Inflammatory biomarkers in infective endocarditis: machine learning to predict mortality.

Infective endocarditis (IE) is the cardiac disease with the highest rates of mortality. New biomarkers that are able to identify patients at risk for death are required to improve patient management and outcome. This study aims to investigate if cytokines, chemokines and growth factors measured at IE diagnosis can predict mortality. Patients with definite IE, according to the Duke's modified criteria, were included. Using high-performance Luminex assay, 27 different cytokines, chemokines and growth factors were analyzed. Machine learning techniques were used for the prediction of death and subsequently creating a decision tree, in which the cytokines, chemokines and growth factors were analyzed together with C-reactive protein (CRP). Sixty-nine patients were included, 41 (59%) male, median age 54 [interquartile range (IQR) = 41-65 years] and median time between onset of the symptoms and diagnosis was 12 days (IQR = 5-30 days). The in-hospital mortality was 26% (n = 18). Proinflammatory cytokines interkeukin (IL)-15 and C-C motif chemokine ligand (CCL4) were found to predict death, adding value to CRP levels. The decision tree predicted correctly the outcome of 91% of the patients at hospital admission. The high-risk group, defined as CRP ≥ 72 mg/dL, IL-15 ≥ 5·6 fg/ml and CCL4 ≥ 6·35 fg/ml had an 88% in-hospital mortality rate, whereas the patients classified as low-risk had a mortality rate of 8% (P = < 0·001). Cytokines IL-15 and CCL4 were predictors of mortality in IE, adding prognostic value beyond that provided by CRP levels. Assessment of cytokines has potential value for clinical risk stratification and monitoring in IE patients.

Exploring a rare case of occupational senna allergy.

BACKGROUND: Cassia angustifolia, or senna, is a plant belonging to the Fabaceae family, widely used as a laxative and as a colouring agent in hair dyes. Senna is rarely reported as an occupational allergic sensitizer in the current literature. AIMS: To describe the case and diagnostic approach of a suspected occupational senna allergy. CASE REPORT: A male phytopharmaceutical warehouse worker reported bronchial, conjunctival and nasal symptoms immediately upon exposure to senna. We were able to document in vitro sensitization, finding IgE-binding proteins in senna, and in vivo sensitization through positive skin tests and conjunctival provocation test. CONCLUSION: Our study confirms that senna may cause occupational rhinoconjunctivitis symptoms with an IgE-dependent mechanism and is the first to confirm it through specific conjunctival provocation test.

17α-Ethinylestradiol and 17ß-estradiol removal from a secondary urban wastewater using an RBC treatment system.

The presence of micropollutants that include endocrine-disrupting compounds (EDC) in aquatic environments is currently one of the most relevant aspects of water quality due to their adverse effects on aquatic organisms and human health. From the several categories of EDC, 17ß-estradiol (E2) is a natural hormone, which is prevalent in vertebrates, associated with the female reproductive system and maintenance of the sexual characters. 17α-Ethinylestradiol (EE2) is a synthetic hormone produced from the natural hormone E2 and is an essential component of oral contraceptives. These compounds are susceptible to bioconcentration and have high potential to bioaccumulation. Wastewater treatment plants are the main point source of E2 and EE2 into aquatic environments, but conventional wastewater treatment systems are not specifically designed for steroid removal. To overcome this problem, biological tertiary treatment may be a solution for the removal of emergent pollutants such as E2 and EE2. The main purpose of the present study is to provide a solution based on the optimization of a rotating biological contactor system to remove estrogens, specifically E2 and EE2, and to quantify their removal efficiency on different matrices, namely real wastewater and different synthetic wastewaters. All assays presented viable removal efficiencies for compound E2 with values always above 50%; real wastewater yielded the highest removal efficiencies. EE2 removal had better removal efficiencies with synthetic wastewater as feed solution, with removals above 15%, whereas the removal efficiency with real wastewater was inexistent.

