Complete response to capmatinib in a patient with metastatic lung adenocarcinoma harboring CD47-MET fusion: a case report.

Comprehensive genomic profiling is highly recommended for treatment decision in nonsquamous, non-small cell lung cancer (NSCLC). However, rare genomic alterations are still being unveiled, with scarce data to guide therapy. Herein, we describe the treatment journey of a 56-year-old, never-smoker Caucasian woman with a metastatic NSCLC harboring a CD47-MET fusion, initially classified as a variant of unknown significance. She had undergone 3 lines of therapy over the course of 3 years, including chemotherapy, immunotherapy, and anti-angiogenic therapy. After reanalysis of her next-generation sequencing data in our service, the fusion was reclassified as likely oncogenic. The patient was started with fourth-line capmatinib, with a good tolerance so far and a complete metabolic response in the active sites of disease, currently ongoing for 18 months. In conclusion, we highlight the sensitivity of a novel MET fusion to capmatinib and emphasize the need for comprehensive panels in NSCLC and molecular tumor board discussions with specialized centers when rare findings arise.

Facial and ocular thermal mapping in black-and-gold howler monkey (Alouatta caraya) by infrared thermography: An ex situ study.

BACKGROUND: This study used infrared thermography (IRT) for mapping the facial and ocular temperatures of howler monkeys, to determine parameters for the diagnosis of febrile processes. There are no published IRT study in this species. METHODS: Were evaluated images of a group of monkeys kept under human care at Sorocaba Zoo (São Paulo, Brazil). The images were recorded during 1 year, in all seasons. Face and eye temperatures were evaluated. RESULTS: There are statistically significant differences in face and eye temperatures. Mean values and standard deviations for facial and ocular temperature were respectively: 33.0°C (2.1) and 36.5°C (1.9) in the summer; 31.5°C (4.5) and 35.3°C (3.6) in the autumn; 30.0°C (4.3) and 35.6°C (3.9) in the winter; 30.8°C (2.9) and 35.5°C (2.1) in the spring. CONCLUSIONS: The IRT was effective to establish a parameter for facial and ocular temperatures of black-and-gold howler monkeys kept under human care.

Forensic Geochemistry Reveals International Ship Dumping as a Source of New Oil Spill in Brazil's Coastline (Bahia) in Late 2023.

In the present study, we applied forensic geochemistry to investigate the origin and fate of spilled oils like tarballs stranded at the beaches of Bahia, in northeastern Brazil, in September 2023, based on their fingerprints. Saturated and aromatic compounds were assessed by gas chromatography, and the oceanic surface circulation patterns were deciphered to determine the geographic origin of the spill. Contamination by petroleum represents an enormous threat to the unique, species-rich ecosystems of the study area. The geochemical fingerprint of the oil spilled in 2023 did not correlate with those of previous events, including the one in 2019, the one in early 2022 in Ceará, and an extensive spill across the Brazilian Northeast in late 2022. However, the fingerprint did correlate with crude oils produced by Middle Eastern countries, most likely Kuwait. The oil of the 2023 spill had a carbonate marine origin from early mature source rocks. These findings, together with the moderate weathering of the 2023 tarballs and the ocean circulation patterns at the time of the event, indicate that the oil was discharged close to the shore of Brazil, to the east or southeast of Salvador, by a tanker on an international route in the South Atlantic.

Diagnostic criteria and case definitions for abdominal angiostrongyliasis: a systematic review from the Brazilian experience.

Although rare, Angiostrongylus costaricensis infection may be a more prevalent etiology of inflammatory bowel disease than ulcerative colitis and Chron's disease in endemic areas in Central and South America. The present study reviewed the occurrence of A. costaricensis in Brazil, its clinical presentation and pathology; and proposed diagnostic criteria and case definitions for abdominal angiostrongyliasis (AA). Southern and southeastern Brazilian regions are the main endemic areas, and AA affects both genders and all age groups. A review of all 23 published reports of 51 Brazilian patients highlighted the following features that were subsequently classified as minor diagnostic criteria: abdominal pain, palpable mass in the right lower abdominal quadrant, history of exposure, ileocecal tumor, and intestinal perforation with wall thickening. Proposed major criteria include right lower quadrant abdominal pain, blood eosinophilia, positive serology (antibody detection), intense eosinophilic infiltration that involves all strata of the intestinal wall, eosinophilic granulomatous reaction, and eosinophilic vasculitis. In addition to the definitions of suspected and possible cases according to increasing strength of evidence of this infection, demonstration of worms/eggs/larvae in tissues or Angiostrongylus DNA in tissues or serum are required for a confirmed diagnosis. The application of the proposed criteria and definitions may improve patient management, epidemiologic surveillance, and identification of new endemic areas.

