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Abstract Alongside vaccines, antiviral drugs are becoming an integral part of our response to the SARS‐CoV‐2 pandemic. Nirmatrelvir—an orally available inhibitor of the 3‐chymotrypsin‐like cysteine protease—has been shown to reduce the risk of progression to severe COVID‐19. However, the impact of nirmatrelvir treatment on the development of SARS‐CoV‐2‐specific adaptive immune responses is unknown. Here, by using mouse models of SARS‐CoV‐2 infection, we show that nirmatrelvir administration blunts the development of SARS‐CoV‐2‐specific antibody and T cell responses. Accordingly, upon secondary challenge, nirmatrelvir‐treated mice recruited significantly fewer memory T and B cells to the infected lungs and mediastinal lymph nodes, respectively. Together, the data highlight a potential negative impact of nirmatrelvir treatment with important implications for clinical management and might help explain the virological and/or symptomatic relapse after treatment completion reported in some individuals.

Brucellosis is an economically important zoonotic disease affecting humans, livestock, and wildlife health globally and especially in Africa. Brucella abortus and B. melitensis have been isolated from human, livestock (cattle and goat), and wildlife (sable) in South Africa (SA) but with little knowledge of the population genomic structure of this pathogen in SA. As whole genome sequencing can assist to differentiate and trace the origin of outbreaks of Brucella spp. strains, the whole genomes of retrospective isolates (n = 19) from previous studies were sequenced. Sequences were analysed using average nucleotide identity (ANI), pangenomics, and whole genome single nucleotide polymorphism (wgSNP) to trace the geographical origin of cases of brucellosis circulating in human, cattle, goats, and sable from different provinces in SA. Pangenomics analysis of B. melitensis (n = 69) and B. abortus (n = 56) was conducted with 19 strains that included B. abortus from cattle (n = 3) and B. melitensis from a human (n = 1), cattle (n = 1), goat (n = 1), Rev1 vaccine strain (n = 1), and sable (n = 12). Pangenomics analysis of B. melitensis genomes, highlighted shared genes, that include 10 hypothetical proteins and genes that encodes for acetyl-coenzyme A synthetase (acs), and acylamidase (aam) amongst the sable genomes. The wgSNP analysis confirmed the B. melitensis isolated from human was more closely related to the goat from the Western Cape Province from the same outbreak than the B. melitensis cattle sample from different cases in the Gauteng Province. The B. melitensis sable strains could be distinguished from the African lineage, constituting their own African sub-clade. The sequenced B. abortus strains clustered in the C2 lineage that is closely related to the isolates from Mozambique and Zimbabwe. This study identified genetically diverse Brucella spp. among various hosts in SA. This study expands the limited known knowledge regarding the presence of B. melitensis in livestock and humans in SA, further building a foundation for future research on the distribution of the Brucella spp. worldwide and its evolutionary background. [ABSTRACT FROM AUTHOR]

We report the long-term results of a randomized trial (GITMO, AML-R2), comparing 1:1 the combination of busulfan and cyclophosphamide (BuCy2, n = 125) and the combination of busulfan and fludarabine (BuFlu, n = 127) as conditioning regimen in acute myeloid leukemia patients (median age 51 years, range 40–65) undergoing allogeneic hematopoietic stem cell transplantation. With a median follow-up of 6 years, significantly better non-relapse mortality (NRM) was confirmed in BuFlu recipients, which is sustained up to 4 years after transplant (10% vs. 20%, p = 0.0388). This difference was higher in patients older than 51 years (11% in BuFlu vs. 27% in BuCy2, p = 0.0262). The cumulative incidence of relapse, which was the first cause of death in the entire study population, did not differ between the two randomized arms. Similarly, the leukemia-free survival (LFS) and overall survival (OS) were not different in the two cohorts, even when stratifying patients per median age. Graft-and relapse-free survival (GRFS) in BuFlu arm vs. the BuCy2 arm was 25% vs. 20% at 4 years and 20% vs. 17% at 10 years. Hence, the benefit gained by NRM reduction is not offsets by an increased relapse. Leukemia relapse remains a major concern, urging the development of new therapeutic approaches. [ABSTRACT FROM AUTHOR]

The prevalence of multidrug resistant (MDR) bacterial infections continues to rise as the development of antibiotics needed to combat these infections remains stagnant. MDR enterococci are a major contributor to this crisis. A potential therapeutic approach for combating MDR enterococci is bacteriophage (phage) therapy, which uses lytic viruses to infect and kill pathogenic bacteria. While phages that lyse some strains of MDR enterococci have been identified, other strains display high levels of resistance and the mechanisms underlying this resistance are poorly defined. Here, we use a CRISPR interference (CRISPRi) screen to identify a genetic locus found on a mobilizable plasmid from Enterococcus faecalis involved in phage resistance. This locus encodes a putative serine recombinase followed by a Type IV restriction enzyme (TIV-RE) that we show restricts the replication of phage phi47 in vancomycin-resistant E. faecalis. We further find that phi47 evolves to overcome restriction by acquiring a missense mutation in a TIV-RE inhibitor protein. We show that this inhibitor, termed type IV restriction inhibiting factor A (tifA), binds and inactivates diverse TIV-REs. Overall, our findings advance our understanding of phage defense in drug-resistant E. faecalis and provide mechanistic insight into how phages evolve to overcome antiphage defense systems. Using a CRISPR interference genetic approach, Bullen, Johnson, and colleagues discover a type IV restriction (TIV-RE) enzyme encoded on a mobilizable plasmid of multidrug resistant Enterococcus faecalis. This TIV-RE is a potent inhibitor of bacteriophage infection. [ABSTRACT FROM AUTHOR]

Human RAD52 (RAD52) is a DNA-binding protein involved in many DNA repair mechanisms and genomic stability maintenance. In the last few years, this protein was discovered to be a promising novel pharmacological target for anticancer strategies. Although the interest in RAD52 has exponentially grown in the previous decade, most information about its structure and mechanism still needs to be elucidated. Here, we report the 2.2 Å resolution cryo-EM reconstruction of the full-length RAD52 (FL-RAD52) protein. This allows us to describe the hydration shell of the N-terminal region of FL-RAD52, which is structured in an undecamer ring. Water molecules coordinate with protein residues to promote stabilization inside and among the protomers and within the inner DNA binding cleft to drive protein-DNA recognition. Additionally, through a multidisciplinary approach involving SEC-SAXS and computational methods, we comprehensively describe the highly flexible and dynamic organization of the C-terminal portion of FL-RAD52. This work discloses unprecedented structural details on the FL-RAD52, which will be critical for characterizing its mechanism of action and inhibitor development, particularly in the context of novel approaches to synthetic lethality and anticancer drug discovery. A cryo-EM reconstruction with 2.2 Å resolution of the full-length RAD52 protein highlights the hydration shell of the DNA-binding region and the highly flexible C-terminal portion, obtained by combining SEC-SAXS and computational methods. [ABSTRACT FROM AUTHOR]