Gene-gene interactions in the NAMPT pathway, plasma visfatin/NAMPT levels, and antihypertensive therapy responsiveness in hypertensive disorders of pregnancy.

Nicotinamide phosphorybosil transferase (NAMPT) polymorphisms affect visfatin/NAMPT levels and may affect the responsiveness to therapy in hypertensive disorders of pregnancy. We examined whether NAMPT polymorphisms (rs1319501 T>C and rs3801266 A>G), or haplotypes, and gene-gene interactions in the NAMPT pathway affect plasma visfatin/NAMPT levels and the response to antihypertensive therapy in 205 patients with preeclampsia (PE) and 174 patients with gestational hypertension. We also studied 207 healthy pregnant controls. Plasma visfatin/NAMPT levels were measured by ELISA. Non-responsive PE patients with the TC+CC genotypes for the rs1319501 T>C, and with the AG+GG genotypes for the rs3801266 A>G polymorphism had lower and higher visfatin/NAMPT levels, respectively. The 'C, A' haplotype was associated with response to antihypertensive therapy, and with lower visfatin/NAMPT levels in PE. Interactions among NAMPT, TIMP-1 and MMP-2 genotypes were associated with PE and with lack of response to antihypertensive therapy in PE. Our results suggest that NAMPT polymorphisms affect plasma visfatin/NAMPT levels in nonresponsive PE patients, and that gene-gene interactions in the NAMPT pathway not only promote PE but also decrease the response to antihypertensive therapy in PE.

Investigation on the association between thyroid tumorigeneses and herpesviruses.

Herpesviruses have been associated with various human malignancies and with thyroid autoimmunity. Aiming to investigate the presence of these viruses in thyroid nodules, we analyzed serum and thyroid tissue from 183 patients (83 benign and 100 malignant thyroid nodules). We also obtained 104 normal thyroid tissues extracted from the contralateral lobe of these patients. We used ELISA to screen the serology of all patients and a real-time quantitative PCR to analyze thyroid tissue viral load in antibody-positive patients. In addition, the presence of herpesviruses was tested by histological analysis in 20 EBV-positive tissues using the expression of LMP-1 by immunohistochemistry (IHC) and EBER by in situ hybridization (ISH). There was no evidence of HSV-2 or CMV DNA, but we found EBV DNA sequences in 29 (16%) thyroid tissue samples. We also found 7 positive EBV cases out of 104 normal tissues. Viral load was higher in tumors than in their respective normal tissues (p = 0.0002). ISH analysis revealed EBER expression in 11 out of 20 (52%) EBV-positive tissues, mostly in malignant cases (8/11, 73%). The presence of high EBV copy numbers in thyroid tumors and the expression of EBER only in malignant cases suggest an association between EBV and thyroid malignancies. However, we did not find any association between the presence of EBV and/or its viral load and any clinical or pathological tumor feature. Further studies aiming to clarify the mechanisms of EBV infection in thyroid cells are necessary to support a possible role in the development of thyroid cancer.

The Vespid Allergy Quality of Life Questionnaire - cultural adaptation and translation to Portuguese.

SUMMARY: A cross-cultural translation of the Vespid Allergy Quality of Life Questionnaire (VQLQ) to the Portuguese population (VQLQ-P) was performed, assessing its applicability in wasp and in non-beekeeper bee venom allergic patients. Additionally, we evaluated a Visual Analogue Scale (VAS) to estimate hymenoptera allergy interference with daily life. Methods. Cross-cultural translation was performed according to recommendations. The final VQLQ-P version, the Expectation of Outcome questionnaire (EoQ), EQ-5D and VAS were applied to wasp (n = 19) and non-beekeeper bee venom allergic patients (n = 30). Results. VQLQ-P significantly correlated with EoQ, (r = 0.76, p < 0.01), EQ-5D (usual activities and anxiety / depression dimensions) and VAS, with a good internal consistency (Cronbach α = 0.88) in wasp allergic individuals. VQLQ-P and EoQ correlation was also high (r = 0.67, p < 0.01) in bee allergy. Conclusion. The VQLQ-P is a valuable tool to evaluate quality of life impairment in Portuguese hymenoptera venom allergic individuals.

