Primary Gastric Tuberculosis in an Immunocompetent Patient: The Truth Lying beneath the Surface.

Gastrointestinal tuberculosis is an uncommon entity, in which clinical presentation can be widely variable, from mild and nonspecific symptoms to an acute abdomen and gastrointestinal bleeding. Gastric involvement by Mycobacterium tuberculosis is rare, especially when it occurs without other recognized infectious foci - primary gastric tuberculosis - with only a few reported cases. Endoscopic findings can be very heterogeneous, from areas of hyperemia to pseudotumor lesions. We present a case of primary gastric tuberculosis in an immunocompetent patient, in which the absence of an epidemiological context and nonspecific endoscopic findings led to a delay in the diagnosis. Bite-on-bite biopsies proved to be essential, allowing to obtain samples from deeper layers of the submucosa where M. tuberculosis was identified. This case aimed to increase awareness for this entity, especially in endemic countries or regions with a high prevalence of tuberculosis since the diagnosis is based mainly on a high index of suspicion.

A tuberculose gastrointestinal é uma entidade pouco comum, com uma apresentação clínica amplamente variável, desde sintomas ligeiros e inespecíficos até quadros de abdómen agudo e hemorragia digestiva. O envolvimento gástrico pelo Mycobacterium tuberculosis é raro, especialmente quando ocorre sem outros focos infeciosos reconhecidos ­ tuberculose gástrica primária ­, havendo apenas alguns casos descritos na literatura. Os achados endoscópicos podem ser muito heterogéneos, variando desde áreas de mucosa hiperemiada até lesões pseudo-tumorais. Apresentamos o caso de uma doente imunocompetente com diagnóstico de tuberculose gástrica primária, em que a ausência de um contexto epidemiológico e achados endoscópicos inespecíficos conduziram a um atraso no diagnóstico. As biópsias sobre biópsias mostraram ser essenciais para o diagnóstico, pois permitiram obter amostras de camadas mais profundas da submucosa do antro gástrico onde foi identificado o agente infecioso. Este caso pretende sensibilizar para existência desta entidade, especialmente em países endémicos ou regiões com alta prevalência de tuberculose, uma vez que o seu diagnóstico implica um elevado grau de suspeição.

Autoimmune Hepatitis Induced by Hepatitis Delta Virus: A Conundrum.

Introduction: The association of hepatitis delta virus (HDV) infection with positive autoantibodies and autoimmune features has been known for decades. However, to date, very few cases of clinical autoimmune hepatitis (AIH) have been reported in association with HDV infection, most of them being in the context of treatment with peginterferon. Case Report: This case refers to a 46-year-old woman born in Guinea-Bissau who moved to Portugal in 2018 to investigate complaints of diffuse abdominal discomfort and nausea. Her initial work-up, including laboratory and liver histology, was consistent with type 1 AIH. She had HBe antigen-negative chronic hepatitis B virus infection with negative DNA and also a positive total anti-HDV antibody, with negative IgM and undetectable RNA. Therefore, after initiating prophylactic tenofovir difumarate, she was started on prednisolone followed by azathioprine, which was later stopped due to presumed hepatotoxicity. Repeated histology showed signs of viral superinfection, and she was treated with acyclovir due to a positive herpes simplex IgM, with HDV RNA remaining negative. A third flare in transaminases prompted the introduction of mycophenolate mofetil (MMF) after a thorough exclusion of additional causes of liver disease. About 6 months later, during another bout of hepatitis, HDV RNA was finally positive and classified as genotype 5. MMF was stopped, and, considering a contraindication to interferon, the patient was offered therapy with bulevirtide, which she refused for personal reasons as she is currently living in her home country. Discussion: This is a challenging case of autoimmune or "autoimmune-like" hepatitis, probably induced by chronic HDV infection. High suspicion of HDV was essential because, had the case been interpreted as refractory AIH, with escalation of immunosuppression, a more severe course of the viral infection might have ensued. Recently, HDV suppression with bulevirtide was shown to reverse autoimmune liver disease. We hypothesize that the same could have happened to our patient, had she accepted this treatment.

