Identifying biomarkers for tDCS treatment response in Alzheimer's disease patients: a machine learning approach using resting-state EEG classification.

Background: Transcranial direct current stimulation (tDCS) is a promising treatment for Alzheimer's Disease (AD). However, identifying objective biomarkers that can predict brain stimulation efficacy, remains a challenge. The primary aim of this investigation is to delineate the cerebral regions implicated in AD, taking into account the existing lacuna in comprehension of these regions. In pursuit of this objective, we have employed a supervised machine learning algorithm to prognosticate the neurophysiological outcomes resultant from the confluence of tDCS therapy plus cognitive intervention within both the cohort of responders and non-responders to antecedent tDCS treatment, stratified on the basis of antecedent cognitive outcomes. Methods: The data were obtained through an interventional trial. The study recorded high-resolution electroencephalography (EEG) in 70 AD patients and analyzed spectral power density during a 6 min resting period with eyes open focusing on a fixed point. The cognitive response was assessed using the AD Assessment Scale-Cognitive Subscale. The training process was carried out through a Random Forest classifier, and the dataset was partitioned into K equally-partitioned subsamples. The model was iterated k times using K-1 subsamples as the training bench and the remaining subsample as validation data for testing the model. Results: A clinical discriminating EEG biomarkers (features) was found. The ML model identified four brain regions that best predict the response to tDCS associated with cognitive intervention in AD patients. These regions included the channels: FC1, F8, CP5, Oz, and F7. Conclusion: These findings suggest that resting-state EEG features can provide valuable information on the likelihood of cognitive response to tDCS plus cognitive intervention in AD patients. The identified brain regions may serve as potential biomarkers for predicting treatment response and maybe guide a patient-centered strategy. Clinical Trial Registration: https://classic.clinicaltrials.gov/ct2/show/NCT02772185?term=NCT02772185&draw=2&rank=1, identifier ID: NCT02772185.

Effects of Smoking Marijuana on the Respiratory System: A Systematic Review.

BACKGROUND: The prevalence of marijuana use and its derivatives has surged over the past century, largely due to increasing legalization globally. Despite arguments advocating its benefits, marijuana smoking exposes the lungs to harmful combustion byproducts, leading to various respiratory issues such as asthma, pneumonia, emphysema, and chronic obstructive pulmonary disease. METHODS: We embarked on an extensive literature search, utilizing PubMed/Medline, Scopus, Web of Science, and Google Scholar databases, identifying 200 studies. After the elimination of duplicates, and meticulous review of abstracts and full texts, 55 studies were included in our analysis. RESULTS: Current literature demonstrates that marijuana use negatively impacts lung function, triggering symptoms like chronic cough, sputum production, and wheezing, and diminishing FEV1/FVC ratio in spirometry tests. Moreover, prolonged or chronic marijuana use augments the risk of respiratory function impairment. While the carcinogenic effects of marijuana are still contested, a weak correlation between marijuana use and lung cancer has been observed in some studies. Additionally, instances of other pathologies linked to marijuana use have been reported, including the development of COPD, pulmonary bullae, spontaneous pneumothorax, pleuritic pain, chronic pulmonary aspergillosis, hemoptysis, and pulmonary Langerhans cell histiocytosis. CONCLUSIONS: The evidence underscores that marijuana use is detrimental to respiratory health. In light of the escalating trend of marijuana use, particularly among the youth, it is imperative to advocate public health messages discouraging its consumption.

A hierarchical assembly pathway directs the unique subunit arrangement of TRiC/CCT.

How the essential eukaryotic chaperonin TRiC/CCT assembles from eight distinct subunits into a unique double-ring architecture remains undefined. We show TRiC assembly involves a hierarchical pathway that segregates subunits with distinct functional properties until holocomplex (HC) completion. A stable, likely early intermediate arises from small oligomers containing CCT2, CCT4, CCT5, and CCT7, contiguous subunits that constitute the negatively charged hemisphere of the TRiC chamber, which has weak affinity for unfolded actin. The remaining subunits CCT8, CCT1, CCT3, and CCT6, which comprise the positively charged chamber hemisphere that binds unfolded actin more strongly, join the ring individually. Unincorporated late-assembling subunits are highly labile in cells, which prevents their accumulation and premature substrate binding. Recapitulation of assembly in a recombinant system demonstrates that the subunits in each hemisphere readily form stable, noncanonical TRiC-like HCs with aberrant functional properties. Thus, regulation of TRiC assembly along a biochemical axis disfavors the formation of stable alternative chaperonin complexes.

