Search

OBJECTIVE: We investigated whether echocardiography may help identify, among patients admitted with a suspect of non- ST-segment elevation acute myocardial infarction (NSTEMI), those with athero-thrombotic coronary artery disease (CAD). PATIENTS AND METHODS: We studied consecutive patients admitted with a clinical suspect of first NSTEMI. Echocardiography was assessed within 24 hours from admission. Patients were divided into two groups, according to the results of coronary angiography: 1) patients with obstructive stenosis (≥ 50%) and/or images of thrombosis in one or more coronary arteries (CAD group); 2) patients with no evidence of obstructive coronary arteries (NOCAD group). RESULTS: Of 101 patients enrolled in the study, 53 (52.5%) showed obstructive CAD and 48 (47.5%) NOCAD. At echocardiographic examination, regional wall motion abnormalities were found in 52.8% of patients in the CAD group and 43.7% in the NOCAD group (p=0.43). Left ventricle ejection fraction was 56.4±6.8 vs. 54.7±9.8% (p=0.30) and wall motion score index was 1.16±0.26 vs. 1.21±0.32 ( p=0.39) in the two groups, respectively. A multivariable logistic regression independent predictors of obstructive CAD included age, male gender, typical angina, diabetes and hypertension. CONCLUSIONS: Our data showed that, in patients with acute chest pain and increased serum troponin T concentration, routine standard echocardiography does not significantly improve the diagnostic accuracy for the presence of obstructive CAD. [ABSTRACT FROM AUTHOR]

Alternaria mycotoxins may pose significant challenges to food safety and public health due to the wide spectrum of reported adverse effects. Despite this, critical information on the immunomodulatory and antiestrogenic properties of most of these contaminants is still lacking. The present study aimed to identify the mycotoxins responsible for the immunosuppressive and antiestrogenic effects of a complex extract of Alternaria mycotoxins (CE) obtained by growing an Alternaria alternata strain on rice. Through a toxicity-guided fractionation procedure involving the production of CE-fractions by supercritical fluid chromatography and mycotoxin quantification by LC-MS/MS, the mycotoxins alternariol (AOH), tenuazonic acid (TeA), altertoxin I (ATX-I), and alterperylenol (ALTP) were identified as potential toxicologically relevant constituents contributing to the in vitro effects exerted by the extract. The assessment of the immunomodulatory effects, performed by applying the NF-κB reporter gene assay in THP1-Lucia™ monocytes, revealed the scarce contribution of AOH to the effects exerted by the CE. TeA showed no effect on the NF-κB pathway up to 250 µM, whereas ATX-I and ALTP suppressed the LPS-mediated pathway activation at concentrations ≥ 1 µM. The evaluation of antiestrogenic effects, performed in Ishikawa cells by applying the alkaline phosphatase assay, revealed the ability of ALTP (≥ 0.4 µM) and ATX-I (≥ 2 µM) to suppress the estrogen-dependent expression of enzyme activity. Given the risk of detrimental impacts stemming from alterations in endocrine and systemic immune responses by the investigated mycotoxins, further studies are needed to elucidate their underlying mechanisms of action and comprehensively evaluate the health risks posed by these toxins., (© 2024. The Author(s).)

Risk assessment of food and environmental contaminants is faced by substantial data gaps and novel strategies are needed to support science-based regulatory actions. The Alternaria mycotoxins alternariol (AOH) and altertoxin II (ATXII) have garnered attention for their possible genotoxic effects. Nevertheless, data currently available are rather scattered, hindering a comprehensive hazard characterization. This study combined in vitro/in silico approaches to elucidate the potential of AOH and ATXII to induce double-strand breaks (DSBs) in HepG2 cells. Furthermore, it examines the impact of co-exposure to AOH and the DSB-inducing drug doxorubicin (Doxo) on γH2AX expression. AOH slightly increased γH2AX expression, whereas ATXII did not elicit this response. Interestingly, AOH suppressed Doxo-induced γH2AX expression, despite evidence of increased DNA damage in the comet assay. Building on these observations, AOH was postulated to inhibit γH2AX-forming kinases. Along this line, in silico analysis supported AOH potential interaction with the ATP-binding sites of these kinases and immunofluorescence experiments showed decreased intracellular phosphorylation events. Similarly, in silico results suggested that ATXII might also interact with these kinases. This study emphasizes the importance of understanding the implications of AOH-induced γH2AX expression inhibition on DNA repair processes and underscores the need for caution when interpreting γH2AX assay results., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Co-author serving as Guest Editor of Toxicology Letters - G.D.F. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Fungi of the genus Alternaria are ubiquitous plant pathogens and saprophytes which are able to grow under varying temperature and moisture conditions as well as on a large range of substrates. A spectrum of structurally diverse secondary metabolites with toxic potential has been identified, but occurrence and relative proportion of the different metabolites in complex mixtures depend on strain, substrate, and growth conditions. This review compiles the available knowledge on hazard identification and characterization of Alternaria toxins. Alternariol (AOH), its monomethylether AME and the perylene quinones altertoxin I (ATX-I), ATX-II, ATX-III, alterperylenol (ALP), and stemphyltoxin III (STTX-III) showed in vitro genotoxic and mutagenic properties. Of all identified Alternaria toxins, the epoxide-bearing analogs ATX-II, ATX-III, and STTX-III show the highest cytotoxic, genotoxic, and mutagenic potential in vitro. Under hormone-sensitive conditions, AOH and AME act as moderate xenoestrogens, but in silico modeling predicts further Alternaria toxins as potential estrogenic factors. Recent studies indicate also an immunosuppressive role of AOH and ATX-II; however, no data are available for the majority of Alternaria toxins. Overall, hazard characterization of Alternaria toxins focused, so far, primarily on the commercially available dibenzo-α-pyrones AOH and AME and tenuazonic acid (TeA). Limited data sets are available for altersetin (ALS), altenuene (ALT), and tentoxin (TEN). The occurrence and toxicological relevance of perylene quinone-based Alternaria toxins still remain to be fully elucidated. We identified data gaps on hazard identification and characterization crucial to improve risk assessment of Alternaria mycotoxins for consumers and occupationally exposed workers., (© 2023. The Author(s).)

