Geoepidemiology, seroprevalence and factors associated with Toxoplasma gondii infection in domicilied cats from Paraíba (Brazil).

Toxoplasma gondii is a parasite responsible for toxoplasmosis, an emerging and often neglected zoonosis in South America, particularly Brazil. Felines, the only definitive hosts, excrete oocysts in their feces, potentially infecting all homeotherms. Domestic cats are primarily responsible for contaminating human environments with these oocysts. Monitoring their populations is therefore essential to ensure proper toxoplasmosis prophylaxis. The aim of this study was to estimate the prevalence of T. gondii and exposure factors in a population of owner cats in the city of João Pessoa, Paraíba, Brazil. A total of 267 blood samples were collected from domestic cats aged between 1 and 15 years and tested with an immunofluorescence antibody test. The seroprevalence of antibodies against T. gondii was only 17.22% (46/267 individuals). This result therefore suggests a low contribution of domestic cats to T. gondii contamination of the urban environment. The cats' age and living environment were identified as risk factors for cat exposure to T. gondii.

Title: Géoépidémiologie, séroprévalence et facteurs associés à l'infection à Toxoplasma gondii chez les chats domiciliés à Paraíba (Brésil). Abstract: Toxoplasma gondii est le parasite responsable de la toxoplasmose, une zoonose émergente et souvent négligée en Amérique du Sud, notamment au Brésil. Les félins, seuls hôtes définitifs, excrètent des oocystes dans leurs selles, infectant potentiellement tous les homéothermes. Les chats domestiques sont les premiers responsables de la contamination des environnements humains avec ces oocystes. La surveillance de leurs populations est donc essentielle pour garantir une prophylaxie adéquate contre la toxoplasmose. Le but de cette étude était d'estimer la prévalence de T. gondii et les facteurs d'exposition dans une population de chats domestiques de la ville de João Pessoa, Paraíba, Brésil. Au total, 267 échantillons de sang ont été prélevés sur des chats domestiques âgés de 1 à 15 ans et testés avec un test d'immunofluorescence des anticorps. La séroprévalence des anticorps contre T. gondii n'était que de 17,22 % (46/267 individus). Ce résultat suggère donc une faible contribution des chats domestiques à la contamination du milieu urbain par T. gondii. L'âge et le milieu de vie des chats ont été identifiés comme facteurs de risque d'exposition du chat à T. gondii.

Opposing effects of the purinergic P2X7 receptor on seizures in neurons and microglia in male mice.

BACKGROUND: The purinergic ATP-gated P2X7 receptor (P2X7R) is increasingly recognized to contribute to pathological neuroinflammation and brain hyperexcitability. P2X7R expression has been shown to be increased in the brain, including both microglia and neurons, in experimental models of epilepsy and patients. To date, the cell type-specific downstream effects of P2X7Rs during seizures remain, however, incompletely understood. METHODS: Effects of P2X7R signaling on seizures and epilepsy were analyzed in induced seizure models using male mice including the kainic acid model of status epilepticus and pentylenetetrazole model and in male and female mice in a genetic model of Dravet syndrome. RNA sequencing was used to analyze P2X7R downstream signaling during seizures. To investigate the cell type-specific role of the P2X7R during seizures and epilepsy, we generated mice lacking exon 2 of the P2rx7 gene in either microglia (P2rx7:Cx3cr1-Cre) or neurons (P2rx7:Thy-1-Cre). To investigate the protective potential of overexpressing P2X7R in GABAergic interneurons, P2X7Rs were overexpressed using adeno-associated virus transduction under the mDlx promoter. RESULTS: RNA sequencing of hippocampal tissue from wild-type and P2X7R knock-out mice identified both glial and neuronal genes, in particular genes involved in GABAergic signaling, under the control of the P2X7R following seizures. Mice with deleted P2rx7 in microglia displayed less severe acute seizures and developed a milder form of epilepsy, and microglia displayed an anti-inflammatory molecular profile. In contrast, mice lacking P2rx7 in neurons showed a more severe seizure phenotype when compared to epileptic wild-type mice. Analysis of single-cell expression data revealed that human P2RX7 expression is elevated in the hippocampus of patients with temporal lobe epilepsy in excitatory and inhibitory neurons. Functional studies determined that GABAergic interneurons display increased responses to P2X7R activation in experimental epilepsy. Finally, we show that viral transduction of P2X7R in GABAergic interneurons protects against evoked and spontaneous seizures in experimental temporal lobe epilepsy and in mice lacking Scn1a, a model of Dravet syndrome. CONCLUSIONS: Our results suggest a dual and opposing action of P2X7R in epilepsy and suggest P2X7R overexpression in GABAergic interneurons as a novel therapeutic strategy for acquired and, possibly, genetic forms of epilepsy.