Comparative analysis of long-term self-reported COVID-19 symptoms among pregnant women.

BACKGROUND: The negative effects of COVID-19 infections during pregnancy have been amply described, however, the persistent sequels of this infection have not been explored so far. OBJECTIVE: The aim of this study was to describe persisting symptoms after COVID-19 infection in pregnant and non-pregnant women in Ecuador. METHODS: A cross-sectional analysis based on an online, self-reporting questionnaire was conducted in Ecuador from April to July 2022. Participants were invited by social media, radio, and TV to voluntarily participate in our study. A total of 457 surveys were included in this study. We compared risk factor variables and long-term persisting symptoms of pregnant and non-pregnant women in Ecuador. RESULTS: Overall, 247 (54.1 %) responders claimed to have long-term symptoms after SARS-CoV-2 infection. Most of these symptoms were reported by non-pregnant women (94.0 %). The most common Long-COVID symptoms in pregnant women were fatigue (10.6 %), hair loss (9.6 %), and difficulty concentrating (6.2 %). We found that pregnant women who smoked had a higher risk of suffering fatigue. CONCLUSIONS: The most frequent Long-COVID symptoms in pregnant women were fatigue, hair loss, and difficulty concentrating. Apparently, the patterns of presentation of long-term sequelae of SARS-CoV-2 infection in pregnant women do not differ significantly from reports available from studies in the general population.

Long COVID at Different Altitudes: A Countrywide Epidemiological Analysis.

BACKGROUND: Several reports from around the world have reported that some patients who have recovered from COVID-19 have experienced a range of persistent or new clinical symptoms after a SARS-CoV-2 infection. These symptoms can last from weeks to months, impacting everyday functioning to a significant number of patients. METHODS: A cross-sectional analysis based on an online, self-reporting questionnaire was conducted in Ecuador from April to July 2022. Participants were invited by social media, radio, and TV to voluntarily participate in our study. A total of 2103 surveys were included in this study. We compared socio-demographic variables and long-term persisting symptoms at low (<2500 m) and high altitude (>2500 m). RESULTS: Overall, 1100 (52.3%) responders claimed to have Long-COVID symptoms after SARS-CoV-2 infection. Most of these were reported by women (64.0%); the most affected group was young adults between 21 to 40 years (68.5%), and most long-haulers were mestizos (91.6%). We found that high altitude residents were more likely to report persisting symptoms (71.7%) versus those living at lower altitudes (29.3%). The most common symptoms were fatigue or tiredness (8.4%), hair loss (5.1%) and difficulty concentrating (5.0%). The highest proportion of symptoms was observed in the group that received less than 2 doses. CONCLUSIONS: This is the first study describing post-COVID symptoms' persistence in low and high-altitude residents. Our findings demonstrate that women, especially those aging between 21-40, are more likely to describe Long-COVID. We also found that living at a high altitude was associated with higher reports of mood changes, tachycardia, decreased libido, insomnia, and palpitations compared to lowlanders. Finally, we found a greater risk to report Long-COVID symptoms among women, those with previous comorbidities and those who had a severer acute SARS-CoV-2 infection.

Habilidades de comprensión y producción narrativa en niños montevideanos de 5 años. Una comparación por nivel socioeconómico / Narrative abilities in a group of Uruguayan preschoolers from different socioeconomic backgrounds

Resumen Este estudio caracteriza y compara las habilidades narrativas y el vocabulario receptivo de 54 preescolares montevideanos de nivel socioeconómico medio (NSM) y bajo (NSB). Los niños realizaron tareas de vocabulario receptivo, producción narrativa (en dos condiciones: manipulando títeres al contar la historia y sin manipularlos), y comprensión narrativa (recuento oral y preguntas posteriores a la reconstrucción). Las narrativas fueron transcritas, codificadas y analizadas en términos de super y macroestructura siguiendo la gramática de historias de Stein y Glenn (1979) (coherencia) y de microestructura (productividad y complejidad). Los niños de ambos grupos tuvieron un desempeño acorde a su edad en comprensión y producción narrativa, a pesar de que el grupo de NSM tuvo un mejor desempeño en vocabulario receptivo. Hubo diferencias en comprensión (cantidad de episodios recuperados y en la respuesta a preguntas) que favorecieron al NSM, pero no en la cantidad de categorías recuperadas ni en la extensión y complejidad del recuento. Para producción narrativa no hubo diferencias en secuencia narrativa, ni en la cantidad de episodios completos en ninguna de las condiciones, pero sí en cuanto a la complejidad sintáctica en la condición sin títeres. Los resultados muestran una relación compleja entre vocabulario y habilidades narrativas, dado que diferencias importantes en vocabulario no se reflejaron de manera homogénea en el desempeño narrativo. Estos resultados aportan a los debates actuales sobre el papel del vocabulario en el desarrollo de habilidades narrativas, así como a pensar la validez ecológica de las evaluaciones en el desarrollo cognitivo y lingüístico.

