indicated that addition of LW or ACIDAL® ML improved hens' performance by modifying gut pH and microflora.

Validation and reliability of a Spanish version of Simple Shoulder Test (SST-Sp).

BACKGROUND: The Simple Shoulder Test (SST-Sp) is a widely used outcome measure. OBJECTIVE: The purpose of this study was to develop and validate a Spanish-version SST (SST-Sp). METHODS: A two-stage observational study was conducted. The SST was initially cross-culturally adapted to Spanish through double forward and backward translation and then validated for its psychometric characteristics. Participants (n = 66) with several shoulder disorders completed the SST-Sp, DASH, VAS and SF-12. The full sample was employed to determine factor structure, internal consistency and concurrent criterion validity. Reliability was determined in the first 24-48 h in a subsample of 21 patients. RESULTS: The SST-Sp showed three factors that explained the 56.1% of variance, and the internal consistency for each factor was α = 0.738, 0.723 and 0.667, and reliability was ICC = 0.687-0.944. The factor structure was three-dimensional and supported construct validity. Criterion validity determined from the relationship between the SST-Sp and DASH was strong (r = -0.73; p < 0.001) and fair for VAS (r = -0.537; p < 0.001). Relationships between SST-Sp and SF-12 were weak for both physical (r = -0.47; p < 0.001) and mental (r = -0.43; p < 0.001) dimensions. CONCLUSIONS: The SST-Sp supports the findings of the original English version as being a valid shoulder outcome measure with similar psychometric properties to the original English version.

An assessment of morphometric indices, blood chemistry variables and an energy meter as indicators of the whole body lipid content in Micropterus dolomieu, Sander vitreus and Ictalurus punctatus.

The effectiveness of several non-lethal techniques as indicators of total lipid content in smallmouth bass Micropterus dolomieu, walleye Sander vitreus and channel catfish Ictalurus punctatus was investigated. The techniques included (1) the Fulton and relative condition factors, (2) relative mass, (3) plasma indicators of nutritional status (alkaline phosphatase, calcium, cholesterol, protein, triglycerides and glucose) and (4) readings from a hand-held, microwave energy meter. Although simple linear regression analysis showed that lipid content was significantly correlated with several predictor variables in each species, the r2 values for the relations ranged from 0·17 to 0·50 and no single approach was consistent for all species. Only one model, between energy-meter readings and lipid content in I. punctatus, had an r2 value (0·83) high enough to justify using it as a predictive tool. Results indicate that no single variable was an accurate and reliable indicator of whole body lipid content in these fishes, except the energy meter for I. punctatus.

Alterations in the antioxidant defense system in prepubertal children with a history of extrauterine growth restriction.

PURPOSE: The role of oxidative stress is well known in the pathogenesis of acquired malnutrition. Intrauterine growth restriction has been associated with an imbalance in oxidative stress/antioxidant system. Therefore, early postnatal environment and, consequently, extrauterine growth restriction might be associated with alterations in the antioxidant defense system, even in the prepubertal stage. METHODS: This is a descriptive, analytical, and observational case-control study. The study included two groups; 38 Caucasian prepubertal children born prematurely and with a history of extrauterine growth restriction as the case group, and 123 gender- and age-matched controls. Plasma exogenous antioxidant (retinol, ß-carotene, and α-tocopherol) concentrations were measured by HPLC; antioxidant enzyme activities of catalase, glutathione reductase, glutathione peroxidase, and superoxide dismutase were determined in lysed erythrocytes by spectrophotometric techniques. RESULTS: Catalase and glutathione peroxidase concentrations were significantly lower in extrauterine growth restriction children than in controls (P < 0.001). Lower plasma retinol concentrations were found in the case group (P = 0.029), while concentrations of ß-carotene and α-tocopherol were higher (P < 0.001) in extrauterine growth restriction prepubertal children as compared with controls. After correction by gestational age, birth weight, and length, statistically significant differences were also found, except for retinol. CONCLUSIONS: Prepubertal children with a history of extrauterine growth restriction present alterations in their antioxidant defense system. Knowing these alterations may be important in establishing pharmacological and nutritional treatments as this situation might be associated with higher metabolic disorders in adulthood.

Spinal cord infarction in carriers of methylenetetrahydrofolate reductase-polymorphism-like unique risk factor: report of two cases.

