Influence of irradiated dentin, biofilm and different artificial saliva formulations on root dentin demineralization.

The aim of this study was evaluated the influence of radiation as well as of new formulations of artificial saliva on the development of root dentin lesions. Bovine root samples were divided into: irradiated (70 Gy) dentin or not; the type of biofilm (from irradiated patient-experimental or non-irradiated patient-control) and the type of artificial saliva (for the condition irradiated dentin/biofilm from irradiated patient): Control Artificial Saliva (inorganic); Control Saliva + 1 mg/ml hemoglobin; Control Saliva +0.1 mg/ml cystatin; Control Saliva + hemoglobin + cystatin; Bioextra (positive control) and deionized water (DiW, negative control) (n = 12/group). Biofilm was produced using human biofilm and McBain saliva (0.2 % of sucrose, 37o C and 5 % CO2); the treatments were done 1x/day, for 5 days. Colony-forming units (CFU) counting was performed; demineralization was quantified by transversal microradiography. Two-way ANOVA/Bonferroni or Sidak test for the comparison between biofilm x dentin and ANOVA/Tukey or Kruskal-Wallis/Dunn for comparing artificial saliva were done (p < 0.05). The type of biofilm had no influence on CFU and demineralization. Sound dentin under control biofilm presented the lowest Lactobacillus ssp. and Streptococcus mutans CFU and the lowest mean mineral loss (R) (25.6 ± 2.2; 23.7 ± 2.9 %) compared to irradiated dentin (26.1 ± 2.8; 28.1 ± 3.3, p < 0.004) for both types of biofilms (experimental and control, respectively). Bioextra was the only artificial saliva that reduced R (10.8 ± 2.5 %) and Lesion Depth (LD) (35 ± 15 µm) compared to DiW (17.3 ± 3.3 %, 81 ± 18 µm, p < 0.0001). Irradiation has impact on caries development; the experimental saliva were unable to reduce its occurrence.

Impact of ultrasound process on cassava starch nanoparticles and Pickering emulsions stability.

Using green techniques to convert native starches into nanoparticles is an interesting approach to producing stabilizers for Pickering emulsions, aiming at highly stable emulsions in clean label products. Nanoprecipitation was used to prepare the Pickering starch nanoparticles, while ultrasound technique has been used to modulate the size of these nanoparticles at the same time as the emulsion was developed. Thus, the main objective of this study was to evaluate the stabilizing effect of cassava starch nanoparticles (SNP) produced by the nanoprecipitation technique combined with ultrasound treatment carried out in the presence of water and oil (more hydrophobic physicochemical environment), different from previous studies that carry out the mechanical treatment only in the presence of water. The results showed that the increased ultrasound energy input could reduce particle size (117.58 to 55.75 nm) and polydispersity (0.958 to 0.547) in aqueous dispersions. Subsequently, Pickering emulsions stabilized by SNPs showed that increasing emulsification (ultrasonication) time led to smaller droplet sizes and monomodal size distribution. Despite flocculation, long-term ultrasonication (6 and 9 min) caused little variation in the droplet size after 7 days of storage. The cavitation effects favored the interaction between oil droplets through weak attraction forces and particle sharing, favoring the Pickering stabilization against droplet coalescence. Our results show the potential to use only physical modifications to obtain nanoparticles that can produce coalescence-stable emulsions that are environmentally friendly.

Single-cell long-read targeted sequencing reveals transcriptional variation in ovarian cancer.

Single-cell RNA sequencing predominantly employs short-read sequencing to characterize cell types, states and dynamics; however, it is inadequate for comprehensive characterization of RNA isoforms. Long-read sequencing technologies enable single-cell RNA isoform detection but are hampered by lower throughput and unintended sequencing of artifacts. Here we develop Single-cell Targeted Isoform Long-Read Sequencing (scTaILoR-seq), a hybridization capture method which targets over a thousand genes of interest, improving the median number of on-target transcripts per cell by 29-fold. We use scTaILoR-seq to identify and quantify RNA isoforms from ovarian cancer cell lines and primary tumors, yielding 10,796 single-cell transcriptomes. Using long-read variant calling we reveal associations of expressed single nucleotide variants (SNVs) with alternative transcript structures. Phasing of SNVs across transcripts enables the measurement of allelic imbalance within distinct cell populations. Overall, scTaILoR-seq is a long-read targeted RNA sequencing method and analytical framework for exploring transcriptional variation at single-cell resolution.