Abstract Narrative abilities are an important part of communication, academic success, and healthy relationships. These abilities involve complex language and cognitive skills, such as precise vocabulary, control of the coherence markers, relations of cause-effect, and planning. They are also relevant during the elementary school years and interact with the socio-emotional skills necessary to understand different points of view. Oral narrative production develops dramatically from 3 to 5 years of age and is a key factor in a child's ability to communicate about the world. During this period narratives are a product of increasing linguistic sophistication over the preschool period and there is a complex relationship between early narratives and language proficiency. So far, most research about this topic has been pursued in populations other than Latin American preschoolers. At the same time, a considerably lesser number of studies about narrative abilities development have been carried out comparing typically developing children from different socioeconomic backgrounds. To our knowledge, there are no studies in Uruguay that assess the narrative abilities development in typically developing preschool children who grow up in vulnerable contexts. It is therefore of the utmost relevance to produce empirical evidence for this population. For these reasons, this study aimed at characterizing and comparing narrative abilities and receptive vocabulary in a group of a total of 54 Uruguayan preschoolers from different socioeconomic backgrounds (middle and low socioeconomic status, SES). Children were assessed in receptive vocabulary and narrative abilities across two task conditions: (1) narrative comprehension through a story retelling task which included some final questions about the story; (2) narrative production elicited from a set of thematically related puppets. The examiner gives a child a puppet set and asks him/her to elaborate a narrative using them. After that, puppets are removed and the child is asked to retell the story without puppets. Children's oral productions were video-taped and then transcribed and categorized using the ELAN software (Max Planck Institute for Psycholinguistics, 2019). The verbal information was categorized according to Stein and Glenn's (1979) story grammar and considering the microstructural aspects (productivity and complexity). Analyses showed that both groups performed according to their stage of development in both narrative task conditions. With regards to the narrative comprehension task, no differences in the number of recovered categories, extension, or narrative complexity were observed. Concerning the narrative production task, there were no differences between the groups in narrative sequences, nor in the number of completed episodes in conditions neither with puppets nor without puppets. Results showed that children who grow up in poverty perform more poorly than their peers from middle-income families in receptive vocabulary, in the number of recovered episodes, ask-answer items of narrative comprehension tasks. Moreover, concerning the microstructural parameters analyses showed that children from middle socioeconomic backgrounds scored better in syntactic complexity in the without puppets condition. No differences between the groups were observed in syntactic complexity in the puppets condition. Taken together these results indicate a complex link between vocabulary and narrative abilities. It is worth noting that important differences in vocabulary did not reflect in the children's narrative performance. These findings are also relevant as a contribution to an ongoing debate about the role of vocabulary in the development of narrative abilities. Furthermore, these results could inform the discussion about the ecological validity of the test of cognitive and linguistic development. Finally, to provide some additional evidence to Uruguayan Spanish language about the relationships between oral language and cognitive development allows to carry out early interventions before formal schooling sets children for success in school and life.

Habilidades prelectoras en niños uruguayos de diferente nivel socioeconómico / Differential pre-literacy skills development in Uruguayan children from different socioeconomic backgrounds

Resumen El objetivo del presente estudio fue comparar las habilidades prelectoras en 50 preescolares uruguayos de 5 años de edad de diferente nivel socioeconómico (NSE) y analizar el impacto de estas habilidades en el aprendizaje de la lectura. Para ello, se evaluó a los niños mediante pruebas de vocabulario receptivo, conciencia fonológica, conocimiento sobre el nombre y el sonido de las letras, y denominación rápida de objetos a fin del nivel preescolar Tiempo 1 (T1). Un año más tarde, se evaluó a un subgrupo de la muestra inicial mediante una prueba de lectura de palabras Tiempo 2 (T2). Los resultados señalaron la existencia de correlaciones significativas entre los predictores (T1) y la lectura de palabras (T2) y entre todas las variables evaluadas y el nivel socioeconómico de los niños. La comparación del desempeño intergrupal señaló la existencia de diferencias significativas en todas las habilidades evaluadas a favor del nivel socioeconómico medio. Sin embargo, el desempeño en la lectura de palabras de ambos grupos fue bajo. Por otra parte, un análisis de regresión mostró que, para los niños de nivel socioeconómico bajo, el nivel de conciencia fonológica fue el que explicó la mayor parte de la varianza en la eficiencia lectora. El nivel de lectura de los niños de nivel socioeconómico medio fue mayormente explicado por el conocimiento del nombre de las letras. Los resultados ponen en evidencia la importancia de atender a las diferencias que se generan temprano en el desarrollo de habilidades lingüísticas fundamentales para aprender a leer.

