Explore the vast range of titles available.

As an intrinsically disordered protein, monomeric alpha-synuclein (aSyn) occupies a large conformational space. Certain conformations lead to aggregation prone and non-aggregation prone intermediates, but identifying these within the dynamic ensemble of monomeric conformations is difficult. Herein, we used the biologically relevant calcium ion to investigate the conformation of monomeric aSyn in relation to its aggregation propensity. We observe that the more exposed the N-terminus and the beginning of the NAC region of aSyn are, the more aggregation prone monomeric aSyn conformations become. Solvent exposure of the N-terminus of aSyn occurs upon release of C-terminus interactions when calcium binds, but the level of exposure and aSyn’s aggregation propensity is sequence and post translational modification dependent. Identifying aggregation prone conformations of monomeric aSyn and the environmental conditions they form under will allow us to design new therapeutics targeted to the monomeric protein. In Parkinson’s disease (PD) the monomeric protein alpha-synuclein (aSyn) misfolds and aggregates into insoluble fibrils. Here the authors use NMR measurements and hydrogen–deuterium exchange mass spectrometry and find that the more solvent exposed the N-terminus of aSyn is, the more aggregation prone its conformation becomes, and further show how PD mutations and post translational modifications influence the extent of the N-terminus solvent exposure.

Increasing evidence suggests that amyloid polymorphism gives rise to different strains of amyloids with distinct toxicities and pathologyspreading properties. Validating this hypothesis is challenging due to a lack of tools and methods that allow for the direct characterization of amyloid polymorphism in hydrated and complex biological samples. Here, we report on the development of 11- mercapto-1-undecanesulfonate-coated gold nanoparticles (NPs) that efficiently label the edges of synthetic, recombinant, and native amyloid fibrils derived from different amyloidogenic proteins. We demonstrate that these NPs represent powerful tools for assessing amyloid morphological polymorphism, using cryogenic transmission electron microscopy (cryo-EM). The NPs allowed for the visualization of morphological features that are not directly observed using standard imaging techniques, including transmission electron microscopy with use of the negative stain or cryo-EM imaging. The use of these NPs to label native paired helical filaments (PHFs) from the postmortem brain of a patient with Alzheimer’s disease, as well as amyloid fibrils extracted from the heart tissue of a patient suffering from systemic amyloid light-chain amyloidosis, revealed a high degree of homogeneity across the fibrils derived from human tissue in comparison with fibrils aggregated in vitro. These findings are consistent with, and strongly support, the emerging view that the physiologic milieu is a key determinant of amyloid fibril strains. Together, these advances should not only facilitate the profiling and characterization of amyloids for structural studies by cryo-EM, but also pave the way to elucidate the structural basis of amyloid strains and toxicity, and possibly the correlation between the pathological and clinical heterogeneity of amyloid diseases.

Patients with mental health disorders often have to endure the burdens of the condition itself and the stigma that follows. Since no study has been conducted in Lebanon on this topic, our objective was to assess the knowledge, attitude and behaviors towards public stigma of mental health diseases, among a sample of the Lebanese population. A cross-sectional study, conducted between November 2017 and May 2018, enrolled 2289 participants. The Mental Health Knowledge Schedule (MAKS), the Community Attitudes toward Mental Illness (CAMI) and the Reported and Intended Behavior Scale (RIBS) were used to assess knowledge, attitude and behaviors toward mental illness respectively. The 25th, 50th and 75th percentile of the MAKS, CAMI and RIBS scales scores were considered as cutoff points for low, medium and high scores respectively. A high knowledge score was found in 33.0% of the participants, whereas a high attitude score and a higher behavior score were found in 32.2% and 26.9% of the participants respectively. Living in North Lebanon (Beta = 1.331) and being familiar with a non-close person with mental illness (Beta = 0.811) were associated with higher knowledge of mental illness (higher MAKS score), whereas living in Bekaa (Beta = -8.693) and being 70 years old and above (Beta = -5.060) were associated with lower knowledge toward mental illness (lower MAKS score). Higher knowledge of mental illness (higher MAKS score) (Beta = 0.670), having a high level of education (university (Beta = 8.785), secondary (Beta = 6.084) and technical (Beta = 5.677)) were associated with less stigmatizing attitudes (higher CAMI scale). Being familiar with close people with mental illness (Beta = 0.577), less stigmatizing attitudes (higher CAMI scale) (Beta = 0.077) and higher knowledge of mental illness (higher MAKS score) (Beta = 0.115) were associated with higher favorable behaviors (higher RIBS score), whereas knowing a non-close person who have a mental illness (Beta = -0.720) was associated with lower favorable behaviors (lower RIBS score). A mass media awareness campaigns that could transmit health messages to a wide public audience in the country to fight stigma toward mental illness, seems warranted.