Real-time qPCR coupled with high-resolution melting curve analysis for the detection of the internal transcribed spacer 1 of Angiostrongylus costaricensis.

Abdominal angiostrongyliasis (AA) is a zoonotic and severe parasitic infection caused by Angiostrongylus costaricensis. AA is currently diagnosed by the observation of A. costaricensis-compatible structures in biopsies or the detection of antibodies in serological tests. However, molecular methods targeting homologous sequences of A. costaricensis have not been designed before, and therefore, an HRM-coupled qPCR was developed to detect the internal transcribed spacer 1 (ITS1) of the parasite. The present assay successfully amplified DNA of A. costaricensis obtained from different hosts and identified slight sequence differences through the HRM analysis. The detection limit of the HRM-qPCR was 0.00036 ng/µL, 1.0 ng/µL, and 0.1 ng/µL when A. costaricensis DNA was diluted in nuclease-free water, whole blood, and sera, respectively, which highlights its potential use for cell-free DNA detection. Moreover, the reaction did not cross-amplify DNA of Angiostrongylus cantonensis, Strongyloides stercoralis, and other nematodes, thus emphasizing its specificity. Additionally, the assay tested positive in formalin-fixed paraffin embedded biopsies with visible A. costaricensis adults or eggs, but not in samples without evident parasites or a low number of larvae, which suggests that the reaction is useful for confirming the presence of the nematode in clinical samples. Finally, DNA of sera from patients with AA was evaluated with the HRM-qPCR but none tested positive, possibly due to long storage periods of the samples which could have led to cfDNA degradation. These results indicate that this assay may be useful in the confirmation of AA and its prospection for cell-free DNA detection protocols.

Hepatosplenic involvement of tuberculosis: an uncommon presentation that demands attention in specific scenarios.

Abdominal tuberculosis (TB), a potential differential diagnosis for acute and chronic abdomen, should be considered in specific situations, such as immunosuppressant or biological drug use, HIV, or in patients residing in endemic areas. Although the presence of thoracic tuberculosis may indicate abdominal TB, only 15% of patients with abdominal TB have evidence of pulmonary disease. Involvement of the liver and spleen is a common autopsy finding in patients with disseminated TB. However, the most common pattern is of fine miliary lesions. Hepatic involvement with a macronodular pattern, a rare occurrence, is linked to dissemination through the portal vein. The splenic macronodular form, an extremely rare presentation, can manifest as solitary or multiple nodules, oval or round, with a variable appearance reflecting different stages of the disease, adding to the uniqueness of this case.

Trousseau syndrome preceding the diagnosis of colon cancer.

Trousseau Syndrome (TS) is defined as the occurrence of thromboembolic events prior to or simultaneously with the diagnosis of visceral neoplasia. In cases of multiple thromboembolisms, considering the possibility of TS, a screening for neoplasms may be warranted. We present a case study of a 61-year-old female who presented a neurological deficit. Brain magnetic resonance imaging (MRI) showed multiple hyperintense bihemispheric foci in subcortical and cortical regions involving three different vascular territories in the FLAIR sequence, associated with restricted diffusion inferring cytotoxic edema and indicating that they were all recent ischemic lesions, raising the hypothesis of TS. The patient underwent neoplastic screening with a subsequent diagnosis of colon cancer. TS should be considered when the patient presents thromboembolic events without an established cause. The three-territories-sign (TTS) is an essential radiographic biomarker related to cancer-associated ischemic stroke (CAIS). We propose that our findings be considered for the inclusion of guidelines that determine the investigation of an occult tumor (particularly gastric, pancreatic, lung, and colorectal) in patients who present thrombotic events, especially TTS.