Context: Growth hormone (GH) deficiency in a child with short stature is diagnosed by GH secretion provocative tests. When the test response is considered adequate, the short stature is considered idiopathic (ISS). Objective: To determine the effect of GH provocative tests on the growth rate in children with idiopathic short stature. Design: Children with short stature with a normal response to at least one GH provocative test were enrolled. Height and growth velocity were measured prior to and after stimulus tests during the follow-up. Methods: Height, mid-parental height, body weight, and body mass index were measured. The height and growth rate were converted to percentiles and Standard Deviation Scores (SDS) using reference ranges standardized by age and sex. GH provocative tests employed arginine or clonidine as secretagogues. Results: Fourty-six children of both genders were enrolled. In thirty-six children, height was measured at the time of testing and on an average time prior to and after the tests of 210 days and 180 days respectively. After testing the children displayed a 3.4-fold increase in their estimated 90-day growth rate. The median (inter-quartile range, IQR) 90 days growth of children pre-and post-tests were 0.7 (0.2–1.0) cm and 2.4 (1.7–3.1) cm respectively with a mean 3,4-fold increase (p < 0.0001). The median (IQR) 90 days growth of children pre- and post-tests calculated as standard deviation scores (SDS) were −4.0 (−5.4–−2.1) SDS and 0.1 (−1.9–1.4) SDS respectively (p < 0.0001). Ten children with ISS were observed for about 5 months before the GH provocative tests. A small increase in the growth rate was seen only in 2 out of 10 children before testing while it increased in all of them after the tests. The difference in the median growth rate at the first and the second observation was not significant (p = 0.219). Conclusions: Two sequential somatotropic axis provocative tests increase the growth rate in children with idiopathic short stature. The duration of this effect is yet to be determined. [ABSTRACT FROM AUTHOR]

Background and Objective: Blood-based small molecule metabolites offer easy accessibility and hold significant potential for insights into health processes, the impact of lifestyle, and genetic variation on disease, enabling precise risk prevention. In a prospective study with records of heart failure (HF) incidence, we present metabolite profiling data from individuals without HF at baseline. Methods: We uncovered the interconnectivity of metabolites using data-driven and causal networks augmented with polygenic factors. Exploring the networks, we identified metabolite broadcasters, receivers, mediators, and subnetworks corresponding to functional classes of metabolites, and provided insights into the link between metabolomic architecture and regulation in health. We incorporated the network structure into the identification of metabolites associated with HF to control the effect of confounding metabolites. Results: We identified metabolites associated with higher and lower risk of HF incidence, such as glycine, ureidopropionic and glycocholic acids, and LPC 18:2. These associations were not confounded by the other metabolites due to uncovering the connectivity among metabolites and adjusting each association for the confounding metabolites. Examples of our findings include the direct influence of asparagine on glycine, both of which were inversely associated with HF. These two metabolites were influenced by polygenic factors and only essential amino acids, which are not synthesized in the human body and are obtained directly from the diet. Conclusion: Metabolites may play a critical role in linking genetic background and lifestyle factors to HF incidence. Revealing the underlying connectivity of metabolites associated with HF strengthens the findings and facilitates studying complex conditions like HF. [ABSTRACT FROM AUTHOR]

Objectives: Chemoprevention can be a treatment for potentially malignant lesions (PMLs). We aimed to evaluate whether artemisinin (ART) and cisplatin (CSP) are associated with apoptosis and immunogenic cell death (ICD) in vitro, using oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC) cell lines, and whether these compounds prevent OL progression in vivo. Methods: Normal keratinocytes (HaCat), Dysplastic oral cells (DOK), and oral squamous cell carcinoma (SCC-180) cell lines were treated with ART, CSP, and ART + CSP to analyze cytotoxicity, genotoxicity, cell migration, and increased expression of proteins related to apoptosis and ICD. Additionally, 41 mice were induced with OL using 4NQO, treated with ART and CSP, and their tongues were histologically analyzed. Results: In vitro, CSP and CSP + ART showed dose-dependent cytotoxicity and reduced SCC-180 migration. No treatment was genotoxic, and none induced expression of proteins related to apoptosis and ICD; CSP considerably reduced High-mobility group box-1 (HMGB-1) protein expression in SCC-180. In vivo, there was a delay in OL progression with ART and CSP treatment; however, by the 16th week, only CSP prevented progression to OSCC. Conclusion: Expression of proteins related to ICD and apoptosis did not increase with treatments, and CSP was shown to reduce immunogenic pathways in SCC-180, while reducing cell migration. ART did not prevent the malignant progression of OL in vivo; CSP did despite significant adverse effects. [ABSTRACT FROM AUTHOR]

Balneotherapy includes practices and methods using medically and legally recognized mineral-medicinal waters, muds and natural gases from natural springs for therapeutic purposes. One of the most widely used method in balneotherapy is bathing with thermal mineral water. In the course of the years, scientific community has produced an increasing number of evidences that this practice is an effective method for treating signs and symptoms of several pathologies such as rheumatic, cardiovascular and dermatological diseases. This systematic review is aimed at evaluating the effect of balneotherapy with thermal water baths as a treatment to manage signs and symptoms of patients affected by all types of dermatological diseases. The systematic review was conducted according to the PRISMA Statement, and its protocol was registered on PROSPERO platform (CRD42022295913). The research was performed on the databases Pubmed, Scopus, Web of Science and Cochrane. We included clinical trials evaluating the effects of balneotherapy using thermal mineral water baths for managing dermatological diseases in humans, published in English and Italian language. Eight studies were included, seven of them enrolled adults affected by psoriasis and one studied atopic dermatitis patients. The common result of all the articles included was a clear improvement of signs and symptoms of psoriasis and eczematous diseases after use of thermal mineral water baths. These effects seem to be strictly related to physical and chemical properties of thermal water used for balneotherapy. However, studies in this field are still limited to support robust evidence of the effectiveness of balneotherapy using thermal mineral water baths and often their quality is low. Thus, new clinical studies need to be carried out, using more correct methods for conducting the studies and for processing statistical data. [ABSTRACT FROM AUTHOR]