Humans are constantly exposed to mixtures of different xenobiotics through their diet. One emerging concern is the Alternaria mycotoxin alternariol (AOH), which can occur in foods typically contaminated by the process contaminant acrylamide (AA). AA is a byproduct of the Maillard reaction produced in carbohydrate-rich foods during thermal processing. Given the genotoxic properties of AOH and AA as single compounds, as well as their potential co-occurrence in food, this study aimed to assess the cytotoxic, genotoxic, and mutagenic effects of these compounds in combination. Genotoxicity was assessed in HepG2 cells by quantifying the phosphorylation of the histone γ-H2AX, induced as a response to DNA double-strand breaks (DSBs). Mutagenicity was tested in Salmonella typhimurium strains TA98 and TA100 by applying the Ames microplate format test. Our results showed the ability of AOH and AA to induce DSBs and increase revertant numbers in S. typhimurium TA100, with AOH being more potent than AA. However, no synergistic effects were observed during the combined treatments. Notably, the results of the study suggest that the compounds exert mutagenic effects primarily through base pair substitutions. In summary, the data indicate no immediate cause for concern regarding synergistic health risks associated with the consumption of foods co-contaminated with AOH and AA.

The intestinal compartment ensures nutrient absorption and barrier function against pathogens. Despite decades of research on the complexity of the gut, the adaptive potential to physical cues, such as those derived from interaction with particles of different shapes, remains less understood. Taking advantage of the technological versatility of silica nanoparticles, spherical, rod-shaped, and virus-like materials were synthesized. Morphology-dependent interactions were studied on differentiated Caco-2/HT29-MTX-E12 cells. Contributions of shape, aspect ratio, surface roughness, and size were evaluated considering the influence of the mucus layer and intracellular uptake pathways. Small particle size and surface roughness favored the highest penetration through the mucus but limited interaction with the cell monolayer and efficient internalization. Particles of a larger aspect ratio (rod-shaped) seemed to privilege paracellular permeation and increased cell-cell distances, albeit without hampering barrier integrity. Inhibition of clathrin-mediated endocytosis and chemical modulation of cell junctions effectively tuned these responses, confirming morphology-specific interactions elicited by bioinspired silica nanomaterials.