STUDY DESIGN: A case report. OBJECTIVE: To present two cases of spinal cord infarction (SCI) in carriers of the C677T methylenetetrahydrofolate reductase (MTHFR) polymorphism. SETTING: Physical Medicine and Rehabilitation Department, Section for Rehabilitation and Traumatology, Hospital Virgen de las Nieves, Granada, Spain. METHODS: Two cases are presented, one with SCI at the C7 level American Spinal Injury Association (ASIA) A and one at the C5 level (ASIA A). One patient presented an acute onset of tetraplegia and the other a centromedular syndrome. In both cases the patients were carriers of the MTHFR polymorphism, which is a unique risk factor. RESULTS: Increased blood levels of homocysteine related to mutation of the MTHFR gene increase the risk of a thrombotic episode, triggering the development of SCI. These two cases increase the limited number reported in the recent literature regarding MTHFR polymorphism carriers suffering from thrombotic SCI. CONCLUSION: MTHFR mutation can be considered a risk factor for thrombotic SCI, but it is not the sole risk factor. We propose that a consensus regarding the inclusion of anticoagulation treatment after confirmation of the diagnosis in these patients is needed.

Effects of parenteral nutrition formulas on plasma lipid profile in children with bone marrow transplantation.

BACKGROUND/AIMS: Children undergoing bone marrow transplantation (BMT) often require parenteral nutrition (PN). This is a comparative study of plasma lipid profiles in BMT children after fish oil or soybean PN. METHODS: A total of 14 children with BMT requiring PN for at least 10 days were recruited during 24 months. They were randomized to receive a lipid emulsion enriched with ω3 polyunsaturated fatty acid, or soybean oil. Clinical monitoring was performed. Blood samples were collected before and after administration of PN to analyze the lipid profile. RESULTS: There were no complications associated with PN. The increase in TG levels was more pronounced after administration of an enriched ω3 emulsion and the decrease in cHDL and apo A was greater after administration of soybean. The ω3 group showed an increase in eicosapentaenoic and a decrease in arachidonic acids compared to the soybean group. Both groups showed similar levels of linolenic acid. CONCLUSION: PN with soybean or ω3 emulsions for 10 days is safe in children. However, research in children are necessary in order to examine the impact of the duration of PN and the type of lipid formula used, and determine their health benefits in relation to the fatty acid profile.

Allergen-specific immunotherapy: update on immunological mechanisms.

UNLABELLED: Immunotherapy selectively modulates the allergen-specific immune response. It involves the gradual administration of increasing amounts of allergen for the purpose of inducing protective immunological changes and it is the only curative approach for specific type I allergy. AIM: Description of the allergic inflammation.- Comprehension of the early cellular changes after specific immunotherapy has been initiated. Exposure of the mechanisms involved in tolerance induction by regulatory T cells (Treg) with the inhibition of the Th2 responses. Comprehension of IL-10 and transforming growth factor (TGF- ) roles. Explanation of specific IgE, IgG and IgA changes. Description of the suppression of inflammatory responses during immunotherapy.

Life-history traits and population decline of the Atlantic mackerel Scomber scombrusin the Adriatic Sea.

This study investigated demographic structure and reproductive characteristics of the Atlantic mackerel Scomber scombrus, in relation to landing trends in the northern-central Adriatic Sea. Results highlighted the occurrence of only small-sized and young-age individuals, and a marked decline from the 1990s to the present in maximum age (from 8 to 3 years) and total length (L(T); from 420 to 360 mm). Fecundity ranged between 40,000 and 190,000 eggs, and was related to female L(T). High levels of atresia implied lower values of actual fecundity. Sexual maturity was attained by 72·8% of individuals in their first year of life at 200 mm. The reduction in maximum L(T) resulted in a marked decline in the population egg production, while the reduction in maximum age implied that females participated in fewer spawning events.

Spine apparatus modulates Ca 2+ in spines through spatial localization of sources and sinks.

