Aphandra natalia  Barfod; Eugenia stipitate McVaugh; Gustavia macarenensis Philipson; Mauritia flexuosa L.f; Myrciaria dubia (Kunth) McVaugh; Oenocarpus bataua Mart; Plukenetia volubilis L.; Pouteria caimito (Ruiz and Pav.) Radlk.; and Solanum quitoense Lam. The analyzed Amazonian fruits contained bioactive compounds such as total polyphenols, flavonoids, carotenoids, and anthocyanins. This information highlights their potential as functional foods and the need for further research on underutilized crops.In the Ecuadorian Amazon region, there are various types of edible fruits that have distinct qualities and benefits. Understanding the uses, properties, and functions of these fruits is important for researching products that are only available in local markets. This review aims to gather and summarize the existing scientific literature on the ethnobotany, physicochemical composition, and bioactive compounds of these native fruits to highlight the potential of the region’s underutilized biodiversity. A systematic review was carried out following the PRISMA methodology, utilizing databases such as Web of Science, Scopus, Pubmed, Redalyc, and SciELO up to August 2023. The research identified 55 edible fruits from the Ecuadorian Amazon and reported their ethnobotanical information. The most common uses were fresh fruit consumption, preparation of typical food, and medicine. Additionally, nine native edible fruits were described for their physicochemical characteristics and bioactive components:  The Amazon is one of the most biodiverse ecosystems in the world; one-tenth of all living species are found in this biome . It coveMost tropical fruit production comes from Latin American and Caribbean countries. Brazil, Ecuador, México, and Costa Rica are the main producers and exporters of fresh tropical fruits worldwide . HoweverBioactive components of fruits, such as vitamins, carotenoids, and phenolic compounds, are associated with the prevention of chronic pathologies, including cancer, cardiovascular diseases, type 2 diabetes, and Alzheimer’s disease . These cLocal markets are a source of information on how botanical resources are used in different regions and on traditional knowledge in general . Among tOnce the importance of the bioactive profiles of fruits and their nutritional and functional properties have been established, and considering their high diversity in the Ecuadorian Amazon region, there has been little scientific exploration, which has prevented the deepening of new knowledge and their correct use. In this sense, the present work aimed to synthesize the available information on ethnobotany, physicochemical composition, and bioactive compounds of edible fruits present in the Ecuadorian Amazon to know and promote their importance, as well as to evaluate their existing biodiversity.After implementing the methodology, a thorough review of 66 documents was conducted, out of which 27 were considered relevant for the selection of edible fruits from the Ecuadorian Amazon and ethnobotanical description ,40,41,42The results of this work are presented in three subsections: the first one shows an analysis of the use, origin, and location of the fruits in the Ecuadorian Amazon, responding to the objective of analyzing their ethnobotany in a preliminary way. In the The analysis of the information made it possible to identify 55 species of edible fruits studied in the Ecuadorian Amazon . The proAphandra natalia; Eugenia stipitate; Gustavia macarenensis; Mauritia flexuosa; Myrciaria dubia; Oenocarpus bataua; Plukenetia volubilis; Pouteria caimito; Solanum quitoense , ethylene production (1.6 mg C2H4/kg⋅h), and pH (2.96 ± 0.20–3.3); this is probably because it is one of the fruits cultivated in the Ecuadorian Amazon that is marketed nationally, as well as yellow pitahaya, which is grown mainly in the province of Morona Santiago, city Palora, and it is mainly destined for exported [Plukenetia volubilis has high protein content, while Aphandra natalia, Gustavia macarenensis, and Plukenetia volubilis all have lipid content above 30%, indicating their potential as sources of vegetable fats.exported . Informaexported . PlukeneIdentifying and quantifying bioactive components can greatly impact the recognition and commercial success of fruits. Açaí, for example, was relatively unknown in the 1990s but became the third most popular fruit juice in the U.S. by 2008. Its high antioxidant capacity earned it the label of a superfood . The bioOenocarpus bataua reported transresveratrol content , and Gustavia macarenensis reported as non-detected [Aphandra natalia and Gustavia macarenensis reported α-tocopherols concentrations of 21.52 ± 1.30 and 90.23 ± 2.32 mg/Kg, respectively [In addition to the bioactive compounds shown in detected . This fodetected ; it is pdetected . Pulp oiectively ,27. Thesectively .Orellana, Sucumbíos, and Napo are the provinces of the Ecuadorian Amazon with the most records of useful species. In Ecuador, fruits are part of the plants mostly used by animals as food, and it has been recorded that the animals that mainly feed on fruits are birds, followed by mammals, fish, and reptiles . Fruits The second category of use of fruits is medicinal, followed by animal feed and materials. Regarding the use of fruits as medicine, younger generations may be less familiar with their properties, while women tend to be the main source of traditional knowledge and plant conservation. Communities located far from health centers tend to have more knowledge about plant use due to limited transportation and resources for accessing medicine. This contrasts with communities located closer to health centers .In Ecuador, fruits, seeds, and leaves are the most consumed parts of the food species . InteresAphandra natalia and Plukenetia volubilis, which are irregularly shaped. Morphometric characterization of fruits and seeds is essential for taxonomic identification and verification of environmental, phenotypic, and genetic variation in plant populations [The fruits from the Ecuadorian Amazon that reported morphometric weight data  are mostulations . Fresh fulations . Fruit wulations . Pulp yiulations .Fruits from the Ecuadorian Amazon are consumed by local people, especially for their sweet and exotic flavor. For farmers, fruit trees are not the main crops; rather, they are species that are kept on the farm to diversify products for self-consumption and to market their surplus at local fairs during the harvest season. The Amazon fruit season in Ecuador occurs once a year between November and March. Indigenous women are the main traders of Amazonian fruits and are the ones who report uses in addition to food, such as cosmetic and medicinal use. The difficulties that exist for the use of these fruits are the long distances that must be traveled to harvest them, the fact that they are highly perishable products, the scarce and inadequate transportation, and the low, unregulated prices. Despite this, it is encouraging that the younger generations still like Amazonian fruits, and there is a high demand from local people during the harvest season.Aphandra natalia, Gustavia macarenensis, and Plukenetia volubilis. The fat content of Aphandra natalia sampled in the Amazon region of Ecuador (57.92 ± 3.05 dry wt%) is higher than that of fruits of the same Aracaceae family, such as Mauritia flexuosa (38.38 dry wt%) and Oenocarpus bataua (21.65 dry wt%) sampled in the Brazilian Amazon [Aphandra natalia 71.92%; Mauritia flexuosa 75.7%; Oenocarpus bataua 76.8% in dry wt), so this fruit can be considered a source of high-quality vegetable oil [Gustavia macarenensis has a lipid profile composed of palmitic (42.89%) and oleic (43.30%) acids [In the nutritional composition of the fruits studied in the Ecuadorian Amazon , fiber an Amazon ; howeverable oil . In contpalmitic .89% and Plukenetia volubilis is characterized by a high content of polyunsaturated (51.5%) and monounsaturated (32.5%) fatty acids, which differ from a Peruvian accession that shows values of 46.6% and 36.5%, respectively. This is probably due to influential factors such as genetic differences and growing conditions like elevation and temperature [Eugenia stipitata can be explained by the amount of total sugars (50% dry wt%) and dietary fiber (39 dry wt%) [Eugenia stipitate, Gustavia macarenensis, Plukenetia volubilis, and Solanum quitoense is high compared to the 3.5% generally present in fruits [Myrciaria dubia and Pouteria caimito report low lipid and protein values but