Diatoms are microalgae that live in marine and freshwater environments and are responsible for about 20% of the world's carbon fixation. Population dynamics of these cells is finely regulated by intricate signal transduction systems, in which oxylipins are thought to play a relevant role. These are oxygenated fatty acids whose biosynthesis is initiated by a lipoxygenase enzyme (LOX) and are widely distributed in all phyla, including diatoms. Here, we present a de novo transcriptome obtained from the RNA-seq performed in the diatom species Pseudo-nitzschia arenysensis, using both a wild-type and a LOX-silenced strain, which will represent a reliable reference for comparative analyses within the Pseudo-nitzschia genus and at a broader taxonomic scale. Moreover, the RNA-seq data can be interrogated to go deeper into the oxylipins metabolic pathways. [ABSTRACT FROM AUTHOR]

NASA uses a continuous risk management process to seek out new knowledge of spaceflight-induced risk to human health and performance. The evidence base that informs the risk assessments in this domain is constantly changing as more information is gleaned from a continuous human presence in space and from ongoing research. However, the limitations of this evidence are difficult to characterize because fewer than 700 humans have ever flown in space, and information comes from a variety of sources that span disciplines, including engineering, medicine, food and nutrition, and many other life sciences. The Human System Risk Board (HSRB) at NASA is responsible for assessing risk to astronauts and communicating this risk to agency decision-makers. A critical part of that communication is conveying the uncertainty regarding the understanding of the changes that spaceflight induces in human processes and the complex interactions between humans and the spacecraft. Although the strength of evidence grades is common in the academic literature, these scores are often not useful for the problems of human spaceflight. The HSRB continues to update the processes used to report the levels of evidence. This paper describes recent updates to the methods used to assign the level of evidence scores to the official risk postures and to the causal diagrams used by the HSRB. [ABSTRACT FROM AUTHOR]

For over a decade, the National Aeronautics and Space Administration (NASA) has tracked and configuration-managed approximately 30 risks that affect astronaut health and performance before, during and after spaceflight. The Human System Risk Board (HSRB) at NASA Johnson Space Center is responsible for setting the official risk posture for each of the human system risks and determining—based on evaluation of the available evidence—when that risk posture changes. The ultimate purpose of tracking and researching these risks is to find ways to reduce spaceflight-induced risk to astronauts. The adverse effects of spaceflight begin at launch and continue throughout the duration of the mission, and in some cases, across the lifetime of the astronaut. Historically, research has been conducted in individual risk "silos" to characterize risk, however, astronauts are exposed to all risks simultaneously. In January of 2020, the HSRB at NASA began assessing the potential value of causal diagramming as a tool to facilitate understanding of the complex causes and effects that contribute to spaceflight-induced human system risk. Causal diagrams in the form of directed acyclic graphs (DAGs) are used to provide HSRB stakeholders with a shared mental model of the causal flow of risk. While primarily improving communication among those stakeholders, DAGs also allow a composite risk network to be created that can be tracked and configuration managed. This paper outlines the HSRB's pilot process for this effort, the lessons learned, and future goals for data-driven risk management approaches. [ABSTRACT FROM AUTHOR]

Background: The immunosuppressive tumor microenvironment (TME) of colorectal cancer (CRC) is a major hurdle for immune checkpoint inhibitor-based therapies. Hence characterization of the signaling pathways driving T cell exhaustion within TME is a critical need for the discovery of novel therapeutic targets and the development of effective therapies. We previously showed that (i) the adaptor protein Rai is a negative regulator of T cell receptor signaling and T helper 1 (Th1)/Th17 cell differentiation; and (ii) Rai deficiency is implicated in the hyperactive phenotype of T cells in autoimmune diseases. Methods: The expression level of Rai was measured by qRT-PCR in paired peripheral blood T cells and T cells infiltrating tumor tissue and the normal adjacent tissue in CRC patients. The impact of hypoxia-inducible factor (HIF)-1α on Rai expression was evaluated in T cells exposed to hypoxia and by performing chromatin immunoprecipitation assays and RNA interference assays. The mechanism by which upregulation of Rai in T cells promotes T cell exhaustion were evaluated by flow cytometric, qRT-PCR and western blot analyses. Results: We show that Rai is a novel HIF-1α-responsive gene that is upregulated in tumor infiltrating lymphocytes of CRC patients compared to patient-matched circulating T cells. Rai upregulation in T cells promoted Programmed cell Death protein (PD)-1 expression and impaired antigen-dependent degranulation of CD8+ T cells by inhibiting phospho-inactivation of glycogen synthase kinase (GSK)-3, a central regulator of PD-1 expression and T cell-mediated anti-tumor immunity. Conclusions: Our data identify Rai as a hitherto unknown regulator of the TME-induced exhausted phenotype of human T cells. [ABSTRACT FROM AUTHOR]

Inclusions comprised of microtubule-associated protein tau (tau) are implicated in a group of neurodegenerative diseases, collectively known as tauopathies, that include Alzheimer’s disease (AD). The spreading of misfolded tau “seeds” along neuronal networks is thought to play a crucial role in the progression of tau pathology. Consequently, restricting the release or uptake of tau seeds may inhibit the spread of tau pathology and potentially halt the advancement of the disease. Previous studies have demonstrated that the Mammalian Suppressor of Tauopathy 2 (MSUT2), an RNA binding protein, modulates tau pathogenesis in a transgenic mouse model. In this study, we investigated the impact of MSUT2 on tau pathogenesis using tau seeding models. Our findings indicate that the loss of MSUT2 mitigates human tau seed-induced pathology in neuron cultures and mouse models. In addition, MSUT2 regulates many gene transcripts, including the Adenosine Receptor 1 (A1AR), and we show that down regulation or inhibition of A1AR modulates the activity of the “ArfGAP with SH3 Domain, Ankyrin Repeat, and PH Domain 1 protein” (ASAP1), thereby influencing the internalization of pathogenic tau seeds into neurons resulting in reduction of tau pathology. [ABSTRACT FROM AUTHOR]

