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Abstract Alzheimer’s disease begins with mild memory loss and slowly destroys memory and thinking. Cognitive impairment in Alzheimer’s disease has been associated with the localization of the microtubule-associated protein Tau at the postsynapse. However, the correlation between Tau at the postsynapse and synaptic dysfunction remains unclear. Here, we show that Tau arrests liquid-like droplets formed by the four postsynaptic density proteins PSD-95, GKAP, Shank, Homer in solution, as well as NMDA (N-methyl-D-aspartate)-receptor-associated protein clusters on synthetic membranes. Tau-mediated condensate/cluster arrest critically depends on the binding of multiple interaction motifs of Tau to a canonical GMP-binding pocket in the guanylate kinase domain of PSD-95. We further reveal that competitive binding of a high-affinity phosphorylated peptide to PSD-95 rescues the diffusional dynamics of an NMDA truncated construct, which contains the last five amino acids of the NMDA receptor subunit NR2B fused to the C-terminus of the tetrameric GCN4 coiled-coil domain, in postsynaptic density-like condensates/clusters. Taken together, our findings propose a molecular mechanism where Tau modulates the dynamic properties of the postsynaptic density.

RESUMO O trabalho teve como objetivo desenvolver painel em madeira de reflorestamento e chapas de partículas de bagaço de cana-de-açúcar e resina poliuretana bicomponente à base de óleo de mamona, como alternativa para o sistema convencional de fechamento lateral do tronco coletivo de centro de manejo para bovinos de corte. A caracterização físico-mecânica do material forneceu um indicativo das possibilidades de uso para esse produto, que associado a pilares roliços de eucalipto compõem o sistema modular estrutural. A avaliação da resistência ao impacto do sistema modular, que procurou simular o efeito provocado pelo animal, em condições de uso, demonstrou a eficiência do modelo estrutural proposto para uso em centro de manejo.

Background and purposeThe persistent challenges in thrombectomy for large-vessel occlusion, such as suboptimal complete recanalization and first-pass effect imply an insufficient understanding of the artery-clot-device interaction. In this study, we present a thrombectomy model using fresh human brains, which can capture the artery-clot-device interaction through concurrent transmural and angiographic visualizations.Materials and methodsFresh nonfrozen whole adult human brains were collected and connected to a customized pump system tuned to deliver saline flow at a physiologic flow rate and pressure. Angiography was performed to verify the flow in the anterior-posterior and vertebrobasilar circulations and collaterals. Large-vessel occlusion was simulated by embolizing a radiopaque clot analog. Thrombectomy was tested, and the artery-clot-device interactions were recorded by transmural and angiographic videos.ResultsBaseline cerebral angiography revealed excellent penetration of contrast in the anterior-posterior and vertebrobasilar circulations without notable arterial cutoffs and with robust collaterals. Small branches (

Abstract Background The terms metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) categorize subjects with obesity based on the presence or absence of cardio-metabolic risk factors. Detecting MUO phenotype is crucial due to the high risk of cardio-metabolic complications, requiring tailored and intensive follow-up. However, diagnosing MUO is time-consuming and costly. Thus, we aimed to investigate the role of Mediterranean diet (MD) in determining MHO/MUO phenotypes and whether adherence to MD could serve as an additional screening tool for MUO phenotype. Methods The study population of this cross-sectional observational study consisted of 275 subjects with obesity. We assessed their lifestyle habits (physical activity and smoking habits), anthropometric measurements (weight, height, waist circumference, body mass index), blood pressure, metabolic parameters, inflammatory marker (high sensitivity C reactive protein levels), adherence to MD (by PREvención con DIetaMEDiterránea (PREDIMED) questionnaire), and MHO/MUO phenotypes. Results The study included 275 individuals with obesity (256F/19M; 34.0 ± 10.5 years; BMI 38.3 ± 5.95 kg/m2). Among them, 114 (41.5%) exhibited MHO phenotype, while 161 (58.5%) had MUO phenotype. MHO phenotype exhibited favorable anthropometric and cardio-metabolic profiles, characterized by lower waist circumference (p

