Unravelling the Gut Microbiome Role in Cardiovascular Disease: A Systematic Review and a Meta-Analysis.

A notable shift in understanding the human microbiome's influence on cardiovascular disease (CVD) is underway, although the causal association remains elusive. A systematic review and meta-analysis were conducted to synthesise current knowledge on microbial taxonomy and metabolite variations between healthy controls (HCs) and those with CVD. An extensive search encompassing three databases identified 67 relevant studies (2012-2023) covering CVD pathologies from 4707 reports. Metagenomic and metabolomic data, both qualitative and quantitative, were obtained. Analysis revealed substantial variability in microbial alpha and beta diversities. Moreover, specific changes in bacterial populations were shown, including increased Streptococcus and Proteobacteria and decreased Faecalibacterium in patients with CVD compared with HC. Additionally, elevated trimethylamine N-oxide levels were reported in CVD cases. Biochemical parameter analysis indicated increased fasting glucose and triglycerides and decreased total cholesterol and low- and high-density lipoprotein cholesterol levels in diseased individuals. This study revealed a significant relationship between certain bacterial species and CVD. Additionally, it has become clear that there are substantial inconsistencies in the methodologies employed and the reporting standards adhered to in various studies. Undoubtedly, standardising research methodologies and developing extensive guidelines for microbiome studies are crucial for advancing the field.

Effects of natural products-based dentifrices on acrylic resin for denture bases: A simulated period of 4 years.

PURPOSE: To evaluate the antimicrobial activity of dentifrices based on Malva sylvestris and propolis and the effect on the acrylic resin. METHODS: The inhibitory effect against Candida albicans, Enterococcus faecalis and Streptococcus mutans was determined. The specimens of resin were divided into groups: Control (brushing with distilled water); brushing with Colgate; brushing with Protex; brushing with Malvatricin, brushing with Proporalcare Dental Gel and brushing with Green Propolis Dental Gel. Brushing was carried out in a brushing machine. Roughness and color were assessed. The data were analyzed by ANOVA, followed by the Bonferroni post test (α= 0.05). RESULTS: The products evaluated showed antimicrobial activity against all microorganisms (P< 0.05), except Proporalcare Dental Gel, which was not effective against E. faecalis. Greater roughness (P< 0.05) was observed in the samples treated with Colgate. The samples from control and Protex groups showed the lowest color variation and the highest luminosity, with a difference in relation to the others (P< 0.05), which showed higher values, although clinically acceptable. CLINICAL SIGNIFICANCE: The dentifrices based on natural products can be indicated for cleaning prostheses, since they showed antimicrobial activity and did not cause perceptible color changes of the resin tested. The dentifrices did not produce adverse effects on the surface of the resin or did so less than the conventional dentifrice.

Advances in ex vivo expansion of hematopoietic stem and progenitor cells for clinical applications.

As caretakers of the hematopoietic system, hematopoietic stem cells assure a lifelong supply of differentiated populations that are responsible for critical bodily functions, including oxygen transport, immunological protection and coagulation. Due to the far-reaching influence of the hematopoietic system, hematological disorders typically have a significant impact on the lives of individuals, even becoming fatal. Hematopoietic cell transplantation was the first effective therapeutic avenue to treat such hematological diseases. Since then, key use and manipulation of hematopoietic stem cells for treatments has been aspired to fully take advantage of such an important cell population. Limited knowledge on hematopoietic stem cell behavior has motivated in-depth research into their biology. Efforts were able to uncover their native environment and characteristics during development and adult stages. Several signaling pathways at a cellular level have been mapped, providing insight into their machinery. Important dynamics of hematopoietic stem cell maintenance were begun to be understood with improved comprehension of their metabolism and progressive aging. These advances have provided a solid platform for the development of innovative strategies for the manipulation of hematopoietic stem cells. Specifically, expansion of the hematopoietic stem cell pool has triggered immense interest, gaining momentum. A wide range of approaches have sprouted, leading to a variety of expansion systems, from simpler small molecule-based strategies to complex biomimetic scaffolds. The recent approval of Omisirge, the first expanded hematopoietic stem and progenitor cell product, whose expansion platform is one of the earliest, is predictive of further successes that might arise soon. In order to guarantee the quality of these ex vivo manipulated cells, robust assays that measure cell function or potency need to be developed. Whether targeting hematopoietic engraftment, immunological differentiation potential or malignancy clearance, hematopoietic stem cells and their derivatives need efficient scaling of their therapeutic potency. In this review, we comprehensively view hematopoietic stem cells as therapeutic assets, going from fundamental to translational.