Hemispheric asymmetries in subcortical visual and auditory relay structures in congenital deafness.

Neuroplasticity - the capacity of the brain to change as a response to internal and external pressures - has been studied from a number of different perspectives. Perhaps one of the most powerful models is the study of populations that have been congenitally deprived of a sense. It has been shown that the right Auditory Cortex (AC) of congenitally deaf humans is neuroplastically modified in order to represent visual properties of a stimulus. One unresolved question is how this visual information is routed to the AC of congenitally deaf individuals. Here, we performed volumetric analysis of subcortical auditory and visual brains regions - namely the thalamus (along with three thalamic nuclei: the pulvinar, the lateral geniculate nucleus and the medial geniculate nucleus), and the inferior and superior colliculi - in deaf and hearing participants in order to identify which structures may be responsible for relaying visual information toward the altered AC. Because there is a hemispheric asymmetry in the neuroplastic changes observed in the AC of the congenitally deaf, we reasoned that subcortical structures that also showed a similar asymmetry in their total volume could have been enlisted in the effort of relaying visual information to the neuroplastically altered right AC. We show that for deaf, but not for hearing individuals, the right thalamus, right lateral geniculate nucleus and right inferior colliculus are larger than their left counterparts. These results suggest that these subcortical structures may be responsible for rerouting visual information to the AC in congenital deafness.

A practical approach to diseases affecting dentate nuclei.

A wide variety of diseases affect the dentate nuclei. When faced with the radiological demonstration of signal changes in the dentate nuclei, radiologists and clinical neurologists have to sieve through the many possibilities, which they do not encounter on a regular basis. This task can be challenging, and therefore, developing a clinical, radiological, and laboratory approach is important. Information on the topic is scattered and the subject has not yet been reviewed. In this review, a combined clinicoradiological approach is presented. The signal changes in T1, T2, fluid-attenuated inversion recovery (FLAIR), diffusion, susceptibility weighted, and gadolinium-enhanced images can give specific or highly suggestive patterns, which are illustrated. The role of computed tomography (CT) in the diagnostic process is discussed. Specific radiological patterns do not exist in a significant proportion of patients where the clinical and laboratory analysis becomes important. In this review, we group the clinical constellations to narrow down the differential diagnosis and highlight the diagnostic clinical signs, such as tendon xanthomas and Kayser-Fleischer rings. As will be seen, a number of these conditions are potentially reversible, and hence, their early diagnosis is desirable. Finally, key diagnostic tests and available therapies are outlined. The practical approach thus begins with the radiologist and winds its way through the clinician, towards carefully selected diagnostic tests defining the therapy options.

Detection of pathogenic Escherichia coli and microbiological quality of chilled shrimp sold in street markets.

UNLABELLED: Foodborne illnesses caused by Escherichia coli are one of the most important gastrointestinal diseases and therefore represent a public health risk. The presence of E. coli in water or in products such as shrimp indicates faecal contamination. However, indicator micro-organisms can be used to evaluate the microbiological quality of food sold in markets. This study focused on detecting isolates of E. coli containing the genes stx1A, stx2A, eae, LTI, STa, STb, aggR and pCVD432 in chilled shrimp sold in street markets in the municipality of São Paulo, Brazil, and to assess the microbiological quality of this product. Enteropathogenic and enterotoxigenic E. coli pathotypes were detected on the surface of two chilled shrimp samples. Salmonella spp. was not isolated. In addition, contamination of surface and muscle of the shrimp samples was found to be correlated. The detection of EPEC and ETEC pathotypes in chilled shrimp sold in street markets in Brazil provides useful epidemiological information for public health authorities to improve food safety and public health. SIGNIFICANCE AND IMPACT OF THE STUDY: Shrimps are crustaceans commonly produced and consumed in Brazil. Specimens of Farfantepenaeus brasiliensis and Litopenaeus schmitti sold in street markets were examined by PCR to detect the presence of Escherichia coli pathotypes (enteropathogenic, enterotoxigenic, enterohemorrhagic and enteroinvasive). EPEC and ETEC strains were detected in whole shrimp. These findings provide useful information for public health authorities to improve the food safety and health of the Brazilian population.