Abstract The combination of atezolizumab and nab-paclitaxel is recommended in the EU as first-line treatment for PD-L1-positive metastatic triple-negative breast cancer (mTNBC), based on the results of phase III IMpassion130 trial. However, ‘real-world’ data on this combination are limited. The ANASTASE study (NCT05609903) collected data on atezolizumab plus nab-paclitaxel in PD-L1-positive mTNBC patients enrolled in the Italian Compassionate Use Program. A retrospective analysis was conducted in 29 Italian oncology centers among patients who completed at least one cycle of treatment. Data from 52 patients were gathered. Among them, 21.1% presented de novo stage IV; 78.8% previously received (neo)adjuvant treatment; 55.8% patients had only one site of metastasis; median number of treatment cycles was five (IQR: 3–8); objective response rate was 42.3% (95% CI: 28.9–55.7%). The median time-to-treatment discontinuation was 5 months (95% CI: 2.8–7.1); clinical benefit at 12 months was 45.8%. The median duration of response was 12.7 months (95% CI: 4.1–21.4). At a median follow-up of 20 months, the median progression-free survival was 6.3 months (95% CI: 3.9–8.7) and the median time to next treatment or death was 8.1 months (95% CI: 5.5–10.7). At 12 months and 24 months, the overall survival rates were 66.3% and 49.1%, respectively. The most common immune-related adverse events included rash (23.1%), hepatitis (11.5%), thyroiditis (11.5%) and pneumonia (9.6%). Within the ANASTASE study, patients with PD-L1-positive mTNBC treated with first-line atezolizumab plus nab-paclitaxel achieved PFS and ORR similar to those reported in the IMpassion130 study, with no unexpected adverse events.

Abstract Background Obesity is a condition that is often associated with sleep disorders, including reduced sleep quality (SQ). Very low calorie ketogenic diet (VLCKD) has proven to be effective in the management of obesity and associated metabolic disorders. However, little is still known about the effects of this promising nutritional protocol on SQ. Thus, the purpose of this study was to investigate the short-term effect of VLCKD on SQ in women with overweight/obesity and if any changes, to identify the predictive factor that through VLCKD modified SQ. Methods Were consecutively enrolled a total of 324 subjects, who met the inclusion criteria and accepted to adhere to VLCKD. Assessment of nutritional status, including anthropometric measurements (height, weight, and waist circumference), bioelectrical impedance analysis (phase-sensitive system, 50 kHz BIA 101 RJL, Akern Bioresearch, Florence, Italy Akern), high sensitivity C reactive protein levels (hs-CRP), and SQ were carried out at baseline and after 31 days of active stage of VLCKD. SQ was evaluated using the validated questionnaire Pittsburgh Sleep Quality Index (PSQI). Results In addition to the expected general improvement of anthropometric parameters and body composition, VLCKD improved significantly SQ, as demonstrated by the improvement of all parameters included in the PSQI questionnaire (p − 8.4% predicted improvement in SQ (p

Abstract In this study, concentrated cement pore solution (CPS) was prepared and coconut fibre was soaked in it, to mimic worst condition of cementitious medium. Four coconut fibre samples were studied; the first was untreated fibre (NT), the second sample was NaOH treated fibre, while the third and fourth samples were NT and NaOH fibres soaked in CPS for 28 days, respectively. Each fibre was characterized by determining their physical and mechanical properties. Hydrophilic/hydrophobic characters were determined by measuring contact angles in water, while surface morphology of the fibre samples were studied with the aid of scanning electron microscopy. EDS was used to determine the elemental composition of the fibres, while Thermogravimetric analysis was performed to assess thermal stability of the fibre samples. Crystallinity of the fibres as well as the functional group composition present in each fibre samples, was determined using XRD and FTIR respectively. The results showed that fibres treated with NaOH and those exposed to CPS had higher densities (1.94 g/cm3) than untreated fibre (1.64 g/cm3), while the tensile strength was greatly increased by about 120%. SEM images of the fibres indicated that NaOH and CPS caused removal of lignin and hemicellulose, making the lumens to be smaller compared to untreated fibre. Similarly, crystallinity of the fibre was increased due to NaOH and CPS treatment, compared to the untreated fibres. CPS was found to improve thermal stability of the fibres. It was concluded that CPS did not pose any threat to performance of fibre.