Authentication of fish oil (omega-3) supplements using class-oriented chemometrics and comprehensive two-dimensional gas chromatography coupled to mass spectrometry.

Food supplement authentication is an important concern worldwide due to the ascending consumption related to health benefits and its lack of effective regulation in underdeveloped countries, making it a target of fraudulent activities. In this context, this study evaluated fish oil supplements by comprehensive two-dimensional gas chromatography coupled to mass spectrometry (GC×GC-MS) to obtain fingerprints, which were used to build predictive models for automated authentication of the most popular products sold in Brazil. The authentication process relied on a one-class classifier model using data-driven soft independent modeling of class analogy (DD-SIMCA). The output of the model was a binary classifier: certified IFOS fish oils and non-certified ones - regardless of the source of adulteration. The compositional analysis showed a significant variation in the samples, which validated the need for reliable statistical models. The DD-SIMCA algorithm is still incipient in GC×GC studies, but it proved to be an excellent tool for authenticity purposes, achieving a chemometric model with a sensitivity of 100%, specificity of 98.6%, and accuracy of 99.0% for fish oil authentication. Finally, orthogonalized partial least square discriminant analysis (OPLS-DA) was used to identify the features that distinguished the groups, which ascertained the results of the DD-SIMCA model that IFOS-certified oils are positively correlated to omega-3 fatty acids, including eicosapentaenoic acid (EPA, C20:5 n-3) and docosahexaenoic acid (DHA, C22:6 n-3).

A review of serological tests available in Brazil for intestinal schistosomiasis diagnosis.

The World Health Organization (WHO) roadmap and recommendations for elimination of schistosomiasis were recently updated. With significant reductions in the prevalence and intensity of schistosomiasis infections worldwide, there is a need for more sensitive diagnostic methods. There are a few remaining transmission hotspots in Brazil, although low endemicity settings comprise most of the endemic localities. For the latter, serology may represent a tool for population screening which could help eliminate transmission of schistosomiasis. Here, we review serology tests currently available in Brazil from both public health and private laboratories: immunofluorescent antibody tests (IFATs) on adult worm sections and enzyme-linked immunosorbent assays (ELISAs) with soluble egg and adult worm antigens. Both in-house and commercially available tests have received less than adequate performance evaluations. Our review of immediate basic and operational research goals may help identify local adjustments that can be made to improve control interventions aimed at elimination of schistosomiasis as a public health problem.

Molecular diagnosis of abdominal angiostrongyliasis by PCR using serum samples.

Abdominal angiostrongyliasis (AA) is a zoonotic disease caused by the nematode Angiostrongylus costaricensis, which is endemic in southern Brazil. Humans become infected by ingesting third-stage (L3) larvae and are considered accidental hosts since neither eggs nor first-stage (L1) larvae are found in feces. The definitive diagnosis can be made by histopathologic examination of surgical specimens or intestinal biopsies. The present study assessed the use of PCR to carry out the molecular detection of AA from serum samples. A total of 62 human serum samples were divided into three groups: (i) 28 serum samples from human patients with presumptive histopathological diagnosis of AA; (ii) 23 serum samples from individuals with unknown serology for AA; (iii) 11 serum samples from patients that suffered from different parasitosis were included. The serum samples were initially tested by in-house indirect ELISA and then by PCR. A total of 14 samples were positive by ELISA, and 6 were positive by PCR. Six samples that were negative by ELISA were positive by PCR. Amplicons were sequenced, and Angiostrongylus DNA was confirmed. We conclude that PCR amplification can be used to confirm Angiostrongylus DNA in serum, which is especially important in cases where antibody levels are too low to be detected. It may also serve as a useful target for survey studies.

Budd-Chiari syndrome in Behçet's disease.