Analyzing hate speech dynamics on Twitter/X: Insights from conversational data and the impact of user interaction patterns.

This paper investigates the pervasive issue of hate speech within Twitter/X Portuguese network conversations, offering a multifaceted analysis of its characteristics. This study utilizes a mixed-method approach, combining several methodologies of network analysis (triad census and participation shifts) over the network of interaction between users. Qualitative manual content annotation was applied to the dataset to dissect different patterns of hate speech on the platform. Key findings reveal that the number of users followed by an individual and potentially reads is a relevant predictor for a user's propensity to post aggressive content. We concluded also that during a conversation thread, hate speech happens significantly more within the first 2 h of interaction. Transitivity of interactions and individual expression are considerably lower as more hate speech is prevalent in conversations. Our research confirms that hate speech is usually expressed by external individuals who intrude into conversations. Conversely, the expression of hate speech of indirect type by third parties interfering in conversations is uncommon. We also found that counter-speech discourse is strongly correlated with a type of discourse that typically avoids conflict and is not privately held.

Person-centred care intervention to promote self-efficacy in patients following a myocardial infarction (P2MIR): a protocol of a qualitative study for cultural adaptation within a Portuguese healthcare context.

INTRODUCTION: Cardiovascular diseases remain a leading cause of death worldwide. Recovery from myocardial infarction is challenging as the causes of symptoms span multiple aspects of health not just physical conditions. Evidence has shown a gap between the waycare is provided in the clinical setting and the person's needs and preferences. The implementation of person-centred care (PCC) interventions can promote recovery from myocardial infarction by allowing a greater understanding of the person's perception and its role on the overall recovering process. This study aims to culturally adapt an evidence-based PCC intervention to enhance self-efficacy in patients after myocardial infarction within a Portuguese healthcare context. METHODS AND ANALYSIS: The Portuguese person-centred care for myocardial infarction recovery (P2MIR) intervention is set to be developed from an evidence-based intervention, rooted in the ethics of PCC. An intervention of PCC for patients with acute coronary syndrome, which has been successfully implemented and evaluated in the Swedish healthcare context will be validated, culturally adapted and harmonised to the Portuguese healthcare context by using qualitative methods. To evaluate its acceptability, appropriateness and feasibility, a sample of stakeholders, consisting of a sample of healthcare professionals and a sample of people who suffered a myocardial infarction, will be recruited from a hospital, including both inpatient and outpatient departments. The stakeholders will be invited to semistructured focus group discussions, aiming to gather their perceptions about the P2MIR intervention, which will be previously presented to them. Data analysis will be conducted using content analysis following a deductive-inductive approach to further inform the intervention adaptation process to its final intervention in a Portuguese healthcare context. ETHICS AND DISSEMINATION: The study has been reviewed and approved by the Health Ethics' Committees of the Centro Hospitalar Lisboa Ocidental, Lisbon, Portugal (registry number 20170700050). The results will be disseminated through peer-reviewed journals and conference presentations.

Fibulin-2 is an extracellular matrix inhibitor of oligodendrocytes relevant to multiple sclerosis.

Impairment of oligodendrocytes and myelin contributes to neurological disorders including multiple sclerosis (MS), stroke, and Alzheimer's disease. Regeneration of myelin (remyelination) decreases the vulnerability of demyelinated axons, but this repair process commonly fails with disease progression. A contributor to inefficient remyelination is the altered extracellular matrix (ECM) in lesions, which remains to be better defined. We have identified fibulin-2 (FBLN2) as a highly upregulated ECM component in lesions of MS and stroke and in proteome databases of Alzheimer's disease and traumatic brain injury. Focusing on MS, the inhibitory role of FBLN2 was suggested in the experimental autoimmune encephalomyelitis (EAE) model, in which genetic FBLN2 deficiency improved behavioral recovery by promoting the maturation of oligodendrocytes and enhancing remyelination. Mechanistically, when oligodendrocyte progenitors were cultured in differentiation medium, FBLN2 impeded their maturation into oligodendrocytes by engaging the Notch pathway, leading to cell death. Adeno-associated virus deletion of FBLN2 in astrocytes improved oligodendrocyte numbers and functional recovery in EAE and generated new myelin profiles after lysolecithin-induced demyelination. Collectively, our findings implicate FBLN2 as a hitherto unrecognized injury-elevated ECM, and a therapeutic target, that impairs oligodendrocyte maturation and myelin repair.