Introdução: A associação da infeção pelo vírus da hepatite delta (VHD) com a presença de autoanticorpos e outros aspetos de autoimunidade é conhecida desde há várias décadas. Contudo, até à data, muito poucos casos de hepatite autoimune (HAI) clínica foram reportados em relação com a infeção VHD, sendo a maioria destes no contexto de terapêutica com interferão peguilado. Caso clínico: O caso refere-se a uma mulher de 46 anos natural da Guiné-Bissau, que se mudou para Portugal em 2018 para investigação de queixas de desconforto abdominal difuso e náuseas. A avaliação laboratorial inicial e a histologia hepática foram compatíveis com HAI tipo 1. A doente apresentava também infeção crónica a VHB (vírus da hepatite B) antigénio HBe negativa, com DNA negativo, e anti-VHD (vírus da hepatite delta) total positivo, com IgM negativo e RNA indetetável. Assim, após início de tenofovir difumarato profilático, foi iniciada terapêutica com prednisolona seguida de azatioprina, que posteriormente se interrompeu por presumível hepatotoxicidade. Uma segunda biópsia mostrou aspetos de superinfeção viral e como tal a doente foi tratada com aciclovir, tendo em conta IgM positivo para Herpes Simplex, mantendo-se o RNA VHD negativo. Um terceiro flare de transaminases motivou o início de micofenolato de mofetil, após extensa investigação e exclusão de outras causas de doença hepática. Cerca de 6 meses mais tarde, durante novo episódio de hepatite, o RNA VHD revelou-se finalmente positivo e este foi classificado como genotipo 5. O MMF foi suspenso e, considerando a contra-indicação para interferão, foi proposto à doente tratamento com bulevirtide, que esta recusou, alegando motivos pessoais, visto estar atualmente a residir no seu país de origem. Discussão: Este é um caso desafiante de hepatite autoimune, ou autoimune-like, provavelmente induzida pela infeção crónica pelo VHD. Um elevado índice de suspeição para VHD foi essencial porque, se o caso tivesse sido interpretado como HAI refratária, com incremento de imunossupressão, poderia ter-se verificado um agravamento da hepatite viral. Recentemente, foi reportado que a supressão do VHD pelo bulevirtide pode reverter a doença hepática autoimune. Questionamo-nos se o mesmo poderia ter sucedido com a nossa doente, caso esta tivesse aceite este tratamento.

Rare Earth Element Accumulation in Fiddler Crabs (Minuca rapax) from the Rio Doce Tropical Estuary Strongly Affected by Mine Tailings Following the Fundão Disaster.

A mining tailing dam rupture in Brazil in November 2015 released millions of tons of mining waste into the Rio Doce ecosystem, leading to long-term aquatic ecosystem impacts. Although multiple lines of evidence indicate tailings associations with potentially toxic elements in estuarine sediments and biological impact and bioaccumulation pathways in fishes, the extent of contamination in base benthic species is still largely unknown. Moreover, Rare Earth Elements (REE) have not received any attention in this regard. This study assessed REE in fiddler crabs (Minuca rapax) sampled from the Rio Doce estuary in 2017, nearly 2 years after the disaster. The ΣREE in crab hepatopancreas and muscle were high (327.83 mg kg-1 w.w. and 33.84 mg kg-1 w.w., respectively, compared to other assessments in crabs, indicating a preference for REE bioaccumulation in the hepatopancreas compared to muscle. Neodimium, La, and Ce were detected at the highest concentrations. The REE from the Rio Doce Basin were, thus, transported and deposited in the estuary with the mine tailings slurry, leading to bioaccumulation in crabs. This may lead to trophic effects and other ecological impacts not readily measured by typical impact assessment studies, revealing an invisible and not typically acknowledged damage to the Rio Doce estuary.

A multi-biomarker approach to verify chronic effects on Eisenia andrei earthworms exposed to tailings from one of the world's largest mining disasters.