A 36-year-old man was admitted to the emergency department due to a 30-day history of abdominal distention and epigastralgia. He had described a non-intentional 10kg weight loss, dry cough, and fever 6 months before his admission. He had a history of tobacco and cocaine abuse and reported recurrent oral and genital ulcers. Physical examination showed an extensive area of venous collateral circulation on the abdominal wall, hepatomegaly, signs of a moderate ascites, and lower limb edema. Liver and renal function tests were normal. The ascitic fluid analysis did not show an inflammatory or infectious pattern. Upper flexible endoscopy revealed esophageal fine-caliber varices and colonoscopy showed an isolated terminal ileal ulcer. Abdominal imaging revealed hepatomegaly, voluminous ascites, and thrombosis of hepatic veins, inferior and superior vena cava (Figure 1). Infections and coagulation or lymphoproliferative disorders were excluded. Thereafter, the diagnosis of Budd-Chiari Syndrome in Behçet disease was established and immunosuppression treatment was started with good initial clinical evolution.

Intestinal pneumatosis as a manifestation of systemic sclerosis.

A 60-year-old female patient was admitted to the emergency room for a 7-day history of abdominal bloating, nausea, vomiting, constipation, and lack of flatus. She had been diagnosed with systemic sclerosis (SSc) 10 years ago and had been using methotrexate, sildenafil, and prednisone. She did not present any signs of instability, but physical examination showed malnourishment status and abdominal tenderness and distention. Plain abdominal radiography was suggestive of sigmoid volvulus, confirmed and successfully resolved after endoscopic decompression therapy. Eight months later, the patient developed a new episode of abdominal obstruction. Computed Tomography (CT) scan identified a distended sigmoid colon due to its torsion with gas areas within the bowel wall. This time, endoscopic decompression had failed to treat, so exploratory laparotomy was performed. Colonic distention and sigmoid volvulus were identified during the procedure, after which sigmoidectomy followed by primary anastomosis was performed. Neither perforation nor masses were found. Furthermore, the anatomopathological study was inconsistent with vascular, inflammatory, or neoplastic diseases.

SEROLOGICAL SURVEY FOR SELECTED PATHOGENS IN FREE-RANGING COUGARS (PUMA CONCOLOR) IN SÃO PAULO, BRAZIL.

This study performed a serological assay to assess the exposure of free-ranging cougars (Puma concolor) to four selected infectious agents, including Toxoplasma gondii, Leptospira spp., the feline immunodeficiency virus (FIV), and the feline leukemia virus (FeLV). Serum samples were collected from 27 free-ranging cougars along the Tietê River Basin, in the central region of the State of São Paulo, Brazil. The presence of antibodies against T. gondii was detected in 59.3% (16/27) of the serum samples through the modified agglutination test (MAT-t), which was the most prevalent agent. The microscopic agglutination technique (MAT-1) was used to investigate the occurrence of anti-Leptospira spp. antibodies, showing that 11.1% (3/27) of the sampled cougars were seropositive. The only serovar detected was Djasiman (L. interrogans). A commercial enzyme-linked immunosorbent assay (ELISA) licensed for use in domestic felines was used to investigate the occurrence of retroviruses. The ELISA test kits detected a prevalence of 11.1% (3/27) of FIV antibodies, while none of the samples tested showed any evidence of FeLV antigen. These results suggest that free-ranging cougars are exposed to potentially pathogenic agents. This study presented the first recorded occurrence of the serovar Djasiman in P. concolor.

Schistosoma mansoni miracidia: revisiting motility and survival parameters for improved computational modelling.

Schistosoma mansoni is the main causative agent of intestinal schistosomiasis which affects millions of people worldwide. At the larval stage, miracidia are released into bodies of water where they utilize their motility to successfully infect their intermediate host, snails. Here, we revisit the motility and survival of S. mansoni miracidia throughout its life span. Briefly, miracidia motility was monitored at 30-min and 60-min intervals under the presence/absence of natural/artificial light. Based on a subjective evaluation of activity, body shape and transparency, 6 categories of miracidia activity were established from its fully active stage to its immobile larva stage. The estimated life span of miracidia was 5.8 and 3.5 h in the experiments with 60-min and 30-min observation intervals, respectively. Death was defined by an absence of cilia and body movement. When mobility was used as a proxy for infectivity, infective miracidia were detected at 2.5 and 4.5 h, respectively. The present miracidia motility and survival re-evaluation supports parameters optimization for computational modelling of schistosomiasis transmission dynamics. Target control interventions, especially at late stages next to transmission interruption, may greatly benefit from improved modelling studies.

Assessing the effects of diagnostic sensitivity on schistosomiasis dynamics.