Neglected tropical diseases are a group of 20 disabling diseases, which, in particular, are the most common chronic infections in the most vulnerable people. This study aimed to characterize the infection by intestinal parasites (IPs) in dwellings from a peri-urban neighborhood in Pampa del Indio, Chaco (Argentina), and its association with socioeconomic and environmental variables. Single stool samples were collected from all individuals older than 1 year through household visits and processed using coprological sedimentation and flotation techniques. Standardized questionnaires were used at the household level to collect socio-economic information. Environmental variables were obtained from the Planetscope image, Landsat 8 images and remote sensors, while land-use layers were obtained through the use of a maximum likelihood algorithm. Stool samples were provided by 314 individuals. The prevalence of IPs found was 30.6% (n = 96), with a predominance of Giardia lamblia (12.7%, n = 40) and Hymenolepis nana (7.6%, n = 24). The only soil-transmitted helminth found was Strongyloides stercoralis with a 2.5% prevalence (n = 8). Individuals of adult age (> 18 years) were 0.65 times less likely to present parasitic infections with respect to children and adolescents. The only environmental variable that was closely associated with the presence of IPs, was the Normalized Difference Water Index (NDWI), a measure of humidity; being higher around houses with positive individuals. Most of the IPs found in this study were of water-borne transmission and those transmitted directly from person-to-person, therefore fecal contamination is present. We believe that the low prevalence of STH in this area, which requires a passage through the soil, is related to the environmental characteristics, which are unsuitable for the development/permanence of the infective stages of these parasites. The geospatial data and tools used herein proved to be useful for the study of the relationship between the different factors that influence the presence of IPs in a community, from an eco-health approach., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Scavuzzo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Date palm ( Phoenix dactylifera L.), is a widely cultivated crop across North Africa, with about 300 thousand tons of fruits produced per year, in Tunisia. A wide range of fungal pathogens has been associated with leaf spots of date palm, Alternaria species being the most frequently reported. Symptomatic leaves of Deglet Nour variety were randomly collected in six localities in Tunisia. We used a polyphasic approach to identify 45 Alternaria and five Curvularia strains isolated from date palm, confirming their pathogenicity. Sequencing of allergen Alt-a1 , glyceraldehyde-3-phosphate dehydrogenase ( gpd ) and calmodulin genes allowed us to group 35 strains in Alternaria Section, and 10 strains in Ulocladioides section. Based on sequencing analyses of Internal Transcribed Spacer , gpd and elongation factor genomic regions, all Curvularia strains were identified as Curvularia spicifera . All Alternaria and Curvularia species tested on date palm plantlets proved to be pathogenic, fulfilling Koch's postulates. Although no significant differences were observed among the species, the highest mean disease severity index was observed in A. arborescens , while the lowest corresponded to C. spicifera . The capability of these strains to produce mycotoxins in vitro was evaluated. None of the A. consortialis strains produced any known Alternaria mycotoxin, whereas more than 80% of the strains included in Alternaria section Alternaria produced variable amounts of multiple mycotoxins such as alternariol, alternariol monomethyl ether, altenuene, tenuazonic acid and tentoxin. Curvularia spicifera strains produced detectable traces of fumonisins B. This work reports a first comprehensive multidisciplinary study of mycotoxigenic Alternaria species and C. spicifera associated with leaf spot disease on date palm., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rabaaoui, Masiello, Somma, Crudo, Dall’Asta, Righetti, Susca, Logrieco, Namsi, Gdoura, Werbrouck and Moretti.)

Objective: We analysed calprotectin in sinonasal secretions of different chronic rhinosinusitis with nasal polyps (CRSwNP) endotypes to assess its role as a biomarker of non-type 2 inflammation., Methods: We included primary diffuse CRSwNP patients (n = 41) and three different control groups [non-allergic rhinitis (NAR) (n = 13), non-allergic eosinophilic syndrome (NARES) (n = 10) and healthy subjects (n = 12)]. Calprotectin levels were detected in nasal secretions using a chemiluminescent immunoassay (CLIA)., Results: Calprotectin levels in nasal secretions were significantly higher in all non-type 2 endotypes of CRSwNP compared to healthy controls (p < 0.05). In contrast, in type-2 CRSwNP calprotectin was significantly lower compared to controls (p < 0.05). A significant correlation between calprotectin levels and neutrophilic count/HPF was found in CRSwNP (p < 0.01). Clinically, mean levels of calprotectin and neutrophilia were significantly higher in patients who previously underwent 3 or more endoscopic sinus surgeries (p < 0.05)., Conclusions: Calprotectin in nasal secretions may be a biomarker of non-type 2 inflammation. Low levels of calprotectin are indicative of a type-2 immune response in both CRSwNP and non-allergic rhinitis. We observed that calprotectin levels significantly increased based on the number of previous surgeries., (Copyright © 2022 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

Objectives: We aim to analyse long-term voice outcomes and quality of life (QoL) in patients undergoing open partial horizontal laryngectomy type II (OPHL type II) and to compare them to those obtained by patients undergoing total laryngectomy (TL) with voice prosthesis (VP)., Design: Cross-sectional cohort study., Setting: Patients undergoing surgery for advanced laryngeal cancer, assessed during the usual follow-up consultations at the Phoniatric Unit (February 2020-December 2020)., Participants: Forty-five patients were enrolled and divided into two groups: OPHL group and TL group., Main Outcomes Measures: Acoustic analysis, maximum phonation time, INFV 0  scale, I-SECEL, UW-QoL-V4 and MDADI questionnaires were used to assess the long-term outcomes., Results: Voices of patients undergoing OPHL Type II were worse than those of laryngectomised patients with VP. Nevertheless, scores in voice and dysphagia-related QoL were comparable and scores in the social domain of QoL were higher in OPHL group., Conclusions: Open partial horizontal laryngectomy Type II allows an acceptable voice recovery and a satisfactory QoL., (© 2022 John Wiley & Sons Ltd.)