The biotechnology revolution in textile dyeing.

Biotechnology holds the potential to revolutionize textile dyeing by utilizing biopigments, biodegradable dyes, and fermentative dyeing methods as alternatives to synthetic options. While some challenges exist, these biotechnological approaches offer innovative solutions to minimize environmental impact and foster sustainable practices, leading toward a greener, circular and efficient textile bioindustry.

Tailor-made solvents for microbial carotenoids recovery.

In recent years, microbial carotenoids have emerged as a promising alternative for the pharmaceutical and food industries, particularly in promoting human health due to their potent antioxidant and antimicrobial properties. Microbial carotenoids, particularly those produced by yeast, bacteria, and microalgae, are synthesized intracellularly, requiring the use of solvents for their effective extraction and recovery. The conventional use of toxic volatile organic solvents (VOCs) like hexane, petroleum ether, and dimethyl sulfoxide in the extraction of microbial carotenoids has been common. However, ongoing research is introducing innovative, non-toxic, environmentally friendly tailor-made solvents, such as ionic liquids (IL) and deep eutectic solvents (DES), indicating a new era of cleaner and biocompatible technologies. This review aims to highlight recent advancements in utilizing IL and DES for obtaining carotenoids from microorganisms. Additionally, we explore the utilization of in silico tools designed to determine the solubilities of microbial carotenoids in tailor-made DES and ILs. This presents a promising alternative for the scientific community, potentially reducing the need for extensive experimental screening of solvents for the recovery of microbial carotenoids in the separation processing. According to our expert perspective, both IL and DES exhibit a plethora of exceptional attributes for the recovery of microbial carotenoids. Nevertheless, the current employment of these solvents for recovery of carotenoids is restricted to scientific exploration, as their feasibility for practical application in industrial settings has yet to be conclusively demonstrated. KEY POINTS: • ILs and DES share many tailoring properties for the recovery of microbial carotenoids • The use of ILs and DES for microbial carotenoid extraction remains driven by scientific curiosity. • The economic feasibility of ILs and DES is yet to be demonstrated in industrial applications.

The association between asthma and atrial fibrillation: systematic review and meta-analysis.

Respiratory disease and atrial fibrillation (AF) frequent coexist, but the risk of AF among asthma patients is less characterized. Growing evidence suggest that AF shares with asthma a systemic inflammation background and asthma treatments, such as beta agonists, have been associated with increased risk of cardiac arrhythmias. The aim of this systematic review was to assess the risk of AF in patients with asthma in observational studies. We search for longitudinal studies reporting AF outcome in asthma and control patients through MEDLINE, Cochrane Central Register of Controlled Trials and EMBASE. Pooled estimates of odds ratios (ORs) and 95% confidence intervals (CIs) were derived by random effects meta-analysis. Heterogeneity was assessed using the I2 test. The risk of bias of individual studies was evaluated using the ROBINS-E tool. The study protocol was registered at PROSPERO: CRD42020215707. Seven cohort/nested case-control studies with 1 405 508 individuals were included. The mean follow-up time was 9 years, ranging from 1 to 15 years. Asthma was associated with a higher risk of AF (OR 1.15. 95% CI 1.01-1.29). High heterogeneity (I2 = 81%) and overall "serious" risk of bias, lead to a very low confidence in in this result. Asthma was associated with an increased risk of AF. However, the high risk of bias and high heterogeneity reduces the robustness of these results, calling for further high-quality data.

Night-Time Noise and Sleep Quality in an Internal Medicine Ward in Portugal: An Observational Study.