Autistic spectrum disorder children and adolescents' oral health characteristics - scoping review.

This study aimed to conduct a scoping review to know children and adolescents' main oral health concerns with Autism Spectrum Disorder (ASD) and thus identify any oral characteristic that stands out, aiming at preventive and interceptive clinical conduct. A search was performed in the three electronic databases and the gray literature; in September 2021. A total of 562 studies were identified, and after applying the eligibility criteria, 73 articles were included in the synthesis of this scoping review. The mean decayed, lost, and restored teeth index (DMFT/dfmt) ranged from 0 to 12.37; the mean DMFT index (permanent dentition) from 0.06 to 6.2; and the average dmft index (deciduous dentition) ranged from 0.29 to 9.91. The mean simplified oral hygiene index (OHIS) ranged from 0 to 3.4; gingival index (GI) from 0.29 to 2; and plaque index (PI) from 0.005 to 3.15. Plaque prevalence was 25.9% to 90%; dental calculus from 4.7% to 59.41%; gingivitis from 36.7% to 100%. Bruxism was 10.3% to 73%, and dental trauma was 4.7% to 100%. This disparity in the results shows the heterogeneity of this population, with different degrees of socio-behavioral impairment, which can directly influence oral hygiene and the consequent accumulation of biofilm.

Additive Cytotoxic and Colony-Formation Inhibitory Effects of Aspirin and Metformin on PI3KCA-Mutant Colorectal Cancer Cells.

Human malignancies are one of the major health-related issues throughout the world and are anticipated to rise in the future. Despite huge investments made in anticancer drug development, limited success has been obtained and the average number of FDA approvals per year is declining. So, an increasing interest in drug repurposing exists. Metformin (MET) and aspirin (ASP) possess anticancer properties. This work aims to test the effect of these two drugs in combination on colorectal cancer (CRC) cells in vitro. The effects of MET and/or ASP on cell proliferation, viability, migratory ability, anchorage-independent growth ability (colony formation), and nutrient uptake were determined in two (HT-29 and Caco-2) human CRC cell lines. Individually, MET and ASP possessed antiproliferative, cytotoxic, and antimigratory effects and reduced colony formation in HT-29 cells (BRAF- and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PI3KCA)-mutant), although MET did not affect either 3H-deoxy-D-glucose or 14C-butyrate uptake and lactate production, and ASP caused only a small decrease in 14C-butyrate uptake. Moreover, in these cells, the combination of MET and ASP resulted in a tendency to an increase in the cytotoxic effect and in a potentiation of the inhibitory effect on colony formation, although no additive antiproliferative and antimigratory effects, and no effect on nutrient uptake and lactate production were observed. In contrast, MET and ASP, both individually and in combination, were almost devoid of effects on Caco-2 cells (BRAF- and PI3KCA-wild type). We suggest that inhibition of PI3K is the common mechanism involved in the anti-CRC effect of both MET, ASP and their combination and, therefore, that the combination of MET + ASP may especially benefit PI3KCA-mutant CRC cases, which currently have a poor prognostic.

construção de uma proposta de educação continuada sobre vacinação infantil para agentes comunitários de saúde / Construction of a continuing education proposal on childhood vaccination for community health agents / Construcción de una propuesta de educación continua sobre vacunación infantil para agentes comunitarios de salud

O objetivo deste estudo foi relatar a experiência do desenvolvimento de uma proposta de educação continuada executada pela equipe de enfermagem com agentes comunitários de saúde (ACS), considerando como foco a vacinação infantil. Trata-se de um relato de experiência elaborado e vivenciado por enfermeiro e acadêmico de enfermagem em novembro de 2019, com a participação de duas equipes pertencentes a uma Unidade Básica de Saúde do município de Arapiraca (AL). Através da metodologia de ensino da problematização por meio do Arco de Maguerez, foram realizadas oficinas e ações educativas para os ACS, a partir das necessidades relatadas por esses profissionais em relação à vacinação infantil. Tais atividades proporcionaram maior aproximação com a realidade vivenciada por quem ocupa a posição de educador e incentivador do cuidado da saúde durante a visita domiciliar. Além disso, enfatizaram a importância do enfermeiro enquanto responsável pela educação continuada da equipe. Verificou-se ainda que o diálogo aberto e horizontal, de modo empático, proporcionou a construção de uma ferramenta eficaz, de fácil manuseio e de baixo custo, que gerou uma melhor memorização e segurança não somente para os ACS nas visitas domiciliares, mas também nas atividades de outros profissionais atuantes no campo da promoção da saúde infantil.

