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Polyurethanes (PURs) are versatile polymers used in a wide variety of fields, such as the medical, automotive, textile, thermal insulation, and coating industries as well as many everyday objects. Many PURs have applications that require a long service life, sometimes with exposure to aggressive conditions. They can undergo different types of physicochemical and biological degradation, but they are not compostable, and many of them constitute persistent waste in the environment. Although both bacteria and fungi can be involved in the degradation of PURs, fungi are often the main biodegradation agents. The chemical structure of PURs determines their degree of biodegradation. Fungal biodegradation of PURs is linked to the production of enzymes, mainly esterases and proteases, alongside laccases, peroxidases, and tyrosinases, which can modify the structure of polyurethane compounds by forming carbonyl groups. The experimental analysis of the biodegradation of PUR can be carried out by bringing the polymer into contact with a mold in pure culture or with a microbial consortium. Then, global measurements can be taken, such as weight loss, tensile tests, or the ability of microorganisms to grow in the presence of PUR as the sole carbon source. The analysis of the chemical structure of the polymer and its degradation products after fungal growth can confirm biodegradation and specify the mechanism. The main avenues of future research are directed towards the development of fully biodegradable PURs and, on the contrary, towards the development of PURs that are more resistant to degradation phenomena, in particular biodegradation, for applications where the material is in contact with living organisms.

Acute liver failure and chronic liver disease are associated with a wide spectrum of neurological changes, of which the best known is hepatic encephalopathy (HE). Historically, hyperammonemia, causing astrocyte swelling and cerebral oedema, was considered the main etiological factor in the pathogenesis of cerebral dysfunction in patients with acute and/or chronic liver disease. However, recent studies demonstrated a key role of neuroinflammation in the development of neurological complications in this setting. Neuroinflammation is characterized by activation of microglial cells and brain secretion of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, which alter neurotransmission, leading to cognitive and motor dysfunction. Changes in the gut microbiota resulting from liver disease play a crucial role in the pathogenesis of neuroinflammation. Dysbiosis and altered intestinal permeability, resulting in bacterial translocation and endotoxemia, are responsible for systemic inflammation, which can spread to brain tissue and trigger neuroinflammation. In addition, metabolites derived from the gut microbiota can act on the central nervous system and facilitate the development of neurological complications, exacerbating clinical manifestations. Thus, strategies aimed at modulating the gut microbiota may be effective therapeutic weapons. In this review, we summarize the current knowledge on the role of the gut–liver–brain axis in the pathogenesis of neurological dysfunction associated with liver disease, with a particular focus on neuroinflammation. In addition, we highlight emerging therapeutic approaches targeting the gut microbiota and inflammation in this clinical setting.

Pancreatic Carcinoma (PC) cells have the ability to induce patient immunosuppression and to escape immunosurveillance. Low circulating lymphocytes are associated with an advanced stage of PC and reduced survival. Blood lymphocytes expressed as a percentage of Total White Blood Cells (L% TWBC) could predict chemotolerance (n° of tolerated cycles), survival time and Body Weight (BW) more effectively than lymphocytes expressed as an absolute value (LAB > 1500 n°/mm3) or lymphocytes >22%, which is the lowest limit of normal values in our laboratory. Forty-one patients with advanced PC, treated with chemotherapy, were selected for this observational retrospective study. Patients were evaluated at baseline (pre-chemotherapy), and at 6, 12 and 18 months, respectively, after diagnosis of PC. The study found L ≥ 29.7% to be a better predictor of survival (COX model, using age, sex, BW, serum creatinine, bilirubin and lymphocytes as covariates), chemotolerance (r = +0.50, p = 0.001) and BW (r = +0.35, p = 0.027) than LAB > 1500 or L > 22%. BW did not significantly correlate with chemotolerance or survival. The preliminary results of this study suggest that L ≥ 29.7% is more effective than LAB > 1500 or L > 22% at predicting chemotolerance, survival time and nutritional status. A possible impact of nutritional status on chemotherapy and survival seems to be lymphocyte-mediated given the association between BW and L%. This study may serve as the basis for future research to explore whether nutritional interventions can improve lymphopenia, and if so, how this may be possible.