The long-term outcomes of newborns exposed to SARS-CoV-2 infection in utero or during the first hours of life are still unknown. We performed a single-center, prospective, observational study of newborns born from mothers with microbiologically confirmed SARS-CoV-2 infection in pregnancy or at time of delivery. Infants were offered a multidisciplinary follow-up consisting of nasopharyngeal Polymerase Chain Reaction test at birth and at 48-72 h of life, auxological growth and neurological development, serologic testing, and audiological and ophthalmological assessments. One-hundred ninety-eight mothers and 199 newborns were enrolled. Of the 199 newborns, 171 underwent nasopharyngeal swab, four (2.3%) and two (1.15%) children tested positive at birth and 48-72 h of life, respectively. None had SARS-CoV-2 related symptoms. Auxologic and neurologic development were normal in all children during follow-up. Nine out of 59 infants had SARS-CoV-2 IgG at 3 months of life, which was associated with a positive nasopharyngeal swab at birth (P = 0.04). Twenty seven out of 143 (18.8%) newborns had pathologic transitory evoked otoacoustic emissions at birth, although 14/27 repeated after 1 month were normal. Audiological evaluation was completed with Auditory Brainstem Response between the third and sixth month of life in 34 children, showing in all normal hearing threshold. The ophthalmological evaluation found retinal vascular anomalies in 3/20 (15%) children, immature visual acuity in 5/20 (25%) children, and reduced distance attention in 6/20 cases (30%)., Conclusions: Our study showed that the neonatal and mid-term multidisciplinary outcomes of newborns exposed to SARS-CoV-2 infection in utero or during the first hours of life are mostly positive, with the exception of ophthalmologic findings which, in a preliminary cohort, were abnormal in about 15% of cases. Further prospective, longitudinal studies are needed to better understand the clinical outcomes of children exposed to SARS-CoV-2 in utero and in the early postnatal life., What Is Known: • In utero mother-to-child transmission of SARS-CoV-2 has been documented by several independent studies. • Neonatal COVID-19 is a systemic disease that can be severe, although rarely., What Is New: • Newborns exposed in utero to SARS-CoV-2 have mostly a normal auxological, audiological, and neurological development during the first months of life. • Fundus fluorescein angiography revealed that up to 5% of newborns exposed in utero to SARS-CoV2 can show retinal and choroidal abnormalities, including peripheral hypofluorescence of the choroid and increased vascular tortuosity., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Several Alternaria mycotoxins are believed to act as endocrine disruptive chemicals (EDCs), since they are reported to bind estrogen receptors in several experimental models. After ingestion of contaminated food commodities, the mycotoxins reach the intestine, where they come into direct contact with food constituents as well as the gut microbiota. Thus, the aim of the present work was to evaluate the modulatory potential of a complex extract of cultured Alternaria fungi (CE; containing eleven chemically characterized compounds) on the estrogenic signaling cascade of mammalian cells before and after anaerobic incubation with fecal slurries, in order to simulate an in vivo-like condition in the gut. Assessing alkaline phosphatase expression in Ishikawa cells as a measure for estrogenicity, we found the CE to partially quench the intrinsic estrogenic properties of fecal slurries and fecal waters, even after 3 h of fecal incubation. Investigation of the mechanisms underlying the effects observed carried out through an in vitro/in silico approach revealed the ability of the extract to decrease the ERα/ERβ nuclear ratio, while a possible action of the mycotoxins as ER-antagonists was excluded. Our results suggest that Alternaria mycotoxins might act as EDCs in vivo, and warrant further investigation in animal models., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Strongyloidiasis and Chagas disease are endemic in northern Argentina. In this study we evaluate the association between S. stercoralis and T. cruzi infections in villages with diverse prevalence levels for these parasites. Further understanding in the relationship between these Neglected Tropical Diseases of South America is relevant for the design of integrated control measures as well as exploring potential biologic interactions., Methodology: Community based cross-sectional studies were carried in different villages of the Chaco and Yungas regions in Argentina. Individuals were diagnosed by serology for S. stercoralis and T. cruzi. The association between S. stercoralis and T. cruzi, and between anemia and the two parasites was evaluated using two approaches: marginal (Ma) and multilevel regression (Mu)., Results: A total of 706 individuals from six villages of northern Argentina were included. A total of 37% were positive for S. stercoralis, 14% were positive for T. cruzi and 5% were positive for both. No association was found between infection with S. stercoralis and T. cruzi in any of the models, but we found a negative correlation between the prevalence of these species in the different villages (r = -0.91). Adults (> 15 years) presented association with S. stercoralis (Ma OR = 2.72; Mu OR = 2.84) and T. cruzi (Ma OR = 5.12; Mu OR = 5.48). Also, 12% and 2% of the variance of infection with S. stercoralis and T. cruzi, respectively, could be explained by differences among villages. On the other hand, anemia was associated with infection with S. stercoralis (Ma OR = 1.73; Mu OR = 1.78) and was more prevalent in adults (Ma OR = 2.59; Mu OR = 2.69)., Conclusion: We found that coinfection between S. stercoralis and T. cruzi is not more frequent than chance in endemic areas. However, the high prevalence for both parasites, raises the need for an integrated strategy for the control of STH and Chagas disease., Competing Interests: The authors have declared that no competing interests exist.