This study reports the experience of developing an educational product based on continued education carried out by a nursing team with community health agents (CHA) considering childhood vaccination as the focus. This is an experience report that was prepared and experienced by a nurse and nursing student in November 2019, with the participation of two teams belonging to a basic health unit in the municipality of Arapiraca, Alagoas, Brazil. Using the problematization teaching methodology by Arco de Marguerez, workshops and educational actions were carried out for the CHA based on the needs they reported regarding childhood vaccination, which provided a greater approximation with the reality experienced by those in the position of educators and encouragers of health care during home visits. Furthermore, it emphasized the importance of nurses as responsible for the team's continuing education. It was also verified that open and horizontal dialogue empathetically provided the construction of an effective, easy to use, low cost tool, bringing better memorization and safety not only for community agents during home visits but also in activities from other professionals working in the field of child health promotion.

El objetivo de este estudio fue reportar la experiencia de desarrollo de una propuesta de educación continua realizada por el equipo de enfermería con agentes comunitarios de salud (ACS), considerando como enfoque la vacunación infantil. Este es un reporte de experiencia elaborado y vivido por un enfermero y un estudiante de enfermería en noviembre de 2019, con la participación de dos equipos de una unidad básica de salud de la ciudad de Arapiraca, Brasil. Utilizando la metodología de enseñanza de problematización del Arco de Maguerez, se realizaron talleres y acciones educativas para ACS a partir de las necesidades reportadas por estos profesionales con relación a la vacunación infantil. Estas actividades proporcionaron una mayor aproximación a la realidad vivida por quienes ocupan la posición de educador y motivador del cuidado de la salud durante la visita domiciliaria. Además, destacaron la importancia del enfermero como responsable de la formación continua del equipo. También se constató que el diálogo abierto y horizontal, de manera empática, propició la construcción de una herramienta efectiva, fácil de usar y de bajo costo, que generó una mejor memorización y seguridad no solo para los ACS durante las visitas domiciliarias, sino también en las actividades de otros profesionales que trabajan en el campo de la promoción de la salud infantil.

Assessing Postural Control From Birth to Adulthood Among Individuals Born Preterm: A Systematic Review.

Premature life exposure, meaning an immature central nervous system, presents a significant challenge for the development of postural control and, in turn, overall motor development. Preventing motor delay thus requires identifying, characterizing, and quantifying deficit in postural control as early as possible. In our study, we reviewed the procedures used in past studies to assess postural control among individuals born preterm, specifically the characterization of participants, the instruments and motor tasks involved, the types of data collected and analyzed, and the outcomes. To that end, we performed a literature search on PubMed, Wiley Online Library, Web of Science, and Scopus using Boolean logic and assessed the quality of the studies with a standardized assessment based on the Strengthening the Reporting of Observational Studies in Epidemiology guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. Of 35 potential studies, 24 were included; all evaluated infants born preterm, but six did not include a control group of full-term infants. Although the heterogeneity of measurements, variability of instruments, and divergence in motor tasks examined limit definitive conclusions based on quantitative synthesis and the generalization of the results, most studies revealed dysfunctional postural control among individuals born preterm.

Upper motor neuron signs in primary lateral sclerosis and hereditary spastic paraplegia.

INTRODUCTION/AIMS: The frequency and distribution of upper motor neuron (UMN) signs in primary lateral sclerosis (PLS) are unknown. We aimed to study the spectrum of UMN signs in PLS and compare it with hereditary spastic paraplegia (HSP). METHODS: We retrospectively analyzed the frequency of different UMN signs, including hyperreflexia (limbs and jaw), limb and tongue spasticity, Babinski, and Hoffman signs, in PLS patients at first observation and compared this respect to onset region and symptom duration. We also compared PLS versus HSP patients. RESULTS: We included 34 PLS and 20 HSP patients, with a median symptom duration at first visit of 3.0 (interquartile range, IQR = 4.0) and 19.0 (IQR = 22.0) years, respectively. In PLS patients, hyperreflexia of upper (UL) (88.2%) and lower (LL) (91.2%) limbs, and LL spasticity (79.4%) were the most common findings. Spasticity of LL was significantly (p = .012) more frequent in LL-spinal onset subgroup, tongue spasticity in bulbar-onset subgroup (p = .021), and Hoffman sign in UL-spinal onset subgroup (p = .024). The PLS subgroup with shorter disease duration had a higher frequency of abnormal jaw jerk reflex (p = .037). Compared with HSP, PLS patients had a higher frequency of UL hyperreflexia (88.2% vs. 42.1%, p < .001) and UL spasticity (44.1% vs. 0.0%, p < .001). Asymmetric distribution of UMN signs was present in PLS and not in HSP. DISCUSSION: In PLS, UL UMN signs are nearly always present and UMN sign distribution appears to be associated with onset region. At first observation, bulbar involvement, asymmetrical distribution of UMN signs and UL spasticity may indicate PLS versus HSP.