Abstract Learning to read transforms lives. Reading contributes to knowledge acquisition, cultural engagement, and success in the school. The unequal distribution of literacy skills in a society is associated with economic and social inequalities as a result, children with a poor foundation in literacy before entering formal schooling are more likely to struggle academically and to drop out of school. For these reasons, there has been an intense scientific interest for decades in understanding how children learn to read. It is well established that in the early stages of reading development, phonological awareness, letter name-sounds knowledge, and the naming speed are three independent longitudinal predictors of children's later word-reading skills in alphabetic-writing systems. Phonological awareness constitutes the ability to recognize and manipulate the sounds of their own language, meanwhile letter knowledge promotes the discovery of systematic relationships between writing and oral language. As early readers develop some level of phonological awareness and some level of letter knowledge, they can recognize written words through phonological recoding processes, in which graphemes are recoded as phonemes and assembled to pronounce words. In addition, rapid naming expresses the speed at which phonological information is accessed from a graphic label. Phonological processing and letter knowledge are powerfully affected by the experience, stimulation, and support that children receive before beginning formal education. Most children acquire these abilities relatively effortlessly during early childhood. However, there is a significant number of children in Latin America who experience difficulties in their pre-literacy skills development. This study examined the cognitive profiles of a total of 50 Uruguayan preschoolers from different socioeconomic backgrounds from two public schools in Montevideo, Uruguay. Twenty-six children from low-income households were compared to peers from middle-income. At the end of the pre-schooling period (time 1) receptive vocabulary, phonological awareness, letter name-sounds knowledge, and object naming speed tests were administered to children. One year later (time 2), word -reading of a subgroup of children was measured. Significant correlations were observed between all predictors at time 1; between predictors at time 1 and word reading at time 2; and between all measured abilities and socioeconomic status. Comparative analysis between children of different socioeconomic status showed that children growing up in poverty contexts performed more poorly than their peers from middle-income families in all the tests. Nonetheless, both groups performed poorly in word reading. Descriptive statistics indicated that, out of a total of 26 words, low SES children correctly read a total of 7 words per minute, and medium SES children a total of 14 words. Finally, regression analyses indicated that phonological awareness contributed 30 % variance in predicting the total score achieved in a reading-word test in children of low-income families, meanwhile letter name knowledge contributed 74 % variance in predicting the total score achieved in a reading-word test in their peers from middle-income families. In general terms, results of pre-reading skills and reading performance seem to indicate that children of different socioeconomic status use different word recognition strategies according to their level of letter-knowledge of and phonological processing. Discussion considers international literature pointing out that children who enter elementary school with limited reading-related skills are unlikely to be able to keep pace with their peers. These findings warn about the importance to elaborate systematic and high-quality educational proposals to try to reduce the gap in reading development for children from low-income families. Developing literacy and language skills before formal schooling sets a child up for success in school and life. Results also suggest the importance of analyzing the variables that affect reading development in populations that are not the majority described.

A Comparative Analysis of a Self-Reported Adverse Events Analysis after Receiving One of the Available SARS-CoV-2 Vaccine Schemes in Ecuador.