Mining is of great relevance to the global economy, but its activities are challenging due to socio-environmental impacts. In January 2019, an iron ore tailings dam collapsed in Brumadinho (Minas Gerais, Brazil) releasing 12 × 106 m3 of tailings, causing human losses and devastation around 3.13 × 106 m2 of a watershed. In this context, the present study aimed to investigate the potential toxic effects of tailings from the collapsed dam using earthworms Eisenia andrei as a model organism for terrestrial environments. An extensive set of tests was performed, including behavioral (avoidance), acute (mortality and biomass) and chronic tests, such as biomass, reproduction and cytotoxicity (viability and cell density and change in coelomocyte pattern). The physical-chemical characterization revealed a higher density of the tailings in relation to the control soil, which can result in physical changes, such as soil compaction and surface sealing. Aluminum, Ca, Fe, Hg, Mg, Mn, K, Na and P registered higher concentrations in the tailings compared to the control soil, while Total Nitrogen, Total Organic Carbon and Organic Matter were higher in the natural soil. Based on the avoidance test, an EC50 of 27.18 ± 2.83% was estimated. No lethality was observed in the acute exposure, nor variations in biomass in the acute and chronic assays. However, there was a tendency to reduce the number of juveniles in relation to cocoons in the proportions of 3125; 12.5 and 25%. Significant changes in viability, cell density and pattern of amebocytes and eleocytes were observed up to the 35th day of exposure. A multi-biomarker approach (Integrated Biological Response version 2) indicated concentration-dependent effects and attenuation of cellular changes over time. These are the first results of chronic effects on earthworms exposed to tailings from the B1 dam. Despite being conclusive, we highlight the possible heterogeneity of the tailings and the necessary care in extrapolating the results.

Biomarker response index in earthworms following chronic exposure to leachate from a closed dumpsite: Behavioral, cytotoxicity and antioxidant system alterations.

Leachate, an effluent produced during solid waste decomposition, interacts directly with soil, mainly in dumpsite areas. Studies on terrestrial animal exposure to leachate are, however, lacking. Plants are the most frequently studied organisms, while animal studies, especially earthworms, are limited. Nevertheless, ecotoxicological assessments involving earthworms are crucial due to their role in soil health and ecosystem maintenance, which are paramount in understanding potential terrestrial ecosystem leachate effects. In this context, this study aimed to evaluate behavioral effects, sublethal cytotoxicity and antioxidant system alterations in Eisenia andrei earthworms chronically exposed to leachate from a closed dumpsite. Cytotoxicity was determined by coelomocyte density, viability and cell typing, while antioxidant system alterations were assessed through superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), reduced glutathione (GSH) and metallothionein (MT) determinations. Malondialdehyde (MDA) and protein carbonylation (PTC) levels were also determined as oxidative effect markers. Finally, the Biomarker Response Index (BRI) was assessed, aiming to quantitatively integrate the results of the investigated endpoints and establish a biological health state (BHS) for each leachate concentration. Leachate exposure led to leak responses at concentrations of up to 50%, but attraction at higher concentrations. Decreased cell density (28%) was observed after 48 days and reduced viability (50%), after 14 days of leachate exposure. The observed cell typing changes indicate anti-inflammatory immune system effects. Leachate exposure led to several antioxidant system alterations, increasing SOD (2-6 %), CAT (5-35 %) and GST (5-70 %) activities and GSH (7-37%) and MT (3-67%) levels. Earthworm antioxidant defenses were, however, able to prevent lipid peroxidation, which decreased (11-37%) following leachate exposure to concentrations above 12.5%, and PTC, which increased at 42 days (26%) and reduced at 56 days (12 %). This is the first PTC assessment in leachate-exposed earthworms. The increased carbonylation levels observed after 42 days alongside MDA decreases highlight the need for further research employing oxidative effect biomarkers other than MDA. Finally, an integrated approach employing the BRI was carried out, revealing mild initial changes evolving to moderate to major effects at the highest leachate exposure concentration, with an effect attenuation detected at the end of the experiment. In this sense, this study brings forth a significant novelty, employing a biomarker previously not assessed in earthworms, demonstrating an oxidative effect, alongside the use of the BRI as an integrative tool for the endpoints applied in this assessment.

Antioxidant system alterations, oxidative, and genotoxic effects in Danio rerio (zebrafish) exposed to leachate from a dumpsite.