Shiga toxigenic and enteropathogenic Escherichia coli in water and fish from pay-to-fish ponds.

UNLABELLED: Escherichia coli is part of the normal microflora of the intestines of mammals. However, among the enteric pathogens, it is one of the leading causes of intestinal diseases, especially Shiga toxigenic E. coli, which can cause diarrhoea, haemorrhagic colitis and complications like haemolytic uraemic syndrome and thrombotic thrombocytopaenic purpura. Escherichia coli is considered a serious public health problem. Water and fish samples were subjected to biochemical tests to confirm the presence of E. coli and by PCR to verify the presence of pathogenic strains (O157, enteropathogenic and shiga toxigenic) in water and fish (skin, gastrointestinal tract and muscles) from pay-to-fish ponds located in the Córrego Rico watershed in the northeastern region of the state of São Paulo, Brazil. Of the 115 E. coli isolates from fish or water, five (4·34%) contained eae and stx2 genes, one had only the eae gene and two had the stx1 gene. An isolate containing the stx2 gene was also found in the water sample. In addition, eight isolates (6·95%) from the fish gastrointestinal tract contained rfbEO157:H7 (O157 gene), and three (2·61%) contained stx2 and eae genes, demonstrating the potential risk to the environment and public health. The results provide useful basic information for the proper management of these environments and animals in order to prevent faecal pollution, reducing health risks to the Brazilian population. SIGNIFICANCE AND IMPACT OF THE STUDY: Pay-to-fish ponds are a common commercial activity in Brazil. Samples of water and Oreochromis niloticus were examined by PCR to detect the presence of pathogenic strains of Escherichia coli (O157, enteropathogenic and shiga toxigenic). Several pathogenic strains were detected in this study, providing useful epidemiological information for the proper management of these environments and animals in order to prevent faecal pollution, reducing health risks to the Brazilian population.

Study of the genetic diversity and structure of a natural population of Nectandra megapotamica (Spreng.) Mez. using RAPD markers.

Nectandra megapotamica (Spreng.) Mez. is a tree species that naturally occurs in the Atlantic Forest, Brazil. The aim of this study was to evaluate the genetic diversity and structure of a natural population of 12 N. megapotamica individuals using random amplified polymorphic DNA markers. Eleven primers were used in this study, producing 81 bands, of which 98.99% were polymorphic. Analysis using STRUCTURE defined three different clusters (K = 3), results that were consistent with those of principal coordinates analysis. Both Nei's genetic diversity (h = 0.33) and Shannon's diversity index (I = 0.49) were relatively high. Analysis of molecular variance indicated that 24.89% of the genetic variability was among clusters, while the remaining 75.11% was within clusters. The Mantel test showed a weak correlation between genetic and geographic distances (r = 0.25, P = 0.105). Overall, the results revealed high levels of genetic diversity within clusters and high genetic differentiation among clusters without any spatial pattern of genetic variability. In addition, gene flow was independent of the geographical distribution and was compatible with the hierarchical island model.

Tissue inhibitor of matrix metalloproteinase-1 polymorphism, plasma TIMP-1 levels, and antihypertensive therapy responsiveness in hypertensive disorders of pregnancy.