The COVID-19 pandemic has put a lot of pressure on health systems worldwide. Mass vaccination against SARS-CoV-2 has reduced morbidity and mortality worldwide. Despite their safety profiles, vaccines, as with any other medical product, can cause adverse events. Yet, in countries with poor epidemiological surveillance and monitoring systems, reporting vaccine-related adverse events is a challenge. The objective of this study was to describe self-reported vaccine adverse events after receiving one of the available COVID-19 vaccine schemes in Ecuador. A cross-sectional analysis based on an online, self-reported, 32-item questionnaire was conducted in Ecuador from 1 April to 15 July 2021. Participants were invited by social media, radio, and TV to voluntarily participate in our study. A total of 6654 participants were included in this study. Furthermore, 38.2% of the participants reported having at least one comorbidity. Patients received AstraZeneca, Pfizer, and Sinovac vaccines, and these were distributed 38.4%, 31.1%, and 30.5%, respectively. Overall, pain or swelling at the injection site 17.2% (n = 4500) and headache 13.3% (n = 3502) were the most reported adverse events. Women addressed events supposedly attributable to vaccination or immunization [ESAVIs] (66.7%), more often than men (33.2%). After receiving the first dose of any available COVID-19 vaccine, a total of 19,501 self-reported ESAVIs were informed (87.0% were mild, 11.5% moderate, and 1.5% severe). In terms of the vaccine type and brand, the most reactogenic vaccine was AstraZeneca with 57.8%, followed by Pfizer (24.9%) and Sinovac (17.3%). After the second dose, 6776 self-reported ESAVIs were reported (87.1% mild, 10.9% moderate, and 2.1% severe). AstraZeneca vaccine users reported a higher proportion of ESAVIs (72.2%) in comparison to Pfizer/BioNTech (15.9%) and Sinovac Vaccine (11.9%). Swelling at the injection site, headache, muscle pain, and fatigue were the most common ESAVIs for the first as well as second doses. In conclusion, most ESAVIs were mild. AstraZeneca users were more likely to report adverse events. Participants without a history of COVID-19 infection, as well as those who received the first dose, were more prone to report ESAVIs.

Phosphorous and Silica Recovery from Rice Husk Poultry Litter Ash: A Sustainability Analysis Using a Zero-Waste Approach.

Phosphate rocks are a critical resource for the European Union, and alternative sources to assure the future production of a new generation of fertilizers are to be assessed. In this study, a statistical approach, combined with a sustainability evaluation for the recovery of materials from waste containing phosphorus (P), is presented. This work proposes a strategy to recover P and silica (SiO2) from rice husk poultry litter ash (RHPLA). The design of experiment (DoE) method was applied to maximize the P extraction using hydrochloric acid (HCl), with the aim to minimize the contamination that can occur by leachable heavy metals present in RHPLA, such as zinc (Zn). Two independent variables, the molar concentration of the acid, and the liquid-to-solid ratio (L/S) between the acid and RHPLA, were used in the experimental design to optimize the operating parameters. The statistical analysis showed that a HCl concentration of 0.34 mol/L and an L/S ratio of 50 are the best conditions to recover P with low Zn contamination. Concerning the SiO2, its content in RHPLA is too low to consider the proposed recovery process as advantageous. However, based on our analysis, this process should be sustainable to recover SiO2 when its content in the starting materials is more than 80%.

Native mass spectrometry analyses of chaperonin complex TRiC/CCT reveal subunit N-terminal processing and re-association patterns.

The eukaryotic chaperonin TRiC/CCT is a large ATP-dependent complex essential for cellular protein folding. Its subunit arrangement into two stacked eight-membered hetero-oligomeric rings is conserved from yeast to man. A recent breakthrough enables production of functional human TRiC (hTRiC) from insect cells. Here, we apply a suite of mass spectrometry techniques to characterize recombinant hTRiC. We find all subunits CCT1-8 are N-terminally processed by combinations of methionine excision and acetylation observed in native human TRiC. Dissociation by organic solvents yields primarily monomeric subunits with a small population of CCT dimers. Notably, some dimers feature non-canonical inter-subunit contacts absent in the initial hTRiC. This indicates individual CCT monomers can promiscuously re-assemble into dimers, and lack the information to assume the specific interface pairings in the holocomplex. CCT5 is consistently the most stable subunit and engages in the greatest number of non-canonical dimer pairings. These findings confirm physiologically relevant post-translational processing and function of recombinant hTRiC and offer quantitative insight into the relative stabilities of TRiC subunits and interfaces, a key step toward reconstructing its assembly mechanism. Our results also highlight the importance of assigning contacts identified by native mass spectrometry after solution dissociation as canonical or non-canonical when investigating multimeric assemblies.

Simultaneous amorphous silica and phosphorus recovery from rice husk poultry litter ash.

The livestock sector is one of the most important sectors of the agricultural economy due to an increase in the demand for animal protein. This increase generates serious waste disposal concerns and has negative environmental consequences. Furthermore, the food production chain needs phosphorus (P), which is listed as a critical raw material due to its high demand and limited availability in Europe. Manure contains large amounts of P and other elements that may be recycled, in the frame of circular economy and "zero waste" principles, and reused as a by-product for fertilizer production and other applications. This paper focuses on the extraction and recovery of amorphous silica from rice husk poultry litter ash. Two different extraction procedures are proposed and compared, and the obtained silica is characterized. This work shows that amorphous silica can be recovered as an almost pure material rendering the residual ash free of P. It also addresses the possibility of more specific phosphorous extraction procedures via acid leaching.