Background: The first case of SARS-CoV-2 was reported in Argentina on 3 March 2020. Measures to limit the spread of the virus were implemented, including complete lockdown (26 March). Nonetheless, the virus spread throughout the country, with a first peak of almost a million cases in October. On 30 November, the government's recommendation switched from social, preventive and compulsory isolation, to social, preventive and compulsory distancing., Objectives: To describe a tailored public health strategy to mitigate the spread of SARS-CoV-2 and determine its behaviour in San Antonio de Areco district from Buenos Aires province (Argentina) through a private-public association., Design, Setting and Participants: Surveillance of the virus was performed with the local healthcare system, through early identification of cases and the systematic study of each infected individual and contact, regardless of symptomatology, using telemedicine and a COVID-19-specific outpatient clinic. Real-time PCR was used for detection using both individual and pooled samples, with a 12-hour turnaround time., Results: Up to 30 November, a total of 2426 suspected cases were analysed and 578 were confirmed. Surveillance of health personnel and at-risk populations proved effective, mitigating viral spread. Pooling samples allowed reduction of operator time, helped reduce costs, and allowed detection of both symptomatic and asymptomatic cases., Conclusion: After 8 months of protocol implementation, the strategy to intensively survey groups at higher epidemiological risk and the systematic search for asymptomatic cases with the incorporation of pooled PCR for diagnosis, in combination with individual testing, is an efficient and viable option in populations with similar characteristics, in the frame of social isolation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Crizotinib was a first generation of ALK tyrosine kinase inhibitor approved for the treatment of ALK -positive non-small-cell lung carcinoma (NSCLC) patients. COMPARE and cluster analyses of transcriptomic data of the NCI cell line panel indicated that genes with different cellular functions regulated the sensitivity or resistance of cancer cells to crizotinib. Transcription factor binding motif analyses in gene promoters divulged two transcription factors possibly regulating the expression of these genes, i.e., RXRA and GATA1, which are important for leukemia and erythroid development, respectively. COMPARE analyses also implied that cell lines of various cancer types displayed varying degrees of sensitivity to crizotinib. Unexpectedly, leukemia but not lung cancer cells were the most sensitive cells among the different types of NCI cancer cell lines. Re-examining this result in another panel of cell lines indeed revealed that crizotinib exhibited potent cytotoxicity towards acute myeloid leukemia and multiple myeloma cells. P-glycoprotein-overexpressing CEM/ADR5000 leukemia cells were cross-resistant to crizotinib. NCI-H929 multiple myeloma cells were the most sensitive cells. Hence, we evaluated the mode of action of crizotinib on these cells. Although crizotinib is a TKI, it showed highest correlation rates with DNA topoisomerase II inhibitors and tubulin inhibitors. The altered gene expression profiles after crizotinib treatment predicted several networks, where TOP2A and genes related to cell cycle were downregulated. Cell cycle analyses showed that cells incubated with crizotinib for 24 h accumulated in the G 2 M phase. Crizotinib also increased the number of p-H3(Ser10)-positive NCI-H929 cells illustrating crizotinib's ability to prevent mitotic exit. However, cells accumulated in the sub-G 0 G 1 fraction with longer incubation periods, indicating apoptosis induction. Additionally, crizotinib disassembled the tubulin network of U2OS cells expressing an α-tubulin-GFP fusion protein, preventing migration of cancer cells. This result was verified by in vitro tubulin polymerization assays. In silico molecular docking also revealed a strong binding affinity of crizotinib to the colchicine and Vinca alkaloid binding sites. Taken together, these results demonstrate that crizotinib destabilized microtubules. Additionally, the decatenation assay showed that crizotinib partwise inhibited the catalytic activity of DNA topoisomerase II. In conclusion, crizotinib exerted kinase-independent cytotoxic effects through the dual inhibition of tubulin polymerization and topoisomerase II and might be used to treat not only NSCLC but also multiple myeloma.

Objectives: Rheumatoid arthritis (RA) may affect the postural control through abnormal sensory inputs and impaired motor responses. Sensory Organization Test (SOT) objectively evaluates contribution of different sensorial afferences in postural control. The aim of the study is to assess mechanisms of postural instability and their relations with disability and disease characteristics in an early RA(ERA) cohort., Methods: The equilibrium scores were assessed in 30 ERA patients and 30 age- and sex-matched controls. The somatosensory (SOM), visual (VIS) and vestibular (VEST) ratios were computed to assess the use of different sensory and the composite equilibrium score (CES) as a measure of global balance performance., Results: ERA patients had lower CES (78.4±6.0% vs. 83.4±5.0%, p=0.002), SOM ratio (98.5±1.8% vs. 99.6±2.1%, p=0.035), VIS ratio (85.2±7.6% vs. 91.5±6.0%, p=0.001) and VEST ratio (70.8±10.0% vs. 80.3±7.8%, p<0.001) compared to controls. The presence of ankle arthritis correlated negatively to both SOM (r=-0.369, p=0.045) and VIS ratio (r=0.470, p=0.009), pain severity to CES (r=-0.389, p=0.045) and VIS ratio (r=-0.385, p=0.048) and HAQ-DI to CES (r=-0.591, p=0.001), SOM (r=-0.510, p=0.004) and VIS ratio (r=-0.390, p=0.033.). Patients-reported postural instability was associated with lower CES (75.4±5.4% vs. 80.7±5.5%, p=0.016) and VEST ratios (66.5±10.1% vs. 74.1±8.8%, p=0.036). SOT outcomes did not differ according to acute phase reactants, disease activity or autoantibody positivity., Conclusions: RA patients showed an early impairment of postural control related to the degree of disability and subjective postural instability. Our data suggest that the lack of balance could result from both impaired motor response and abnormal sensory organisation.