Tissue inhibitor of metalloproteinase (TIMP)-1 is a major endogenous inhibitor of matrix metalloproteinase (MMP)-9, which may affect the responsiveness to therapy in hypertensive disorders of pregnancy. We examined whether TIMP-1 polymorphism (g.-9830T>G, rs2070584) modifies plasma MMP-9 and TIMP-1 levels and the response to antihypertensive therapy in 596 pregnant: 206 patients with preeclampsia (PE), 183 patients with gestational hypertension (GH) and 207 healthy pregnant controls. We also studied the TIMP-3 polymorphism (g.-1296T>C, rs9619311). Plasma MMP-9 and TIMP-1 levels were measured by ELISA. GH patients with the GG genotype for the TIMP-1 polymorphism had lower MMP-9 levels and MMP-9/TIMP-1 ratios than those with the TT genotype. PE patients with the TG genotype had higher TIMP-1 levels. The G allele and the GG genotype were associated with PE and responsiveness to antihypertensive therapy in PE, but not in GH. Our results suggest that the TIMP-1 g.-9830T>G polymorphism not only promotes PE but also decreases the responses to antihypertensive therapy.

Larvicidal activity of Brazilian plant essential oils against Coenagrionidae larvae.

Odonate larvae can be serious pests that attack fish larvae, postlarvae, and fingerlings in fish culture tanks, causing significant loss in the supply and production of juveniles. This study reports a screen of the essential oils (EOs) of Nectandra megapotamica (Sprengel) Mez, Nectandra grandiflora Nees, Hesperozygis ringens (Bentham) Epling, Ocimum gratissimum L., Aloysia gratissima (Gillies & Hooker) Troncoso, and Lippia sidoides Chamisso against Coenagrionidae larvae. In addition, the most effective EO and its 50% lethal concentration (LC50) and chemical analysis are described. The larvae of Acanthagrion Selys, Homeoura Kennedy, Ischnura Charpentier, and Oxyagrion Selys were used to assess the EO effects. EO obtained from H. ringens, O. gratissimum, and L. sidoides showed the highest larvicidal effects at 19 h of treatment. The major constituents of the EO of H. ringens include pulegone and limonene, while eugenol and Z-beta-ocimene predominate in the EO of O. gratissimum, and carvacrol and rho-cymene were the major compounds of the EO of L. sidoides. Leaf EOs from H. ringens, O. gratissimum, and L. sidoides showed activity against Coenagrionidae larvae at similar concentrations with LC50s of 62.92, 75.05, and 51.65 microl liter(-1), respectively, and these were considered the most promising treatments.

Systematic review and evidence gap mapping of biomarkers associated with neurological manifestations in patients with COVID-19.

OBJECTIVE: This study aimed to synthesize the existing evidence on biomarkers related to coronavirus disease 2019 (COVID-19) patients who presented neurological events. METHODS: A systematic review of observational studies (any design) following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and the Cochrane Collaboration recommendations was performed (PROSPERO: CRD42021266995). Searches were conducted in PubMed and Scopus (updated April 2023). The methodological quality of nonrandomized studies was assessed using the Newcastle‒Ottawa Scale (NOS). An evidence gap map was built considering the reported biomarkers and NOS results. RESULTS: Nine specific markers of glial activation and neuronal injury were mapped from 35 studies published between 2020 and 2023. A total of 2,237 adult patients were evaluated in the included studies, especially during the acute phase of COVID-19. Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) biomarkers were the most frequently assessed (n = 27 studies, 77%, and n = 14 studies, 40%, respectively). Although these biomarkers were found to be correlated with disease severity and worse outcomes in the acute phase in several studies (p < 0.05), they were not necessarily associated with neurological events. Overall, 12 studies (34%) were judged as having low methodological quality, 9 (26%) had moderate quality, and 9 (26%) had high quality. CONCLUSIONS: Different neurological biomarkers in neurosymptomatic COVID-19 patients were identified in observational studies. Although the evidence is still scarce and conflicting for some biomarkers, well-designed longitudinal studies should further explore the pathophysiological role of NfL, GFAP, and tau protein and their potential use for COVID-19 diagnosis and management.

Onchocerciasis-associated epilepsy: Charting a path forward.