[Prevalence of the use of integrative and complementary practices and chronic diseases: 2019 National Health Survey]. / Prevalência de uso de práticas integrativas e complementares e doenças crônicas: Pesquisa Nacional de Saúde 2019.

The study sought to investigate the association between having a chronic disease or condition and the prevalence of having recourse to Integrative and Complementary Practices (ICP) among the Brazilian adult population. Chronic diseases are a serious public health issue and there are limitations of Western medicine to offer effective answers. Thus, the demand for ICP has increased as they constitute a humanized treatment option, with low cost and ease of acquisition. A cross-sectional population-based study was carried out using data from the 2019 National Health Survey. The prevalence of ICP use was estimated by categories of the other variables (presence or absence of chronic conditions) and prevalence ratios (PR) were adjusted for sociodemographic variables. The prevalence of the use of a given ICP, in the last 12 months, by the adult Brazilian population (18 years of age and over) was 5.5% (95%CI: 5.2%-5.8%), and adults with a chronic condition had a higher prevalence of use (PR: 2.11; 95%CI: 1.89-2.36), even after adjusting for sociodemographic characteristics. Stroke, asthma, arthritis, work-related musculoskeletal disorders, depression and other mental illnesses, chronic obstructive pulmonary disease, cancer and heart disease such as hypertension were associated with a higher prevalence of ICP use.

O estudo investigou a associação entre ter alguma doença ou agravo crônicos e a prevalência de uso de práticas integrativas e complementares (PIC) na população adulta brasileira. As doenças crônicas constituem uma séria questão de saúde pública e há limitações de respostas satisfatórias pela medicina ocidental. Assim, tem aumentado a procura pelas PIC por serem uma alternativa humanizada, de menor custo e de fácil aquisição. Foi realizado um estudo transversal de base populacional utilizando dados da Pesquisa Nacional de Saúde de 2019. Foram estimadas as prevalências de uso das PIC por categorias das demais variáveis (presença ou não de agravos crônicos), além de razões de prevalência (RP) ajustadas por características sociodemográficas. A prevalência de uso de alguma PIC, nos últimos 12 meses, pela população brasileira (a partir de 18 anos) foi de 5,5% (IC95%: 5,2%-5,8%), e os adultos com algum agravo crônico tiveram maior prevalência de uso (RP: 2,11; IC95%: 1,89-2,36), mesmo após ajuste sociodemográfico. Acidente vascular cerebral, asma, artrite, doenças osteomusculares relacionadas ao trabalho, depressão e outras doenças mentais, doença pulmonar obstrutiva crônica, câncer e doenças cardíacas, como hipertensão arterial, tiveram associação com maior uso de PIC.

Effectiveness of Fluoride Varnishes for White Spot Lesion Prevention and Remineralization during Orthodontic Treatment: A Randomized Controlled Trial.