Pre-Licensure Inter-Professional Perspectives: Pelvic Health Physiotherapy.

Purpose: In this study, we examined knowledge and perspectives pertaining to pelvic health physiotherapy among medical, midwifery, nursing, and physician assistant students at McMaster University. Moreover, we identified opportunities to improve knowledge translation to facilitate inter-professional education in urogynecological care. Method: A cross-sectional design was created to distribute an online survey to participants using a modified Dillman approach. The survey assessed areas of clinical interest in, knowledge of the scope of practice of, and regulations governing pelvic health physiotherapy in specific, in addition to clinical applications. Fisher's exact and Kruskal-Wallis tests were used to assess statistical significance. Results: A total of 90% of the participants incorrectly indicated that internal digital exams could be delegated to physiotherapy assistants, and 50% believed that Kegel exercises were appropriate for all presentations of pelvic floor dysfunction. Moreover, when prompted to select conditions that could be treated by pelvic health physiotherapists, only 2% of the participants selected the correct conditions. Conclusions: Knowledge in all four programmes about the scope of practice, authorized activities, and application of pelvic health physiotherapy is inadequate. To foster the optimal integration of urogynecology into the relevant health science curriculums, enhanced inter-professional education, inclusive of pelvic health physiotherapy knowledge, appears to be needed.

Objectif : examiner les connaissances et les points de vue relatifs à la physiothérapie pelvienne des personnes étudiant pour devenir médecins, sages-femmes, infirmières ou auxiliaires médicales à l'université McMaster; établir des possibilités d'améliorer l'application des connaissances pour faciliter l'enseignement interprofessionnel en soins urogynécologiques. Méthodologie : les chercheurs ont créé un sondage transversal en ligne au moyen de la méthode de Dillman modifiée. Ce sondage évaluait les secteurs d'intérêt clinique, les connaissances sur le champ d'exercice et les applications cliniques de la physiothérapie pelvienne, de même que la réglementation s'y rapportant. Ils ont utilisé la méthode exacte de Fisher et le test de Kruskal-Wallis pour évaluer la signification statistique des résultats. Résultats : au total, 90 % des participants ont indiqué à tort que les examens digitaux internes pouvaient être délégués à des assistants-physiothérapeutes et 50 % croyaient que les exercices de « Kegel ¼ convenaient à toutes les présentations des dysfonctions pelviennes. De plus, lorsqu'on les invitait à sélectionner des affections qui pouvaient être traitées par des physiothérapeutes pelviens, seulement 2 % des participants choisissaient les bonnes. Conclusion : les connaissances sont insuffisantes dans les quatre programmes à l'égard du champ d'exercice, des activités autorisées et de l'application de la physiothérapie pelvienne. Pour favoriser l'intégration optimale de l'urogynécologie aux programmes pertinents en sciences de la santé, il semble nécessaire d'améliorer l'enseignement interprofessionnel, y compris les connaissances sur la physiothérapie pelvienne.

Citrobacter freundii infection in silver catfish (Rhamdia quelen): Hematological and histological alterations.

Citrobacter freundii is a fish pathogen known for its ability to cause injury and high mortality. There have been no studies reporting the effect of this bacterium on hematological parameters and internal organ histology in silver catfish (Rhamdia quelen). Therefore, the aim of this study is to evaluate the hematological and histopathological effects of an experimentally induced C. freundii infection in silver catfish. Twenty fish were divided into healthy and infected groups. The fish of the infected group were inoculated intramuscularly with 100 µL of bacterial suspension (6.4 × 108 CFU mL-1), while healthy control animals received 100 µL of sterile saline. On day 18 post-infection, blood and tissues (cephalic kidneys, livers, and spleens) were collected for histological analysis. The infected animals presented high mortality, as well as hematological and histological changes. In relation to hematology, the infected fish presented aregenerative anemia, protein loss, leukopenia with neutropenia, lymphocytosis, and leukoblastosis. Regarding histology, there was liver degeneration, decrease in the amount of renal hematopoietic tissue, and the presence of melanomacrophage centers (MMCs) in the spleen and cephalic kidney of infected fish. In summary, these alterations may contribute to disease pathophysiology, contributing to high mortality of affected fish.

Acute and subacute toxicity and chemical constituents of the hydroethanolic extract of Verbena litoralis Kunth.