Dendritic spines are small protrusions on dendrites in neurons and serve as sites of postsynaptic activity. Some of these spines contain smooth endoplasmic reticulum (SER), and sometimes an even further specialized SER known as the spine apparatus (SA). In this work, we developed a stochastic spatial model to investigate the role of the SER and the SA in modulating Ca 2+ dynamics. Using this model, we investigated how ryanodine receptor (RyR) localization, spine membrane geometry, and SER geometry can impact Ca 2+ transients in the spine and in the dendrite. Our simulations found that RyR opening is dependent on where it is localized in the SER and on the SER geometry. In order to maximize Ca 2+ in the dendrites (for activating clusters of spines and spine-spine communication), a laminar SA was favorable with RyRs localized in the neck region, closer to the dendrite. We also found that the presence of the SER without the laminar structure, coupled with RyR localization at the head, leads to higher Ca 2+ presence in the spine. These predictions serve as design principles for understanding how spines with an ER can regulate Ca 2+ dynamics differently from spines without ER through a combination of geometry and receptor localization. Highlights: 1RyR opening in dendritic spine ER is location dependent and spine geometry dependent. Ca 2+ buffers and SERCA can buffer against runaway potentiation of spines even when CICR is activated. RyRs located towards the ER neck allow for more Ca 2+ to reach the dendrites. RyRs located towards the spine head are favorable for increased Ca 2+ in spines.

Tools for comprehensive evaluation of sexual function in patients with multiple sclerosis.

INTRODUCTION: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) that affects young adults, causing a variety of symptoms (motor alterations, visual alterations, loss of sphincter control, gait alterations) that impair the patient's functional status. However, other symptoms, such as sexual dysfunction, can also have an effect on quality of life. DEVELOPMENT: Sexual dysfunction can occur at any time during the course of the disease; its prevalence varies between 50% and 90%, and it can be secondary to demyelinating lesions in the spinal cord and/or brain or caused by symptoms that do not directly involve the nervous system (fatigue; psychological, social, and cultural factors; etc.). Although its prevalence and impact on quality of life are well known, sexual dysfunction is still frequently underestimated. Therefore, in this article we review the different scales for assessing presence or severity of sexual dysfunction, in order to offer early multidisciplinary management. CONCLUSION: We evaluated 5 questionnaires that could identify the presence of sexual dysfunction in patients with MS and determine its aetiology, assisting in treatment decision making. MS must be understood as a complex disease that encompasses and compromises different aspects of patients' health, and goes beyond simply measuring disability.

Consensus on complementary feeding from the Latin American Society for Pediatric Gastroenterology, Hepatology and Nutrition: COCO 2023.

Complementary feeding (CF) is defined as the feeding of infants that complements breastfeeding, or alternatively, feeding with a breast milk substitute, and is a process that is more than simply a guide as to what and how to introduce foods. The information provided by healthcare professionals must be up-to-date and evidence-based. Most of the recommendations that appear in the different international guidelines and position papers are widely applicable, but some must be regionalized or adapted to fit the conditions and reality of each geographic zone. The Nutrition Working Group of the Latin American Society for Pediatric Gastroenterology, Hepatology and Nutrition (LASPGHAN) summoned a group of experts from each of the society's member countries, to develop a consensus on CF, incorporating, whenever possible, local information adapted to the reality of the region. The aim of the present document is to show the results of that endeavor. Utilizing the Delphi method, a total of 34 statements on relevant aspects of CF were evaluated, discussed, and voted upon.

[Rehabilitation and COVID disease: characterization and follow-up of hospitalized patients in Granada, Spain]. / Tratamiento rehabilitador de la infección por COVID: caracterización y seguimiento de pacientes hospitalizados en Granada, España.

OBJECTIVE: The characterization of a sample of patients hospitalized with complications of the COVID-19 infection regarding potential prognostic factors, clinical evolution, and impact of rehabilitation treatment on functional, motor, and respiratory outcomes. METHOD: Descriptive, retrospective, longitudinal study of a cohort of patients under rehabilitation treatment admitted at Virgen de las Nieves University Hospital in Granada from March to June 2020, assessed upon admission, discharge and at 3 rd month using physical condition scales (IFIS) and functional assessment: general (Rankin, Barthel), respiratory (mMRC, BORG) and gait (FAC). RESULTS: 30 patients with a mean age of 62.8 (54-70) years were included, 80% with comorbidity: hypertension 66.7%, obesity 36.7%, diabetes 33.3%. The mean hospital stay was 45.4 days, with 86.7% requiring ICU (29.1 days) and 76.7% of them required mechanical ventilation. An 86.7% of the patients presented with complications, mostly with polyneuropathy-myopathy of the critical patient (83.3%). At discharge, 80% required walking assistance. The functionality index showed a "U"-evolution at admission, discharge and at 3 rd month (Barthel 93.8; 60.0; 91.6 respectively). A greater functional decline (Barthel < 60) was found in male patients, COPD, HT, obesity, and elevated protein C reactive at admission; and a more favourable evolution in those with elevated D-dimer and lymphocyte values upon admission. CONCLUSIóN: Hospital admission for COVID-19 patients involve complications at the functional, respiratory and gait levels that are mostly serious but partially reversible at 3 months with rehabilitation treatment. Potential prognostic factors are described and deserve prospective studies.