INTRODUCTION: This study investigated the effectiveness of titanium tetrafluoride (TiF4) varnish compared to sodium fluoride (NaF) varnish for preventing and remineralizing white spot lesions (WSLs) in individuals undergoing orthodontic treatment. METHODS: This randomized, placebo-controlled, and double-blinded study was conducted with sixty-five adolescents who were selected based on caries activity and then randomized into three parallel groups: G1 (placebo varnish), G2 (5%-NaF varnish) and G3 (4%-TiF4 varnish). Volunteers received varnish application weekly for the first 4 weeks, after 6 (T1) and 12 (T2) months. The measured outcomes included: prevention of new WSLs, and reversal/progression of WSLs, assessed by Nyvad and ICDAS indices, as well as quantitative light-induced fluorescence (QLF). Chi-square, ANOVA, and Kruskall-Wallis tests were applied. The level of significance was set at 0.05, and post hoc Bonferroni test for p values were performed to correct for multiple comparisons. RESULTS: 1,274 teeth were included; 70.5% were Nyvad 0, and 29.5% were Nyvad 1, with no differences between the groups at baseline (T0). Regarding ICDAS, 70.5% were ICDAS 0, 21.6% were ICDAS 1, and 7.9% were ICDAS 2. G1 showed an increasing prevalence of WSLs at T1 and maintained stable at T2; G2 exhibited a decline at T2, while G3 experienced a decrease at T1 and T2 (p < 0.01). Incidence of WSLs at T2 was 10.2% (G1), 5.6% (G2) and 1.4% (G3). The percentage of teeth initially scored as Nyvad 0 that progressed to Nyvad 1 was 13%, 6.8%, and 1% for G1, G2, and G3, respectively. Conversely, the percentage of teeth initially scored as Nyvad 1 that regressed to Nyvad 0 or Nyvad 2 (T0-T2) was 14%, 49.3%, and 74.4%, respectively (p < 0.001). As for ICDAS index, regression was observed in 6.5%, 17.8% and 24%, while progression was observed in 14.9%, 7.7% and 0.9% for G1, G2 and G3, respectively (p < 0.001). Significant differences among the 3 groups for integrated fluorescence loss (mean±SD, G1: -14.28±9.47, G2: -11.10±11.49 and G3: -6.77±11.00) were found at T2 (p < 0.01). CONCLUSION: Both varnishes demonstrated the ability to prevent and remineralize WSLs. However, TiF4 varnish exhibited the most effective control over WSLs during the 12-month orthodontic treatment.

Challenges of safety culture in Surgical Center: mixed methods study.

OBJECTIVE: to analyze the safety attitudes of health and support areas professionals working in Surgical Center. METHOD: sequential explanatory mixed methods study. The quantitative stage covered 172 health and support professionals in eight Surgical Centers of a hospital complex. The Safety Attitudes Questionnaire/Surgical Center was applied. In the subsequent qualitative stage, 16 professionals participated in the Focus Group. Photographic methods were used from the perspective of ecological and restorative thinking, and data analysis occurred in an integrated manner, through connection. RESULTS: the general score, by group of Surgical Centers, based on the domains of the Safety Attitudes Questionnaire/Surgical Center, reveals a favorable perception of the safety climate, with emphasis on the domains Stress Perception, Communication in the Surgical Environment, Safety Climate and Perception of Professional Performance. The overall analysis of the domain Communication and Collaboration between Teams appears positive and is corroborated by data from the qualitative stage, which highlights the importance of interaction and communication between healthcare teams as fundamental for daily work. CONCLUSION: the perception of safety attitudes among health and support professionals was positive. The perception of the nursing team stands out as closer or more favorable to attitudes consistent with the safety culture.

Desenvolvimento de competências clínicas e de investigação com o estudo: Adaptação à reforma e satisfação com a vida conjugal em casais a partir da meia-idade / Development of clinical and research competences with the study: Adaptation to retirement and satisfaction with married life in middle-aged couples