Our objective is to determine the protein and complements constituents of Cord blood Platelet-rich plasma (CB-PRP), based on the hypothesis that it contains beneficial components capable of arresting or potentially decelerating the advancement of atrophic age-related macular degeneration (dry-AMD), with the support of radiomics. Two distinct pools of CB-PRP were assessed, each pool obtained from a total of 15 umbilical cord-blood donors. One aliquot of each pool respectively was subjected to proteomic analysis in order to enhance the significance of our findings, by identifying proteins that are shared between the two sample pools and gaining insights into the pathways they are associated with. The bioinformatics analysis was developed using Reactome software. Three-hundred-seven (307) distinct proteins were found. Two hundred fifteen (215) of the elements mentioned above are shared by both pools. Seventy (70) elements are exclusive to pool S1, while pool S2 contains 22. We detected 109 representative and statistically significant pathways out of 549. We found proteins related to the immune system, signal transduction, vesicle-mediated transport, cell–cell communication, hemostasis, cellular responses to stimuli, cell cycle, and developmental biology. The analysis showed the presence of P15692-12, representing VEGF factor A, long form. With over 200 proteins, the CB-PRP can increase the immune response, including BCR, CD-22, FCGR, phospholipids, IL-10, FCGR-3A, and others. Discovering crucial trophic and complement-regulating variables is highly significant for potential applications in dry AMD. Our future research will examine the effects of intravitreal CB-PRP on dry-AMD eyes. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate characteristic imaging findings and functional outcomes of Cilioretinal Artery Occlusion (CLRAO) associated with giant cell arteritis (GCA). Observations: We report the case of a 70-year-old woman presenting with sudden vision loss caused by a GCA-associated-CLRAO in her left eye (LE). A thorough ophthalmologic examination together with optical coherence tomography (OCT), OCT-Angiography (OCT-A), fluorescein angiography and fundus autofluorescence were performed. At presentation, the best corrected visual acuity in the LE was 20/200 and funduscopic examination revealed optic disc edema associated with retinal whitening along the area perfused by the CLRA. After 1 month, OCT and OCT-A revealed an improvement of the retinal edema and a partial reduction of the non-perfused areas in the superficial and deep capillary plexuses, as well as in the outer retina and in the choriocapillaris. Fluorescein angiography showed a reduction in the perfusion of the affected area, a delayed perfusion of the temporal sector of the optic disc, as well as areas of choroidal hypoperfusion in the peripheral temporal retina. The patient's visual acuity did not change during the follow up. Conclusion and importance: Despite a partial recanalization of the occluded vasculature being possible after GCA-associated-CLRAO, the patient's visual prognosis remains poor.

Craft beer represents a dynamic and creative segment within the food and beverage industry, emphasizing quality, aroma, health, sustainability, locality, and tailored brewing techniques. This paper explores the multifaceted roles of craft beer’s production and consumption growth dynamics. Both a bibliometric analysis and a systematic literature review were conducted on a sample of 239 scientific papers to provide an in-depth evaluation of the main characteristics and influences that craft beer has in the field of food science. Based on the identified roles of craft beer/breweries in the selected sample of literature, a conceptual framework was constructed to serve as a guideline for policymakers and different stakeholders. In this way, our findings enrich the existing literature and contribute to a better understanding of craft beer production and surroundings, which can be beneficial for promoting sustainable policies and innovative strategies for the growth of small/micro-producers and entrepreneurs in this niche market. Furthermore, this evidence can stimulate clear and ethical information to enhance consumers’ knowledge and agendas to strengthen the identity of local communities.