Schistosomiasis is a parasite infection that affects millions of people around the world. It is endemic in 13 different states in Brazil and responsible for increasing morbidity in the population. One of its main characteristics is a heterogeneous distribution of worm burden in the human population, which makes the diagnosis difficult. We aimed to investigate how the sensitivity of the diagnostic method may contribute to successful control interventions against infections in a population. In order to do that, we present an ordinary differential equations model that considers three levels of worm burden in the human population, a snail population, and a miracidium reservoir. Through a steady-state analysis and its local stability, we show how this worm-burden heterogeneity can be responsible for the persistence of infection, especially due to reinfection in the highest level of worm burden. The analysis highlights sensitive diagnosis, besides treatment and sanitary improvements, as a key factor for schistosomiasis transmission control.

De novo transcriptome reveals blood coagulation/antithrombin factors and infection mechanisms in Angiostrongylus cantonensis adult worms.

Angiostrongylus cantonensis is the main aetiological agent of eosinophilic meningoencephalitis in humans. Several outbreaks have been documented around the world, cementing its status as an emerging global public health concern. As a result, new strategies for the diagnosis, prophylaxis and treatment of cerebral angiostrongyliasis are urgently needed. In this study, we report on the de novo assembly of the A. cantonensis transcriptome, its full functional annotation and a reconstruction of complete metabolic pathways. All results are available at AngiostrongylusDB (http://angiostrongylus.lad.pucrs.br/admin/welcome). The aim of this study was to identify the active genes and metabolic pathways involved in the mechanisms of infection and survival inside Rattus norvegicus. Among 389 metabolic mapped pathways, the blood coagulation/antithrombin pathways of heparan sulphate/heparin are highlighted. Moreover, we identified genes codified to GP63 (leishmanolysin), CALR (calreticulin), ACE (peptidyl-dipeptidase A), myoglobin and vWD (von Willebrand factor type D domain protein) involved in the infection invasion and survival of the parasite. The large dataset of functional annotations provided and the full-length transcripts identified in this research may facilitate future functional genomics studies and provides a basis for the development of new techniques for the diagnosis, prevention and treatment of cerebral angiostrongyliasis.

Environmental implications of stored cattle slurry treatment with sulphuric acid and biochar: A life cycle assessment approach.

With the increase of animal slurry produced from livestock production, the monitoring and mitigation of greenhouse gas (GHG) and ammonia (NH3) emissions represent a major issue. Life cycle assessment (LCA) has been used to evaluate the long-term environmental effects of applied strategies and technologies on cattle slurry management for mitigation of environmental harmful gases. This study was carried on two main aims: first, the effect of the addition of sulphuric acid (SA), biochar (SBi) or A + Bi to liquid cattle-slurry (treated systems) on gas emissions during storage compared to the untreated system (S) was investigated in a laboratory-controlled experiment; second, the environmental implications of each treated or untreated system were assessed through a LCA approach according to ISO 14040/44. Five CML 2001 impact categories were used: eutrophication potential (EP), acidification potential (AP), global warming potential (GWP), human toxicity potential (HTP) and Ozone Layer Depletion Potential (ODP). Comparisons were based on 1 ton fresh dairy cattle slurry. The environmental profile of untreated system showed lower efficiency in mitigation of total GHG and NH3 emissions (0.0312 and 0.0001 kg CO2-eq respectively), during storage period and greater impact on GWP and HTP categories. The electricity consumption in mechanical separation dominated the environmental impacts. From the three proposed treated systems, SA showed the highest efficiency on mitigation of gas emissions compared to the other treatments, reducing NH3, CH4 and CO2 emissions respectively in 61%, 98% and 15%, when compared to the SBi system. In all categories, acidified slurry also showed the lowest environmental impact relative to other treated systems and the benefit was more evident when the impacts were expressed per kilogram of nitrogen in the slurry. Therefore, LCA methodology was of great importance to assess the environmental implications of the treatments and acidification can be considered as an effective technique on the mitigation of environmental implications of livestock production and cattle-effluent valorization. Optimization and uniformity of performed studies are essential to validate new strategies to improve the sustainability of this sector in the management of animal wastewater.