A Enfermagem de Saúde Familiar emergiu como área de especialidade, com foco na família como unidade de cuidados, considerando a sua unicidade e especificidade. Surge para dar resposta às necessidades de saúde das famílias ao longo do ciclo vital e nas suas transições. A transição para a reforma é um evento do ciclo vital, que ocorre normalmente no final da meia-idade. Esta envolve mudanças, implica adaptações e reorganizações dos padrões de vida individuais, familiares e restruturação de papéis sociais. Estas mudanças ocorrem num contexto de interação sistémica e a adaptação concretiza-se pela ?reaprendizagem? na forma como a família passa a estar, sentir e ser. Objetivos: Descrever criticamente as atividades clínicas desenvolvidas para alcançar as competências comuns e específicas do enfermeiro especialista e do enfermeiro especialista em enfermagem comunitária na área de enfermagem de saúde familiar durante as atividades clínicas e apresentar estudo de investigação intitulado ?Avaliar a adaptação à reforma e satisfação com a vida conjugal em casais a partir da meia-idade.? Metodologia: Na atividade clínica foram utilizados referenciais teóricos de enfermagem de saúde familiar, bem como utilizada a classificação internacional para descrever as práticas. Na atividade de investigação realizou-se um estudo quantitativo descritivo-correlacional. Numa amostra de 41 casais reformados, inscritos numa Unidade de Saúde Familiar. Foi aplicado um questionário sociodemográfico, a Escala de Posicionamento Face à Adaptação à Reforma e a Escala de Avaliação da Satisfação em Áreas da Vida Conjugal. Resultados: O Modelo Dinâmico de Avaliação e Intervenção Familiar serviu de base para a avaliação e intervenção familiar permitindo implementar cuidados integrais às famílias. No estudo verificou-se que a maior idade e a coabitação com os filhos revelam-se facilitadores da adaptação à reforma. A nível da satisfação conjugal as famílias alargadas apresentam maior intimidade emocional, maior satisfação na dimensão comunicação/conflito e na dimensão tempos livres. Conclusão: A componente clínica proporcionou o desenvolvimento de competências comuns e específicas inerentes ao Enfermeiro Especialista em Enfermagem Comunitária - Área de Enfermagem de Saúde Familiar. Avaliar a adaptação à reforma e a satisfação com a vida conjugal possibilita aos enfermeiros conhecer o ajustamento e implementar melhores práticas na área da enfermagem de saúde familiar.

In vitro effect of TiF4/NaF solution on the development of radiation-induced dentin caries.

OBJECTIVE: To evaluate the protective effect of an experimental solution containing TiF4/NaF on the development of radiation-induced dentin caries lesions. METHODOLOGY: bovine root samples were irradiated (70Gy) and distributed as following (n=12/group): Commercial Saliva (BioXtra), NaF (500 ppm F-), TiF4 (500 ppm F), TiF4/NaF (TiF4: 300 ppm F-, NaF: 190 ppm F-), and Phosphate buffer solution (PBS, negative control). Biofilm was produced using biofilm from irradiated patients and McBain saliva (0.2% of sucrose, at 37oC and 5% CO2) for five days. The treatments were applied 1x/day. Colony-forming units (CFU) were counted and demineralization was quantified by transversal microradiography. The ANOVA/Tukey test was applied for all parameters. RESULTS: All treatments reduced CFU for total microorganisms. TiF4 reduced Lactobacillus sp. (7.04±0.26 log10 CFU/mL) and mutans streptococci (7.18±0.28) CFU the most, when compared to PBS (7.58±0.21 and 7.75±0.17) and followed by NaF (7.12±0.31 and 7.34±0.22) and TiF4/NaF (7.16±0.35 and 7.29± 0.29). TiF4 and Commercial saliva showed the lowest integrated mineral loss (ΔZ-vol%.mm) (1977±150 and 2062±243, respectively) when compared to PBS (4540±335), followed by NaF (2403±235) and TiF4/NaF (2340±200). Commercial saliva was the only to significantly reduce mineral loss (LD-µm) (111±25) compared to PBS (153±24).Mean mineral loss (R-vol%) decreased by 35.2% for TiF4 (18.2±3.3) when compared to PBS (28.1±2.9) Conclusion: TiF4/NaF has a comparable anti-cariogenic effect to TiF4 and Commercial saliva under the model in this study.

Acquired pellicle and biofilm engineering with CaneCPI-5: Insights from proteomic and microbiomics analysis.