Water body contamination by leachate originated from dumpsites is a concern for municipal solid waste (MSW) management. In this context, this study aimed to evaluate antioxidant system alterations and oxidative and genotoxic effects in Danio rerio (zebrafish) exposed to leachate from a closed dumpsite. Groups comprising 50 fish were exposed (96 h) to different leachate concentrations (5, 15, 30, and 50%) to evaluate effects on liver and brain superoxide dismutase (SOD), catalase (CAT), and glutathione-S-transferase (GST) activities and reduced glutathione (GSH) and metallothionein (MT) concentrations, as well as malondialdehyde (MDA) and protein carbonylation (PTC) levels. Blood genotoxicity was evaluated by the comet assay. The investigated dumpsite leachate pond presented high chloride concentrations (Cl-; 2288.4 ± 69.5 mg L-1) and high electrical conductivity (EC; 8434.0 mS cm-1), indicating the presence of leachate. Concerning Danio rerio exposure, higher SOD (37%), CAT (67%), and GST (39%) activities and higher GSH (57%) concentrations were observed in liver following exposure to 50% leachate, while decreased brain GST (42%) activities and GSH (90%) levels were observed at the same leachate concentration. A significant increase in the olive tail moment (OTM; 280%) indicative of genotoxicity in blood was observed. A principal component analysis indicated that increased enzymatic activities and high levels of both GSH and MT were not sufficient to prevent the accumulation of reactive oxygen species, resulting in PTC and genotoxicity. Therefore, leachate exposure causes sublethal Danio rerio effects, altering the antioxidant system, increasing ROS production, and leading to PTC and genotoxicity. The findings demonstrate the need to further develop sublethal level assessments in zebrafish using leachate from different sources to subsidize risk assessments regarding MSW management.

A comprehensive overview on solid waste leachate effects on terrestrial organisms.

Leachate is a highly complex waste with high toxicological potential that poses a significant threat to the terrestrial environment. Determining leachate physicochemical parameters and identifying xenobiotics alone is, however, not enough to determine the real environmental impacts. In this context, the use of terrestrial model organisms has been highlighted as a tool in ecotoxicological leachate assessments and as a guiding principle in risk assessments. In this context, this review aimed to present the most current state of knowledge concerning leachate toxicity and the bioassays employed in this evaluation concerning terrestrial plants and animals. To this end, a literature search on leachate effects on terrestrial organisms was carried out using ten search terms, in 32 different combinations, at the Web of Science and Scopus databases. A total of 74 eligible articles were selected. The retrieved studies analyzed 42 different plant and animal species and employed nine endpoints, namely phytotoxicity, genotoxicity, bioaccumulation, antioxidant system, cytotoxicity, reproduction, physiological changes, behavior and lethality. A frequent association of toxic leachate effects with metals was observed, mainly Pb, Cd, Cr, Mg, Zn and Cr, which can cause antioxidant system alterations and cyto- and genotoxicity. These elements have also been associated to reproductive effects in earthworms and mice. Specifically concerning plants, most of the retrieved studies employed Allium cepa in toxicity assays, reporting phytotoxic effects frequently associated to metals and soil parameter changes. Animal studies, on the other hand, mostly employed mice and evaluated genotoxicity and antioxidant system effects. Even with the description of toxic leachate effects in both plants and animals, a lack of knowledge is still noted concerning reproductive, physiological, cytotoxic, and behavioral effects in terrestrial species. We, thus, suggest that further studies be carried out on other animals, advancing our understanding on potential environmental leachate effects, also allowing for human health risk assessments.

A Rare First Presentation of Hodgkin's Lymphoma: Symptomatic Pericardial Effusion.

Symptomatic pericardial effusion occurring as the initial manifestation of Hodgkin's lymphoma is exceedingly uncommon, and there are limited documented instances in the available literature. Pericardial effusion can present various differential diagnoses, and among these, malignancy is an important yet less frequently encountered cause. A heightened level of suspicion is crucial for establishing an accurate diagnosis, particularly when the patient's clinical course deviates from the anticipated trajectory. Through this case, we aim to emphasize the significance of considering lymphoproliferative diseases as a pertinent possibility in the differential diagnosis of pericardial effusion. Additionally, we underscore the importance of promptly reaching a diagnosis, as it can help prevent severe complications and enhance the patient's prognosis.

Anti-tumor necrosis factor therapy is associated with attenuated humoral response to SARS-COV-2 vaccines in patients with inflammatory bowel disease.