The production of beer, a beverage of global cultural and industrial importance, has a significant impact on the environment due to the use of natural resources and the emissions generated during the various stages of the production process. Therefore, this article examines the sustainability of beer production through a review of literature articles that have used Life Cycle Assessment (LCA) to assess its environmental impacts. A systematic literature review was conducted by selecting peer-reviewed articles published between 2001 and July 2024 using databases such as Scopus and Google Scholar. The search included studies analyzing different stages of the beer life cycle, from raw material production to packaging and distribution, using specific keywords related to LCA and brewing. The results showed that energy use and packaging are the two critical aspects identified in the review, which represent a significant part of the environmental footprint. However, it is important to note that the available studies on the subject are few and heterogeneous and they use different methodologies, impact categories, and functional units, which complicates the comparison and synthesis of results, limiting the ability to draw definitive conclusions. Recommendations were made to improve sustainability, including the adoption of more efficient technologies, the use of recycled materials for packaging, and the implementation of sustainable agricultural practices. These strategies could aim to significantly reduce the overall environmental impact of beer production.

This paper presents the characterization of a binary mixture of construction and demolition waste (CDW) and bamboo leaf ash (BLAsh) calcined at 600 °C (novel mixture) and the study of its pozzolanic behavior. Different dosages in a pozzolan/Ca(OH)2 system were employed. The aim is the valorization of fine-fraction CDW that achieves a more reactive binary mixture and allows an adequate use of CDW as waste, as CDW is a material of limited use due to its low pozzolanic activity. The pozzolanic behavior of the mixture was analyzed using the conductometric method, which measures the electrical conductivity in the CDW + BLAsh/CH solution versus reaction time. With the application of a kinetic–diffusive mathematical model, the kinetic parameters of the pozzolanic reaction were quantified. This allowed a quantitative evaluation of the pozzolanic activity based on the values of these parameters. To validate these results, other experimental techniques were used: X-ray diffraction, thermogravimetry and scanning electron microscopy. Also, mechanical compressive strength assays were carried out. The results show an increase in the pozzolanic activity of binary mixes of CDW + BLAsh for all the dosages used in comparison to the pozzolanic activity of CDW alone. The quantitative assessment (kinetic parameters) shows that the binary mixture CDW50 + BLAsh50 is the most reactive (reaction rate constant of 7.88 × 10−1 h−1) and is superior to the mixtures CDW60 + BLAsh40 and CDW70 + BLAs30. Compressive strength tests show higher strength values for the ternary mixes (OPC + CDW + BLAsh) compared to the binary mixes (OPC + CDW). In view of the results, the binary blend of pozzolans CDW + BLAsh is suitable for the manufacture of future low-carbon ternary cements.

BackgroundEvidence of the association between AMplitude Spectral Area (AMSA) of ventricular fibrillation and outcome after out-of-hospital cardiac arrest (OHCA) is limited to short-term follow-up. In this study, we assess whether AMSA can stratify the risk of death or poor neurological outcome at 30 days and 1 year after OHCA in patients with an initial shockable rhythm or with an initial non-shockable rhythm converted to a shockable one.MethodsThis is a multicentre retrospective study of prospectively collected data in two European Utstein-based OHCA registries. We included all cases of OHCAs with at least one manual defibrillation. AMSA values were calculated after data extraction from the monitors/defibrillators used in the field by using a 2-s pre-shock electrocardiogram interval. The first detected AMSA value, the maximum value, the average value, and the minimum value were computed, and their outcome prediction accuracy was compared. Multivariable Cox regression models were run for both 30-day and 1-year deaths or poor neurological outcomes. Neurological cerebral performance category 1–2 was considered a good neurological outcome.ResultsOut of the 578 patients included, 494 (85%) died and 10 (2%) had a poor neurological outcome at 30 days. All the AMSA values considered (first value, maximum, average, and minimum) were significantly higher in survivors with good neurological outcome at 30 days. The average AMSA showed the highest area under the receiver operating characteristic curve (0.778, 95% CI: 0.7–0.8, p