Electromobility offers great potentials to the decarbonisation of the transport sector. The purpose of this study is to analyse the development of electromobility in the European Union (EU) and in the United Kingdom (UK) by 2030. The study is based on the objectives provided by the EU Member States and UK in their national implementation reports, as foreseen by the Directive 2014/94/EU on the deployment of alternative fuels infrastructure. As the initial data coverage was not full, in order to produce a complete data set on registered electric vehicles and public recharging points, we estimated missing values with different statistical techniques and critical analysis of the initial data. A set of proposed indicators, namely the share of electric vehicles, the density of publicly accessible recharging points, the electric vehicles and recharging points annual growth rates and the sufficiency index, were averaged at EU27+UK level to depict the envisaged evolution of electromobility in the present decade. The results show that the objectives of the countries’ governments are overall less ambitious than the goals defined in the EU Green Deal for 2025 and in the Sustainable and Smart Mobility Strategy for 2030. Most of the indicators vary significantly in the 2016–2030 period, often revealing an increased divergence between the development of electric vehicles and public recharging points. Two policy implications are derived: (i) the use of a combined set of indicators to assess the governments’ electromobility plans could be pursued, while the ratio of ten electric vehicles per recharging point may no longer be a useful benchmark; and (ii) measures supporting the uptake of recharging infrastructure are still needed to mitigate the divergence with electric vehicles and to meet the ambitious objectives of the EU Green Deal and Sustainable and Smart Mobility Strategy. [ABSTRACT FROM AUTHOR]

With respect to ozonation, plasma treatment involves direct contact between the discharge and the contaminated water therefore benefiting, in addition to ozone, also of short-lived reactive species. This paper focuses on mechanistic aspects of water treatment based on plasma activation (in-situ discharge) and ozonation (ex-situ discharge), using maleic acid and fumaric acid as model substrates and dielectric barrier discharges (DBDs) for producing plasma and ozone. Both types of experiments were carried out at different pH values and degradation profiles of residual concentration vs treatment time were compared in experiments in which each acid was treated individually and in mixture with the other. It was found that, under all conditions examined, plasma treatment was more efficient than ozonation for both acids, and that fumaric acid was always more reactive than maleic acid. Peculiar S-shaped degradation curves were obtained for the decay of maleic acid when treated in mixture with fumaric acid under acidic and neutral pH conditions in ozonation and in plasma experiments. This effect was not observed when maleic acid was treated in mixture with phenol instead of fumaric acid. The experimental data are nicely fitted with a simple kinetic model which assumes that a single reactive species, in steady state concentration, is responsible for the attack initiating the pollutants degradation. Based on the complete set of results obtained the conclusion is reached that, in the DBD reactor used, under acidic and neutral pH conditions ozone plays a major role in the degradation of maleic and fumaric acids also in direct plasma treatment. [ABSTRACT FROM AUTHOR]

Extraction of α-Synuclein (αSyn) aggregates from Lewy body disease (LBD) brains has been widely described yet templated fibrillization of LB-αSyn often fails to propagate its structural and functional properties. We recently demonstrated that aggregates amplified from LB-αSyn (ampLB) show distinct biological activities in vitro compared to human αSyn preformed fibrils (hPFF) formed de novo. Here we compare the in vivo biological activities of hPFF and ampLB regarding seeding activity, latency in inducing pathology, distribution of pathology, inclusion morphology, and cell-type preference. Injection of ampLB into mice expressing only human αSyn (male Thy1:SNCA/Snca–/– mice) induced pathologies similar to those of LBD subjects that were distinct from those induced by hPFF-injection or developing spontaneously with aging. Importantly, αSyn aggregates in ampLB-injected Thy1:SNCA/Snca–/– mice maintained the unique biological and conformational features of original LB-αSyn. These results indicate that ampLB-injection, rather than conventional PFF-injection or αSyn overexpression, faithfully models key aspects of LBD. α-Synuclein aggregates in Lewy bodies (LBs) have not been widely used for research due to the limited availability of diseased brains. Here, the authors report a mouse model that recapitulates LB diseases using the LB amplification method. [ABSTRACT FROM AUTHOR]

Negative emotional stimuli can strongly bias attention, particularly in individuals with high levels of dispositional negative affect (NA). The current study investigated whether the prefrontal cortex (PFC), a brain region involved in the top-down regulation of emotional processing, plays a different role in controlling attention to emotions, depending on the individual NA. Sham and anodal transcranial direct current stimulation (tDCS) was delivered over the right or left PFC while assessing attentional bias (AB) to emotions (happy, angry, sad faces) in individuals with higher and lower trait NA. When tDCS was inactive (sham), individuals with higher trait NA showed AB toward angry and away from sad faces, while individuals with lower trait NA presented with no AB. Right anodal-tDCS abolished the AB toward angry faces and induced an AB toward sad faces in individuals with higher trait NA, while no effect was found in individuals with lower trait NA. Left anodal-tDCS abolished any AB in individuals with higher trait NA and induced an AB away from happy faces in individuals with lower trait NA. These findings confirm a critical role of trait NA in AB to emotions and demonstrate a different involvement of PFC in emotional processing based on dispositional affect. [ABSTRACT FROM AUTHOR]

Research Institutions are tackling the ever so increasing challenge to share the outcomes of scientific research and technological innovations with a forthright method in order to increase involvement of the community. To achieve that aim, the main recipients of the information must be the focus point on which outreach and educational activities concentrate. Standard analysis of visitor's experiences within informal learning activities can provide useful information on the activity impacts. In fact, evaluating the performance allows to improve the effects, achievements and benefits in the audiences. This research was carried out by analysing quantitative and qualitative studies performed in the occasion of a temporary outreach event, in which visitors were the focal point. Different types of audiences were examined during an Open Day at the Istituto Nazionale di Geofisica e Vulcanologia (INGV)—Italian Institute of Geophysical and Volcanological Research—based in Rome, leading to the results we present in this work. The event was remarkable as it brought together a broad selection of scientific laboratories, exhibition spaces and meetings with researchers, all custom tailored towards the specific audiences. At the end of the event, questionnaires were handed over to the visitors, both young and adults, and to any stakeholder that were present. The answers and the open feedbacks from the visitors have disclosed valuable information on INGV's audience, and allowed the events organization and contents to be refined and improved. This procedure can most certainly be turned into a methodical system to obtain a general picture of the cognitive and emotional effects on visitors participating in scientific itineraries. The quantitative method used in this research involved analysing the answers in the questionnaires with a statistical approach and was blended with the qualitative method that took into account the visitor's personal feedback and input. The aftermath of the study allows to pinpoint the main event issues and to take actions aimed to enrich visitor's satisfaction and experience. In fact, advertising of the events ahead of time, arranging a well designed and implemented online information and booking system in order to better accommodate for the number of visitors, realizing dedicated apps for the each tours, creating a shorter questionnaire for children, and creating standards for questionnaires that would be used in the future. [ABSTRACT FROM AUTHOR]