INTRODUCTION: Hospitals should provide a quiet environment to promote patient healing and well-being. However, published data indicates that World Health Organization's guidelines are frequently not met. The aim of the present study was to quantify night-time noise levels in an internal medicine ward and evaluate sleep quality, as well as the use of sedative drugs. MATERIAL AND METHODS: Prospective observational study in an acute internal medicine ward. Between April 2021 and January 2022, on random days, noise was recorded using a smartphone app (Apple® iOS, Decibel X). Night-time noise was recorded from 10 p.m. to 8 a.m. During the same period, hospitalized patients were invited to respond to a questionnaire regarding their sleep quality. RESULTS: A total of 59 nights were recorded. The average noise level recorded was 55 dB with a minimum of 30 dB and a maximum of 97 dB. Fifty-four patients were included. An intermediate score for night-time sleep quality (35.45 out of 60) and noise perception (5.26 out of 10) was reported. The main reasons for poor sleep were related to the presence of other patients (new admission, acute decompensation, delirium, and snoring), followed by equipment, staff noise and surrounding light. Nineteen patients (35%) were previous users of sedatives, and during hospitalization 41 patients (76%) were prescribed sedatives. CONCLUSION: The noise levels detected in the internal medicine ward were higher than the levels recommended by the World Health Organization. Most patients were prescribed sedatives during hospitalization.

Artificial cornea transplantation and visual rehabilitation: an integrative review / Transplante de córnea artificial e reabilitação visual: uma revisão integrativa

ABSTRACT Due to the development of complications and the biocompatibility and scarcity of transplant donor tissues, artificial corneas, which can be used for the rehabilitation of optical functions, have been developed. The current study aimed to analyze the visual rehabilitation effects of the Boston type I keratoprosthesis, Boston type II keratoprosthesis, Aurolab keratoprosthesis, osteo-odonto-keratoprosthesis, and tibial bone keratoprosthesis. Results showed that the Boston type I keratoprosthesis was the most effective for visual rehabilitation in patients with moist ocular surfaces. The Aurolab keratoprosthesis had a lower efficacy for visual rehabilitation. Nevertheless, it is still a viable option for individuals in economically restricted countries. In patients with dry eyes, the Boston type II keratoprosthesis was associated with the best visual rehabilitation. However, the final visual acuity of patients who received osteo-odonto-keratoprosthesis and tibial bone keratoprosthesis implantation was not evaluated as the necessary information was not available.

RESUMO Em decorrência de complicações, da biocompatibilidade e da escassez de tecido doador para transplantes de córnea natural, foram elaboradas córneas artificiais que são potenciais para reabilitar funções ópticas. Nessa perspectiva, objetivou-se a análise da eficácia da reabilitação visual entre os implantes: Boston tipo I, Boston tipo II, Aurolab, osteo-odonto-ceratoprótese e ceratoprótese de Osso Tibial. De modo geral, a princípio observou-se uma tendência de melhoria da Best-corrected visual acuity em todos os tipos de lentes, mas considerável queda durante acompanhamento a longo prazo. O dispositivo com melhor reabilitação visual em pacientes com superfícies oculares úmidas é a Boston tipo I, seguida pela Aurolab, que é economicamente viável em países emergentes. Ao considerar pacientes com olhos secos, o implante de Boston tipo II apresenta maior reabilitação visual. Por fim, em virtude de não apresentarem dados equiparáveis, as lentes osteo-odonto-ceratoprótese e de osso tibial não puderam ser analisadas.

Echinometra lucunter molecules reduce Aß42-induced neurotoxicity in SH-SY5Y neuron-like cells: effects on disaggregation and oxidative stress.