BACKGROUND: Immunosuppressive therapy used in the treatment of inflammatory bowel disease (IBD) is known to reduce vaccine immunogenicity. AIMS: This study aimed to 1) predict the humoral response elicited by SARS-CoV-2 vaccination in IBD patients based on their ongoing treatment and other relevant patient and vaccine characteristics and 2) assess the humoral response to a booster dose of mRNA vaccine. METHODS: We conducted a prospective study in adult IBD patients. Anti-spike (S) IgG antibodies were measured after initial vaccination and again after one booster dose. A multiple linear regression model was created to predict anti-S antibody titer following initial complete vaccination in different therapeutic groups (no immunosuppression, anti-TNF, immunomodulators and combination therapy). A two-tailed Wilcoxon test for two dependent groups was performed to compare anti-S values before and after the booster dose. RESULTS: Our study included 198 IBD patients. The multiple linear regression identified anti-TNF and combination therapy (versus no immunosuppression), current smoking, viral vector (versus mRNA) vaccine and interval between vaccination and anti-S measurement as statistically significant predictors of the log anti-S antibody levels (p < 0.001). No statistically significant differences were found between no immunosuppression and immunomodulators (p = 0.349) and between anti-TNF and combination therapy (p = 0.997). Statistically significant differences for anti-S antibody titer before and after the booster dose of mRNA SARS-CoV-2 vaccine were found, both for non-anti-TNF and anti-TNF groups. CONCLUSIONS: Anti-TNF treatment (either alone or in combination therapy) is associated with lower anti-S antibody levels. Booster mRNA doses seem to increase anti-S both in non-anti-TNF and anti-TNF treated patients. Special attention should be paid to this group of patients when planning vaccination schemes.

Acute toxicity of single and combined rare earth element exposures towards Daphnia similis.

The increasing use of Rare Earth Elements (REE) in emerging technologies, medicine and agriculture has led to chronic aquatic compartment contamination. In this context, this aimed to evaluate the acute toxic effects of lanthanum (La), neodymium (Nd) and samarium (Sm), as both single and binary and ternary mixtures on the survival of the microcrustacean Daphnia similis. A metal solution medium with (MS) and without EDTA and cyanocobalamin (MSq) as chelators was employed as the assay dilution water to assess REE bioavailability effects. In the single exposure experiments, toxicity in the MS medium decreased following the order La > Sm > Nd, while the opposite was noted for the MSq medium, which was also more toxic than the MS medium. The highest MS toxicity was observed for the binary Nd + La (1:1) mixture (EC50 48 h of 11.57 ± 1.22 mg.L-1) and the lowest, in the ternary Sm + La + Nd (2:2:1) mixture (EC50 48 h 41.48 ± 1.40 mg.L-1). The highest toxicity in the MSq medium was observed in the single assays and in the binary Sm + Nd (1:1) mixture (EC50 48 h 10.60 ± 1.57 mg.L-1), and the lowest, in the ternary Sm + La + Nd (1:2:2) mixture (EC50 48 h 36.76 ± 1.54 mg.L-1). Concerning the MS medium, 75 % of interactions were additive, 19 % antagonistic, and 6 % synergistic. In the MSq medium, 56 % of interactions were synergistic and 44 % additive. The higher toxicity observed in the MSq medium indicates that the absence of chelators can increase the concentrations of more toxic free ions, suggesting that the MS medium should be avoided in REE assays. Additive interactions were observed in greater or equivalent amounts in both media and were independent of elemental mixture ratios. These findings improve the understanding of environmental REE effects, contributing to the establishment of future guidelines and ecological risk calculations.

Zebrafish (Danio rerio) as a model to assess the effects of cocaine as a drug of abuse and its environmental implications.

Cocaine (COC) use concerns are on the increase for both authorities and civil society. Despite this, it is important to investigate COC effects or those of its main metabolite, belzoylecgonine (BE), in consolidated aquatic model organisms, such as the zebrafish (Danio rerio). This (mini) review consists in an assessment regarding toxicological studies carried out employing zebrafish (embryos, larvae or adults) exposed to COC and/or BE indexed at the SCOPUS and Web of Science databases. Ten different endpoints were analyzed in both embryos and larvae, whereas only four were analyzed in adults. Of the 23 studies, only five investigated COC and/or BE effects following an environmental approach when exposing zebrafish, while most (18 studies) analyzed COC effects under a drug of abuse approach. Cocaine exposure was noted as altering the expression of several genes, such as those linked to COC transport proteins, dopamine receptors, SP substance production, the tachykinin system, and the tyrosine hydroxylase enzyme. BE exposure resulted in more oxidative and proteomic effects than COC in embryos. Cocaine abstinence resulted in hyperactivity associated with stereotypy in adult fish, in addition to reduced responses to visual stimuli to red light and neuronal development pattern alterations. Cocaine was noted as accumulating in zebrafish eyes, possibly due to melanin binding, and causing dose-response cardiac effects in both embryos and adults. Despite the different effects addressed by our survey, we emphasize the lack of COC and BE exposure assessments in zebrafish employing an environmental point of view.