Purpose: Physical activity is associated with a reduction in mortality and recurrence risks in patients with cancer. Despite the well-recognized benefits of exercise, patients' adherence to an exercise program remains a challenge. The present study aimed to assess the experiences of patients with cancer participating in a 12-week exercise program. Methods: A total of 21 survivors participated in focus group discussions after the conclusion of the exercise intervention. Semi-structured interview questions were developed according to the theory of the Health Belief Model. Data were analyzed using thematic analysis and categorized into perceived benefits, barriers, and cues to action. Results: Patients described a series of benefits achieved during the exercise program, from physical to psychological domains. Treatment-related side effects and logistic factors, including distance from the gym facility, were the most commonly reported barriers to adherence. Concerning cues to action, expected benefits from exercise were the most important reason to participate, while a patient-center program, supervised by skilled experts, highly stimulated patients to complete the program. Conclusion: Overall, patients with cancer reported a positive experience participating in a supervised exercise program. A variety of factors influencing participation and adherence were individuated. This study may help design and develop effective and sustainable programs addressing individuals' needs. [ABSTRACT FROM AUTHOR]

This systematic review is aimed to evaluate the effects of balneotherapy with thermal mineral water for managing the symptoms and signs of osteoarthritis located at any anatomical site. The systematic review was conducted according to the PRISMA Statement. The following databases were consulted: PubMed, Scopus, Web of Science, Cochrane Library, DOAJ and PEDro. We included clinical trials evaluating the effects of balneotherapy as a treatment for patients with osteoarthritis, published in English and Italian language, led on human subjects. The protocol was registered in PROSPERO. Overall, 17 studies have been included in the review. All of these studies were performed on adults or elderly patients suffering from osteoarthritis localized to knees, hips, hands or lumbar spine. The treatment assessed was always the balneotherapy with thermal mineral water. The outcomes evaluated were pain, palpation/pressure sensibility, articular tenderness, functional ability, quality of life, mobility, deambulation, ability to climb stairs, medical objective and patients' subjective evaluation, superoxide dismutase enzyme activity, serum levels of interleukin-2 receptors. The results of all the included studies agree and demonstrated an improvement of all the symptoms and signs investigated. In particular, pain and quality of life were the main symptoms evaluated and both improved after the treatment with thermal water in all the studies included in the review. These effects can be attributed to physical and chemical-physical properties of thermal mineral water used. However, the quality of many studies resulted not so high due and, consequently, it is necessary to perform new clinical trial in this field using more correct methods for conducting the study and for processing statistical data. [ABSTRACT FROM AUTHOR]

Purpose: Middle cerebral aneurysms were underrepresented in the two largest trials (BRAT and ISAT) for the treatment of ruptured intracranial aneurysms. Recent institutional series addressing the choice between endovascular or open repair for this subset of aneurysms are few and have not yielded a definitive conclusion. We compare clinical outcomes of patients presenting with acute subarachnoid hemorrhage from ruptured middle cerebral artery aneurysms undergoing either open or endovascular repair. Methods: We conducted a retrospective review of 138 consecutive patients with ruptured middle cerebral artery aneurysms admitted into our institution from January 2008 to March 2019 to compare endovascular and open surgical outcomes. Results: Of the ruptured middle cerebral artery aneurysms, 57 underwent endovascular repair while 81 were treated with open surgery. Over the study period, there was a notable shift in practice toward more frequent endovascular treatment of ruptured MCA aneurysms (31% in 2008 vs. 91% in 2018). At discharge (49.1% vs 29.6%; p =.002) and at 6 months (84.3% vs 58.6%; p = 0.003), patients who underwent endovascular repair had a higher proportion of patients with good clinical outcomes (mRS 0–2) compared to those undergoing open surgery. Long-term follow-up data (endovascular 54.9 ± 37.9 months vs clipping 18.6 ± 13.4 months) showed no difference in rebleeding (1.8% vs 3.7%, p = 0.642) and retreatment (5.3% vs 3.7%, p = 0.691) in both groups. Conclusion: Our series suggests equipoise in the treatment of ruptured middle cerebral artery aneurysms and demonstrates endovascular repair as a potentially feasible treatment strategy. Future randomized trials could clarify the roles of these treatment modalities. [ABSTRACT FROM AUTHOR]

The development of new biomaterials with improved properties is a trend in tissue regeneration. In this way, an innovative approach is employed in this work for obtaining polymer fibers coated with nanoparticles resulting from the simultaneous application of poly (lactic acid) (PLA)/polycaprolactone (PCL) electrospinning and bioactive particles from an amorphous multicomponent silica–calcium–phosphorus system (AMS) electrospraying. The osteogenesis was evaluated in vitro and in vivo using male rats, in which total protein, alkaline phosphatase, and biological performance through histological and histomorphometric analysis were discussed. The morphological results assessed by scanning electron microscopy showed a mesh of PLA/PCL fibers associated with AMS. The spraying of 17.44% of AMS particles in the PLA/PCL electrospun fibers decreased the Young's modulus and tensile strength. However, the amount of AMS particles sprayed was enough to promote a reduction of 17.8% in the measured contact angle values. Phosphatase alkaline higher mean value was also observed in the fibers when in contact with the AMS, but nonstatistical difference was observed (p > 0.05). It was possible to observe the presence of mineralized nodules deposited on the bottom of the plate and between the fibers. The newly formed bone into defect filled with PLA/PCL-AMS fibers was higher than that observed in the control group. These findings suggest PLA/PCL-AMS fibers as a multifunctional composite system that may be attractive for both bone and dental tissue engineering applications. [ABSTRACT FROM AUTHOR]