The human gut microbiota plays an important role in the maintenance of human health. Factors able to modify its composition might predispose the host to the development of pathologies. Among the various xenobiotics introduced through the diet, Alternaria mycotoxins are speculated to represent a threat for human health. However, limited data are currently available about the bidirectional relation between gut microbiota and Alternaria mycotoxins. In the present work, we investigated the in vitro effects of different concentrations of a complex extract of Alternaria mycotoxins (CE; containing eleven mycotoxins; e.g. 0.153 µM alternariol and 2.3 µM altersetin, at the maximum CE concentration tested) on human gut bacterial strains, as well as the ability of the latter to metabolize or adsorb these compounds. Results from the minimum inhibitory concentration assay showed the scarce ability of CE to inhibit the growth of the tested strains. However, the growth kinetics of most of the strains were negatively affected by exposure to the various CE concentrations, mainly at the highest dose (50 µg/mL). The CE was also found to antagonize the formation of biofilms, already at concentrations of 0.5 µg/mL. LC-MS/MS data analysis of the mycotoxin concentrations found in bacterial pellets and supernatants after 24 h incubation showed the ability of bacterial strains to adsorb some Alternaria mycotoxins, especially the key toxins alternariol, alternariol monomethyl ether, and altersetin. The tendency of these mycotoxins to accumulate within bacterial pellets, especially in those of Gram-negative strains, was found to be directly related to their lipophilicity.

Alternariol is a mycotoxin produced by Alternaria spp. relevant to the food safety area due to its abundance in certain foods. The shortage of data on its toxicology, also as a part of chemical mixtures, prevents setting regulation to limit its abundance in food. To extend knowledge on the possible mechanisms underpinning alternariol toxicology in chemical mixtures, this work assessed the effects of urolithin C, a structurally related gut ellagitannin-derived metabolite, on its absorption and phase II metabolism in a monolayer of Caco-2 cells. A computational study was also used to provide a mechanistic explanation for the results obtained. Urolithin C influenced transport and phase II metabolism of alternariol with a late reduction of transport to the basolateral compartment. Moreover, it caused an early effect in terms of accumulation of alternariol glucuronides in the basolateral compartment, followed by a late reduction of glucuronides in both compartments. Concerning alternariol sulfates, the data collected pointed to a possible competition of urolithin C for the sulfotransferases resulting in a reduced production of alternariol sulfates. Our results provide a compelling line-of-evidence pointing to the need to systematically tackle the evaluation of mycotoxin toxicity in the context of chemical mixture., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: passive immunotherapy is a therapeutic alternative for patients with COVID-19. Equine polyclonal antibodies (EpAbs) could represent a source of scalable neutralizing antibodies against SARS-CoV-2., Methods: we conducted a double-blind, randomized, placebo-controlled trial to assess efficacy and safety of EpAbs (INM005) in hospitalized adult patients with moderate and severe COVID-19 pneumonia in 19 hospitals of Argentina. Primary endpoint was improvement in at least two categories in WHO ordinal clinical scale at day 28 or hospital discharge (ClinicalTrials.gov number NCT04494984)., Findings: between August 1st and October 26th, 2020, a total of 245 patients were enrolled. Enrolled patients were assigned to receive two blinded doses of INM005 ( n  = 118) or placebo ( n  = 123). Median age was 54 years old, 65•1% were male and 61% had moderate disease at baseline. Median time from symptoms onset to study treatment was 6 days (interquartile range 5 to 8). No statistically significant difference was noted between study groups on primary endpoint (risk difference [95% IC]: 5•28% [-3•95; 14•50]; p  = 0•15). Rate of improvement in at least two categories was statistically significantly higher for INM005 at days 14 and 21 of follow-up. Time to improvement in two ordinal categories or hospital discharge was 14•2 (± 0•7) days in the INM005 group and 16•3 (± 0•7) days in the placebo group, hazard ratio 1•31 (95% CI 1•0 to 1•74). Subgroup analyses showed a beneficial effect of INM005 over severe patients and in those with negative baseline antibodies. Overall mortality was 6•9% the INM005 group and 11•4% in the placebo group (risk difference [95% IC]: 0•57 [0•24 to 1•37]). Adverse events of special interest were mild or moderate; no anaphylaxis was reported., Interpretation: Albeit not having reached the primary endpoint, we found clinical improvement of hospitalized patients with SARS-CoV-2 pneumonia, particularly those with severe disease., Competing Interests: MC, SS, VZ, LM, LS, FG received grants from Ministries of Science and Production of Argentina. MD, JF, GV, AB, FC, MFA, LB, RT, SL, DS, MI, VS, RS, PC, MMC, LA, HLL, AC, DC declare reimbursement for conduction of clinical trial as investigator of the study. PC, OS, YK report other funds from Inmunova S.A. EN, GL, WHB, SPLL report personal fees from Inmunova S.A. SM reports non-financial support from Inmunova S.A. AP, B de M, Gabriel L declare no competing interests. SPLL declare personal fees from Movement Disorders Society, Laboratorio Elea and Merck pharmaceuticals. MC, SS, VZ, LM, LS are employed by Inmunova S.A., (© 2021 The Author(s).)