A comprehensive assessment of leachate contamination at a non-operational open dumpsite: mycoflora screening, metal soil pollution indices, and ecotoxicological risks.

The final disposal of municipal solid waste (MSW) in dumpsites is still a reality worldwide, especially in low- and middle-income countries, leading to leachate-contaminated zones. Therefore, the aim of this study was to carry out soil and leachate physicochemical, microbiological, and toxicological characterizations from a non-operational dumpsite. The L-01 pond samples presented the highest physicochemical parameters, especially chloride (Cl; 4101 ± 44.8 mg L-1), electrical conductivity (EC; 10,452 ± 0.1 mS cm-1), and chemical oxygen demand (COD; 760 ± 6.6 mg L-1) indicating the presence of leachate, explained by its close proximity to the landfill cell. Pond L-03 presented higher parameters compared to pond L-02, except for N-ammoniacal and phosphorus levels, explained by the local geological configuration, configured as a slope from the landfill cell towards L-03. Seven filamentous and/or yeast fungi genera were identified, including the opportunistic pathogenic fungi Candida krusei (4 CFU) in an outcrop sample. Regarding soil samples, Br, Se, and I were present at high concentrations leading to high soil contamination (CF ≤ 6). Pond L-02 presented the highest CF for Br (18.14 ± 18.41 mg kg-1) and I (10.63 ± 3.66 mg kg-1), while pond L-03 presented the highest CF for Se (7.60 ± 1.33 mg kg-1). The most severe lethal effect for Artemia salina was observed for L-03 samples (LC50: 79.91%), while only samples from L-01 were toxic to Danio rerio (LC50: 32.99%). The highest lethality for Eisenia andrei was observed for L-02 samples (LC50: 50.30%). The applied risk characterization indicates high risk of all proposed scenarios for both aquatic (RQ 375-909) and terrestrial environments (RQ > 1.4 × 105). These findings indicate that the investigated dumpsite is contaminated by both leachate and metals, high risks to living organisms and adjacent water resources, also potentially affecting human health.

Effects of rare earth elements (REE) on terrestrial organisms: current status and future directions.

Rare Earth Elements (REE) are becoming increasingly important economically and highly exploited, thus contributing to REE increases in ecosystems. The ecotoxicological effects of REE on the terrestrial environment are, however, not fully understood and information on the biological effects of REE is urgently required for environmental risk assessments. In this review, studies and gaps in the existing scientific literature regarding the toxicological effects of REE on terrestrial organisms are presented. A total of 41 articles from the Web of Science database are discussed. La and Ce are the most studied elements, while little information is found concerning heavy REE. Most studies have been performed on plant species and few investigations are available for animals. Plant effects such as reduced mitotic index, germination and photosynthesis and antioxidant system enzyme alterations have been reported. Invertebrate effects include mortality, reproduction alterations and reduced locomotion. Based on the limited number of articles on terrestrial environment REE effects, this review highlights the need for more detailed studies in order to elucidate the effects associated with the REE hormesis and perform complete risk assessments with the establishment of safe REE usage limits.

Oxidative stress and metal homeostasis alterations in Danio rerio (zebrafish) under single and combined carbamazepine, acetamiprid and cadmium exposures.

Contaminants of emerging concern (CEC) are routinely detected in aquatic environments, especially pharmaceuticals, such as carbamazepine (CBZ), and neonicotinoid pesticides, like acetamiprid (ACT). CECs can interact with each other and with other legislated contaminants like Cd, resulting in unknown effects. Most studies evaluate only the effects of single contaminant exposures on aquatic biota. Therefore, the aim of the present study was to assess the effects of both single and combined CBZ, ACT and Cd exposures on zebrafish brain and liver oxidative stress parameters and metal homeostasis. The biomarkers catalase (CAT), glutathione-S-transferase (GST), total thiols (TOT), metallothionein (MT) and malondialdehyde (MDA) and the essential elements Ca, Cu, K, Na, Mg, Mn and Zn were evaluated after 96-hour static exposures. CBZ, ACT and Cd single (brain and liver) and combined (liver) treatments resulted in oxidative effects in both fish organs, also leading to metal (Ca, Mg, K, Mn, Zn and Cu) homeostasis alterations. ACT exposure resulted in the greatest adverse effects in the brain, while CBZ was the cause of major element homeostasis and oxidative stress alterations in the liver. Lower LPO levels were observed in the combined treatments compared to single treatments, suggesting interactions and contaminant effect attenuation. This study is the first to evaluate the initial effects of combined CBZ, ACT and Cd exposures in zebrafish, paving the way for further investigations concerning other biomarkers during longer exposure times.