Background: Leukodystrophy with vanishing white matter (LVWM) is an autosomal recessive disease with typical pediatric-onset caused by mutations in one of the five EIF2B genes. Adult-onset (AO) cases are rare. Methods: In this observational study, we reviewed clinical and laboratory information of the patients with AO-LVWM assessed at two referral centers in Italy and Portugal from Jan-2007 to Dec-2019. Results: We identified 18 patients (13 females) with AO-LVWM caused by EIF2B5 or EIF2B3 mutations. Age of neurological onset ranged from 16 to 60 years, with follow-ups occurring from 2 to 37 years. Crucial symptoms were cognitive and motor decline. In three patients, stroke-like events were the first manifestation; in another, bladder dysfunction remained the main complaint across decades. Brain MRI showed white matter (WM) rarefaction in all cases, except two. Diffusion-weighted imaging documented focal hyperintensity in the acute stage of stroke-like events. 1H-spectroscopy primarily showed N-acetyl-aspartate reduction; 18fluorodeoxyglucose-PET revealed predominant frontoparietal hypometabolism; evoked potential studies demonstrated normal-to-reduced amplitudes; neuro-ophthalmological assessment showed neuroretinal thinning, and b-wave reduction on full-field electroretinogram. Interestingly, we found an additional patient with LVWM-compatible phenotype and monoallelic variants in two distinct eIF2B genes, EIF2B1 and EIF2B2. Conclusions: AO-LVWM presents varying clinical manifestations at onset, including stroke-like events. WM rarefaction is the most consistent diagnostic clue even in the latest onset cases. Spectroscopy and electrophysiological features are compatible with axon, rather than myelin, damage. Cerebral glucose metabolic abnormalities and retinal alterations can be present. LVWM might also be caused by a digenic inheritance affecting the eIF2B complex. [ABSTRACT FROM AUTHOR]

In 2015, the International Association of Geodesy published a resolution on the International Height Reference System definition. It is defined that the vertical coordinate must be given in geopotential number and that the realization of this system must be done considering gravity values arranged homogeneously around the stations. However, it should be regarded that for the stations that are located on the coast. This fact can cause a loss in accuracy in determining the potential gravity. Until now, the studies consider only global gravity models, coming from satellite gravity missions to complement the data in the oceanic region and not considering high-frequency components of the gravity field measured at the surface. Consequently, this research considered shipboard-measured marine gravity data integrated with global marine gravity model data derived from altimetric satellites (DTU17 and GRAV31.1) to compute the gravity potential for the two coastal stations that are part of the International Height Reference Frame (IHRF) in Brazil, CEFT and IMBT stations. The gravity potential was computed following the standardization determinations for the IHRF, and the results showed that the marine gravity data incorporated into the computation did not contribute to accuracy. [ABSTRACT FROM AUTHOR]

Since the COVID-19 pandemic, intimate partner violence (IPV) rates have increased in the United States. Although accumulating research has documented the effectiveness of couple-based interventions in reducing HIV/STIs, it remains unclear whether they are effective and safe for couples experiencing IPV. We used moderation analysis from a randomized clinical trial to evaluate whether a couples-based HIV/STI intervention may have differential effectiveness in reducing HIV/STI risks among couples where one or both partners reported experiencing IPV compared to couples without such IPV among a sample of 230 men at risk for HIV/STIs who reported using drugs and were mandated to community supervision settings in New York City and their main female sexual partners. The findings of this study suggest that the effectiveness of this evidence-based couple HIV intervention in reducing condomless sex and other HIV/STI risks did not differ between couples with IPV compared to couples without IPV. Intimate partners who use drugs and are involved in the criminal legal system are disproportionately impacted by both HIV/STIs and IPV, underscoring the importance of couple-level interventions that may be scaled up to address the dyadic HIV risks and IPV together in community supervision settings. [ABSTRACT FROM AUTHOR]

Epoxy resins are widely used in a variety of application fields, thanks to their good mechanical strength, chemical resistance and adhesion to several substrates. Nowadays, the quite majority of epoxy resins are based on derivatives of bisphenol A (BPA), which poses serious health concerns. This issue is pushing the research towards suitable bio-based alternatives to this product, being furan-based epoxies very promising in this respect. In a previous work, 2,5-bis[(oxiran-2-ylmethoxy)methyl]furan (BOMF) was cured with methyl nadic anhydride (MNA), and successfully used as tinplate coating. Herein, in a view of increasing the sustainability of these epoxy resins, we have replaced MNA with maleic anhydride (MA), which can be derived from vegetable feedstocks, thus obtaining a fully bio-based epoxy resin. This latter has then been used as adhesive for carbon fiber-reinforced thermosetting plastics (CFRP). The curing process of the resin was monitored by differential scanning calorimetry (DSC) and chemo-rheological analysis. The results highlighted the significantly higher reactivity of BOMF towards MA compared to the diglycidyl ether of BPA (DGEBA). The crosslinked samples were characterized in their thermal, mechanical and adhesive properties. In comparison to DGEBA/MA and BOMF/MNA, BOMF/MA showed higher ultimate strain and slightly lower glass transition temperature, tensile modulus and ultimate strength. Interestingly, BOMF/MA displayed outstanding adhesive strength on CFRP joints, outperforming the DGEBA-based counterpart by three times. Indeed, by properly selecting the anhydride curing agent, a highly ductile fully bio-based material was developed for high performance adhesive applications. The overall results demonstrate that the properties of BOMF-based epoxy resins can be tailored to meet technical and safety requirements of downstream applications, representing a sustainable alternative to traditional systems containing DGEBA. [ABSTRACT FROM AUTHOR]

We analyse the 3-point CFT correlators involving non-conserved spinning operators in momentum space. We derive a general expression for the conformal Ward identities defining the 3-point functions involving two generic spin s non-conserved operators and a spin 1 conserved current. We give explicit expressions for the 3-point function when the two non-conserved operators have spins 1 and 2 and generic conformal dimensions. We also systematically analyse the divergences appearing in these 3-point functions when the conformal dimensions of the two non-conserved operators coincide. [ABSTRACT FROM AUTHOR]

The quantitative assessment of the carbonate system represents one of the biggest challenges toward the "Sustainable Development Goals" defined by the United Nations in 2015. In this sense, the present study investigated the Spatio-temporal dynamics of the carbonate system and the effects of the El Niño and La Niña phenomena over the Cabo Frio upwelling area. The physical characterization of the site was carried out through data on wind speed and sea surface temperature. Water samples were also collected during the oceanographic cruise onboard the Diadorim R/V (Research Vessel). From these samples, the parameters of absolute and practical salinity, density, pH, total alkalinity, carbonate, calcite, aragonite, bicarbonate dissolved inorganic carbon, carbon dioxide, partial pressure of carbon, calcium, and total boron were obtained. The highest average concentration of bicarbonate in S1 (2018 µmol/kg) seems to contribute to the dissolved inorganic carbon values (2203 µmol/kg). The values of calcite saturation state, aragonite saturation state, and carbonate were higher on the surface of each station (calcite saturation state = 4.80–5.48; aragonite saturation state = 3.10–3.63, and carbonate = 189–216 µmol/kg). The mean values of pH were similar in the day/night samples (7.96/7.97). The whole carbonate system was calculated through thermodynamic modeling with the Marine Chemical Analysis (AQM) program loaded with the results of the following parameters: temperature, salinity, total alkalinity, and pH parameters. This manuscript presents original data on the carbonate system and the "acidification" process influenced by the Cabo Frio upwelling, which directly depends on the El Niño and La Niña phenomena oscillations in the sea surface temperature. [ABSTRACT FROM AUTHOR]