Infection by Trypanosoma cruzi (Chagas disease [ChD]) affects around 7 million people in the Americas, most of whom are unaware of their status due to lack of clinical manifestations and poor access to diagnosis. Rapid diagnostic tests (RDTs) are widely used for screening for different infections (HIV, hepatitis B, and syphilis), and their application for ChD would facilitate access to diagnosis, especially in remote areas where health services have scarce resources. We conducted a prospective intervention study in 2018 to evaluate in the field two in vitro RDTs for ChD, authorized by the National Administration of Medicaments, Aliments, and Medical Technologies of Argentina (ANMAT), in areas of endemicity and nonendemicity in Argentina. We recruited 607 volunteers older than 18 years in Salta province and the city of Buenos Aires. The RDTs Ab Standard Diagnostics SD Bioline (SD) and Check Chagas Wiener Lab (WL) were performed in situ with whole-blood samples, and confirmatory serology was done at a reference center. The rate of infection with T. cruzi was 17.8% (108/607). The SD test showed 97.2% sensitivity (95% confidence interval [CI], 93.5 to 100) and 91.7% specificity (95% CI, 96.2 to 99.2%), and the WL test showed 93.4% sensitivity (95% CI, 88.2 to 98.6%) and 99.1% specificity (95% CI, 91.9 to 100%). The sensitivity and specificity for the two RDTs tested were higher than previously reported. These results encourage the use of the tested RDTs in Salta province and for further field studies for the implementation of these RDTs in other epidemiological scenarios. This will be very important to improve access to diagnosis of Chagas and its clinical management as a neglected disease, especially in remote areas with health access barriers., (Copyright © 2020 Lopez-Albizu et al.)

Alternaria molds produce a variety of chemically diverse secondary metabolites with potentially adverse effects on human health. However, data on occurrence in food and human exposure is inconsistent for some of these mycotoxins. Membrane filtration is a frequent step in many sample preparation procedures for LC-MS-based methods analyzing food contaminants. Yet, little is known about the possibility of adsorptive phenomena that might result in analyte losses. Thus, we treated a complex extract of Alternaria toxins with several types of syringe filters and unraveled the impact on its chemical composition by LC-MS/MS. We observed significant, and in some cases complete, losses of compounds due to filtration. Particularly, two key Alternaria toxins, alternariol (AOH) and its monomethyl ether (AME), were heavily affected. As a comparison with published food surveys indicating a correlation of the type of filtration used with lower incidence reports in food, our results point at a possible underestimation of AME in past exposure assessment. Also, perylene quinones were greatly affected by filtration, underlining the importance to take this into consideration during analytical method development. Furthermore, we applied the comet assay in HT-29 cells to elucidate the impact of filtration on the genotoxicity of the extract. We observed strong coincidences with the loss of epoxide-carrying metabolites and also an intriguing induction of oxidative DNA damage by yet toxicologically uncharacterized Alternaria toxins. In conclusion, we highlight potential issues with sample filtration and call for a critical re-evaluation of previous food occurrence data in the light of the results at hand.

Molds of the genus Alternaria produce several mycotoxins, some of which may pose a threat for health due to their genotoxicity. Due to the lack of adequate toxicological and occurrence data, they are currently not regulated. Interactions between mycotoxins, gut microbiota and food constituents might occur after food ingestion, modifying the bioavailability and, therefore, overall toxicity of mycotoxins. The present work aimed to investigate the impact of in vitro short-term fecal incubation on the in vitro DNA-damaging effects exerted by 5 µg/mL of an Alternaria alternata extract, containing, among others, 15 nM alternariol, 12 nM alternariol monomethyl ether, 241 nM altertoxin II and 301 nM stemphyltoxin III, all of which are known as genotoxic. The involvement of microorganisms, undigested food constituents and soluble substances of human fecal samples in modifying the composition and the genotoxicity of the extract was investigated through the application of LC-MS/MS analysis and comet assays in HT-29 cells. Results showed that the potential of the mycotoxins to induce DNA strand breaks was almost completely quenched, even before anaerobic incubation, by contact with the different fractions of the fecal samples, while the potency to induce formamidopyrimidine DNA glycosylase (FPG)-sensitive sites was only slightly reduced. These effects were in line with a reduction of mycotoxin concentrations found in samples analyzed by LC-MS/MS. Although a direct correlation between the metabolic activity of the gut microbiota and modifications in mycotoxin contents was not clearly observed, adsorptive phenomena to bacterial cells and to undigested food constituents might explain the observed modifications.