Antioxidant system alterations and biological health status of earthworms following long-term exposure to antibiotic-contaminated poultry litter.

Poultry litter is widely applied as a fertilizer even though it is one of the main antibiotic sources to agricultural soils. Long-term sublethal effects (56 days) on the antioxidant system of Eisenia andrei earthworms following exposure to fluoroquinolone-contaminated poultry litter (enrofloxacin + ciprofloxacin) at 5.0, 10, and 20 g kg-1 were evaluated. The following biomarkers were assessed: superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), reduced glutathione (GSH), and a lipid peroxidation (LPO) proxy. Significant CAT and SOD increases, and a moderate positive correlation (ρ = 0.67, p < 0.05) between these enzymes was observed. Glutathione-S-transferase levels increased significantly at 10 g kg-1, while GSH exhibited a dose-dependent response at 5.0 mg kg-1 (4-106%), 10 mg kg-1 (28-330 %), and 20 mg kg-1 (45-472%). LPO levels exhibited a decreasing trend with increasing poultry litter concentrations of 8-170% (5.0 g kg-1), 7-104% (10 mg kg-1), and 3-6% (20 mg kg-1). A principal component analysis (PCA) highlighted increased SOD and CAT activities, possibly due to increased reactive oxygen species (ROS) concentrations. Biological health status assessments based on the biomarker response index indicate major alterations in the first month of exposure and becoming moderate in the second month. These findings indicate an antioxidant system attenuation trend. It is possible, however, that successive poultry litter applications may reduce the long-term recovery capacity of the evaluated biomarkers.

Artificial intelligence application in diagnostic gastrointestinal endoscopy - Deus ex machina?

The close relationship of medicine with technology and the particular interest in this symbiosis in recent years has led to the development of several computed artificial intelligence (AI) systems aimed at various areas of medicine. A number of studies have demonstrated that those systems allow accurate diagnoses with histological precision, thus facilitating decision-making by clinicians in real time. In the field of gastroenterology, AI has been applied in the diagnosis of pathologies of the entire digestive tract and their attached glands, and are increasingly accepted for the detection of colorectal polyps and confirming their histological classification. Studies have shown high accuracy, sensitivity, and specificity in relation to expert endoscopists, and mainly in relation to those with less experience. Other applications that are increasingly studied and with very promising results are the investigation of dysplasia in patients with Barrett's esophagus and the endoscopic and histological assessment of colon inflammation in patients with ulcerative colitis. In some cases AI is thus better than or at least equal to human abilities. However, additional studies are needed to reinforce the existing data, and mainly to determine the applicability of this technology in other indications. This review summarizes the state of the art of AI in gastroenterological pathology.

Long-term landfill leachate exposure modulates antioxidant responses and causes cyto-genotoxic effects in Eisenia andrei earthworms.

It is estimated that approximately 0.4% of the total leachate produced in a landfill is destined for treatment plants, while the rest can reach the soil and groundwater. In this context, this study aimed to perform leachate toxicity evaluations through immune system cytotoxic assessments, genotoxic (comet assay) appraisals and antioxidant system (superoxide dismutase - SOD; catalase - CAT, glutathione-S-transferase - GST; reduced glutathione - GSH and metallothionein - MT) evaluations in Eisenia andrei earthworms exposed to a Brazilian leachate for 77 days. The leachate sample contained high organic matter (COD - 10,630 mg L-1) and ammoniacal nitrogen (2398 mg L-1), as well as several metals, including Ca, Cr, Fe, Mg, Ni and Zn. Leachate exposure resulted in SOD activity alterations and increased CAT activity and MT levels. Decreased GST activity and GSH levels were also observed. Antioxidant system alterations due to leachate exposure led to increased malondialdehyde levels as a result of lipid peroxidation after the 77 day-exposure. An inflammatory process was also observed in exposed earthworms, evidenced by increased amoebocyte density, and DNA damage was also noted. This study demonstrates for the first time that sublethal effect assessments in leachate-exposed earthworms comprise an important tool for solid waste management.

Gitelman Syndrome: A Rare Case of Hypokalaemia and a Novel Mutation.