Arrows and gaze stimuli lead to opposite spatial congruency effects. While standard congruency effects are observed for arrows (faster responses for congruent conditions), responses are faster when eye-gaze stimuli are presented on the opposite side of the gazed-at location (incongruent trials), leading to a reversed congruency effect (RCE). Here, we explored the effects of implicit vs. explicit processing of arrows and eye-gaze direction. Participants were required to identify the direction (explicit task) or the colour (implicit task) of left or right looking/pointing gaze or arrows, presented to either the left or right of the fixation point. When participants responded to the direction of stimuli, standard congruency effects for arrows and RCE for eye-gaze stimuli were observed. However, when participants responded to the colour of stimuli, no congruency effects were observed. These results suggest that it is necessary to explicitly pay attention to the direction of eye-gaze and arrows for the congruency effect to occur. The same pattern of data was observed when participants responded either manually or verbally, demonstrating that manual motor components are not responsible for the results observed. These findings are not consistent with some hypotheses previously proposed to explain the RCE observed with eye-gaze stimuli and, therefore, call for an alternative plausible hypothesis. [ABSTRACT FROM AUTHOR]

Introduction: Delirium is an acute fluctuating disorder of attention and awareness, which often complicates the clinical course of several conditions, including acute stroke. The aim of the present study was to determine whether delirium occurrence impacts the outcome of patients with acute stroke. Methods: The study design is single center, prospective, observational. We consecutively enrolled patients admitted to the stroke unit from April to October 2020. Inclusion criteria were age ≥ 18 years and diagnosis of acute stroke. Exclusion criteria were stroke mimics, coma, and terminal conditions. All patients were screened for delirium upon admission, within 72 h, and whenever symptoms suggesting delirium occurred by means of the Confusion Assessment Method for Intensive Care Unit and the Richmond Agitation Sedation Scale. Outcomes were evaluated with the 90-days modified Rankin Scale (mRS) by telephone interview. Results: The final study cohort consisted of 103 patients (62 men; median age 75 years, interquartile range 63–81). Thirty-one patients (30%) developed delirium. In the multivariate ordinal logistic regression, patients with delirium had higher mRS scores at 3 months (DLR + : mRS = 4 (3–6); DLR–: mRS = 1 (1–3); adjusted odds ratio = 4.83; CI = 1.88–12.35; p = 0.006). Delirium was a risk factor for death (mRS = 6) in the univariate logistic regression (OR 4.5, CI = 1.44–14.07; p = 0.010), but not in the adjusted analysis (OR 3.45; CI = 0.66–17.95; p = 0.142). Survival time during 90-days follow-up was shorter in the delirium group (Log Rank χ2 3.89; p = 0.048). Conclusion: Delirium negatively impacts the prognosis of patients with acute stroke. Patients with post-stroke delirium have a worse functional outcome and a shorter survival. [ABSTRACT FROM AUTHOR]

The integration of biomaterials in tissue regeneration has been showing effectiveness in the treatment of diseases related to bone structure and tissue repair. Membranes have aroused interest due to their ease of manufacture, variation in composition, and the structure of the biomaterial. The incorporation of bioactive glass (BG) increases bioactivity, and when doped with therapeutic ions, changes in the physical-chemical composition of the biomaterial are expected to enhance its biological effect. This study aimed to produce polycaprolactone (PCL) membranes incorporated with 58S bioactive glass, doped with Zinc (Zn) by the electrospinning technique, and evaluate the influence of this biomaterial in the activity and differentiation of mesenchymal stem cells. The BG was produced by using the sol-gel process; next, before the PCL preparation, the BG was doped with zinc in a solution. Then, PCL solutions were prepared with 7% by weight of BG and doped with 10% ZnCl2. Afterward, the electrospinning process was carried out using the fixed parameters: 2mLh-1 flow rate, 10kV voltage, and 12cm distance. Before the biological assays, the chemical elements present in the fibers were evaluated by energy dispersion X-ray spectroscopy (EDS), and the mapping technique. The morphology of the biomaterial and the diameter of fibers were analyzed by scanning electron microscopy (SEM), and the hydrophilicity of the membranes was evaluated by the contact angle technique. The in vitro tests consisted of cell plating with mesenchymal stem cells (MSC's), previously obtained from rat femurs, at a density of 1x104 per well that contained three different groups: a) P: mesenchymal stem cells plated with PCL; b) PB: mesenchymal stem cells plated with the composite of PCL / BG; c) PBZ: mesenchymal stem cells plated with the Zn doped PCL / BG composite. To evaluate the influence of the biomaterial on osteoblastic activity and differentiation, osteogenic and non-osteogenic media were used in tests of cell viability (MTT assay), total protein content, alkaline phosphatase activity (ALP), and mineralization nodules. The analysis by SEM proved that the electrospinning technique was efficient for producing fibers incorporated with bioactive glass, and EDS and the mapping technique confirmed the chemical components of each group of fibers, including the doped zinc in the bioactive glass. The analysis of fibers diameter showed that P and PBZ had presented fibers with a larger diameter than the PB group, and the contact angle technique showed an increase in the hydrophilicity of the group containing doped Zinc when compared to the other groups analyzed. The MTT assay confirmed that the membranes weren´t cytotoxic and allowed cell viability, total protein content showed that all the groups had cell activity, with a statistically significant difference between the groups (p<0,05). Even with no statistically significant difference, osteogenesis was proved by ALP activity and the formation of mineralization nodules. Based on the results, the PCL membranes incorporated with 58S bioactive glass doped with zinc have shown promise in tissue engineering for use in bone tissue regeneration. [ABSTRACT FROM AUTHOR]