Ruptured Intracranial Aneurysm in a 60-Day-Old Infant: An Extreme Case.

The prevalence of aneurysms in children is low when compared to adults, being even rarer in the first year of life. They can be secondary to infections, traumatic brain injury, autoimmune diseases, or connective tissue diseases. Dissecting etiology is rare. A 60-day-old female infant, previously healthy, presented to the emergency department (ED) with irritability and loss of appetite since the preceding day, a fever of one-hour duration, and vomiting. Laboratory analysis revealed a hemoglobin level of 6.5 g/dL, without elevation of inflammatory markers. In the ED, she experienced two episodes, with a one-hour interval, of clonic movements of the upper eyelid and right upper limb, along with conjugate gaze deviation to the same side, which resolved after intravenous diazepam. Levetiracetam was initiated after the second episode. The anterior fontanelle became progressively tense. Brain computed tomography (CT) showed a voluminous intraparenchymal and subarachnoid hemorrhage with an aneurysm at the bifurcation of the left middle cerebral artery (MCA). Initially, an endovascular approach was tried but was not successful due to technical problems. Consequently, a Vaso-CT scan was performed that confirmed a dissecting aneurysm/pseudoaneurysm (8 mm × 10 mm × 10 mm) of the left MCA, originating from the upper wall of the M1 segment. Next, she underwent microsurgical exclusion of the aneurysm using microclips. Post-surgery brain CT showed acute ischemia in the entire MCA region. Follow-up angiography showed complete exclusion of the aneurysm. She evolved to grade 3 monoparesis of the upper limb at the six-month interval follow-up, which has been gradually improving with physical rehabilitation. The next-generation sequencing (NGS) panel for aneurysms and arterial dissections did not detect any pathogenic variants. Clinical presentation of cerebral aneurysms in infants can be subtle, and a high index of suspicion is required in cases of irritability, altered consciousness, seizures, bulging fontanelle, and motor deficits. Early detection is of utmost importance as it is associated with moderate mortality. Surgical treatment with the use of clips proved to be effective in this case.

Secretome of bone marrow mesenchymal stromal cells cultured in a dynamic system induces neuroprotection and modulates microglial responsiveness in an α-synuclein overexpression rat model.

BACKGROUND AIMS: Parkinson's disease (PD) is the second most common neurodegenerative disorder. The etiology of the disease remains largely unknown, but evidence have suggested that the overexpression and aggregation of alpha-synuclein (α-syn) play key roles in the pathogenesis and progression of PD. Mesenchymal stromal cells (MSCs) have been earning attention in this field, mainly due to their paracrine capacity. The bioactive molecules secreted by MSCs, i.e. their secretome, have been associated with enhanced neuronal survival as well as a strong modulatory capacity of the microenvironments where the disease develops. The selection of the appropriate animal model is crucial in studies of efficacy assessment. Given the involvement of α-syn in the pathogenesis of PD, the evidence generated from the use of animal models that develop a pathologic phenotype due to the action of this protein is extremely valuable. Therefore, in this work, we established an animal model based on the viral vector-mediated overexpression of A53T α-syn and studied the impact of the secretome of bone marrow mesenchymal stromal cells MSC(M) as a therapeutic strategy. METHODS: Adult male rats were subjected to α-syn over expression in the nigrostriatal pathway to model dopaminergic neurodegeneration. The impact of locally administered secretome treatment from MSC(M) was studied. Motor impairments were assessed throughout the study coupled with whole-region (striatum and substantia nigra) confocal microscopy evaluation of histopathological changes associated with dopaminergic neurodegeneration and glial cell reactivity. RESULTS: Ten weeks after lesion induction, the animals received secretome injections in the substantia nigra pars compacta (SNpc) and striatum (STR). The secretome used was produced from bone marrow mesenchymal stromal cells MSC(M) expanded in a spinner flask (SP) system. Nine weeks later, animals that received the viral vector containing the gene for A53T α-syn and treated with vehicle (Neurobasal-A medium) presented dopaminergic cell loss in the SNpc and denervation in the STR. The treatment with secretome significantly reduced the levels of α-syn in the SNpc and protected the dopaminergic neurons (DAn) within the SNpc and STR. CONCLUSIONS: Our results are aligned with previous studies in both α-syn Caenorhabditis elegans models, as well as 6-OHDA rodent model, revealing that secretome exerted a neuroprotective effect. Moreover, these effects were associated with a modulation of microglial reactivity supporting an immunomodulatory role for the factors contained within the secretome. This further supports the development of new studies exploring the effects and the mechanism of action of secretome from MSC(M) against α-syn-induced neurotoxicity.