Abstract Disturbances of conscious awareness, or self-disorders, are a defining feature of schizophrenia. These include symptoms such as delusions of control, i.e. the belief that one’s actions are controlled by an external agent. Models of self-disorders point at altered neural mechanisms of source monitoring, i.e. the ability of the brain to discriminate self-generated stimuli from those driven by the environment. However, evidence supporting this putative relationship is currently lacking. We performed electroencephalography (EEG) during self-paced, brisk right fist closures in ten (M = 9; F = 1) patients with Early-Course Schizophrenia (ECSCZ) and age and gender-matched healthy volunteers. We measured the Readiness Potential (RP), i.e. an EEG feature preceding self-generated movements, and movement-related EEG spectral changes. Self-disorders in ECSCZ were assessed with the Examination of Anomalous Self-Experience (EASE). Patients showed a markedly reduced RP and altered post-movement Event-Related Synchronization (ERS) in the beta frequency band (14–24 Hz) compared to healthy controls. Importantly, smaller RP and weaker ERS were associated with higher EASE scores in ECSCZ. Our data suggest that disturbances of neural correlates preceding and following self-initiated movements may reflect the severity of self-disorders in patients suffering from ECSCZ. These findings point towards deficits in basic mechanisms of sensorimotor integration as a substrate for self-disorders.

BACKGROUND: Dengue is a major public health problem worldwide. Assessment of adaptive immunity is important to understanding immunopathology and to define correlates of protection against dengue virus (DENV). To enable global assessment of CD4+ T cell responses, we mapped HLA-DRB1-restricted DENV-specific CD4+ T cell epitopes in individuals previously exposed to DENV in the general population of the dengue-endemic region of Managua, Nicaragua. METHODS: HLA class II epitopes in the population of Managua were identified by an in vitro IFNγ ELISPOT assay. CD4+ T cells purified by magnetic bead negative selection were stimulated with HLA-matched epitope pools in the presence of autologous antigen-presenting cells, followed by pool deconvolution to identify specific epitopes. The epitopes identified in this study were combined with those previously identified in the DENV endemic region of Sri Lanka, to generate a megapool (MP) consisting of 180 peptides specifically designed to achieve balanced HLA and DENV serotype coverage. The DENV CD4MP180 was validated by intracellular cytokine staining assays. RESULTS: We detected responses directed against a total of 431 epitopes, representing all 4 DENV serotypes, restricted by 15 different HLA-DRB1 alleles. The responses were associated with a similar pattern of protein immunodominance, overall higher magnitude of responses, as compared to what was observed previously in the Sri Lanka region. Based on these epitope mapping studies, we designed a DENV CD4 MP180 with higher and more consistent coverage, which allowed the detection of CD4+ T cell DENV responses ex vivo in various cohorts of DENV exposed donors worldwide, including donors from Nicaragua, Brazil, Singapore, Sri Lanka, and U.S. domestic flavivirus-naïve subjects immunized with Tetravalent Dengue Live-Attenuated Vaccine (TV005). This broad reactivity reflects that the 21 HLA-DRB1 alleles analyzed in this and previous studies account for more than 80% of alleles present with a phenotypic frequency ≥5% worldwide, corresponding to 92% phenotypic coverage of the general population (i.e., 92% of individuals express at least one of these alleles). CONCLUSION: The DENV CD4 MP180 can be utilized to measure ex vivo responses to DENV irrespective of geographical location.

Assemblage-level studies of mean trait variation are common in macroecology. However, how phylogenetic relationships among species affect trait-based macroecological patterns is still unresolved. I used an approach based on variation partitioning analysis using environmental and phylogenetic lineage variation as predictors to investigate whether variation in mean trait values among Neotropical sigmodontine rodent communities is best explained by macroecological adaptation, biogeographical history, or joint effects of both – the latter resulting in phylogenetic niche conservatism (PNC) at the metacommunity scale. Metacommunity PNC best explained mean variation in body size and skull/mandible shape across assemblages, and the pattern of metacommunity PNC suggests that influence of environmental factors on mean trait variation relies heavily on spatial biogeographical clade sorting. This suggests that biogeographical lineage distribution should be taken into account in analyses seeking to correlate environmental variables with mean trait variation.