Purpose Executive functions (EF) play a fundamental role in planning and executing goal-driven behaviours. The purpose of this systematic review and meta-analysis was to investigate EF skills mastered by preschool/school-age cochlear implanted children (CIC) without morpho-functional abnormalities and to compare their outcomes with typically hearing children (THC). Methods Bibliographic search for observational studies of any language/date up to 16 December 2022 was performed with the following electronic databases: PubMed, Scopus, and Web of Science. After removal of duplicates, 2442 records were subjected to a three-stage screening process and 83 potentially eligible articles were identified. A total of 15 studies was included in the final analysis: 9 articles directly meeting the eligibility criteria plus 6 more studies thanks to the authors sharing their data set, specifically for participants who met present inclusion criteria. Results Meta-analysis showed a statistically significant difference only for verbal short-term memory, whereas group differences for visuospatial short-term memory and verbal/visuospatial working memory were not significant. For fluency skills, meta-analysis revealed statistical significance for the semantic fluency task but not for the rapid naming test. Qualitative analysis reflected group similarities in flexibility but CIC’s difficulties in auditory attention/planning skills. Controversial findings for inhibitory control skills were observed. Conclusions EF performance comparisons between CIC and THC show inter-skill and inter-test variances. Due to the paucity of existing studies, present findings should be interpreted with caution. Future research in this domain is strongly recommended.

Purpose This study aimed to investigate the effects of low frequency (LF) pitch perception on speech-in-noise and music perception performance by children with cochlear implants (CIC) and typical hearing (THC). Moreover, the relationships between speech-in-noise and music perception as well as the effects of demographic and audiological factors on present research outcomes were studied. Methods The sample consisted of 22 CIC and 20 THC (7–10 years). Harmonic intonation (HI) and disharmonic intonation (DI) tests were used to assess LF pitch perception. Speech perception in quiet (WRSq)/noise (WRSn + 10) were tested with the Italian bisyllabic words for pediatric populations. The Gordon test was used to evaluate music perception (rhythm, melody, harmony, and overall). Results CIC/THC performance comparisons for LF pitch, speech-in-noise, and all music measures except harmony revealed statistically significant differences with large effect sizes. For the CI group, HI showed statistically significant correlations with melody discrimination. Melody/total Gordon scores were significantly correlated with WRSn + 10. For the overall group, HI/DI showed significant correlations with all music perception measures and WRSn + 10. Hearing thresholds showed significant effects on HI/DI scores. Hearing thresholds and WRSn + 10 scores were significantly correlated; both revealed significant effects on all music perception scores. CI age had significant effects on WRSn + 10, harmony, and total Gordon scores (p < 0.05). Conclusion Such findings confirmed the significant effects of LF pitch perception on complex listening performance. Significant speech-in-noise and music perception correlations were as promising as results from recent studies indicating significant positive effects of music training on speech-in-noise recognition in CIC.

This work presents the results of research on the thermo-chemical conversion of woody biomass–pine wood coming from lodzkie voivodship forests and sewage sludge from the Group Sewage Treatment Plant of the Łódź Urban Agglomeration. Laboratory scale analyses of the carbonization process were carried out, initially using the TGA technique (to assess activation energy (EA)), followed by a flow reactor operating at temperature levels of 280–525 °C. Both the parameters of carbonized solid biofuel and biochar as a carrier for fertilizer (proximate and ultimate analysis) and the quality of the torgas (VOC) were analyzed. Analysis of the pine wood and sewage sludge torrefaction process shows clearly that the optimum process temperature would be around 325–350 °C from a mass loss ratio and economical perspective. This paper shows clearly that woody biomass, such as pine wood and sewage sludge, is a very interesting material both for biofuel production and in further processing for biochar production, used not only as an energy carrier but also as a new type of carbon source in fertilizer mixtures.