Background: Echinometra lucunter is a sea urchin commonly found on America's rocky shores. Its coelomic fluid contains molecules used for defense and biological processes, which may have therapeutic potential for the treatment of amyloid-based neurodegenerative diseases, such as Alzheimer's, that currently have few drug options available. Methods: In this study, we incubated E. lucunter coelomic fluid (ELCF) and fractions obtained by solid phase extraction in SH-SY5Y neuron-like cells to evaluate their effect on cell viability caused by the oligomerized amyloid peptide 42 (Aß42o). Moreover, the Aß42o was quantified after the incubation with ELCF fractions in the presence or not of cells, to evaluate if samples could cause amyloid peptide disaggregation. Antioxidant activity was determined in ELCF fractions, and cells were evaluated to check the oxidative stress after incubation with samples. The most relevant fraction was analyzed by mass spectrometry for identification of molecules. Results: ELCF and certain fractions could prevent and treat the reduction of cell viability caused by Aß42o in SH-SY5Y neuron-like cells. We found that one fraction (El50) reduced the oligomerized Aß42 and the oxidative stress caused by the amyloid peptide through its antioxidant molecules, which in turn reduced cell death. Mass spectrometry analysis revealed that El50 comprises small molecules containing flavonoid antioxidants, such as phenylpyridazine and dihydroquercetin, and two peptides. Conclusion: Our results suggest that sea urchin molecules may interact with Aß42o and oxidative stress, preventing or treating neurotoxicity, which may be useful in treating dementia.

Endoparasites in domestic cats (Felis catus) in the semi-arid region of Northeast Brazil.

The aim of this study was to evaluate the prevalence of endoparasites in domestic cats (Felis catus) in the city of Sousa, state of Paraíba, Northeast Brazil. A total of 207 samples of fresh feces were randomly collected from domestic and semi-domiciled cats. The samples were analyzed by simple centrifugation and centrifuge-flotation in sucrose solution for the diagnosis of helminth eggs and enteric protozoan oocysts and cysts. Epidemiological information was obtained to determine risk factors related to infections. Among the samples collected, 81.6% (169/207; 95% CI: 77.4-83.8) were positive for at least one parasite genus. Ancylostoma spp. was the most prevalent, at 67.1% (139/207), followed by Taenia spp. at 28.5% (59/207), and Spirometra spp. and Platynosomum sp., both at 17.3% (36/207). The variables associated with helminth infection were a historic lack of deworming (Odds ratio = 12.25) and the presence of dry fur (Odds ratio = 2.15). No risk factors were observed for enteric protozoa infection. This study demonstrated a high prevalence of endoparasites in domestic cats in the city of Sousa, state of Paraíba, and associated risk factors, thus establishing an overview of the main helminths and protozoa that affect cats in this region.

Preliminary Findings on the Salivary Metabolome of Hookah and Cigarette Smokers.

The aim of the study was to evaluate the salivary metabolomic profile of patients who habitually smoke hookah and cigarettes. The groups consisted of 33 regular and exclusive hookah smokers, 26 regular and exclusive cigarette smokers, and 30 nonsmokers. Unstimulated whole saliva was collected for the measurement of salivary metabolites by gas chromatography coupled with tandem mass spectrometry (GC-MS/MS). The MetaboAnalyst software was used for statistical analysis and evaluation of biomarkers. 11 smoking salivary biomarkers were identified using the area under receiving-operator curver criterion and threshold of 0.9. Xylitol and octadecanol were higher in cigarette smokers compared to controls; arabitol and maltose were higher in controls compared to cigarette smokers; octadecanol and tyramine were higher in hookah smokers compared to controls; phenylalanine was higher in controls compared to hookah smokers; and fructose, isocitric acid, glucuronic acid, tryptamine, maltose, tyramine, and 3-hydroxyisolvaleric acid were higher in hookah smokers compared to cigarettes smokers. Conclusions: The evaluation of the salivary metabolome of hookah smokers, showing separation between the groups, especially between the control versus hookah groups and cigarette versus hookah groups, and it seems to demonstrate that the use of hookah tobacco is more damaging to health.

The Impact of the COVID-19 Pandemic on the Psychological Well-Being of Caregivers of People with Dementia or Mild Cognitive Impairment: A Systematic Review and Meta-Analysis.