OBJECTIVE: In this in vivo proof-of-concept study, acquired pellicle engineering was implemented to promote alterations in the protein composition of the acquired enamel pellicle (AEP) and the bacterial composition of the dental biofilm after treatment with Sugarcane cystatin (CaneCPI-5). DESIGN: After prophylaxis, 10 volunteers rinsed (10 mL, 1 min) with the following solutions: 1) deionized water (H2O- negative control or 2) 0.1 mg/mL CaneCPI-5. The AEP and biofilm were formed along 2 or 3 h, respectively. The AEP was collected with electrode filter papers soaked in 3 % citric acid. After protein extraction, samples were analyzed by quantitative shotgun label-free proteomics. The biofilm microbiome was collected with a dental curette. The DNA was extracted, amplified, and analyzed by 16S-rRNA Next Generation Sequencing (NGS). RESULTS: Treatment with CaneCPI-5 increased several proteins with antimicrobial, acid-resistance, affinity for hydroxyapatite, structural and calcium binding properties, such as Cysteine-rich-3 (6-fold-p = 0.03), Cystatin-B (5.5-fold-p < 0.01), Neutrophil-defensin 1 (4.7-fold-p < 0.01), Mucin (3.9-fold-p < 0.01), Immunoglobulin-heavy-constant (3.8-fold-p < 0.01) and Lactotransferrin (2.8-fold-p < 0.01). Microbiome revealed that several commensal bacteria had their abundance increased after rinsing with CaneCPI-5, such as Corynebacterium and Neisseria, while Streptococcus and Prevotella nigrescens were decreased. The results indicate the efficiency of CaneCPI-5 in promoting beneficial changes in the AEP and biofilm, making this phytocystatin a potential target for incorporation into dental products. CONCLUSION: Cane demonstrated the capability to alter the protein composition of the acquired enamel pellicle (AEP) and the initial colonizers of the biofilm, enhancing the presence of proteins and bacteria crucial for dental protection.

Enamel Caries Lesion Depth Obtained by Optical Coherence Tomography and Transverse Microradiography: A Comparative Study.

INTRODUCTION: Visual imaging of subsurface caries lesions is of vital interest in dentistry, which can be obtained by invasive radiography technique as well as by available non-destructive imaging approaches. Thus, as a first step toward the development of a new innovative approach, Spectral-domain optical coherence tomography (SD-OCT) was applied to detect the lesion depth in comparison to the established reference technique (transverse microradiography [TMR]). METHODS: Bovine enamel specimens were demineralized for 5 days, following previous studies. For OCT, the resulting artificial lesions were scanned three-dimensionally (SD-OCT) and semi-automated measured (CarLQuant). For TMR, specimens were sectioned and the lesion depth was manually determined (Inspektor Research System). RESULTS: The range of lesion depth detected with OCT was 24.0-174.0 µm (mouth rinse study), 18.0-178.0 µm (toothpastes study) and with TMR 59.2-198.0 µm (mouth rinse study), 33.2-133.4 µm (toothpastes study). We found a strong correlation between both methods in terms of lesion depth (Spearman rankwith outlierp < 0.001, Rho = 0.75, Spearman rankwithout outlierp = 0.001, Rho = 0.79). The two methods produce similar results (Passing-Bablok regression, 1.16). As deeper is the lesion, the smallest is the difference between both methods as indicated by Bland-Altman-plots. CONCLUSION: Especially in the case of deep lesions, the values obtained by both methods are in agreement, and OCT can potentially substitute TMR to detect and assess lesion depth with the benefit of being non-destructive.

Exposure of Undergraduate Nursing Students to Standing Environments: A Longitudinal Study on Plantar Force and Pressure Distribution.

BACKGROUND: Understanding the link between plantar force, pressure, and foot discomfort is important for nursing students' well-being, given the prevalence of foot and ankle musculoskeletal disorders among nurses. Assessing these factors can inform tailored self-care interventions, supporting holistic nursing education. PURPOSE: To assess the plantar force and pressure distribution of third-year nursing students at baseline and after 5 months of exposure to a clinical setting. METHODS: A prospective cohort study in a Portuguese nursing school measured changes in podiatric profile at 5 months, including peak pressure, maximum force, and contact area. RESULTS: Elevated mean peak pressure in the heel correlated positively with maximum force and contact area. Negative correlations were found between the contact area and edema. Peak pressure correlated positively with thigh pain, indicating pressure transfer to metatarsal heads. CONCLUSIONS: The findings underscore the importance of integrating ergonomic education into nursing curricula and raising awareness of self-care interventions.

Toothpaste containing TiF4 and chitosan against erosive tooth wear in situ.