Competing Interests: The authors have declared that no competing interests exist.

The threadworm, Strongyloides stercoralis , is endemic in tropical and subtropical areas. Data on the prevalence and distribution of infection with this parasite species is scarce in many critical regions. We conducted a seroprevalence study of S. stercoralis infection in 13 locations in the Gran Chaco and Yungas regions of Argentina and Bolivia during the period 2010-2016. A total of 2803 human serum samples were analyzed by ELISA-NIE which has a sensitivity of 75% and specificity of 95%. Results showed that 551 (19.6%) of those samples were positive. The adjusted prevalence was 20.9%, (95% confidence interval (CI) 19.4%-22.4%). The distribution of cases was similar between females and males with an increase of prevalence with age. The prevalence in the different locations ranged from 7.75% in Pampa del Indio to 44.55% in Santa Victoria Este in the triple border between Argentina, Bolivia, and Paraguay in the Chaco region. Our results show that S. stercoralis is highly prevalent in the Chaco and Yungas regions, which should prompt prospective surveys to confirm our findings and the design and deployment of control measures., Competing Interests: The authors declare no conflict of interest.

Mycotoxins are low-molecular weight compounds produced by diverse genera of molds that may contaminate food and feed threatening the health of humans and animals. Recent findings underline the importance of studying the combined occurrence of multiple mycotoxins and the relevance of assessing the toxicity their simultaneous exposure may cause in living organisms. In this context, for the first time, this work has critically reviewed the most relevant data concerning the occurrence and toxicity of mycotoxins produced by Alternaria spp., which are among the most important emerging risks to be assessed in food safety, alone or in combination with other mycotoxins and bioactive food constituents. According to the literature covered, multiple Alternaria mycotoxins may often occur simultaneously in contaminated food, along with several other mycotoxins and food bioactives inherently present in the studied matrices. Although the toxicity of combinations naturally found in food has been rarely assessed experimentally, the data collected so far, clearly point out that chemical mixtures may differ in their toxicity compared to the effect of toxins tested individually. The data presented here may provide a solid foothold to better support the risk assessment of Alternaria mycotoxins highlighting the actual role of chemical mixtures on influencing their toxicity., Competing Interests: The authors declare no conflict of interest.

Strongyloides stercoralis infections have a worldwide distribution with a global burden in terms of prevalence and morbidity that is largely ignored. A public health response against soil-transmitted helminth (STH) infections should broaden the strategy to include S. stercoralis and overcome the epidemiological, diagnostic, and therapeutic challenges that this parasite poses in comparison to Ascaris lumbricoides, Trichuris trichiura, and hookworms. The relatively poor sensitivity of single stool evaluations, which is further lowered when quantitative techniques aimed at detecting eggs are used, also complicates morbidity evaluations and adequate drug efficacy measurements, since S. stercoralis is eliminated in stools in a larval stage. Specific stool techniques for the detection of larvae of S. stercoralis, like Baermann's and Koga's agar plate, despite superiority over direct techniques are still suboptimal. New serologies using recombinant antigens and molecular-based techniques offer new hopes in those areas. The use of ivermectin rather than benzimidazoles for its treatment and the need to have curative regimens rather than lowering the parasite burden are also unique for S. stercoralis in comparison to the other STH due to its life cycle, which allows reproduction and amplification of the worm burden within the human host. The potential impact on STH of the benzimidazoles/ivermectin combinations, already used for control/elimination of lymphatic filariasis, should be further evaluated in public health settings. While waiting for more effective single-dose drug regimens and new sensitive diagnostics, the evidence and the tools already available warrant the planning of a common platform for STH and S. stercoralis control.

Rickettsia parkeri, a recently identified cause of spotted fever rickettsiosis in the United States, has been found in Amblyomma triste ticks in several countries of South America, including Argentina, where it is believed to cause disease in humans. We describe the clinical and epidemiologic characteristics of 2 patients in Argentina with confirmed R. parkeri infection and 7 additional patients with suspected R. parkeri rickettsiosis identified at 1 hospital during 2004-2009. The frequency and character of clinical signs and symptoms among these 9 patients closely resembled those described for patients in the United States (presence of an inoculation eschar, maculopapular rash often associated with pustules or vesicles, infrequent gastrointestinal manifestations, and relatively benign clinical course). Many R. parkeri infections in South America are likely to be misdiagnosed as other infectious diseases, including Rocky Mountain spotted fever, dengue, or leptospirosis.