This narrative review intends to inform neurologists and public health professionals about Onchocerciasis-Associated Epilepsy (OAE), a neglected public health problem in many remote onchocerciasis-endemic areas. For epidemiological purposes, we define OAE as sudden-onset of convulsive and non-convulsive seizure types, including head nodding seizures (nodding syndrome) in a previously healthy child aged 3 to 18 years in the absence of any other obvious cause for epilepsy, all happening within an area with high ongoing Onchocerca volvulus transmission. Several OAE pathophysiological mechanisms have been proposed, but none has been proven yet. Recent population-based studies showed that strengthening onchocerciasis elimination programs was followed by a significant reduction in the incidence of OAE and nodding syndrome. Treating epilepsy in onchocerciasis-endemic regions is challenging. More advocacy is needed to provide uninterrupted, free access to anti-seizure medication to persons with epilepsy in these remote, impoverished areas. It is crucial todevelop policies and increase funding for the prevention and treatment of OAE to reduce the associated burden of disease, notably via the establishment of morbidity management and disability prevention programs (MMDP). Moreover, effective collaboration between onchocerciasis elimination and mental health programs is imperative to alleviate the burden of OAE. This synergy promises reciprocal advantages and underscores the need for a comprehensive approach to address this multifaceted challenge.

Biodegradation or simple adsorption to the support material? Development of a simple, fast and low-cost technique.

Biofilms are present in several areas and are studied in microbiology, medical sciences, biology and, of course, sanitary engineering. Biofilms are used for the treatment of municipal wastewater, and their application was even before the invention of the activated sludge process. The main objective of this work was to develop a simple, fast and low-cost technique to evaluate the nature of the first decay in the concentration of an organic compound in the presence of a solid material. Though simple, the technique developed has allowed the clarification of whether the initial concentration decay is due to adsorption to the support material or a result of biodegradation. The results show that, with two different support materials, adsorption does not take place, and the biodegradation processes are responsible for the first decay in the organic concentration. The technique used offers a fast and low-cost way of studying the existence of adsorption. Two feed concentration solutions and two different support materials were used.

Temporal differences and commonalities between hand and tool neural processing.

Object recognition is a complex cognitive process that relies on how the brain organizes object-related information. While spatial principles have been extensively studied, less studied temporal dynamics may also offer valuable insights into this process, particularly when neural processing overlaps for different categories, as it is the case of the categories of hands and tools. Here we focus on the differences and/or similarities between the time-courses of hand and tool processing under electroencephalography (EEG). Using multivariate pattern analysis, we compared, for different time points, classification accuracy for images of hands or tools when compared to images of animals. We show that for particular time intervals (~ 136-156 ms and ~ 252-328 ms), classification accuracy for hands and for tools differs. Furthermore, we show that classifiers trained to differentiate between tools and animals generalize their learning to classification of hand stimuli between ~ 260-320 ms and ~ 376-500 ms after stimulus onset. Classifiers trained to distinguish between hands and animals, on the other hand, were able to extend their learning to the classification of tools at ~ 150 ms. These findings suggest variations in semantic features and domain-specific differences between the two categories, with later-stage similarities potentially related to shared action processing for hands and tools.

Case definitions for onchocerciasis-associated epilepsy and nodding syndrome: A focused review.

Onchocerciasis-associated epilepsy (OAE) is an important but neglected public health problem in onchocerciasis-endemic areas with insufficient or inadequate onchocerciasis control. Hence, there is a need for an internationally accepted, easy-to-use epidemiological case definition of OAE to identify areas of high Onchocerca volvulus transmission and disease burden requiring treatment and prevention interventions. By including OAE as a manifestation of onchocerciasis, we will considerably improve the accuracy of the overall onchocerciasis disease burden, which is currently underestimated. Hopefully, this will lead to increased interest and funding for onchocerciasis research and control interventions, notably the implementation of more effective elimination measures and treatment and support for affected individuals and their families.