OBJECTIVE: This study compared the protective effect of an experimental TiF4/Chitosan toothpaste with a commercial toothpaste on the prevention of erosive tooth wear (ETW) in situ. METHODS: Fifteen subjects took part in this crossover and double-blind study, in which they wore a palatal appliance containing 4 bovine enamel and 4 dentin in 3 phases (5 days each). Half of the samples were subjected to erosive challenges (90 s in 0.1 % citric acid, pH 2.5, 4 times/day), and the other half to erosive plus abrasive challenges (15 s plus 45 s of contact, 2 times/day). The phases corresponded to the application of the different toothpastes: 1) TiF4 (1400 ppm F-) plus Chitosan, 2) Elmex®, Erosion Protection (1400 ppm F-, Chitosan), and 3) Placebo (negative control). Tooth wear was measured using contact profilometry (µm) and submitted to two-way RM ANOVA/Tukey test (p < 0.05). RESULTS: No significant differences were detected between the experimental and commercial toothpastes, regardless of the challenge on both tissues. Both significantly reduce ETW compared to negative control (p < 0.0006). Tooth wear was increased by brushing only on eroded enamel (p < 0.01), but not on dentin (p = 0.6085). TiF4/Chitosan [erosion 2.98 ± 1.12 µm vs. erosion and abrasion 3.12 ± 1.33 µm] and Elmex® toothpastes [erosion 2.35 ± 0.93 µm vs. erosion and abrasion 2.98 ± 1.0 µm] minimized the impact of brushing compared to placebo on enamel [erosion 4.62 ± 1.48 µm vs. erosion and abrasion 5.15 ± 1.50 µm]. CONCLUSIONS: TiF4 plus chitosan toothpastes showed to be effective in minimizing the ETW as the commercial toothpaste is in situ. CLINICAL RELEVANCE: The experimental toothpaste has similar effect against ETW compared to the commercial toothpaste. Considering the increased ETW prevalence worldwide, this result supports clinical trials and a possible application of this experimental anti-erosive toothpaste in the future.

Determining the widths of the maxillary anterior teeth for esthetics: comparison of the Mondelli and Albers formulas, esthetic proportion, and golden ratio.

The purpose of this study was to compare various formulas for idealized proportions of the maxillary incisors to the actual dimensions of natural teeth. The Mondelli formula 1 (MF1), Mondelli formula 2 (MF2), Albers formula (AF), esthetic proportion (EP) for width and height of anterior teeth, and golden ratio (GR) were calculated for a total of 50 dental students (30 women and 20 men) who participated in the study. The following measurements were obtained directly in the participant's mouth with a digital caliper: the mesiodistal and incisogingival dimensions of the maxillary central incisors, lateral incisors, and canines; the intercanine distance; and the smile width. The participants were photographed, and the smile width was also measured on the photographs. The MF1 and MF2 were each calculated twice, using both direct measurements and photographic measurements. The projected central incisor widths calculated using the MF1, MF2, and AF were compared among themselves and against the actual measurements using analysis of variance and Fisher test for multiple comparisons (α = 0.05). The EP and GR were analyzed using descriptive statistics. There was a statistically significant difference between all of the widths projected by the formulas and the actual widths of the central incisors (P < 0.05). Whether calculated from a direct or a photographic measurement, the incisor widths projected by the MF1 and MF2 were statistically similar to each other (P > 0.05). The EP values were similar to those reported in the literature. Only 2% of the participants had an incisor width ratio (central incisor/lateral incisor) that matched the GR of 1.618, while 86% fell within the range of 1.2 to 1.4. Overall, the proportions calculated with the MF1, MF2, AF, EP, and GR did not exactly match the actual dimensions of natural teeth. The formulas and the proportions available in the literature can assist in esthetic planning, but the individual characteristics of each patient and expertise of the dentist should guide treatment for each case.

Human Herpesvirus 8-Positive Multicentric Castleman Disease in an Immunocompetent Patient: A Diagnostic Challenge.