Dual production of human mesenchymal stromal cells and derived extracellular vesicles in a dissolvable microcarrier-based stirred culture system.

BACKGROUND & AIMS: Cell therapies based on mesenchymal stromal cells (MSCs) have gained an increasing therapeutic interest in the context of multiple disorders. Nonetheless, this field still faces important challenges, particularly concerning suitable manufacturing platforms. Here, we aimed at establishing a scalable culture system to expand umbilical cord-derived Wharton's jelly MSC (MSC(WJ)) and their derived extracellular vesicles (EVs) by using dissolvable microcarriers combined with xeno(geneic)-free culture medium. METHODS: MSC(WJ) isolated from three donors were cultured at a starting density of 1 × 106 cells per spinner flask, i.e., 2.8 × 103 cells per cm2 of dissolvable microcarrier surface area. After a 6-day expansion period of MSC(WJ), extracellular vesicles (EVs) were produced for 24 h. RESULTS: Taking advantage of an intermittent agitation regimen, we observed high adhesion rates to the microcarriers (over 90% at 24 h) and achieved 15.8 ± 0.7-fold expansion after 6 days of culture. Notably, dissolution of the microcarriers was achieved through a pectinase-based solution to recover the cell product, reducing the hurdles of downstream processing. MSC identity was validated by detecting the characteristic MSC immunophenotype and by multilineage differentiation assays. Considering the growing interest in MSC-derived EVs, which are known to be mediators of the therapeutic features of MSC, this platform also was evaluated for EV production. Upon a 24-h period of conditioning, secreted EVs were isolated by ultrafiltration followed by anion-exchange chromatography and exhibited the typical cup-shaped morphology, small size distribution (162.6 ± 30.2 nm) and expressed EV markers (CD63, CD9 and syntenin-1). CONCLUSIONS: Taken together, we established a time-effective and robust scalable platform that complies with clinical-grade standards for the dual production of MSC(WJ) and their derived EV.

Maternal and Offspring Fatty Acid Desaturase Variants, Prenatal DHA Supplementation, and Dietary n-6:n-3 Fatty Acid Ratio in Relation to Cardiometabolic Health in Mexican Children.

BACKGROUND: Single-nucleotide polymorphisms (SNPs) in fatty acid desaturase (FADS) genes may modify dietary fatty acid requirements and influence cardiometabolic health (CMH). OBJECTIVES: We evaluated the role of selected variants in maternal and offspring FADS genes on offspring CMH at the age of 11 y and assessed interactions of genotype with diet quality and prenatal docosahexaenoic acid (DHA) supplementation. METHODS: We used data from offspring (n = 203) born to females who participated in a randomized controlled trial of DHA supplementation (400 mg/d) from midgestation to delivery. We generated a metabolic syndrome (MetS) score from body mass index, high-density lipoprotein cholesterol, triglycerides, systolic blood pressure, and fasting glucose and identified 6 distinct haplotypes from 5 offspring FADS SNPs. Dietary n-6 (ω-6):n-3 fatty acid ratios were derived from 24-h recall data (n = 141). We used generalized linear models to test associations of offspring diet and FADS haplotypes with MetS score and interactions of maternal and offspring FADS SNP rs174602 with prenatal treatment group and dietary n-6:n-3 ratio on MetS score. RESULTS: Associations between FADS haplotypes and MetS score were null. Offspring SNP rs174602 did not modify the association of prenatal DHA supplementation with MetS score. Among children with TT or TC genotype for SNP rs174602 (n = 88), those in the highest n-6:n-3 ratio tertile (>8.61) had higher MetS score relative to the lowest tertile [<6.67) (Δ= 0.36; 95% confidence interval (CI): 0.03, 0.69]. Among children with CC genotype (n = 53), those in the highest n-6:n-3 ratio tertile had a lower MetS score relative to the lowest tertile (Δ= -0.23; 95% CI: -0.61, 0.16). CONCLUSIONS: There was evidence of an interaction of offspring FADS SNP rs174602 with current dietary polyunsaturated fatty acid intake, but not with prenatal DHA supplementation, on MetS score. Further studies may help to determine the utility of targeted supplementation strategies and dietary recommendations based on genetic profile.