have benefits such as reduced oxidative stress and plasma cholesterol, respectively [The fat component of perature . The higdry wt%) . The pron fruits . Fruits ectively ,56. Despectively .Eugenia stipitata, Gustavia macarenensis, Oenocarpus bataua, and Pouteria caimito, confirming the potential of underutilized tropical fruits as functional foods.Antioxidant capacity is reported according to the method of analysis, which makes it difficult to make comparisons. However, it is a measure that allows establishing a reference on the capacity of a food to eliminate free radicals, which cause cell damage and are correlated with mutagenesis, carcinogenesis, and aging . This idMyrciaria dubia (camu-camu), considering that most tropical fruits have concentrations higher than 1000 mg/100 g. For instance, there are poorly known fruits present in the Amazon biome that have the highest reported concentrations; among them are acerola (1600 mg/100 g) and camu-camu (1882 ± 43.2 mg/100 g) [Fruits and vegetables are the best natural source of vitamin C for humans. Vitamin C is an antioxidant capable of terminating free radical chain reactions through disproportion to non-toxic and non-radical products . The frug/100 g) .Myrciaria dubia pulp, as well as the contents of the peel of Gustavia macarenensis, Myrciaria dubia, and Oenocarpus bataua, was higher than 1000 mg GAE/100 g. Mauritia flexuosa and Solanum quitoense have values above 700 mg GAE/100 g, which are higher than those reported for Mauritia flexuosa samples from two Brazilian localities (362.90 ± 7.98–435.08 ± 6.97) [Solanum quitoense collected in the province of Pichincha, Ecuador (1008 mg of GAE/100 g d.w.) [Oenocarpus bataua and Gustavia macarenensis showed values above 600 mg GAE/100 g for the pulp, although the concentration was higher in their peels; a similar result showed the pulp of Oenocarpus bataua collected in the city of Pucallpa in the Peruvian Amazon (672.3 ± 46.9). The variation in phenol concentrations of fruits from different localities may be due to climatic and agronomic factors such as light exposure, rainfall, relief, soil type, location, crop variety, harvest time, crop management, maturity stage of the product, type, and storage conditions of the harvest, etc. [Phenolic compounds are the most abundant dietary antioxidants that protect mammalian systems. Tropical fruits are rich sources of polyphenols compared to temperate climate fruits, especially those with polyphenol concentrations greater than 1000 mg GAE/100 g . Of the  ± 6.97)  and lowe g d.w.) . Oenocarst, etc. .Solanum quitoense and Eugenia stipitata, which report higher values than products considered rich in these nutrients, such as Allium fistulosum L (272.05 mg/100 g of dry weight), Psidium guajava L. (112. 85 mg/100 g), and Camellia chinensis Kuntze (149.10 mg/100 g) [Gustavia macarenensis and Oenocarpus bataua, it is highlighted that the flavonoid content is higher in the peels than in the edible part of the fruit.Flavonoids constitute the largest class of polyphenols. The fruits in which there was a higher number of flavonoids were g/100 g) , but, thg/100 g) . For GusEugenia stipitata and Solanum quitoense were the fruits that reported higher contents of total carotenoids (31 and 34.8 µg β-carotene/g respectively); however, Amazonian fruits studied in Brazil, such as Mauritia flexuosa (234–713 µg/g) and Bactris gasipaes (26–357 µg/g) [Carotenoids are very versatile bioactives because they are precursors of vitamin A, pigments, antioxidants, and health-promoting compounds. In fruits, carotenoids such as xanthophylls are found in greater quantities and are mainly housed in the chromoplasts of ripe fruits  and prov57 µg/g) , showed 57 µg/g) , ripenin57 µg/g) .Gustavia macarenensis, Mauritia flexuosa, Myrciaria dubia, and Oenocarpus bataua, while Solanum quitoense and Eugenia stipitata indicate that these compounds were not detected. However, the reported ranks are low with respect to the anthocyanin content of blackberries (81.3 mg/10 g FW), black grapes (41 mg/10 g FW), and raspberry (22.8 mg/10 g FW), which are anthocyanin-rich [Anthocyanins are flavonoid compounds found in plant tissues and are characterized by their antioxidant properties and pigmenting power. In fruits, they constitute one of the pigments responsible for the color change in the ripening process, which allows their identification for animal consumption and the distribution of viable ripe seeds ,121. Pignin-rich .Aphandra natalia and Gustavia macarenensis recorded in Tocopherols can scavenge free radicals and protect plant tissues from lipid peroxidation and oxidative damage. The concentration of pulp oil from the fruits Considering the characteristics and properties of native Amazonian fruits, it is crucial to expand research on their nutraceutical functions and the domestication process of these species, which begins with the exploitation of wild plants, continues with the cultivation of plants selected by nature, and ends with the fixation of morphological and genetic characteristics through human selection. This will allow for the establishment of appropriate strategies for using genetic resources, as well as for the conservation and extraction of non-timber resources ,126.The study area for this research was the Ecuadorian Amazon region, which, according to the political–territorial division of the country, is subdivided into 6 provinces with administrative autonomy: Sucumbíos; Napo; Orellana; Pastaza; Morona Santiago; and Zamora Chinchipe . The impThe systematic review of the literature conducted from June to August 2023 was carried out following the guidelines for the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) . BrieflyAphandra natalia, Eugenia stipitate, Gustavia macarenensis, Mauritia flexuosa, Myrciaria dubia, Oenocarpus bataua, Plukenetia volubilis, Theobroma cacao); however, Theobroma cacao was excluded because it is a traditional export product. The search for information on the 9 selected fruits was carried out using the keywords in The databases used were Scopus, Web of Science, PubMed, Scielo, and Redalyc. Articles published up to August 2023 were included. The keywords on which the search was based are described in Aphandra natalia; Eugenia stipitate; Gustavia macarenensis; Mauritia flexuosa; Myrciaria dubia; Oenocarpus bataua; and Plukenetia volubilis. The inclusion criterion for the second search was the 10 most-cited documents.The search for the identification of edible fruits studied in the Ecuadorian Amazon region yielded a total of 310 documents, which were screened, including only 27 . In addiAphandra natalia, Solanum quitoense, and Eugenia stipitata. The analysis of the ethnobotanical information identified that the most used part of the fruits is the pulp, that the most frequent uses of the fruits are fresh consumption, preparation of typical dishes, and medicinal use, and that Sucumbíos and Orellana are the Amazonian provinces where the fruits have been investigated the most.The Ecuadorian Amazonian fruit trees with the most studies available were Aphandra natalia, Solanum quitoense, Gustavia macarenensis, and Plukenetia volubilis were relevant with respect to what the fruits generally present, which demonstrates their potential as an alternative for the food industry through their processing, considering their high susceptibility and seasonal production.Within the physicochemical characteristics of fruits, morphometric and nutritional content information is the most regularly reported. The fiber, fat, and protein contents of the Amazonian fruits Solanum quitoense and Eugenia stipitata were the fruits with the highest content of total flavonoids and carotenoids in the pulp, while Gustavia macarenensis and Oenocarpus bataua reported higher amounts of anthocyanins in the pulp and flavonoids in the peel. The amount of these bioactive components reported in Ecuadorian Amazonian fruits are like products characterized by their high content, which allows asserting the nutraceutical capacity of these products.The bioactive components analyzed in all fruits were total polyphenols. Considering the 55 edible fruits identified and 9 fruits selected for this bibliographic review, there is a great need to expand research on quality parameters, bioactive components, and domestication of native Amazonian fruits to establish nutritional alternatives with nutraceutical properties and the commercialization of non-timber resources that can contribute to the sustainable development of the region.