The aim of this systematic review was to investigate the effects of the COVID-19 lockdown on the psychological well-being of caregivers of people with dementia or mild cognitive impairment (PwD/MCI). Electronic databases were searched from inception to August 2022 for observational studies investigating the COVID-19 lockdown and psychological well-being of caregivers of PwD/MCI. Summary estimates of standardized mean differences (SMD) in psychological well-being scores pre- versus during COVID-19 were calculated using a random-effects model. Fifteen studies including 1702 caregivers (65.7% female, mean age 60.40 ± 12.9 years) with PwD/MCI were evaluated. Five studies found no change in psychological well-being parameters, including depression, anxiety, distress, caregiver burden, and quality of life. Ten studies found a worsening in at least one parameter: depression (six studies, n = 1368; SMD = 0.40; 95%CI: 0.09-0.71; p = 0.01, I2 = 86.8%), anxiety (seven studies, n = 1569; SMD = 1.35; 95%CI: 0.05-2.65; I2 = 99.2%), caregiver distress (six studies, n = 1320, SMD = 3.190; 95%CI: 1.42-4.95; p < 0.0001; I2 = 99.4%), and caregiver burden (four studies, n = 852, SMD = 0.34; 95%CI: 0.13-0.56; p = 0.001; I2 = 54.1%) (p < 0.05). There was an increase in depression, anxiety, caregiver burden, and distress in caregivers of PwD/MCI during the lockdown in the COVID pandemic. This could have longer term consequences, and it is essential that caregivers' psychological well-being is assessed and supported, to benefit both themselves and those for whom they care.

Inhibiting SETD7 methyl-transferase activity impairs differentiation, lipid metabolism and lactogenesis in mammary epithelial cells.

SETD7 (SET7/9, KMT7) is a lysine methyltransferase that targets master regulators of cell proliferation and differentiation. Here, the impact of inhibiting SETD7 catalytic activity on mammary epithelial cell differentiation was studied by focusing on genes associated with epithelial differentiation, lactogenesis, and lipid metabolism in HC11 and EpH4 cell lines. Setd7 mRNA and protein levels were induced upon lactogenic differentiation in both cell lines. Inhibition of SETD7 activity by the compound (R)-PFI-2 increased cell proliferation and downregulated E-cadherin, beta-catenin, lactoferrin, insulin-like growth factor binding protein 5, and beta-casein levels. In addition, inhibition of SETD7 activity affected the lipid profile and altered the mRNA expression of the phospholipid biosynthesis-related genes choline phosphotransferase 1, and ethanolamine-phosphate cytidylyltransferase. Altogether, the results suggest that inhibiting SETD7 catalytic activity impairs mammary epithelial and lactogenic differentiation.

CPEB4-CLOCK crosstalk during temporal lobe epilepsy.

OBJECTIVE: Posttranscriptional mechanisms are increasingly recognized as important contributors to the formation of hyperexcitable networks in epilepsy. Messenger RNA (mRNA) polyadenylation is a key regulatory mechanism governing protein expression by enhancing mRNA stability and translation. Previous studies have shown large-scale changes in mRNA polyadenylation in the hippocampus of mice during epilepsy development. The cytoplasmic polyadenylation element-binding protein CPEB4 was found to drive epilepsy-induced poly(A) tail changes, and mice lacking CPEB4 develop a more severe seizure and epilepsy phenotype. The mechanisms controlling CPEB4 function and the downstream pathways that influence the recurrence of spontaneous seizures in epilepsy remain poorly understood. METHODS: Status epilepticus was induced in wild-type and CPEB4-deficient male mice via an intra-amygdala microinjection of kainic acid. CLOCK binding to the CPEB4 promoter was analyzed via chromatin immunoprecipitation assay and melatonin levels via high-performance liquid chromatography in plasma. RESULTS: Here, we show increased binding of CLOCK to recognition sites in the CPEB4 promoter region during status epilepticus in mice and increased Cpeb4 mRNA levels in N2A cells overexpressing CLOCK. Bioinformatic analysis of CPEB4-dependent genes undergoing changes in their poly(A) tail during epilepsy found that genes involved in the regulation of circadian rhythms are particularly enriched. Clock transcripts displayed a longer poly(A) tail length in the hippocampus of mice post-status epilepticus and during epilepsy. Moreover, CLOCK expression was increased in the hippocampus in mice post-status epilepticus and during epilepsy, and in resected hippocampus and cortex of patients with drug-resistant temporal lobe epilepsy. Furthermore, CPEB4 is required for CLOCK expression after status epilepticus, with lower levels in CPEB4-deficient compared to wild-type mice. Last, CPEB4-deficient mice showed altered circadian function, including altered melatonin blood levels and altered clustering of spontaneous seizures during the day. SIGNIFICANCE: Our results reveal a new positive transcriptional-translational feedback loop involving CPEB4 and CLOCK, which may contribute to the regulation of the sleep-wake cycle during epilepsy.