Myotonic dystrophy type 2 (DM2) is caused by CCTG repeat expansions in the CNBP gene, comprising 75 to >11,000 units and featuring extensive mosaicism, making it challenging to sequence fully expanded alleles. To overcome these limitations, we used PCR-free Cas9-mediated nanopore sequencing to characterize CNBP repeat expansions at the single-nucleotide level in nine DM2 patients. The length of normal and expanded alleles can be assessed precisely using this strategy, agreeing with traditional methods, and revealing the degree of mosaicism. We also sequenced an entire ~50 kbp expansion, which has not been achieved previously for DM2 or any other repeat-expansion disorders. Our approach precisely counted the repeats and identified the repeat pattern for both short interrupted and uninterrupted alleles. Interestingly, in the expanded alleles, only two DM2 samples featured the expected pure CCTG repeat pattern, while the other seven presented also TCTG blocks at the 3′ end, which have not been reported before in DM2 patients, but confirmed hereby with orthogonal methods. The demonstrated approach simultaneously determines repeat length, structure/motif, and the extent of somatic mosaicism, promising to improve the molecular diagnosis of DM2 and achieve more accurate genotype–phenotype correlations for the better stratification of DM2 patients in clinical trials.

Introduction Mental health interventions for Italian (and European) prisoners with mental disorders remain a problematic issue, despite radical changes in general psychiatric care and a 2008 major government reform transferring mental health care in prison to the National Health Service. Indeed, according to the American Psychological Association, 64% of incarcerated individuals report mental health concerns. Objectives The aim of this study is to describe the mental health intervention model implemented since January 2020 for prisoners allocated in the Parma Penitentiary Institutes (PPI). This approach is specifically based on specialized, “person-centered” and “person-tailored” therapeutic-rehabilitation plans in line with psychiatric treatments usually provided in community mental health-care centers of the Parma Department of Mental Health. Methods All the processes and procedures included in the PPI intervention model were first carefully described, paying special attention to the service for newly admitted prisoners and each typology of specialized therapeutic-rehabilitation treatment potentially provided. Additionally, a preliminary descriptive process analysis of the first six months of clinical activity was also performed. Results Since January 2020, 178 individuals entered the PPI service for newly admitted prisoners. In total, 83 (46.7%) of them were engaged in the services of the PPI mental health-care team (35 with pathological addiction and 48 with mental disorders): 56 prisoners were offered an integrated mental health intervention and 27 exclusively an individual psychological or psychiatric treatment. Conclusions The results support the potential applicability of an integrated mental health intervention in prison, planning a person-tailored rehabilitation in close collaboration with the prisoners, their families and the local mental health/social services. Disclosure No significant relationships.

Introduction Personal Health Budget (PHB) has been provided to consumers with severe mental illness within a policy shift toward a person-tailored mental healthcare treatment based on individual unmet needs. PHB is an amount of money to support patient’s health and wellbeing needs, which is planned and agreed between patients and their local NHS team. It is not new money, but it may mean spending money differently so that patients can get the care that they need. However, evidence of beneficial effects of PHB is still scarce. Objectives The aim of this study was to provide preliminary data on clinical and social benefits of adding PHB to a standard pharmacotherapy in patients with severe mental illness across a 24-month follow-up period. Methods 137 individuals with severe mental illness (aged 18–50 years) were recruited in one of the adult mental health services of an Italian Department of Mental Health. They completed the Global Assessment of Functioning scale, the Health of the Nation Outcome Scale and the Brief Psychiatric Rating Scale. Friedman’s test for repeated measure was used to assess the longitudinal stability of functioning and clinical parameters. A linear regression analysis was also performed. Results A significant decrease in all GAF scale, HoNOS and BPRS scores along the 24 months of follow-up was observed. Regression analysis results specifically showed a relevant association between a PHB multiaxial intervention and the longitudinal reduction in BPRS ‘Negative Symptoms’ and HoNOS ‘Social Problems’ subscores. Conclusions Our findings support the useful implementation of a PHB approach for severe mental illness patients within the Italian mental health service network. Disclosure No significant relationships.

Abstract Vocalizations including laughter, cries, moans, or screams constitute a potent source of information about the affective states of others. It is typically conjectured that the higher the intensity of the expressed emotion, the better the classification of affective information. However, attempts to map the relation between affective intensity and inferred meaning are controversial. Based on a newly developed stimulus database of carefully validated non-speech expressions ranging across the entire intensity spectrum from low to peak, we show that the intuition is false. Based on three experiments (N = 90), we demonstrate that intensity in fact has a paradoxical role. Participants were asked to rate and classify the authenticity, intensity and emotion, as well as valence and arousal of the wide range of vocalizations. Listeners are clearly able to infer expressed intensity and arousal; in contrast, and surprisingly, emotion category and valence have a perceptual sweet spot: moderate and strong emotions are clearly categorized, but peak emotions are maximally ambiguous. This finding, which converges with related observations from visual experiments, raises interesting theoretical challenges for the emotion communication literature.