To compare the incidence of covid-19 symptoms between informal home-based workers and a control group and to assess the association of these cases with blood elements concentrations and other relevant risk factors for Sars-Cov-2 infection. Welders chemically exposed to potentially toxic elements (PTEs) (n = 26) and control participants (n = 25) answered questionnaires on adherence to social distancing and signs and symptoms of the disease for five months during the covid-19 pandemic. After follow-up, covid-19 serology tests were performed on a subsample of 12 chemically exposed workers and 20 control participants. Before the pandemic, PTE concentrations in blood  were measured by ICP-MS. The chemically exposed group had higher lead and cadmium levels in blood (p < 0.01). The control group presented lower adherence to social distancing (p = 0.016). Although not significant, welders had a 74% greater chance of having at least one covid-19 symptom compared with control participants, but their adherence to social distancing decreased this chance by 20%. The use of taxis for transportation was a risk factor significantly associated with covid-19 symptoms. The lower adherence to social distancing among the control group greatly influences the development of covid-19. The literature lacks data linking exposure to PTEs and Sars-Cov-2 infection and/or severity. In this study, despite chemical exposure, working from home may have protected welders against covid-19, considering that they maintained greater social distancing than control participants. Contamination by PTEs can cause other adverse effects to health and the environment. This risk is even higher when occupational activities are informal and performed at home, where families may be at risk of occupational exposure in the absence of occupational hygiene3.Exposure to potentially toxic elements (PTEs) occurs in many occupational activities. Welding materials can include metal alloys, mixtures made of different steels and chemical elements, which can be inhaled in the form of welding fumes. Thus, welding is one of the occupations most associated with respiratory diseases4, including covid-19, which is caused by the new coronavirus. In 2020, one in six people infected with covid-19 become seriously ill and experience breathing difficulties. Older adults and individuals with underlying health conditions, such as high blood pressure, heart and lung problems, diabetes, or cancer, are at increased risk of becoming seriously ill5.Exposure to pollutants, overcrowded housing, and socioeconomic stress are conditions that may promote greater susceptibility and the development of more severe symptoms of infectious diseases6. In 2019, a proteomic study based on the saliva of informal and home-based jewelry welders showed that exposure to PTEs  modulates protein expression. According to the results, welders may have immunity problems and their genes were overrepresented in metabolic processes, catalytic activity, stimulus-response, response to toxic substances, metabolism activity, apoptosis, changes in the cell cycle, and stress response8.Informal, home-based, and outsourced welders are influenced by their internal exposome and studies on associations with diseases should consider this type of occupational activityThe global scenario of the covid-19 pandemic has increased the importance of assessing this type of occupational exposure and the negative health effects related to infectious diseases. Thus, this study aimed to compare the incidence of covid-19 symptoms between home-based and informal workers engaged in jewelry and fashion jewelry production and a control group, assessing the association of symptomatic episodes with blood metal concentrations and other relevant risk factors for Sars-Cov-2 infection.This longitudinal study included home-based and informal jewelry welders of a local productive arrangement in the city of Limeira, São Paulo, and a control group with individuals who lived in the same neighborhood as the workers, but were not engaged in an occupational activity associated with chemical exposure.9. Previous studies published by the research group present further details on the work processes and characteristics of informal home-based activities13.The local productive arrangement is an important jewelry and fashion jewelry production center in Brazil, responsible for 60% of the country’s jewelry productionA era “omics” voltada para a sociedade: o impacto do trabalho formal e informal sobre o expossoma dos trabalhadores com ênfase em metabolômica, transcriptômica e lipidômica) were invited to participate in this study. The initial recruitment was performed with the help of community agents of family health centers. All participants were women, in order to standardize this variable. Participants in the exposed group performed jewelry welding at home. Participants in the control group lived in the same neighborhood as the workers (at least four houses away) and performed no activity with chemical exposure. Usually, they worked outside the home. Participants who met this inclusion criterion, agreed to participate in the study, and signed the informed consent form were included. Women younger than 18 years and who were pregnant or diagnosed with cancer were excluded.All adults participating in a preliminary study  and control participants (n = 25) were followed up for five months during the covid-19 pandemic (June to September and December 2020) for the characterization of symptoms and preventive behaviors. With a sample size of 51 participants, ratio differences of 40% with a power of 80% could be found for dichotomic variables, as well as differences in means that exceed 1.2 times the standard deviation between samples with a power of 85% for quantitative variables . At the end of the follow-up, covid-19 serology tests were performed on a subsample of 32 participants who agreed to undergo the test, including 12 from the chemically exposed group and 20 from the control group .®). Samples were diluted 1:50 in a 15 mL Falcon® polypropylene tube (Becton Dickinson) with a solution of 0.01% (v v1) Triton® X-100, 0.5% (v v1) nitric acid, and 1 mL of an internal standard solution of Y, Ga, Ir, and Tb. High purity deionized water (resistivity: 18.2 M Ω cm at 25°C) was used to prepare samples and solutions. Quality control of analytical results was performed by calibration curves, blank analysis, and an analysis of the certified reference material  for every 15 samples. A deviation between replicates (RSD) of 30% was considered.Before the pandemic, PTE concentrations in the blood of participants  were measured using an inductively coupled plasma mass spectrometer . Blood samples (6 mL) were collected in October 2019 at the participants’ home and stored in heparin trace element-free tubes  and signs and symptoms of the disease . Participants also answered questions on their current working conditions and the effect of the pandemic on their jobs . Thus, information included all symptoms perceived from October 2020 to the day of serology tests (December 2020). Throughout the five-month follow-up, 197 observations were collected from the 51 participants and 69 symptomatic episodes were identified.® EDTA tubes.The material for blood collection was prepared at the Laboratory for the Analysis of Human Exposure to Environmental Contaminants of the School of Public Health of the Universidade de São Paulo, São Paulo, Brazil. Blood collection was performed by an experienced nurse at the participants’ home by prior appointment. Venous blood was collected in BD Vacutainer® SARS-CoV-2 Total (COV2T) assay  was used for in vitro diagnostics in the qualitative detection of total antibodies (including IgG and IgM) to help with the diagnosis of patients with suspected SARS-CoV-2 infection and the identification of patients with an adaptive immune response, pointing to a recent or previous infection.After blood collection, samples were labeled and transported in an ice box to the laboratory of the Faculdade de Medicina do ABC, where antibody serology tests were performed. First, samples were centrifuged to separate the serum. Then, 10 μL of serum was diluted to 1.0 mL in the sample buffer and mixed thoroughly using a vortex. Analyses were performed for total antibodies and IgG, which was detected using Euroimmun Elisa tests . In these tests, the antigen is the structural recombinant protein, the S1 subunit of the SARS-CoV-2 spike protein, which is more specific than other antigens. The Advia CentaurThe chemically exposed and control groups were compared using chi-square tests for dichotomous variables . Moreover, the t-test (parametric) was used to compare continuous variables . The Mann–Whitney test (nonparametric) was used for body mass index (BMI) and Cr, Co, As, Cd, Hg, and Pb concentrations in blood. The frequency of symptoms  and the difference between symptoms in the groups were assessed (Fisher’s exact test or chi-square test).Participants’ symptoms were also analyzed by assessing the incidence of a composite outcome defined for the presence of at least one covid-19 symptom  during repeated assessments. Later, the associations between this composite outcome and variables, such as social distancing parameters and PTE levels, were assessed using random-effect logistic regression, considering the participant as the clustering variable. Statistical analysis was performed using Stata 14.2.Headache, congestion, and cough were the most frequent symptoms . Congestion was the only symptom that statistically differed between groups (p = 0.02), as it was more frequently among welders. Other symptoms had borderline significance (p = 0.05) at different points during follow-up: cough and diarrhea were more prevalent among welders while control participants reported more tiredness. The control group presented lower adherence to social distancing than the chemically exposed group (p = 0.02), corroborating the greater number of days and hours spent away from home (p < 0.0001) and the higher use of public transportation, such as the bus, by control participants (p = 0.006) compared with chemically exposed participants. This result is in line with participants’ occupational activities, since welders performed informal home-based work whereas control participants needed to leave home for work several days per week and stay out for longer periods.The covid-19 pandemic affected the occupational activity of the chemically exposed group, which decreased or was interrupted more frequently than the activities of the control group (p < 0.001). During follow-up, 41.4% of informal welders reported a reduction in the amount of work and 31% stopped working during the pandemic. For the control group, work conditions were quite different: for 36% of control participants, the pandemic did not affect their work, and 39% were not working before the pandemic.In total, 63% of participants agreed to undergo covid-19 serology tests (n = 32), especially control participants (n = 20). Among participants who refused to undergo the test, 73.7% were from the chemically exposed group (p = 0.012) and most of them did not present the composite outcome of covid-19 symptoms  compared with those who tested positive (0.99 ± 0.53 µg dL1).We observed no significant association between test results and covid-19 symptoms, as presented by the composite outcome (p = 0.96). The results of serology tests also did not differ statistically between the two groups (p = 0.102). PTE levels were also similar for both positive and negative test results, except for Pb (p = 0.0306), as its levels were higher in participants who tested negative . Moreover, 40.9% of the sample had bronchitis, asthma, or upper respiratory infections . Welders are at risk of developing various respiratory signs and symptoms, since they are exposed to fumes made of a complex mixture of toxic elements23. Studies confirmed the association between welding and reduced pulmonary function, chronic bronchitis, and increased prevalence of wheezing24. Based on evidence from human and animal studies, the International Agency for Research on Cancer25 classified welding fumes as possibly carcinogenic to humans. According to the Occupational Safety and Drug Administration, exposure to welding fumes can cause respiratory problems, cancer, ulcers, damage to the kidneys and nervous system, among other diseases26.Some welders already had respiratory symptoms before the pandemic, caused mainly by occupational exposure, which may explain the lack