An Ultrasonic-Capacitive System for Online Characterization of Fuel Oils in Thermal Power Plants.

This paper presents a ultrasonic-capacitive system for online analysis of the quality of fuel oils (FO), which are widely used to produce electric energy in Thermal Power Plants (TPP) due to their elevated heating value. The heating value, in turn, is linked to the quality of the fuel (i.e., the density and the amount of contaminants, such as water). Therefore, the analysis of the quality is of great importance for TPPs, either in order to avoid a decrease in generated power or in order to avoid damage to the TPP equipment. The proposed system is composed of two main strategies: a capacitive system (in order to estimate the water content in the fuel) and an ultrasonic system (in order to estimate the density). The conjunction of the two strategies is used in order to estimate the heating value of the fuel, online, as it passes through the pipeline and is an important tool for the TPP in order to detect counterfeit fuel. In addition, the ultrasonic system allows the estimation of the flow rate through the pipeline, hence estimating the amount of oil transferred and obtaining the total mass transferred as a feature of the system. Experimental results are provided for both sensors installed in a TPP in Brazil.

Enhancement of the Antioxidant and Antimicrobial Activities of Porphyran through Chemical Modification with Tyrosine Derivatives.

The chemical modification of porphyran hydrocolloid is attempted, with the objective of enhancing its antioxidant and antimicrobial activities. Sulfated galactan porphyran is obtained from commercial samples of the red algae Porphyra dioica using Soxhlet extraction with water at 100 °C and precipitation with isopropyl alcohol. The extracted porphyran is then treated with modified L-tyrosines in aqueous medium in the presence of NaOH, at ca. 70 °C. The modified tyrosines L1 and L2 are prepared through a Mannich reaction with either thymol or 2,4-di-tert-butylphenol, respectively. While the reaction with 2,4-di-tert-butylphenol yields the expected tyrosine derivative, a mixture of products is obtained with thymol. The resulting polysaccharides are structurally characterized and the respective antioxidant and antimicrobial activities are determined. Porphyran treated with the N-(2-hydroxy-3,5-di-tert-butyl-benzyl)-L-tyrosine derivative, POR-L2, presents a noticeable superior radical scavenging and antioxidant activity compared to native porphyran, POR. Furthermore, it exhibited some antimicrobial activity against S. aureus. The surface morphology of films prepared by casting with native and modified porphyrans is studied by SEM/EDS. Both POR and POR-L2 present potential applicability in the production of films and washable coatings for food packaging with improved protecting characteristics.

Protective effects of silymarin in broiler feed contaminated by mycotoxins: growth performance, meat antioxidant status, and fatty acid profiles.

The aim of this study was to determine whether the inclusion of silymarin in broiler feed was able to mitigate the adverse effects of mycotoxin on growth performance, health status, liver oxidative stress, and meat fatty acid profiles. A completely randomized design with four treatments, four repetitions, and 15 chicks per repetition was used, with the following groups: (a) feed without additives (NoMyc-NoSil), (b) feed supplemented with silymarin (NoMyc-Sil), (c) feed contaminated with mycotoxin (Myc-NoSil), and (d) feed contaminated with mycotoxin and supplemented with silymarin (Myc-Sil). Growth performance, intestinal and liver health, and meat quality were assessed. The consumption of feed contaminated with mycotoxin delayed weight gain and increased the feed conversion ratio; however, the addition of silymarin prevented these adverse effects on the chicken industry. Serum ALT activity was higher in Myc-NoSil broilers than in other groups. Intake of silymarin in healthy birds increased serum globulin concentration and reduced albumin concentration and ALT and AST serum activities compared to the Myc-NoSil group. The NoMyc-Sil birds had greater villus heights and crypt depths. Luminosity and water loss by cooking were affected by mycotoxin ingestion, changes that did not occur in the meat of birds that were supplemented with silymarin. The sum of saturated and monounsaturated fatty acids in the meat did not change among treatments, unlike the sum of polyunsaturated fatty acids higher in the meat of birds that consumed silymarin. We conclude that silymarin is a potential additive in broiler feed; it reduces impairment of growth performance at the end of the productive cycle, prevents oxidative stress, improves meat quality, and increases polyunsaturated fatty acids.