Direct oral anticoagulants vs vitamin K antagonist on dementia risk in atrial fibrillation: systematic review with meta-analysis.

Oral anticoagulation significantly reduces the incidence of dementia in atrial fibrillation patients. However, this protective effect has not been compared between Direct Oral Anticoagulants (DOAC) and Vitamin K antagonists' anticoagulants (VKA). We conducted an electronic search for potentially eligible studies through the bibliographic databases MEDLINE, CENTRAL, ClinicalTrials.gov, EMBASE and Web of Science. The outcome of interest was dementia. Random-effects meta-analysis was performed. Nine observational studies were included and 1,175,609 atrial fibrillation patients were enrolled. DOAC therapy was associated with a significant reduction when compared with patients under VKA therapy (hazard ratio 0.89; 95% confidence interval 0.80-0.99). The grade of confidence of our results was very low due to the risk of bias. DOAC therapy is associated with a significant decrease in the risk of dementia when compared with VKA therapy. However, the low certainty of the evidence along with the paucityof clinical trials dedicated to answering this important question underscores a need for global clinical research initiatives.

Functional expression of the ATP-gated P2X7 receptor in human iPSC-derived astrocytes.

Activation of the ATP-gated P2X7 receptor (P2X7R), implicated in numerous diseases of the brain, can trigger diverse responses such as the release of pro-inflammatory cytokines, modulation of neurotransmission, cell proliferation or cell death. However, despite the known species-specific differences in its pharmacological properties, to date, most functional studies on P2X7R responses have been analyzed in cells from rodents or immortalised cell lines. To assess the endogenous and functional expression of P2X7Rs in human astrocytes, we differentiated human-induced pluripotent stem cells (hiPSCs) into GFAP and S100 ß-expressing astrocytes. Immunostaining revealed prominent punctate P2X7R staining. P2X7R protein expression was also confirmed by Western blot. Importantly, stimulation with the potent non-selective P2X7R agonist 2',3'-O-(benzoyl-4-benzoyl)-adenosine 5'- triphosphate (BzATP) or endogenous agonist ATP induced robust calcium rises in hiPSC-derived astrocytes which were blocked by the selective P2X7R antagonists AFC-5128 or JNJ-47965567. Our findings provide evidence for the functional expression of P2X7Rs in hiPSC-derived astrocytes and support their in vitro utility in investigating the role of the P2X7R and drug screening in disorders of the central nervous system (CNS).

Impact of Selective Serotonin-Reuptake Inhibitors in Hemorrhagic Risk in Anticoagulated Patients Taking Non-Vitamin K Antagonist Anticoagulants: A Systematic Review and Meta-analysis.

BACKGROUND: Studies show an increase in hemorrhagic risk related to selective serotonin-reuptake inhibitors (SSRIs) alone, but also in association with vitamin K antagonists (VKAs). Non-VKA anticoagulants (NOACs) can be a good substitute to VKAs, but the correlation between them and SSRIs is not well studied. Therefore, we conducted a systematic review to evaluate the risk of major bleeding associated with concomitant use of SSRIs and NOACs. METHODS: MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and PubMed databases were searched, in September 2022, for longitudinal studies evaluating SSRIs' impact on hemorrhagic risk in anticoagulated patients taking NOACs compared with a control group taking non-SSRI medication instead or no antidepressants at all. The outcome of interest was major bleeding. The quality of the included studies was assessed using the ROBINS-I tool. We performed a random-effects meta-analysis to estimate the pooled RRs with 95% confidence intervals (CIs), and heterogeneity was evaluated using the I2 statistic. RESULTS: Eight studies were included in the meta-analysis. From a population of 279,540 anticoagulated patients taking NOACs, the ones taking SSRIs concomitantly were associated with a higher risk of major bleeding (relative risk, 1.33; 95% CI, 1.06-1.66; I2 = 60%). However, the subgroup analysis of cohort studies did not achieve statistical significance (relative risk, 1.05; 95% CI, 0.94-1.66). CONCLUSIONS: The findings show that SSRIs are associated with a greater hemorrhagic risk in patients anticoagulated with NOACs; however, our confidence is reduced because of nonstatistically significant results from more robust studies, as cohort studies.