of association between covid-19 test results and symptoms. In a descriptive analysis performed in 2019, before the covid-19 pandemic27. The adverse effects of toxic environmental and occupational exposure deteriorate the immune system, reducing barrier function, worsening airway inflammation, oxidative stress, and apoptosis, and increasing the likelihood of comorbidities, symptom severity, and covid-19 mortality28. Data show that As, Cd, Hg, and Pb exposure is associated with respiratory dysfunction and the severity of respiratory diseases, including influenza and pneumonia28.Besides its direct effect on respiratory physiology, exposure to toxic metals in welding fumes significantly modulate immune mechanisms, increasing welders’ susceptibility to respiratory infections30. Pb levels in the blood of welders are associated with a significant lack of T helper lymphocytes, IgG, IgM, C3, C4 complement levels, chemotaxis, and neutrophil migration31. Jusko et al.32 found that the odds of children seronegative to measles, mumps, and rubella increased with higher Pb concentrations in blood, which shows potential immunosuppression at Pb concentrations in blood < 5 µg dL1.In this study, participants who tested negative for the SARS-CoV-2 antibody had the highest Pb concentrations in blood, which may be due to possible immunosuppressive effects of Pb. This element can affect humoral immune response by reducing IgA and IgG production33. Public transports are confined spaces conducive for the transmission of infectious diseases caused by respiratory viruses and may play a crucial role in the nationwide spread of covid-1934. To prevent or control the spread of the disease, improving health education of passengers and drivers on the use of masks and hand hygiene and the ventilation and disinfection of vehicles is paramount34.The only risk factor with a significant association with covid-19 symptoms was the use of taxis for transportation. Previous studies presented evidence on human-to-human transmission of covid-19 in public transport vehicles, such as trains, buses, and airplanes35. The performance of other tests to diagnose covid-19, the number of samples analyzed, the nutritional status of participants, and the duration of the observation period can be limitations of this study. The sample size used may produce inaccurate estimates, with wide confidence intervals. Moreover, the power of the study may be insufficient to identify all associations. However, the interpretation of odds ratios shows associations between chemical exposure and covid-19 symptoms. These results point insights raised in an exploratory study. The associations observed between transportation (taxi) and the prevalence of covid-19 symptoms reinforce other studies that found robust associations36. Although the symptom outcome may have other etiologies, acute syndromes are relevant in a pandemic context. Moreover, if we considered a non-differential lack of specificity between different levels of exposure, the association could be even greater with real covid-19 cases37.This study cannot exclude cross-reactivity with SARS-CoV-1 due to the high degree of similarity between S1 of SARS-CoV-1 and SARS-CoV-2. However, SARS-CoV-1 has not circulated since 2003 and specific antibodies were not detected until many years after infection. Thus, the presence of SARS-CoV-1 antibodies in this population is highly unlikelyThis study showed results for a population with difficult access and very peculiar characteristics due to informal work and chemical exposure. The literature lacks data linking exposure to PTEs and Sars-Cov-2 infection and/or severity. Both epidemiological and laboratory studies are required to characterize the association between this exposure and the risk of covid-19. Individual differences in immune defense, nutrient supply, age, sex, comorbidities, socioeconomic class, as well as environmental exposure and its role in susceptibility to infectious diseases, need to be further studied and understood. Despite chemical exposure, working from home may have protected welders against covid-19, considering that they maintained greater social distancing than control participants.We found no significant association between the results of serology tests and the incidence of covid-19 symptoms between groups, although most positive tests belonged to the control group. This may be due to lower adherence to social distancing in this group, along with the greater number of days and hours spent away from home and the higher use of public transportation. The use of taxis for transportation was significantly associated with covid-19 symptoms and users had 6.04 times greater odds of the outcome composite than non-users. Therefore, lower adherence to social distancing among control participants, who need to leave home for work, is probably the major influence on the development of covid-19. However, welders had 74% greater odds of having covid-19 symptoms than the control group, although adherence to social distancing decreased these odds by 20%. Further studies are needed to deeper understand the effect of chemical exposure on Sars-Cov-2 infection.


Colorectal cancer is one of the most frequently occurring cancers today, with a large percentage of cases having a hereditary basis. Lynch syndrome is the most common cause of hereditary colorectal cancer. The genetic defect characteristics of this syndrome involve mutations in mismatch repair (MMR) genes, which result in microsatellite instability. Early detection of the mutation can help evaluate the cancer risk and, consequently, a proper course of clinical management for the person harboring the mutation. Herein, we describe the first report of a c.1458dup (p.Glu487*) new mutation in a 53-year-old colorectal cancer patient with diagnosed Lynch syndrome. Additionally, the existence of lipomas in this patient and his family could be related to this syndrome. Further investigation may provide a possible visual clue that can indicate a need for genetic screening. Colorectal cancer is one of the most commonly diagnosed cancers in the world, with nearly 2 million new cases  and nearly 1 million deaths  globally in 2020 . Lynch sEarly detection of these mutations and a diagnosis of Lynch syndrome are crucial, as they provide a way for the mutation carriers to implement the screening guidelines recommended for cancer risk management, such as colonoscopy, which allows the patient to start treatments in time and thus lower the colorectal cancer mortality rate. Herein, we report a new mutation that, to our knowledge, has not been previously described in colorectal cancer patients and which can help with early detection of cancer risk.A 53-year-old patient presented a lipoma on the abdominal wall upon physical examination, and reported a history of two resections of lipomas in previous years on the back and left axillary lines. The colonoscopy control, at 40 years of age, showed a normal result, while at the age of 50, the patient was diagnosed with sigmoid colorectal cancer, requiring a left hemicolectomy. The patient has an 18-year-old daughter who presented lipomas with benign characteristics upon physical examination and a paternal third-degree relative who was diagnosed with colorectal cancer at the age of 30. The cousin additionally presents rosacea, but information about lipomas is unavailable from him . The patA tumor biopsy was performed, and the histological result of the pathological anatomy revealed a sigmoid poorly differentiated mucoid adenocarcinoma of a high histological grade (WHO). The microscopic tumor extension was serous inclusive, without vascular or lymphatic invasion. Circumferential margins were compromised, while proximal and distal margins were not. Pathological TNM staging classified the tumor as pT4. Twelve lymph nodes were examined and were found to be free of metastases (pT4 pN0). No suggestion of a possible distal metastasis lesion was found at this time. In addition, findings suggesting microsatellite instability  were discovered.https://premm.dfci.harvard.edu/ accessed on 22 June 2022), which yielded a cumulative risk of 12.1% (greater than 2.5% is considered a high probability) [The PREMM5 model is a clinical prediction algorithm that evaluates the probability that one carries a germline mutation in the MLH1, MSH2, MSH6, PMS2, or EPCAM genes. This model also requires an individual to have a family history of colorectal or associated cancer. An algorithm was used with the PREMM5 risk prediction model  was performed to search for a deficit in the expression of DNA repair proteins . The results confirmed a deficit of MSH6 :Anti-hMLH1: intact nuclear positivity in tumor cells.Anti-hMSH2: intact nuclear positivity in tumor cells.Anti-hMSH6: loss of nuclear positivity in tumor cells.Anti-PMS2: intact nuclear positivity in tumor cells.Suspecting the possibility of Lynch syndrome, the patient was referred for genetic counseling.The results up to this point showed that the patient presented a sigmoid poorly differentiated mucoid adenocarcinoma at an early age (≤50 years of age) and had a third-degree relative  who developed colon cancer at 30 years of age. For this reason, the patient met the revised Bethesda criteria, but the lack of the third instance of cancer in his close family makes the Amsterdam criteria non-applicable. The Amsterdam criteria exclude most suspect cases of possible hereditary colorectal cancer, while the revised Bethesda criteria broaden the disease spectrum. Furthermore, the histological and molecular characteristics of the cancer tissue prompt a high level of suspicion of a possible hereditary non-polyposis colorectal cancer syndrome (possibly Lynch syndrome). Finally, IHC demonstrated the deficiency of MSH6 expression.Due to all of the above, a germinal study of the following genes was performed to rule out or confirm the hereditary oncological pathology (possible Lynch syndrome): MLH1, MSH2, MSH6, PMS2, MUTYH, EPCAM, POLE, and POLD1.A genetic panel was performed on the peripheral blood sample. The result showed a new pathogenic variant, a heterozygous mutation in the MSH6 gene c.1458dup (p.Glu487*), which has not previously been reported in LS patients. This variant inserts 1 nucleotide into exon 4 of the MSH6 gene, creating a frameshift and premature translation stop signal.The following genes were also analyzed as a part of the genetic panel, and no pathogenic or likely pathogenic variants associated with an increased risk of hereditary colorectal, male breast, melanoma, pancreatic, prostate, or stomach cancers were identified: APC, ATM, BAP1, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A (p14ARF), CDKN2A (p16INK4a), CHEK2, EPCAM, GREM1, MITF, MLH1, MSH2, MUTYH, NBN, PALB2, PMS2, POLD1, POLE, PTEN, RAD51C, RAD51D, SMAD4, STK11, and TP53.Lynch syndrome patients present a genetic predisposition to and a higher probability of early-onset colorectal cancer. These patients also have an increased risk of other types of cancer, such as cancer of the endometrium, ovaries, prostate, stomach, pancreas, etc. Genetic testing for the diagnosis of this syndrome is critical because it not only allows for a more precise risk evaluation for cancer development, but also helps with clinical management, timing, and extent of surgery for patients with colorectal cancer ,8.https://gnomad.broadinstitute.org/ (accessed on 12 August 2022).Loss of the function of one of the MMR genes, MSH6, is a known mechanism of this disease. The MMR system repairs single base mismatches as well as small insertions and deletions, which occur mainly during replication ,10. HereOn the other hand, the patient presented a past medical history of lipomas upon physical examination. A Lynch syndrome variant, Muir–Torre (MTS), is characterized by the presence of sebaceous neoplasms and/or keratoacantomas, though the loss of MSH2 and MSH6 expression has also been reported . A case Navarro et al. found this mutation in urethral cancer, while Flaum et al. also mention this mutation in endometrial cancer ,14. TakiIn conclusion, to the best of our knowledge, this is the first report of a c.1458dup (p.Glu487*) mutation in a colorectal cancer patient. It could be introduced as a new variant for the Lynch syndrome screening, and, thus, help with early detection of cancer risk. On the other hand, the existence of lipomas in this patient and his family could be further investigated, because further findings may provide a possible visual hint indicating a need for genetic screening.