[Foot and ankle ability measure: Validation of a Spanish version with 29 items in rehabilitation setting]. / Foot and ankle ability measure: validación de la versión española de 29 ítems en el área de rehabilitación.

OBJECTIVE: The Foot and Ankle Ability Measure (FAAM) is an internationally widely used outcome measure of foot and ankle disorders available in several languages. The purpose of this study was to develop and validate a FAAM Spanish-version with 29 items of Activities of Daily Living (ADL) and SPORT subscales in rehabilitation setting. MATERIALS AND METHODS: A two-stage observational study was conducted. The FAAM was cross-culturally adapted to Spanish through a double-forward translation and a double-backward translation; the psychometric properties were then validated. The participants (n = 147), with various chronic foot and ankle disorders, completed the Spanish version of the Foot and Ankle Ability Measure ADL and SPORT, SF-36, and a pain intensity visual analogue scale (Pain VAS). The full sample was used to determine the factor structure, the internal consistency, and the convergent criterion validity, and a subgroup (n = 46) was used to determine the reliability at 48-72 h. RESULTS: The factor structure of Spanish version of FAAM ADL and SPORT subscales were both one-dimensional, demonstrating high internal consistency (α = 0.97 and α = 0.93, respectively). The reliability values were ICC = 0.90 and ICC = 0.76, respectively. The convergent validity criterion of Spanish version of FAAM with the Pain VAS (r = 0.50) and Physical Function of SF-36 (r = 0.64) were moderately correlated. CONCLUSIONS: The Spanish version of FAAM with 29 items are a valid foot and ankle disorder outcome measure with similar psychometric properties to the original version and versions in other languages.

E-1500: Survey on feeding practices in the first 1,500 days of life, recommended by healthcare professionals in Latin America.

INTRODUCTION: Health-disease processes are established and programmed in the first 1500 days of life, a period in which nutrition and the microbiota play a fundamental role. Feeding practices vary, according to regional sociocultural characteristics. The Early Nutrition Group of the Latin American Society for Pediatric Gastroenterology, Hepatology and Nutrition (LASPGHAN) established the goal of identifying the main feeding practices in the first 1500 days that were recommended by health professionals in Latin America. MATERIALS AND METHODS: A survey was conducted on the aspects of maternal-infant and young child nutrition during the first 1500 days of life. An open invitation was extended to Latin American healthcare professionals to anonymously answer the online survey. RESULTS: A total of 1284 surveys from participants in 18 Latin American countries were analyzed. The mean age of the participants was 37.14 ±â€¯11.1 years, 75.7% were women, 64.7% were physicians, and the rest were nutritionists/nutriologists. A total of 71.4% were familiar with the concept of the first 1000 days of life, 95% answered that exclusive breastfeeding should be carried out up to 6 months of age, and 34.3% responded that complementary feeding should be begun between 4 and 6 months of age. There was scant knowledge regarding nutrition in the pregnant woman. Adherence to traditional complementary feeding practices was evident. CONCLUSIONS: In a group of Latin American healthcare professionals, knowledge about nutrition in the first 1000-1500 days of life of an individual is still incomplete and insufficient, showing the need for continued training of healthcare professionals, with respect to those themes.

Surgical wound healing in radio-tagged adult Pacific lamprey Entosphenus tridentatus held on different substrata.

Radio-tagged adult Pacific lamprey Entosphenus tridentatus held in a raceway with Plexiglas-lined walls and bottom healed more slowly and retained sutures longer than fish held in an all-concrete raceway or one with Plexiglas walls and a cobble-lined bottom. On all substrata, healing depended on when sutures were lost, and fish that lost their sutures in <14 days post-surgery healed faster than those that kept sutures longer. Long-term suture retention led to tissue trauma, infection and poor survival.

Complementary experimental/docking approach for determining chitosan and carboxymethylchitosan ability for the formation of active polymer-ß-galactosidase adducts.