Gitelman syndrome (GS) is a hereditary renal tubulopathy caused by mutations in the SLC12A3 gene which encodes the thiazide-sensitive apical sodium-chloride cotransporter. GS is characterized by hypokalaemia, hypomagnesaemia and metabolic alkalosis. Treatment is based on potassium and magnesium replacement ad eternum. We present the case of a young man with palpitations and persistent hypokalaemia, who was diagnosed with GS. Genetic testing revealed 2 mutations in the gene SLC12A3 of combined heterozygosity, both considered pathological. Interestingly, 1 of these mutations was not yet described in the literature or in the reviewed databases. We also discuss the clinical approach and the specificities of managing this rare hereditary renal tubulopathy.. LEARNING POINTS: Gitelman syndrome is a rare cause of persistent hypokalaemia.A definitive diagnosis is determined by the identification of mutations in the SLC12A3 gene.Management consists of chronic potassium and magnesium supplementation aimed at symptom control.

Ecotoxicological evaluation of imazalil transformation products on Eisenia Andrei.

Data concerning the toxicity of the transformation products of some pesticides considered emerging contaminants are still incipient. This study aimed to evaluate acute (filter paper contact and avoidance test) and chronic (assays carried out in Red yellow Ultisoil) effects of the transformation products of the fungicide imazalil (IMZ) by heterogeneous photocatalysis (TiO2/UV) in Eisenia andrei. Some endpoints, i.e. biomass variation, disorder in reproduction and avoidance behavior, cytotoxicity (cell density and feasibility), and coelomic fluid (eleocytes and amoebocytes, immune cell) and antioxidant system (catalase (CAT) and glutathione S-transferase (GST)) changes were assessed. The studied degradation times (6, 18, 35 and 90 min) represented 70; 35; 10 and 0% of the initial IMZ concentration (5 mg L-1). No lethality and no significant difference in biomass variations were noted in the acute contact test. Decreased GST and increased CAT activities, as well as cell typing alterations and decreased cell viability and density detected at the 90-min degradation timepoint (PDT-90) indicate direct cytotoxic IMZ transformation product effects. In the avoidance test, no significant earthworm repulsion or attraction was observed. PDT-90 transformation products were responsible for losses in biomass and a reduction in the number of earthworm cocoons and juveniles present in soil. No cytotoxic effects were observed in the long term, although increased CAT and decreased GST activities were observed. Investigations on the relative toxicity of IMZ transformation products are relevant for future discussions regarding the environmental treatment, control and destination of this compound and its derivatives.

Lethal and long-term effects of landfill leachate on Eisenia andrei earthworms: Behavior, reproduction and risk assessment.

Leachate is difficult to biodegrade, and presents variable physical, chemical and biological characteristics, as well as high toxicological potential for soil, groundwater and water bodies. In this context, untreated leachate toxicity was evaluated through acute and chronic exposures in Eisenia andrei earthworms. Physico-chemical leachate characterizations indicate a complex composition, with high organic matter (COD - 10,634 mg L-1) and ammoniacal nitrogen (2388 mg L-1) concentrations. Metals with carcinogenic potential, such as Cr, As and Pb, were present at 0.60, 0.14 and 0.01 µg L-1, respectively and endocrine disrupting compounds were detected in estradiol equivalents of 660 ± 50 ng L-1. Acute tests with Eisenia andrei indicated an LC50 (72 h) of 1.3 ± 0.1 µL cm-2 in a filter paper contact test and 53.9 ± 1.3 mL kg-1 in natural soil (14 days). The EC50 in a behavioral test was estimated as 31.6 ± 6.8 mL kg-1, indicating an escape effect for concentrations ranging from 35.0 to 70.0 mL kg-1 and habitat loss from 87.5 mL kg-1 of leachate exposure. Chronic exposure (56 days) led to reproduction effects, resulting in a 4-fold decreased cocoon production and 7-fold juvenile decrease. This effect was mainly attributed to the possible presence of endocrine disrupting compounds. An estimated NOAEL of 1.7 mL L-1 and LOAEL of 3.5 mL L-1 were estimated for earthworms exposed to the assessed effluent. Extremely high-risk quotients (RQ ≥ 1) were estimated based on leachate application in irrigation. Thus, adequate municipal solid waste management is paramount, especially with regard to generated by-products, which can result in high toxicological risks for terrestrial organisms.