Altered purinergic P2X7 and A2B receptors signaling limits macrophage-mediated host defense in schistosomiasis.

BACKGROUND: The occurrence of co-infections during schistosomiasis, a neglected tropical disease, with other parasites have been reported suggesting an impaired host immune defense. Macrophage purinergic P2X7 receptor (P2X7R) play an important role against intracellular pathogens. Therefore, we investigated the P2X7R-mediated phagocytosis and killing capacity of Leishmania amazonensis by macrophages during schistosomiasis in vitro and in vivo. METHODS: Swiss and C57BL/6 (Wild type) and P2X7R-/- were randomized in two groups: control (uninfected) and Schistosoma mansoni-infected. Alternatively, control Swiss and S. mansoni-infected mice were also infected with L. amazonensis. RESULTS: The pre-treatment of macrophages with the P2X7R antagonist (A74003) or TGF-ß reduced the phagocytosis index, mimicking the phenotype of cells from S. mansoni-infected mice and P2X7R-/- mice. Apyrase also reduced the phagocytosis index corroborating the role of ATP to macrophage activation. Moreover, l-arginine-nitric oxide pathway was compromised, which could explain the reduced killing capacity in response to ATP in vitro and in vivo. We found an increased extracellular nucleotide (ATP, ADP and AMP) hydrolysis along with an increased frequency of F4/80+ CD39+ macrophages from the S. mansoni-infected group. Moreover, the content of adenosine in the cell supernatant was higher in the S. mansoni-infected group in relation to controls. Schistosomiasis also increased the expression of macrophage adenosine A2BR. In good accordance, both ADA and the selective A2BR antagonist restored the phagocytosis index of macrophages from S. mansoni-infected group. CONCLUSIONS: Altogether, the altered P2X7R and A2BR signaling limits the role of macrophages to host defense against L. amazonensis during schistosomiasis, potentially contributing to the pathophysiology and clinically relevant co-infections.

Evaluation of the theranostic potential of [64Cu]CuCl2 in glioblastoma spheroids.

BACKGROUND: Glioblastoma is an extremely aggressive malignant tumor with a very poor prognosis. Due to the increased proliferation rate of glioblastoma, there is the development of hypoxic regions, characterized by an increased concentration of copper (Cu). Considering this, 64Cu has attracted attention as a possible theranostic radionuclide for glioblastoma. In particular, [64Cu]CuCl2 accumulates in glioblastoma, being considered a suitable agent for positron emission tomography. Here, we explore further the theranostic potential of [64Cu]CuCl2, by studying its therapeutic effects in advanced three-dimensional glioblastoma cellular models. First, we established spheroids from three glioblastoma (T98G, U373, and U87) and a non-tumoral astrocytic cell line. Then, we evaluated the therapeutic responses of spheroids to [64Cu]CuCl2 exposure by analyzing spheroids' growth, viability, and cells' proliferative capacity. Afterward, we studied possible mechanisms responsible for the therapeutic outcomes, including the uptake of 64Cu, the expression levels of a copper transporter (CTR1), the presence of a cancer stem cell population, and the production of reactive oxygen species (ROS). RESULTS: Results revealed that [64Cu]CuCl2 is able to significantly reduce spheroids' growth and viability, while also affecting cells' proliferation capacity. The uptake of 64Cu, the presence of cancer stem-like cells and the production of ROS were in accordance with the therapeutic response. However, expression levels of CTR1 were not in agreement with uptake levels, revealing that other mechanisms could be involved in the uptake of 64Cu. CONCLUSIONS: Overall, our results further support [64Cu]CuCl2 potential as a theranostic agent for glioblastoma, unveiling potential mechanisms that could be involved in the therapeutic response.