Spinal cord injury (SCI) is a major cause of health loss due to premature mortality and long-term disability. We aimed to report on the global, regional, and national incidence, prevalence, and years of life lived with disability (YLDs) for SCI from 1990 to 2019, using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019.Using GBD 2019 data pooled in DisMod-MR 2.1, a Bayesian meta-regression tool, we systematically derived numbers and age-standardised rate changes with 95% uncertainty intervals (95% UIs) for the incidence, prevalence, and YLDs for SCI from 1990 to 2019 for the whole world, 21 GBD regions, and 204 countries and territories. We report trends based on age, sex, year, cause of injury, and level of injury.vs 417 thousand [290 to 585]), prevalence (10·8 million [9·5 to 13·9] vs 9·7 million [9·2 to 10·4]), and YLDs (4·2 million [3·0 to 5·8] vs 1·9 million [1·3 to 2·5]). Falls (477 thousand [327 to 683] cases) and road injuries (230 thousand [122 to 389] cases) were the two leading causes of SCI globally in 2019.Globally, 20·6 million (95% UI 18·9 to 23·6) individuals were living with SCI in 2019. The incidence of SCI was 0·9 million (0·7 to 1·2) cases with an estimated 6·2 million (4·5 to 8·2) YLDs. SCI rates increased substantially from 1990 to 2019 for global prevalence , incidence , and YLDs . However, global age-standardised rates per 100 000 population showed small changes in prevalence , incidence , and YLDs . Data for 2019 shows that the incidence of SCI increases sharply until age 15–19 years, where it remains reasonably constant until 85 years of age and older. By contrast, prevalence and YLDs showed similar patterns to each other, with one peak at around age 45–54 years. The incidence, prevalence, and YLDs of SCI have consistently been higher in men than in women globally, with a slight and steady increase for both men and women from 1990 to 2019. Between 1990 and 2019, SCI at neck level was more common than SCI below neck level in terms of incidence (492 thousand [354 to 675] Although age-standardised rates of incidence, prevalence, and YLDs for SCI changed only slightly, absolute counts increased substantially from 1990 to 2019. Geographical heterogeneity in demographic, spatial, and temporal patterns of SCI, at both the national and regional levels, should be considered by policy makers aiming to reduce the burden of SCI.Bill & Melinda Gates Foundation. Spinal cord injuries (SCIs) are associated with potential long-term disability, decreased life expectancy,10Accurate and up-to-date estimates of the incidence and prevalence of disorders constitute the backbone of evidence-based health-care planning and resource allocation. Because no effective curative treatment for individuals with SCI has been identified,Evidence before this studyWe searched PubMed, MEDLINE (In-Process and Other Non-Indexed Citations), and Embase for previous literature on spinal cord injuries (SCIs) published from database inception to March 17, 2023  2019 has developed systematic methods for quantifying health loss in detail by disease, age, sex, year, and geographical location.The detailed resources search, data processing steps, and modelling methods of GBD 2019 have been delineated in previous GBD studies.A detailed description of injury estimation has been published separately.Data for SCI were available for 93 (46%) of 204 countries for which GBD makes estimates. However, GBD makes predictions for all 204 locations through statistical tools that include predictive covariates and a geographical cascade, from which locations without data can borrow strength from surrounding locations. A detailed description of the GBD methods was published in the We used the SCI International Classification of Diseases (ICD) code list provided by the GBD modelling team for data processing. This list includes all conditions considered as SCI, both traumatic and non-traumatic, that were included in this study . For SCIConsistent with the GBD framework, we provide 95% uncertainty intervals (UIs) for all estimates, using the mean estimate across 1000 draws, with the 25th and 975th ranked values across all 1000 draws as the lower and upper bounds of the 95% UIs. The analysis contained in this Article is the result of an amalgamation of numerous surveys done with varying levels of quality and representativeness; we therefore report estimated results to a level of precision that conveys the true uncertainty of the GBD process. We present the count data in thousands and rates to one decimal place. We also used round outwards  to maintain 95% uncertainty.The funder of the study had no role in study design, data collection, data analysis, data interpretation, or the writing of the report.Globally, there were 20·6 million (95% UI 18·9 to 23·6) individuals with SCI in 2019 with an incidence of 0·9 million (95% UI 0·7 to 1·2) new cases . The YLDRegionally, high-income North America had the highest age-standardised incidence rate in 2019 with 22 (95% UI 17 to 29) cases per 100 000 population, followed by 14 (11 to 17) per 100 000 in Australasia and 14 (10 to 19) per 100 000 in tropical Latin America . Andean Incidence, prevalence, YLDs, and the corresponding percentage changes in age-standardised rates for SCI varied across countries between 1990 and 2019 . Age-staDistribution of global incidence, prevalence, and YLDs for SCI from all causes in 2019 according to age groups is shown in the Global trends of incidence, prevalence, and YLD numbers for SCIs from 1990 to 2019 for males, females, and male and female sexes combined are shown in the vs and 45·8% below neck level). Prevalence of spinal cord lesions at neck level was 10·8 million (95% UI 9·5–13·9) cases, compared with 9·7 million (9·2–10·4) cases below neck level (52·7% at neck level vs 47·3% below neck level). YLDs attributable to SCI differed between spinal cord lesions at neck level  and spinal cord lesions below neck level . The incidence, prevalence, and YLDs for SCI from 1990 to 2019 according to the level of injury  are shown in the In 2019, the global incidence of spinal cord lesions at neck level was 492 thousand (95% UI 354–675) and the incidence of spinal cord lesions below neck level was 417 thousand (290–585) new cases  and road injuries  is not currently available for SCI in the GBD database, owing to the absence of statistical support for presenting such data, our findings support previous research indicating that incidence, prevalence, and YLDs of SCI are higher in high-income regions than in lower-income regions. High-income North America and Australasia, for example, had the highest age-standardised incidence, prevalence, and YLD rates in 2019. One reason for this finding might be the high quality of data coming from these regions, in addition to the number of reports and methods of reporting. In a study by Tropeano and colleagues,Globally, incidence, prevalence, and YLDs were higher in males than in females throughout the period from 1990 to 2019, and the size of the difference between males and females remained almost stagnant for all the three indices, with a slight increase for both sexes during this period. Although the male-to-female ratio for SCI has been reported to vary in previous studies according to their methods, case definitions, and locations,WHO has estimated an annual incidence of SCI at between 250 000 to 500 000 people worldwide.Efforts have been made to describe the true epidemiology of SCI in Iran,vs non-traumatic), which can affect outcome substantially, are not currently retrievable from the GBD database. Traumatic SCI is abrupt and sudden, whereas non-traumatic SCI is usually progressive and gradual. This classification of data could be informative in many ways, including indicating age and sex differences. One other important issue regarding studies addressing SCI is differentiation between complete and incomplete lesions. There is a spectrum of clinical findings for SCI, which can be classified according to the American Spinal Injury Association score and Frankel grading. In other words, not all SCIs are permanent and associated with lost years of life and disability. People with minimal and mild injuries, and even some moderate injuries, can fully or near fully recover and return to healthy function and life. The nature of SCI affects the results and the burden of the disease significantly. Whereas incomplete SCIs are associated with better outcomes and less disability, complete lesions are permanent and carry substantial social, economic, and emotional burdens. Thus, these two entities should be separated when analysing and reporting the results of GBD. In future rounds of GBD, researchers should provide other epidemiological indices, such as YLL, DALYs, mortality, and life expectancy, for SCI so that the total  burden of SCI can be provided, broken down by the cause of injury , and also type of the injury . The unavailability of data for SDI for SCI in the GBD database is another notable limitation of our study. Such data could have provided important information for economic and administrative planning purposes.General limitations of GBD, which have been discussed previously,According to our results, epidemiology of SCI is increasingly affecting people at older ages, and the number of people affected is increasing globally. Although the age-standardised rates of incidence, prevalence, and YLDs showed only slight changes from 1990, the absolute counts of cases increased substantially. Our findings could aid health-care professionals and policy makers at the global or national levels in providing preventive interventions and advance planning for resource allocation to prevent and reduce the burden of SCI. Future studies should focus on considering the attributable risk factors and differences according to the severity and type of injuries, in addition to the potential effect of socioeconomic status on the burden of SCI.Data used in this article are available for download on the Global Health Data Exchange tool,R C Franklin reports grants or contracts from Heatwaves in Queensland—Queensland Government and Arc Flash–Human Factors–Queensland Government; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Honoraria–World Safety Conference 2022–Conference Convener; support for attending meetings or travel from the Australasian College of Tropical Medicine for the Tropical Medicine and Travel Medicine Conference 2022 and from the International Society of Travel Medicine for the Travel Medicine Conference, Basel 2023; and leadership or fiduciary roles in board, society, committee, or advocacy groups, paid or unpaid with Kidsafe as Director, Farmsafe as Director, Auschem as Director, the Public Health Association of Australia Injury Prevention Special Interest Group as Convenor, and the International Society for Agricultural Safety and Health as a member of the Governance Committee, all outside the submitted work. E Trinka reports grants or contracts from the Austrian Science Fund (FWF), Oesterreichische Nationalbank, the EU, GSK, Biogen, Eisai, Novartis, Red Bull, Bayer, and UCB; consulting fees from Angelini, Clexio, Argenx, Arvelle, Epilog, Ever Pharma, UCB, Biogen, GSK, Bial, Eisai, Takeda, Newbridge, GW Pharma, Sunovion, Liva Nova, Marinus, Medtronic, Novartis, Sandoz, and Sanofi; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from UCB, Eisai, Biogen, Novartis, Bial, Sunovion, Ever Pharma, Liva Nova, Sanofi, Hikma, Newbridge, Arvelle, GW Pharma, and Sandoz; and other support from Neuroconsult as CEO, all outside the submitted work. All other authors declare no competing interests.