Epstein–Barr Virus (EBV) is a human gamma-herpesvirus that is widespread worldwide. To this day, about 200,000 cancer cases per year are attributed to EBV infection. EBV is capable of infecting both B cells and epithelial cells. Upon entry, viral DNA reaches the nucleus and undergoes a process of circularization and chromatinization and establishes a latent lifelong infection in host cells. There are different types of latency all characterized by different expressions of latent viral genes correlated with a different three-dimensional architecture of the viral genome. There are multiple factors involved in the regulation and maintenance of this three-dimensional organization, such as CTCF, PARP1, MYC and Nuclear Lamina, emphasizing its central role in latency maintenance.

Several coronaviruses infect humans, with three, including the SARS-CoV2, causing diseases. While coronaviruses are especially prone to induce pandemics, we know little about their evolutionary history, host-to-host transmissions, and biogeography. One of the difficulties lies in dating the origination of the family, a particularly challenging task for RNA viruses in general. Previous cophylogenetic tests of virus-host associations, including in the Coronaviridae family, have suggested a virus-host codiversification history stretching many millions of years. Here, we establish a framework for robustly testing scenarios of ancient origination and codiversification versus recent origination and diversification by host switches. Applied to coronaviruses and their mammalian hosts, our results support a scenario of recent origination of coronaviruses in bats and diversification by host switches, with preferential host switches within mammalian orders. Hotspots of coronavirus diversity, concentrated in East Asia and Europe, are consistent with this scenario of relatively recent origination and localized host switches. Spillovers from bats to other species are rare, but have the highest probability to be towards humans than to any other mammal species, implicating humans as the evolutionary intermediate host. The high host-switching rates within orders, as well as between humans, domesticated mammals, and non-flying wild mammals, indicates the potential for rapid additional spreading of coronaviruses across the world. Our results suggest that the evolutionary history of extant mammalian coronaviruses is recent, and that cases of long-term virus–host codiversification have been largely over-estimated. [ABSTRACT FROM AUTHOR]

The health benefits of nut consumption have been extensively demonstrated in observational studies and intervention trials. Besides the high nutritional value, countless evidences show that incorporating nuts into the diet may contribute to health promotion and prevention of certain diseases. Such benefits have been mostly and certainly attributed not only to their richness in healthy lipids (plentiful in unsaturated fatty acids), but also to the presence of a vast array of phytochemicals, such as polar lipids, squalene, phytosterols, tocochromanols, and polyphenolic compounds. Thus, many nut chemical compounds apply well to the designation "nutraceuticals," a broad umbrella term used to describe any food component that, in addition to the basic nutritional value, can contribute extra health benefits. This contribution analyses the general chemical profile of groundnut and common tree nuts (almond, walnut, cashew, hazelnut, pistachio, macadamia, pecan), focusing on lipid components and phytochemicals, with a view on their bioactive properties. Relevant scientific literature linking consumption of nuts, and/or some of their components, with ameliorative and/or preventive effects on selected diseases – such as cancer, cardiovascular, metabolic, and neurodegenerative pathologies – was also reviewed. In addition, the bioactive properties were analyzed in the light of known mechanistic frameworks. [ABSTRACT FROM AUTHOR]

Dispersion interactions are ubiquitous weak interactions that can play a role in many chemical events. Tailor-made catalysts and additives can lead to more selective reactions by properly exploiting dispersion interactions. Although radical-π dispersion interactions are known to have an important stabilizing role, this concept has been so far overlooked in synthetic photochemistry. We recently proved that similar dispersion interactions can play a profound impact on several reactions involving an energy transfer step. We present herein a study on the co-catalytic effect of tethered bi-naphthyl derivatives on the visible-light-promoted alkene-alkene [2 + 2] cycloaddition. A library of tethered bi-naphthyl derivatives was prepared in order to evaluate the impact of the tether on the efficiency of the prototypical [2 + 2] cycloaddition. The best performing additives showed a dramatic effect on the efficiency of the cyclization, and a rationalization of their relative efficiency was carried out through DFT modeling. The best co-catalyst allowed one to isolate desired products in good to excellent yields even employing several challenging substrates. These results offer new tools to devise optimized [2 + 2] photocycloaddition methods and provide valuable information for the design of organic co-catalyst that can boost photochemical reactions by exploiting dispersion interactions. [ABSTRACT FROM AUTHOR]