Improved L-Asparaginase Properties and Reusability by Immobilization onto Functionalized Carbon Xerogels.

Enzyme immobilization can offer a range of significant advantages, including reusability, and increased selectivity, stability, and activity. In this work, a central composite design (CCD) of experiments and response surface methodology (RSM) were used to study, for the first time, the L-asparaginase (ASNase) immobilization onto functionalized carbon xerogels (CXs). The best results were achieved using CXs obtained by hydrothermal oxidation with nitric acid and subsequent heat treatment in a nitrogen flow at 600 °C (CX-OX-600). Under the optimal conditions (81 min of contact time, pH 6.2 and 0.36 g/L of ASNase), an immobilization yield (IY) of 100 % and relative recovered activity (RRA) of 103 % were achieved. The kinetic parameters obtained also indicate a 1.25-fold increase in the affinity of ASNase towards the substrate after immobilization. Moreover, the immobilized enzyme retained 97 % of its initial activity after 6 consecutive reaction cycles. All these outcomes confirm the promising properties of functionalized CXs as support for ASNase, bringing new insights into the development of an efficient and stable immobilization platform for use in the pharmaceutical industry, food industry, and biosensors.

Strategies for Preventing and Treating Oral Mucosal Infections Associated with Removable Dentures: A Scoping Review.

Oral infections occur due to contact between biofilm rich in Candida albicans formed on the inner surface of complete dentures and the mucosa. This study investigated historical advances in the prevention and treatment of oral mucosal infection and identified gaps in the literature. Bibliographic research was conducted, looking at PubMed, Embase, Web of Science, and Scopus, where 935 articles were found. After removing duplicates and excluding articles by reading the title and abstract, 131 articles were selected for full reading and 104 articles were included. Another 38 articles were added from the gray literature. This review followed the PRISMA-ScR guidelines. The historical period described ranges from 1969 to 2023, in which, during the 21st century, in vitro and in vivo studies became more common and, from 2010 to 2023, the number of randomized controlled trials increased. Among the various approaches tested are the incorporation of antimicrobial products into prosthetic materials, the improvement of oral and denture hygiene protocols, the development of synthetic and natural products for the chemical control of microorganisms, and intervention with local or systemic antimicrobial agents. Studies report good results with brushing combined with sodium hypochlorite, and new disinfectant solutions and products incorporated into prosthetic materials are promising.

Laser fluorescence assessment of dental caries arrest with two silver fluoride agents in patients with special needs- a preliminary report.

PURPOSE: While silver diamine fluoride has been used extensively for caries arrest and desensitising, silver fluoride (AgF) at neutral pH may also have value as a minimally invasive dental caries treatment. This study explored the effectiveness of two AgF products (AgF/KI and AgF/SnF2) when used in adult patients with special needs (SN) who had high caries risk and salivary gland hypofunction. METHODS: This split-mouth clinical study, over two appointments 3-months apart, compared the impact of a single application of AgF/KI (Riva Star Aqua, SDI) and AgF/SnF2 (Creighton Dental CSDS, Whiteley) on matched carious lesions in the same arch, by clinical visual-tactile (cVT) assessment of caries status and laser fluorescence (LF, DIAGNOdent) evaluation of bacterial load in the lesions, using repeated measures analysis. RESULTS: Twelve participants were recruited in the study. A total of 56 teeth (28 pairs) were included. Both AgF products gave a significant decrease in caries activity as measured by cVT (P < 0.0001) and LF (P = 0.0027). There were no statistically significant differences between the two AgF treatments, with response rates for improvements in active lesions of 92% in the AgF/KI arm, and 96% in the AgF/SnF2 arm. There was no effect of tooth type, lesion type, arch type, plaque metabolism and plaque area at the site level on outcomes, nor was there a clustering effect of sites in a patient level analysis. Overall, LF was superior to cVT for detecting lesions that still progressed despite treatment (P = 0.0027). CONCLUSION: A single application of AgF/KI or AgF/SnF2 has high predictability (over 90%) for achieving arrest in active caries lesions in adult patients with SN and high caries risk. Clinical assessment should use visual-tactile examination combined with LF readings to detect lesions that are still progressing and that require additional treatments. Future studies should compare these AgF modalities with SDF and explore factors such as time between applications and the need for repeated applications. TRIAL REGISTRATION: The study was registered with the Australian Clinical Trials Registry (ACTRN12621001139864p) on 23/08/2021.