ETHNOPHARMACOLOGICAL RELEVANCE: Verbena litoralis Kunth is a native species of South America, popularly known as gervãozinho-do-campo or erva-de-pai-caetano. It is used in gastrointestinal disorders, as detoxifying the organism, antifebrile properties and amidaglitis. AIM OF THE STUDY: To identify the chemical constituents of the hydroethanolic extract obtained from the aerial parts of V. litoralis and to evaluate the acute and sub-acute toxicity in male and female rats. MATERIALS AND METHODS: The single dose (2000 mg/kg) of the extract was administered orally to male and female rats. In the subacute study the extract was given at doses of 100, 200 and 400 mg/kg during 28 days orally. Biochemical, hematological and histological analyzes were performed, oxidative stress markers were tested and chemical constituents were identified through UHPLC-ESI-HRMS RESULTS: Six classes of metabolites were identified: iridoids glycosides, flavonoids, phenylpropanoids-derived, phenylethanoid-derived, cinnamic acid-derived and triterpenes. In the acute treatment, the extract was classified as safe (category 5), according to the OECD guide. Our results demonstrated that subacute administration of the crude extract of V. litoralis at 400 mg/kg resulted in an increase in AST in males, whereas ALT enzyme showed a small increase in males that received 200 mg/kg and 400 mg/kg of the extract. CONCLUSIONS: The extract of the aerial parts of Verbena litoralis did not present significant toxicity when administered a single dose. However, when different doses were administered for 28 days, were observed changes in hematological, biochemical and histological parameters in rats.

Aflatoxin B1-contaminated diet disrupts the blood-brain barrier and affects fish behavior: Involvement of neurotransmitters in brain synaptosomes.

It is known that the cytotoxic effects of aflatoxin B1 (AFB1) in endothelial cells of the blood-brain barrier (BBB) are associated with behavioral dysfunction. However, the effects of a diet contaminated with AFB1 on the behavior of silver catfish remain unknown. Thus, the aim of this study was to evaluate whether an AFB1-contaminated diet (1177 ppb kg feed-1) impaired silver catfish behavior, as well as whether disruption of the BBB and alteration of neurotransmitters in brain synaptosomes are involved. Fish fed a diet contaminated with AFB1 presented a behavioral impairment linked with hyperlocomotion on days 14 and 21 compared with the control group (basal diet). Neurotransmitter levels were also affected on days 14 and 21. The permeability of the BBB to Evans blue dye increased in the intoxicated animals compared with the control group, which suggests that the BBB was disrupted. Moreover, acetylcholinesterase (AChE) activity in brain synaptosomes was increased in fish fed a diet contaminated with AFB1, while activity of the sodium-potassium pump (Na+, K+-ATPase) was decreased. Based on this evidence, the present study shows that silver catfish fed a diet containing AFB1 exhibit behavioral impairments related to hyperlocomotion. This diet caused a disruption of the BBB and brain lesions, which may contribute to the behavioral changes. Also, the alterations in the activities of AChE and Na+, K+-ATPase in brain synaptosomes may directly contribute to this behavior, since they may promote synapse dysfunction. In addition, the hyperlocomotion may be considered an important macroscopic marker indicating possible AFB1 intoxication.

Citrobacter freundii impairs the phosphoryl transfer network in the gills of Rhamdia quelen: Impairment of bioenergetics homeostasis.

The precise coupling of spatially separated intracellular adenosine triphosphate (ATP)-producing and ATP-consuming, catalyzed by creatine kinase (CK), adenylate kinase (AK), and pyruvate kinase (PK), is a critical process in the bioenergetics of tissues with high energy demand, such as the branchial tissue. The effects of Citrobacter freundii infection on gills remain poorly understood, limited only to histopathological studies. Thus, the aim of this study was to evaluate whether experimental infection by C. freundii impairs the enzymes of the phosphoryl transfer network in gills of silver catfish (Rhamdia quelen). The CK (cytosolic and mitochondrial) and AK activities decreased in infected compared to uninfected animals, while the PK activity did not differ between groups. The gill histopathology of infected animals revealed extensive degeneration with fusion and necrosis of secondary lamellae, detachment of superficial epithelium, aneurysm, vessel congestion and inflammatory process. Based on these evidences, the inhibition and absence of an efficient communication between CK compartments caused the impairment of the branchial bioenergetics homeostasis, which was not compensated by the augmentation on branchial AK activity in an attempt to restore energy homeostasis. In summary, these alterations contribute to disease pathogenesis linked to branchial tissue in animals infected with C. freundii.