We present a clinical case of a 79-year-old male admitted to inpatient care for longstanding asthenia and respiratory symptoms. Associated features were polyserositis, multiple enlarged lymphatic nodules, acute kidney injury, and heart failure. The patient's recent medical history revealed SARS-CoV-2 vaccination a week prior and an upper respiratory tract infection. The laboratory results from thoracentesis were compatible with a transudate, with no immunological stain. Epstein-Barr virus polymerase chain reaction (PCR) was positive. The thoracic, abdominal, and pelvic CT scans revealed multiple enlarged lymphatic nodules, worsening the pre-existent polyserositis and hepatosplenomegaly. The patient began to show signs of neurologic symptoms and deterioration of the global health status. An enlarged lymphatic nodule was excised and the pathology showed human herpesvirus 8 multicentric Castleman disease. The disease evolved rapidly into hematological dysfunction and blood transfusions were necessary. Even though the patient was started on high-dose rituximab therapy combined with etoposide, the disease evolved into multiorgan dysfunction with a fatal outcome.

α-Synuclein triggers cofilin pathology and dendritic spine impairment via a PrPC-CCR5 dependent pathway.

Cognitive dysfunction and dementia are critical symptoms of Lewy Body dementias (LBD). Specifically, alpha-synuclein (αSyn) accumulation in the hippocampus leading to synaptic dysfunction is linked to cognitive deficits in LBD. Here, we investigated the pathological impact of αSyn on hippocampal neurons. We report that either αSyn overexpression or αSyn pre-formed fibrils (PFFs) treatment triggers the formation of cofilin-actin rods, synapse disruptors, in cultured hippocampal neurons and in the hippocampus of synucleinopathy mouse models and of LBD patients. In vivo, cofilin pathology is present concomitantly with synaptic impairment and cognitive dysfunction. Rods generation prompted by αSyn involves the co-action of the cellular prion protein (PrPC) and the chemokine receptor 5 (CCR5). Importantly, we show that CCR5 inhibition, with a clinically relevant peptide antagonist, reverts dendritic spine impairment promoted by αSyn. Collectively, we detail the cellular and molecular mechanism through which αSyn disrupts hippocampal synaptic structure and we identify CCR5 as a novel therapeutic target to prevent synaptic impairment and cognitive dysfunction in LBD.

A high-cholesterol diet promotes the intravasation of breast tumor cells through an LDL-LDLR axis.

Most metastases in breast cancer occur via the dissemination of tumor cells through the bloodstream. How tumor cells enter the blood (intravasation) is, however, a poorly understood mechanism at the cellular and molecular levels. Particularly uncharacterized is how intravasation is affected by systemic nutrients. High levels of systemic LDL-cholesterol have been shown to contribute to breast cancer progression and metastasis in various models, but the cellular and molecular mechanisms involved are still undisclosed. Here we show that a high- cholesterol diet promotes intravasation in two mouse models of breast cancer and that this could be reverted by blocking LDL binding to LDLR in tumor cells. Moreover, we show that LDL promotes vascular invasion in vitro and the intercalation of tumor cells with endothelial cells, a phenotypic change resembling vascular mimicry (VM). At the molecular level, LDL increases the expression of SERPINE2, previously shown to be required for both VM and intravasation. Overall, our manuscript unravels novel mechanisms by which systemic hypercholesterolemia may affect the onset of metastatic breast cancer by favouring phenotypic changes in breast cancer cells and increasing intravasation.

Resequencing of Brazilian locally adapted cattle breeds revealed variants in candidate genes and transcription factors for meat fatty acid profile.