Anisakis parasite has led to issues of public health concern due to allergic manifestations. We conducted an observational study on the use of an innovative Anisakis allergy diagnostic algorithm in a convenience sample of 53 allergic outpatients recruited in Western Sicily, between April 2021 and March 2022. We included individuals with an anamnesis suggestive of IgE sensitization to Anisakis reporting clinical manifestation in the last month due to allergic reactions after eating fresh fish, or in subjects at high exposure risk with sea products while abstaining from fish ingestion, excluding those with documented fish sensitization. Outpatients were tested via Skin Prick Test, IgE-specific dosage and Basophil Activation Test (BAT). Twenty-six outpatients were diagnosed with Anisakis, while 27 with Chronic Urticaria (CU). We found a seven-fold excess risk for Anisakis (p4) positivity in the Anisakis allergic outpatients, as compared to the CU ones. BAT showed the best diagnostic accuracy (92.45%) and specificity (100%), while specific IgE to Ascaris (p1) documented the best sensitivity (92.31%) but a very low specificity (37.04%). In conclusion, our findings may represent a potentially useful contribution to the future development of updated clinical guidelines. The rising popularity of undercooked or raw seafood containing larvae of the  Anisakis larvae in the ingested preparations [Anisakis among the most significant biological hazards in seafood [Anisakis spp. in the Mediterranean Sea is quite high, on the other, the impact of Anisakiasis and Anisakis allergy could be underestimated [The popularity of undercooked, raw or marinated seafood in recent years has been growing considerably worldwide, becoming a new culinary habit and a public health issue at the same time , becausearations . This paarations . For the seafood . If, on stimated ,6. Partistimated . Moreovestimated ,9.Anisakis allergy has been based on ruling out fish allergy together with a positive IgE-Anisakis allergy test based on ImmunoCAP and Western blotting assay [Anisakis positivity are frequently reported, even if mostly related to cross reactivity with numerous allergens [Anisakis, with a high range of prevalence, although Anisakis was the real triggering cause in a minority of cases only [Anisakiasis shows digestive manifestations that can be accompanied by allergic symptoms (ranging from urticaria–angioedema to anaphylaxis), and the gold standard for its diagnosis is endoscopy of the digestive tube, followed by larval removal and its molecular identification . Insteadng assay . Howeverllergens ,14,15,16llergens ,18,19. Fses only ,21,22.Anisakis allergens; several studies indicated that 16 to 22% of blood donors have specific IgE for Anisakis [Furthermore, in the absence of clinical symptoms, healthy individuals may have high levels of specific IgE for Anisakis ,24.Anisakis allergy suspicion, for ethical reasons, the challenge with food allergens cannot be used, which is considered the gold standard for food allergy [In the case of  allergy ,26,27,28Anisakis allergy diagnosis was previously validated, conceived to investigate the primary sensitizer role of Anisakis simplex (s.s.) and Anisakis pegreffii, and based on a Skin Prick test with Anisakis whole extract, specific IgE to Anisakis, Ascaris and Dermatophagoides pteronysimus whole extracts, specific IgE to shrimp tropomyosin and Basophil Activation Test (BAT) with Anisakis whole extracts [Anisakis simplex s.s and Anisakis pegreffii, together with information on allergic relevance of Anisakis species, allowed us to highlight any possible cross reaction and the clinical relevance of the sensitization [For all the above-mentioned reasons, a comprehensive algorithm for extracts . Followitization .Anisakis allergy diagnostic algorithm in a convenience sample of allergic outpatients from Western Sicily, an epidemiological setting characterized by a high consumption of uncooked, raw or marinated seafood.The aim of this study was to report the use of the proposed Anisakis in individuals reporting clinical manifestation in the last month due to allergic reactions  after eating fresh fish, or in subjects at high exposure risk with sea products  while abstaining from fish ingestion. Patients with urticaria symptoms lasting over six weeks were considered to be affected by a chronic form and were included as well because this could be a possible Anisakis allergy [Anisakis extracts SPT and codfish extracts. IgE-specific levels were detected at the same time for Anisakis (p4) and codfish (f3) extracts and Cyp c1 (f355). Then, outpatients negative for fish allergens and positive to Anisakis extracts underwent IgE-specific testing for Ascaris (p1) and tropomyosins (f351), as second line, and were further checked for Dermatophagoides pteronyssinus (d1) IgE positivity. Lastly, the outpatients who tested positive to the first line were invited to be further tested using BAT, as confirmatory analysis.An observational study was performed considering, as inclusion criteria, an anamnesis suggestive of IgE sensitization to  allergy ,22. Excl allergy , as firsA. pegreffii and A. simplex s.s. were used to perform SPT and BAT analysis [According to a previous validated extraction procedure, the proteins extracted from analysis . The Quianalysis ,30.Anisakis extracts through ALK-Abellò . A positive result was defined by the presence of a wheal ≥ 3 mm in diameter. Specific IgE dosage was performed via ImmunoCAP250 . A specific IgE value > 0.35 kIU/L was considered positive. In addition, a parasitological examination of the feces was carried out to verify the presence of any nematode.Skin Prick test was performed using Anisakis homemade extract. BAT homemade allergenic extracts were obtained from Anisakis pegreffii (A.p.) and Anisakis simplex s.s. (A.S.e.), as described above. The cytometric analysis was carried out using CCR3 and CD63 as markers of identification and activation  and tivation , respectWe performed a BAT dose response curve for each type of allergen at the following concentrations: 112.5 ng/mL, 22.5 ng/mL and 4.5 ng/mL. A threshold value of 15% of activated basophils was considered to be positive, as suggested by the manufacturer for food allergies. Cross reactivity to A.P.e. and A.S.e. extracts was previously assessed . FurtherAnisakis IgE sensitization) and the allergen fonts (A. pegreffi and A. simplex s.s.) in each group of outpatients. Absolute and relative frequencies (percentages) were considered in the descriptive analysis. Permutation tests  were performed to compare the two groups  [p-value < 0.05.The statistical significance of results was also confirmed using (95%CIs) . StatistReceiver operating characteristic (ROC) curve was estimated using DeLong methodology  using anIn Thus, 26 outpatients (40.1%) were diagnosed with AS, while 27 (50.9%) were affected by a documented CU .Anisakis, Ascaris and tropomyosin in AS outpatients is also reported, as compared to subjects with documented chronic urticaria. IgE-specific positivity was more frequently documented in 24 (92.3%) AS outpatients as compared to 17 (63.0%) CU individuals. A 7-fold excess risk for p4 positivity  and p-value = 0.019) was highlighted for the Anisakis allergic group as compared to the CU outpatients’ group. On the contrary, no excess of Anisakis allergy risk was reported between the two groups for Ascaris IgE positivity , p-value = 0.173) and tropomyosin IgE positivity , p-value = 0.239).In Anisakis, Ascaris and tropomyosin are shown, as well as the percentage of activated basophils detected via BAT in outpatients with chronic urticaria compared with Anisakis allergy individuals.In p-value: 0.046) in the median values for Anisakis (p4)-specific IgE levels between the Anisakis allergy group (mean ± SD = 13.2 ± 26.1) and the chronic urticaria group (mean ± SD = 13.2 ± 26.1). In the same direction, higher concentration levels of Ascaris-specific IgE  were found in the Anisakis allergy group (mean ± SD = 1.92 ± 2.43), as compared to the chronic urticaria group (mean ± SD = 0.42 ± 0.54). On the contrary, no statistically significant difference was reported for tropomyosin-specific IgE in two groups .The comparison of the in vitro tests results documented a significant statistical difference .Lastly, we detected a higher percentage of activated basophils in the In Anisakis allergy group highlighted a higher statistically significant level of activation of basophils at concentrations of 22.5 ng/mL  and 4.5 ng/mL  for A.P.e., while the concentration of 112.5 ng/mL did not show any significative difference for both types of extracts .The comparison between the chronic urticaria group and the Anisakis allergy is summarized in The diagnostic performance of the “in vitro” tests used for the diagnosis of The BAT showed the best diagnostic accuracy (92.45%) and the best specificity (100%), while specific IgE (sIgE) to p1 documented the best sensitivity (92.31%) but a very low specificity (37.04%). The area under the curve (AUC) represented in the ROC curve for BAT was equal to 90.53% (95%CI: 90.35–100.00%) , identifAnisakis seroprevalence was mainly reported in coastal communities residing in Morocco, Spain, Croatia and Italy, where a higher intake of marinated or raw sea fish is rooted in local traditions [Anisakis allergy have been reported for a decade [According to fish consumption and culinary habits, Japan and Mediterranean countries are among the countries with the highest worldwide prevalence of Anisakiasis cases and associated IgE hypersensitization, whereas in Northern European countries, rare cases are reported, in particular from the Netherlands and Germany ,36,37. Haditions ,43,44,45a decade .Anisakis allergy using a validated comprehensive diagnostic algorithm for [We report, herein, the findings of an observational study conducted on a series of consecutive outpatients accessing the two reference allergology ambulatories located in Western Sicily, with the aim to assess “in the field” the reliability of the BAT to confirm the diagnosis of ithm for .Anisakis, i.e., Anisakis pegreffii and Anisakis simplex (s.s.), have detected several potential allergens [Anisakis IgE sensitization. Modern allergology involves the importance of direct use in the diagnostic phase of the molecular components of the allergenic sources . In this context, transcriptomic and proteomic studies recently performed on the zoonotic species of the genus llergens ,45,46,47Anisakis spp.) and another towards Ani S3 (Anisakis tropomyosin), respectively [Despite the well-known importance of a CRD in the diagnosis of food allergy and parasite infection , to dateectively .Anisakis tropomyosin available for the ImmunoCAP platform at cheaper prices [Anisakis allergy diagnosis. The proposed diagnostic algorithm was based on commercially available cost-effective tests, including specific IgE, used to investigate any possible cross reaction plus an “in vitro” simulation of allergenic challenge via BAT. Previously, we have not used the commercially available microarrays, not only for their cost but also because data on the diagnostic accuracy have not been reported. With regard to the cross-reactive molecules, there are other tropomyosins, presenting a high analytical accuracy and about 70% of sequence homology with r prices ,17. TherAnisakis larval crude extracts to assess any difference in the response to nematode species. More in depth, in our series, the specific IgE levels for Anisakis extracts (p4) and Ascaris extracts (p1) were found to be statistically significantly higher in the Anisakis allergy group versus the chronic urticaria group. Furthermore, the specific IgE to Anisakis extracts, differently by sIgE to Ascaris or tropomyosin, showed a significative association with Anisakis allergic patients and the best sensitivity on Anisakis allergy diagnosis. On the contrary, the specificity and the positive predictive value were lower , suggesting the need for a confirmatory test. Moreover, the results obtained with IgE for Ascaris were in line with the guidelines of chronic spontaneous urticaria in the absence of the role of parasites in this pathology [In this study, we used homemade athology .Anisakis allergy diagnosis, as reported in previous studies [According to our findings, the BAT showed the best specificity and positive predictive value (both 100%) with the best diagnostic accuracy (92.45%), confirming the high value of the BAT on  studies ,50,51. Anisakis-specific IgE positivity without any clinical relationship with the parasite [Anisakis allergy. The significative difference in basophils activation against extracts of Anisakis-infecting fishes from the Mediterranean Sea (A. pegreffii) and the ones from the Atlantic Ocean (A. simplex s. s.) suggested that A. pegreffii was the source of Anisakis primary sensitization in our sample population, and this was probably related to a higher consumption of fish from the Mediterranean Sea, where this species of parasite is widespread in commercially important fish species. Therefore, the availability of different extracts of Anisakis larvae for BAT may represent a useful tool, both in research and in clinical diagnoses. In order to test the accuracy of BAT under stress conditions, we calculated the ROC curve using the group of patients affected by chronic urticaria as a control group. As previously noted, these patients often present a positive Skin Prick test or parasite ,22,29. TAnisakis sensitization in CU patients was confirmed, suggesting the role of Anisakis hypersensitivity in individuals with CU, with this evidence potentially useful in clinical practice, while considering the significant clinical improvement after a fish-free diet in a part of the CU population [In this study, the occurrence of pulation ,53,54,55Anisakis positivity against extracts of A. pegreffii versus A. simplex (s.s.) in individuals with CU when using basophils activation, suggesting that the food intake was not the cause of sensitization. However, we must consider that there are important differences in the prevalence of Anisakis positivity in different geographical areas that have been related to dietary habits [Our findings showed no significant difference in y habits ,29,54,56Anisakis molecules. This limitation, considering the presence of several cross-reactive molecules in the parasite extract, can lead to residual misdiagnosis.Some limitations of the study must be highlighted. First, the limits related to the observational nature of the study, together with a possible lack of representativeness due to the convenience sample and the limited number of participants, should be considered. Another limitation should be addressed regarding the characteristics of the diagnostic algorithm that does not include specific Anisakis IgE sensitization, supporting, at the same time, the opportunity to implement, as a first approach, the proposed comprehensive diagnostic algorithm for Anisakis allergy, including anamnesis, SPT and the determination of specific IgE for Anisakis, possibly performed via IgE immunoblotting (IgE-WB) analysis, as well as including the specific molecular diagnosis of the removed parasite, when available. In conclusion, our findings confirm a very good specificity of BAT in the detection of Anisakis exposure in epidemiological settings characterized by a high consumption of seafood [Anisakis [Finally, we believe that the proposed approach may represent a potentially useful contribution to the future development of updated clinical guidelines but also may add knowledge to stratify the population according to the health risk related to  seafood ,58, wherAnisakis ,12.