Music, like spoken language, is often characterized by hierarchically organized structure. Previous experiments have shown neural tracking of notes and beats, but little work touches on the more abstract question: how does the brain establish high-level musical structures in real time? We presented Bach chorales to participants (20 females and 9 males) undergoing electroencephalogram (EEG) recording to investigate how the brain tracks musical phrases. We removed the main temporal cues to phrasal structures, so that listeners could only rely on harmonic information to parse a continuous musical stream. Phrasal structures were disrupted by locally or globally reversing the harmonic progression, so that our observations on the original music could be controlled and compared. We first replicated the findings on neural tracking of musical notes and beats, substantiating the positive correlation between musical training and neural tracking. Critically, we discovered a neural signature in the frequency range ~0.1 Hz (modulations of EEG power) that reliably tracks musical phrasal structure. Next, we developed an approach to quantify the phrasal phase precession of the EEG power, revealing that phrase tracking is indeed an operation of active segmentation involving predictive processes. We demonstrate that the brain establishes complex musical structures online over long timescales (>5 s) and actively segments continuous music streams in a manner comparable to language processing. These two neural signatures, phrase tracking and phrasal phase precession, provide new conceptual and technical tools to study the processes underpinning high-level structure building using noninvasive recording techniques. [ABSTRACT FROM AUTHOR]

The synthetic relevance of bicyclo[2.2.2]octadienes is witnessed by their successful application in various chemical domains, promoting a recurrent interest in the concise assembly of these bridged bicycles. Seminal examples of strategies to craft these compounds are presented, together with more-recent applications that exploit visible light. In this context, a general intramolecular method for the para -cycloaddition of an allenamide arm onto simple aryl rings is highlighted. [ABSTRACT FROM AUTHOR]

In 2018 there was a large yellow fever outbreak in São Paulo, Brazil, with a high fatality rate. Yellow fever virus can cause, among other symptoms, hemorrhage and disseminated intravascular coagulation, indicating a role for endothelial cells in disease pathogenesis. Here, we conducted a case-control study and measured markers related to endothelial damage in plasma and its association with mortality. We found that angiopoietin 2 is strongly associated with a fatal outcome and could serve as a predictive marker for mortality. This could be used to monitor severe cases and provide care to improve disease outcome. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has posed unprecedented challenges to global health systems, particularly among vulnerable populations such as the elderly. Understanding the interplay between anthropometric markers, molecular profiles, and disease severity is crucial for effective clinical management and intervention strategies. We conducted a cohort study comprising 43 elderly COVID-19 patients admitted to São Lucas Hospital, PUCRS, Brazil. Anthropometric measurements, including calf circumference (CC) and abdominal circumference (AC), were assessed alongside molecular analyses of peripheral blood samples obtained within 48 h of hospital admission. Sociodemographic data were collected from electronic medical records for comprehensive analysis. Our findings revealed a possible relationship between overweight status, increased abdominal adiposity, and prolonged hospitalization duration, alongside heightened disease severity. We also found no significant correlations between BMI, vitamin D levels, and clinical outcomes. Elevated oxygen requirements were observed in both normal and overweight individuals, with the latter necessitating prolonged oxygen therapy. Molecular analyses revealed changes in the inflammatory profile regarding the outcome of the patients. Our study highlights the critical importance of both anthropometric and molecular markers in predicting disease severity and clinical outcomes in elderly individuals with COVID-19. [ABSTRACT FROM AUTHOR]

Background: The heightened risk of dementia resulting from multiple comorbid conditions calls for innovative strategies. Engaging in physical and cognitive activities emerges as a protective measure against cognitive decline. This protocol aims to discuss a multidomain intervention targeting individuals with dementias secondary to cerebrovascular or other medical diseases, emphasizing an often underrepresented demographic. Methods: This study primary objectives are: a) to identify patients affected by Neurocognitive disorder due to vascular disease or multiple etiologies (screening and diagnostic phase) and b) to evaluate the effectiveness of distinct rehabilitation protocols (intervention phase): motor training alone, paper-based cognitive rehabilitation combined with motor training, digital-based cognitive rehabilitation coupled with motor training. Discussion: Identifying cognitive impairment beyond rigid neurological contexts can facilitate timely and targeted interventions. This protocol strives to address the complex interplay of cognitive decline and comorbidities through a multidimensional approach, providing insights that can shape future interventions and enhancing overall well-being in this vulnerable population. Trial registration: The study has been registered on July 13, 2023 with the ClinicalTrials.gov NCT05954741 registration number (https://classic.clinicaltrials.gov/ct2/show/NCT05954741). [ABSTRACT FROM AUTHOR]

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