The beef cattle industry has experienced a shift driven by a market demand for healthier meat, cost efficiency and environmental sustainability in recent years. Consequently, there has been a growing focus on the fatty acids content and functions of meat in cattle breeding programmes. Besides, a deeper understanding of the biological mechanisms influencing the expression of different phenotypes related to fatty acid profiles is crucial. In this study, we aimed to identify Single-Nucleotide Variants (SNV) and Insertion/Deletion (InDels) DNA variants in candidate genes related to fatty acid profiles described in genomic, transcriptomic and proteomic studies conducted in beef cattle breeds. Utilizing whole-genome re-sequencing data from Brazilian locally adapted bovine breeds, namely Caracu and Pantaneiro, we identified SNVs and InDels associated with 23,947 genes. From these, we identified 318 candidate genes related to fatty acid profiles that contain variants. Subsequently, we select only genes with SNVs and InDels in their promoter, 5' UTR and coding region. Through the gene-biological process network, approximately 19 genes were highlighted. Furthermore, considering the studied trait and a literature review, we selected the main transcription factors (TF). Functional analysis via gene-TF network allowed us to identify the 30 most likely candidate genes for meat fatty acid profile in cattle. LIPE, MFSD2A and SREBF1 genes were highlighted in networks due to their biological importance. Further dissection of these genes revealed 15 new variants found in promoter regions of Caracu and Pantaneiro sequences. The gene networks facilitated a better functional understanding of genes and TF, enabling the identification of variants potentially related to the expression of candidate genes for meat fatty acid profiles in cattle.

Light Cannabis Use and the Adolescent Brain: An 8-years Longitudinal Assessment of Mental Health, Cognition, and Reward Processing.

RATIONALE: For decades, cannabis has been the most widely used illicit substance in the world, particularly among youth. Research suggests that mental health problems associated with cannabis use may result from its effect on reward brain circuit, emotional processes, and cognition. However, findings are mostly derived from correlational studies and inconsistent, particularly in adolescents. OBJECTIVES AND METHODS: Using data from the IMAGEN study, participants (non-users, persistent users, abstinent users) were classified according to their cannabis use at 19 and 22 years-old. All participants were cannabis-naïve at baseline (14 years-old). Psychopathological symptoms, cognitive performance, and brain activity while performing a Monetary Incentive Delay task were used as predictors of substance use and to analyze group differences over time. RESULTS: Higher scores on conduct problems and lower on peer problems at 14 years-old (n = 318) predicted a greater likelihood of transitioning to cannabis use within 5 years. At 19 years of age, individuals who consistently engaged in low-frequency (i.e., light) cannabis use (n = 57) exhibited greater conduct problems and hyperactivity/inattention symptoms compared to non-users (n = 52) but did not differ in emotional symptoms, cognitive functioning, or brain activity during the MID task. At 22 years, those who used cannabis at both 19 and 22 years-old n = 17), but not individuals that had been abstinent for ≥ 1 month (n = 19), reported higher conduct problems than non-users (n = 17). CONCLUSIONS: Impairments in reward-related brain activity and cognitive functioning do not appear to precede or succeed cannabis use (i.e., weekly, or monthly use). Cannabis-naïve adolescents with conduct problems and more socially engaged with their peers may be at a greater risk for lighter yet persistent cannabis use in the future.

A biological guide to glycosaminoglycans: current perspectives and pending questions.

Mammalian glycosaminoglycans (GAGs), except hyaluronan (HA), are sulfated polysaccharides that are covalently attached to core proteins to form proteoglycans (PGs). This article summarizes key biological findings for the most widespread GAGs, namely HA, chondroitin sulfate/dermatan sulfate (CS/DS), keratan sulfate (KS), and heparan sulfate (HS). It focuses on the major processes that remain to be deciphered to get a comprehensive view of the mechanisms mediating GAG biological functions. They include the regulation of GAG biosynthesis and postsynthetic modifications in heparin (HP) and HS, the composition, heterogeneity, and function of the tetrasaccharide linkage region and its role in disease, the functional characterization of the new PGs recently identified by glycoproteomics, the selectivity of interactions mediated by GAG chains, the display of GAG chains and PGs at the cell surface and their impact on the availability and activity of soluble ligands, and on their move through the glycocalyx layer to reach their receptors, the human GAG profile in health and disease, the roles of GAGs and particular PGs (syndecans, decorin, and biglycan) involved in cancer, inflammation, and fibrosis, the possible use of GAGs and PGs as disease biomarkers, and the design of inhibitors targeting GAG biosynthetic enzymes and GAG-protein interactions to develop novel therapeutic approaches.