This study assessed serum, dietary zinc levels, and other risk factors during the third trimester among pregnant women with and without pregnancy-induced hypertension (PIH).This case-control study was conducted in 2022, in the three main Obstetrics and Gynecology departments in Gaza Strip, Palestine. One hundred sixty pregnant women, during the third trimester, aged ≥20 years, were selected using a convenient sampling method. Data were obtained using an interview-based questionnaire, food frequency questionnaire, anthropometric measures, and biochemical tests. Statistical analysis was performed using SPSS version 24.P = <0.005). The mean serum zinc level (μg/dl) was 67.15 ± 16.5 for cases and 68.45 ± 18.0 for controls without significant differences between the two groups (P = 0.636). For newborns, the mean birth weight (g) was 2,904.6 ± 486 for cases, and 3,128.3 ± 501 for controls, and the mean Apgar score was 8.03 ± 0.62 for cases and 8.30 ± 1.17 for controls, with significant differences between the two groups (P = <0.005). Furthermore, 43 (53.8%) of cases have family history of hypertension; 5 (6.2%) were primiparous; 19 (23.8%) have previous caesarian section; 33 (41.2%) have history of preeclampsia; and 62 (77.5%) have edema, with significant differences between the two groups (P = <0.005). Additionally, the total zinc dietary daily intake (mg/day) was 4.15 ± 2.10 for cases and 4.88 ± 3.02 for controls, with significant differences between the two groups (P = 0.041). After adjustment for confounding variables, participants in the case group have higher odds of having low total zinc dietary intake compared to those in the control group .The participants’ mean age was 30.7 ± 5.6 years. A total of 47 (58.8%) of cases and 6 (7.5%) of controls were insufficiently active; and the mean of blood pressure (mmHg) was 133.3 ± 11.9/85.11 ± 10.0 for cases and 112.8 ± 9.5/68.02 ± 7.2 for controls with significant differences between the two groups (The current study showed the main risk factors of PIH among pregnant women in the Gaza Strip, Palestine. Furthermore, low maternal dietary zinc intake was associated with a high level of PIH. Moreover, having PIH could increase the risk of low birth weight and low Apgar scores. Therefore, reducing the main risk factors of PIH could reduce the adverse effect on both mother and birth outcomes. Zinc is an essential trace mineral element vital for many physiological functions and plays an important role in growth, reproduction, and the immune system . AdequatPrevious studies have provided evidence that zinc deficiency is a worldwide public health problem, especially in developing countries, including Palestine , 5. The Diet is the main factor that determines zinc status . In the In fact, data on the prevalence and determinants of zinc deficiency among pregnant women are scanty and inconclusive . In addiThis case-control study was conducted among pregnant women attended the main governmental hospitals in Gaza Strip, Palestine.This study was conducted in the year 2022 in the three main governmental hospitals  of the Palestinian Ministry of Health (MOH), which are considered the main governmental hospitals providing the Obstetrics and Gynecology services to the Palestinians pregnant woman.All pregnant women with and without PIH during the third trimester who attended the main governmental hospitals in Gaza Strip, Palestine, during the study period. The study protocol was approved by the Palestinian Health Research Council (PHRC/HC/116/22). The study was conducted according to the tenets of the Helsinki Declaration. Written informed consent was obtained from each participant. The inclusion criteria include pregnant women aged ≥20 years, women during the third trimester, women who were attending the Obstetrics and Gynecology Departments of Palestinian MOH during the study period and lived in the Gaza Strip for at least 3 years. The inclusion criteria for the cases included pregnant women diagnosed with PIH, and for the controls, we included pregnant women without PIH. On the contrary, pregnant women who were previously diagnosed with chronic hypertension (HTN) or other types of serious illness such as cancer, thyroid diseases, acute myocardial infarction, or end-stage kidney disease; pregnant women taking drugs affecting zinc balance; and pregnant women with a previous history of  were also excluded.The number of pregnant women who attended the governmental hospitals in the Gaza Strip in 2017 was 17.226. In addition, the number of high-risk pregnancies was 5,278 cases, according to a recent report from the Palestinian MOH in 2017 . The repData regarding the characteristics of the study participants, demographic and socioeconomic, medical and gestational history, and diet compliance variables were obtained with an interview-based questionnaire. Additionally, reports and all relevant documentation, including the participant’s medical records, were checked.For pregnant women, height (cm) and weight (kg) were measured on admission using standard methods . FurtherBlood pressure was measured from the left arm (mmHg) by mercury sphygmomanometer. Three readings on different days, while the participant seated, after relaxing for at least 15 min in a quiet environment, empty bladder, and the average of three measurements was recorded .After 12 h fasting, venous blood samples were collected from all participants (case and control) on admission and at the beginning of the third trimester by well-trained and experienced nurses. Venous blood (5.0 ml) was drawn and was used for serum zinc level (μg/dl), hemoglobin level (g/dl), and fasting blood sugar (mg/dl). Mindray BS-300 and Mindray BA-88A chemistry analyzers were used for blood chemistry and serum zinc level analysis . In addiAll participants were examined by the physicians for signs and symptoms of any diseases, including PIH, and for signs and symptoms of zinc deficiency. In addition, the WHO criteria were used by the physicians for the diagnosis of PIH . In the The Apgar score was used to assess the health status of the newborn. The Apgar score is a quick way for various members of the healthcare team, including midwives, nurses, or physicians, to evaluate the health of all newborns at 1 and 5 min after birth and in response to resuscitation .In the current study, a validated Palestinian Arabic version semi-quantitative food frequency questionnaire (FFQ) was used to assess the dietary zinc intake of the pregnant women . The FFQData on physical activity was obtained using the international physical activity questionnaire (IPAQ) short version. According to the IPAQ scoring protocol, the participants were classified based on their weekly energy expenditure as follows: insufficiently active: ≤600 MET/week; sufficiently active: 601–1,500 MET/week; and very active: ≥1,500 MET/week .Pilot study was carried out on 20 participants; the questionnaire and data collection process were modified according to the result of the pilot study. The data was collected by five qualified data collectors (two nurses and three nutritionists).t-test. P-value less than 0.05 was considered as statistically significant.Statistical analysis was performed using SPSS version 24. Dietary intakes were converted into grams per day. The net amount of zinc dietary intake (mg/day) consumed by the study participants were calculated based on the USDA Food Composition Database . In addiP = 0.067). Concerning physical activity levels, a large percentage of the cases were insufficiently active, while the majority of controls were very active, with significant differences found between the case and control group (P = 0.001). In addition, the mean blood pressure for women in the cases group was slightly high compared to women in controls group, but still within the normal levels, with significant differences between the two groups (P = < 0.005). Moreover, the mean serum zinc and hemoglobin levels was slightly low for women in the cases group compared with women in the control group; while the mean of fasting plasma glucose was slightly high compared to women in controls group, without significant differences between the two groups , as shown in The current study was conducted in the three main governmental hospitals of the Palestinian MOH. The results demonstrated that the majority of the study participants were from Al Shifa Medical Complex and Mubarak Hospital. The mean of age for the study participants was 30.7 ± 5.6 years without significant differences between the cases and control groups (2) was slightly high for women in cases group compared with women in the controls group, without significant differences between the two groups (P > 0.005). For newborns, the results revealed that the mean birth weight (g) and the mean of Apgar score were low in the cases group compared with the controls group, with significant differences between the two groups .P = 0.028). In addition, women in the cases group have more family history of DM compared with the controls, without significant differences between the two groups (P = 0.867). The results also revealed that women in the cases group have more history of preeclampsia and complained of edema more than women in the controls group, with significant differences between the two groups .P < 0.005). In addition, women in the cases group using dietary supplements, including multivitamins, received large amounts of iron supplementation, and used zinc supplementation more than women in the controls group, without significant differences between the two groups .P = 0.041).P = 0.030].Finally, Zinc deficiency is common in developing countries, and low maternal serum zinc concentrations have previously been associated with pregnancy complications . Zinc deTwo of previous studies showed that aerobic exercise for about 30–60 min for at least twice per week during pregnancy is associated with a reduced risk of gestational hypertensive disorders, PIH, and cesarean delivery , 35. OurThe International Zinc Nutrition Consultative Group defined zinc deficiency as blood zinc levels below 56 μg/dl in the first trimester or 50 μg/dl in the second or third trimesters . Tesfa evan Middendorp et al.  showed tHromadnikova et al.  demonstrPregnant women need up to 2.6 mg of zinc per day during the second half of their pregnancy . The WHOPrevious studies showed that inadequate nutrition at home could be attributed to a number of factors, including lack of variety in the diet, low consumption of animal products, socioeconomic status, maternal education, pregnancy, hemoglobin concentration, maternal workload, chronic illness, vegetarianism, and a lack of antenatal care , 54 can The main strength of this study is that the results will provide baseline information about zinc levels and PIH during the third trimester among pregnant women in Gaza Strip, Palestine. The main limitations of this study are its non-probability sampling techniques, which limit the generalizability of the results. Furthermore, the possibility of recall bias and misreporting by using FFQ for maternal dietary zinc intake. Unfortunately, we did not record the gestational age at the time of blood collection nor at the time of delivery.The current study showed the main risk factors of PIH among pregnant women in the Gaza Strip, Palestine are family history of hypertension, primiparous, previous caesarian section, history of preeclampsia, complaints of edema, high maternal BMI, physical inactivity, and low maternal dietary zinc intake. Furthermore, low maternal dietary zinc intake was associated with high levels of PIH. Moreover, having PIH could increase the risk of low birth weight and low Apgar scores. Therefore, reducing the main risk factors of PIH could reduce the adverse effect on both mother and birth outcomes. Further future studies with large sample size are recommended.The original contributions presented in this study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.The study protocol was approved by the Palestinian Health Research Council . The patients/participants provided their written informed consent to participate in this study.SA and AME collected, analyzed, and interpreted the data and wrote the first draft of the manuscript. SA, AME, MT, and AHE contributed in the study design and the critical review of the manuscript. AHE contributed to the analysis and interpretation of data and the critical review of the manuscript. All authors contributed to the article and approved the submitted version.