Purpose Auditory selective attention (ASA) is crucial to focus on significant auditory stimuli without being distracted by irrelevant auditory signals and plays an important role in language development. The present study aimed to investigate the unique contribution of ASA to the linguistic levels achieved by a group of cochlear implanted (CI) children. Methods Thirty-four CI children with a median age of 10.05 years were tested using both the “Batteria per la Valutazione dell’Attenzione Uditiva e della Memoria di Lavoro Fonologica nell’età evolutiva-VAUM-ELF” to assess their ASA skills, and two Italian standardized tests to measure lexical and morphosyntactic skills. A regression analysis, including demographic and audiological variables, was conducted to assess the unique contribution of ASA to language skills. Results The percentages of CI children with adequate ASA performances ranged from 50 to 29.4%. Bilateral CI children performed better than their monolateral peers. ASA skills contributed significantly to linguistic skills, accounting alone for the 25% of the observed variance. Conclusions The present findings are clinically relevant as they highlight the importance to assess ASA skills as early as possible, reflecting their important role in language development. Using simple clinical tools, ASA skills could be studied at early developmental stages. This may provide additional information to outcomes from traditional auditory tests and may allow us to implement specific training programs that could positively contribute to the development of neural mechanisms of ASA and, consequently, induce improvements in language skills.

In this paper, we document changes in political trust in the UK throughout 2020 so as to consider wider implications for the ongoing handling of the COVID-19 pandemic. We analysed data from 18 survey organisations with measures on political trust (general, leadership, and COVID-19-related) spanning the period December 2019–October 2020. We examined the percentage of trust and distrust across time, identifying where significant changes coincide with national events. Levels of political trust were low following the 2019 UK General Election. They rose at the onset of UK lockdown imposed in March 2020 but showed persistent gradual decline throughout the remainder of the year, falling to pre-COVID levels by October 2020. Inability to sustain the elevated political trust achieved at the onset of the pandemic is likely to have made the management of public confidence and behaviour increasingly challenging, pointing to the need for strategies to sustain trust levels when handling future crises.

ObjectiveIn this study, we aim to assess the impact of tumor size on clinical and oncological outcomes in patients undergoing laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC).BackgroundLLR has been shown to be feasible, safe, and oncologically efficient. However, it has been slow to develop in patients with HCC who often suffer from chronic liver disease which represents an additional challenge for the surgeon. The experience with large HCCs is even more limited.MethodsBetween 2003 and 2016, 172 patients from two high-volume liver surgery centers underwent LLR for HCC. Prospectively collected data were analyzed after stratification in 3 groups according to tumor major diameter (group 1: < 3 cm; group 2: between 3 and 5 cm; group 3: ≥ 5 cm). Perioperative and long-term outcomes were compared between the three groups and sub-analyses were carried out on the extent and location of the resections.ResultsGroups 1, 2, and 3 consisted of 82, 52, and 38 patients, respectively. Minor and major resections were performed in 98.8% and 1.2% in group 1, in 90.4% and 9.6% in group 2, and in 68.4% and 31.6% in group 3, respectively. Postero-superior “technically major” resections were performed in 15.8% patients in group 1, in 19.2% in group 2, and in 15.8% in group 3, respectively. Group 3 had higher conversion rates (p < 0.001), more frequent (p = 0.056) and more prolonged (p = 0,075) pedicle clamping and longer operative time (p < 0.001), higher blood losses (p = 0.025), and longer total hospital and intensive care unit stays. These differences ceased after removing the major resections from the study population, except for the postoperative length of stay. There were no differences in morbidity, mortality, completeness of resection rates, and long-term outcomes between the three groups.ConclusionLLR for HCC appears to be safe and oncologically efficient when performed in high-volume HPB and laparoscopic centers. Tumor size does not appear to impact negatively on the outcomes except for postoperative hospital stay.