The spontaneous aggregation of chitosan and carboxymethylchitosan polymers can be advantageous for the enzyme confinement on these colloidal systems during immobilization processes. The initial crucial step involves the polymer-enzyme adduct formation. The objective here is to determine the interactions that drive the adduct formation between these polymers and ß-galactosidase from Bacillus circulans. The chemical characterization of chitosan and its carboxymethyl-derivate allowed to explain their colloidal behavior and design the four-unit fragments ligands used for the docking study. The deacetylation degree (0.6 times lower), isoelectric point (5.2 instead 6.4) and substitution degree (DSO = 1.779 and DS2N = 0.441) of carboxymenthylchitosan are due to the hydroxide concentration (>25%) and 30 °C modification conditions. Favorable Van der Waals and H-bond interactions between chitosan-ß-galactosidase and contribution of electrostatic attraction mediated by calcium ions for carboxymethylchitosan-ß-galactosidase explained the zeta potential and dynamic light scattering results at pH 7.0. These interactions occur onto the external surface of this galactosidase, without affecting the catalytic activity. A cross-linked enzyme aggregates-type model was proposed for the formation of the adducts, based on the complementary experimental-docking results. They contribute understanding the behavior of polyelectrolyte chitosan-derived matrices for enzyme immobilization.

[Role of B vitamins, thiamine, pyridoxine, and cyanocobalamin in back pain and other musculoskeletal conditions: a narrative review]. / Papel de las vitaminas B, tiamina, piridoxina y cianocobalamina en el dolor de espalda y otras condiciones musculoesqueléticas: revisión narrativa.

Low back pain, as well as other musculoskeletal disorders (neck pain, osteoarthritis, etc.), are a very frequent cause of consultation both in primary care and in other hospital specialties and are usually associated with high functional and work disability. Acute low back pain can present different nociceptive, neuropathic and nonciplastic components, which leads to consider it as a mixed type pain. The importance of the concept of mixed pain is due to the fact that the symptomatic relief of these pathologies requires a multimodal therapeutic approach to various pharmacological targets. The antinociceptive role of the B vitamin complex has been recognized for several decades, specifically the combination of Thiamine, Pyridoxine and Cyanocobalamin (TPC). Likewise, there is accumulated evidence that indicates an adjuvant analgesic action in low back pain. The aim of the present review is to present the existing evidence and the latest findings on the therapeutic effects of the TPC combination in low back pain. Likewise, some of the most relevant mechanisms of action involved that can explain these effects are analyzed. The reviewed evidence indicates that the combined use of PCT has an adjuvant analgesic effect in mixed pain, specifically in low back pain and other musculoskeletal disorders with nociceptive and neuropathic components. This effect can be explained by an anti-inflammatory, antinociceptive, neuroprotective and neuromodulatory action of the TPC combination on the descending pain system.

Metabolomics in chemical risk analysis - A review.

Exposure to chemical hazards is a growing concern in today's society, and it is of utmost interest to know the levels of exposure to chemicals and the risks associated with such exposure in order to implement effective health prevention strategies. Chemical risk analysis represents a complex and laborious task due to the large number of known substances, but also unknown compounds and emerging risks that must be addressed. In this challenging scenario, the study of metabolic perturbations induced by exposure to a given chemical hazard has recently emerged as an interesting alternative approach to apply in chemical risk analysis. Specifically, the biomarkers of effect identified by metabolomics are expected to reveal the adverse effects of chemicals and further link exposure to disease development. In this context, analytical chemistry has become an essential part of the strategy to highlight such biomarkers. The corollary is that the relevance of the discovered biomarkers will largely depend on both the quality of the analytical approaches implemented and the part of the metabolome covered by the analytical technique used. This review focuses on describing significant applications of metabolomics in the field of chemical risk analysis. The different risk assessment steps, including hazard identification, dose-response assessment and exposure assessment, and risk management are addressed through various examples to illustrate that such an approach is fit-for-purpose and meets the expectations and requirements of chemical risk analysis. It can be considered as an innovative tool for predicting the probable occurrence and nature of risks, while addressing the current challenges of chemical risk analysis (e.g. replacement, reduction and refinement (3R) of animal testing, effects of exposure to chemical mixtures at low doses, etc.), and with the aim of responding to chemical exposures concerns in a holistic manner and anticipating human health problems.