Effectiveness of two home ergonomic programs in reducing pain and enhancing quality of life in informal caregivers of post-stroke patients: A pilot randomized controlled clinical trial.

BACKGROUND: Informal caregivers of post-stroke patients usually undergo high levels of pain and stress and have a reduced quality of life. OBJECTIVE: To evaluate the effectiveness of two home ergonomic interventions aimed at reducing pain intensity and perceived stress and enhancing the quality of life in informal caregivers of chronic post-stroke patients. METHODS: A randomized single-blind controlled clinical trial was conducted, with a sample of 33 informal caregivers of patients with stroke. Three groups were included: one received postural hygiene training and kinesiotherapy, for 12 weeks, two days a week, one hour per session; another received adaptation of the home environment, and the third was a control group. Pain intensity, stress level and general quality of life were evaluated at three-time points: pre-intervention, post-intervention, and after a follow-up period of three months. RESULTS: Neck pain decreased in the two experimental groups, and increased in the control group. Pain in the shoulders and knees was alleviated in the group that received postural hygiene and kinesiotherapy. In addition, regarding quality of life, this group obtained an improvement in the physical health dimension, while the home adaptation group reported improved social relationships. CONCLUSIONS: These results suggest that 12 weeks of training in postural hygiene, combined with kinesiotherapy, and home adaptations can reduce pain and improve several aspects of the quality of life of this population. CLINICALTRIALS. GOV ID: NCT03284580.

Purinergic signaling modulates the cerebral inflammatory response in experimentally infected fish with Streptococcus agalactiae: an attempt to improve the immune response.

Appropriate control of the immune response is a critical determinant of fish health, and the purinergic cascade has an important role in the immune and inflammatory responses. This cascade regulates the levels of adenosine triphosphate (ATP), adenosine diphosphate, adenosine monophosphate and adenosine (Ado), molecules involved in physiological or pathological events as inflammatory and anti-inflammatory mediators. Thus, the aim of this study was to evaluate whether purinergic signaling, through the activities of nucleoside triphosphate diphosphohydrolase (NTPDase), 5'-nucleotidase, and adenosine deaminase (ADA), is capable of modulating the cerebral immune and inflammatory responses in silver catfish that is experimentally infected with Streptococcus agalactiae. Cerebral NTPDase (with ATP as substrate) and 5'-nucleotidase activities increased, while ADA activity decreased in silver catfish that is experimentally infected with S. agalactiae, compared to the control group. Moreover, the cerebral levels of ATP and Ado increased in infected animals compared to the uninfected control group. Brain histopathology in infected animals revealed inflammatory demyelination (the presence of occasional bubbly collections), increased cellular density in the area near to pia-mater and intercellular edema. Based on this evidence, the modulation of the purinergic cascade by the enzymes NTPDase, 5'-nucleotidase, and ADA exerts an anti-inflammatory profile due to the regulation of ATP and Ado levels. This suggests involvement of purinergic enzymes on streptococcosis pathogenesis, through regulating cerebral ATP and Ado levels, molecules known to participate in physiological or pathological events as inflammatory and anti-inflammatory mediators, respectively. In summary, the modulation of the cerebral purinergic cascade exerts an anti-inflammatory profile in an attempt to reduce inflammatory damage.

Involvement of xanthine oxidase activity with oxidative and inflammatory renal damage in silver catfish experimentally infected with Streptococcus agalactiae: Interplay with reactive oxygen species and nitric oxide.

Xanthine oxidase (XO) is a final enzyme of purine metabolism linked with initiation and progression of infectious diseases, since is considered an important source of reactive oxygen species (ROS) and nitric oxide (NO), developing a pro-oxidant and pro-inflammatory profile in some infectious diseases. Thus, the aim of this study was to evaluate the involvement of XO activity in the renal oxidative and inflammatory damage, as well as the interplay with ROS and metabolites of nitric oxide (NOx) levels in silver catfish experimentally infected with Streptococcus agalactiae. Xanthine oxidase activity, and uric acid, ROS and NOx levels increased in renal tissue of infected animals compared to uninfected animals. Moreover, the histopathological analyses revealed the presence of necrosis, generalized edema and nuclear degeneration of renal tubules. Based on these evidences, the upregulation on renal XO activity exerts a pro-oxidant and pro-inflammatory profile in kidney of fish infected with S. agalactiae. The excessive uric acid levels induced the release of oxidative and inflammatory mediators, such as ROS and NOx, that directly contribute to renal oxidative and inflammatory damage. In summary, the upregulation on XO activity may be considered a pathway involved in the renal injury during S. agalactiae infection.