A significant proportion of carbon (C) captured by terrestrial primary production is buried in lacustrine ecosystems, which have been substantially affected by anthropogenic activities globally. However, there is a scarcity of sedimentary organic carbon (OC) accumulation information for lakes surrounded by highly productive rainforests at warm tropical latitudes, or in response to land cover and climate change. Here, we combine new data from intensive campaigns spanning 13 lakes across remote Amazonian regions with a broad literature compilation, to produce the first spatially-weighted global analysis of recent OC burial in lakes (over ~50-100-years) that integrates both biome type and forest cover. We find that humid tropical forest lake sediments are a disproportionately important global OC sink of ~80 Tg C yr−1 with implications for climate change. Further, we demonstrate that temperature and forest conservation are key factors in maintaining massive organic carbon pools in tropical lacustrine sediments. Tropical forest lake sediments are global carbon sinks, representing an important implication for climate change, of which both temperature and forest conservation are key factors in maintaining the carbon burial mechanism in lacustrine ecosystems. [ABSTRACT FROM AUTHOR]

Digital Twins (DT) models are gaining special attention in the management and maintenance of facilities. The quality of data contained in these models may be enhanced by the use of processed information coming from long-term Structural Health Monitoring (SHM). In this case real time processing and updating in systems using sensor networks for SHM need low latency and reliable communication. This paper presents a solution for exploiting DT models for SHM and early warning solutions improvement. The case study scenario resides within the 5G experimentation in the city of L'Aquila and it exploits a highly adaptable sensor board and a 5G Multi-Access Edge Computing architecture. [ABSTRACT FROM AUTHOR]

Attention involves three functionally and neuroanatomically distinct neural networks: alerting, orienting, and executive control. This study aimed to analyze the development of attentional networks in children aged between 3 and 6 years using a child-friendly version of the Attentional Network Test for Interaction (ANTI), the ANTI-Birds. The sample included 88 children divided into four age groups: 3-year-old, 4-year-old, 5-year-old, 6-year-old children. The results of this study would seem to indicate that between 4 and 6 years, there are no significant changes in attentional networks. Instead, between 3 and 4 years of age, children significantly improve all their attentional skills. [ABSTRACT FROM AUTHOR]

We studied the genetic resistance to Campylobacter coli and Campylobacter jejuni in wild boar using both STR analysis and genome-wide association studies (GWAS). A total of 60 wild boars hunted in Tuscany (Italy) during the 2018/2019 hunting season were analyzed and genotyped. During postmortem operations, fecal swabs, liver samples and kidneys were collected. Two groups of animals were considered for the statistical analysis: 28 Campylobacter positive (22 for C. coli and 6 for C. jejuni) and 32 Campylobacter negative. Regarding STR analysis, 15 markers belonging to a marker panel validated by the International Society of Animal Genetics (ISAG) for swine were used: for each marker, alleles and genotype frequencies between the two groups of animals were compared using the Chi-square test and Fisher's exact tests. To analyze the genetic variability within groups, the following parameters were computed: molecular coancestry coefficients (fij), kinship distance (Dk), inbreeding coefficient (Fi), and genetic similarities (GS). The internal relatedness (IR) was also calculated, and ANOVA was used to verify the relationships between IR and Campylobacter groups. For GWAS, the Geneseek Genomic Profiler Porcine HD (70 k), containing 62,330 SNPs, was used. No differences in the internal relatedness (IR) were observed between the two groups (F = 5.64, P = 0.065) and no significant association between STRs and SNPs and Campylobacter positivity was observed. Although genetic resistance to bacterial diseases is often regulated by multiple genes controlling different processes of the host–pathogen interaction, in our studies no candidate genes that could be directly or indirectly involved in the development of the disease were identified. [ABSTRACT FROM AUTHOR]

Purpose: Evaluating the potential of gross Linum usitatissimum L. seed mucilage to be used as a drug release retardant. In order to do so, seeds were subjected to a simple and scalable extractive process comprising few stages, without alcohol-based precipitation. Matrix tablets based on hydrophilic polymers are one of the simplest forms of developing modified release systems. Methods: Flaxseeds were added to distilled water at a flaxseed:water ratio of 1:13; the suspension was continuously stirred at room temperature, for 24 h. Flaxseeds were sieved and the gross linseed mucilage was freeze-dried. Subsequently, the sample was analyzed through Fourier transform infrared spectroscopy (IV-TF) at wavelength ranging from 650 to 4000 cm−1. Results: Infrared (IR) spectroscopy analysis has suggested the presence of flaxseed mucilage polymers in the extracted product. Tablets presenting mucilage or HPMC (hydroxypropyl methylcellulose) and tablets without polymer were prepared based on the wet granulation technique. Matrix tablets presenting mucilage or HPMC have shown similar dissolution profiles, as well as similar potential in drug release control. Conclusion: The product extracted from flaxseed under simple conditions, even without undergoing purification process, can have high technological value in the pharmaceutical industry because it has excellent potential to be used as excipient for matrix tablet manufacturing. [ABSTRACT FROM AUTHOR]

Purpose: Nutrition is an important, modifiable, environmental factor affecting human health by modulating epigenetic processes, including DNA methylation (5mC). Numerous studies investigated the association of nutrition with global and gene-specific DNA methylation and evidences on animal models highlighted a role in DNA hydroxymethylation (5hmC) regulation. However, a more comprehensive analysis of different layers of nutrition in association with global levels of 5mC and 5hmC is lacking. We investigated the association between global levels of 5mC and 5hmC and human nutrition, through the stratification and analysis of dietary patterns into different nutritional layers: adherence to Mediterranean diet (MD), main food groups, macronutrients and micronutrients intake. Methods: ELISA technique was used to measure global 5mC and 5hmC levels in 1080 subjects from the Moli-sani cohort. Food intake during the 12 months before enrolment was assessed using the semi-quantitative EPIC food frequency questionnaire. Complementary approaches involving both classical statistics and supervised machine learning analyses were used to investigate the associations between global 5mC and 5hmC levels and adherence to Mediterranean diet, main food groups, macronutrients and micronutrients intake. Results: We found that global DNA methylation, but not hydroxymethylation, was associated with daily intake of zinc and vitamin B3. Random Forests algorithms predicting 5mC and 5hmC through intakes of food groups, macronutrients and micronutrients revealed a significant contribution of zinc, while vitamin B3 was reported among the most influential features. Conclusion: We found that nutrition may affect global DNA methylation, suggesting a contribution of micronutrients previously implicated as cofactors in methylation pathways. [ABSTRACT FROM AUTHOR]

Objectives: Delirium is an acute fluctuating disorder of attention and awareness. It is associated with autonomic dysfunction and increased mortality. The primary endpoint of our study was to measure autonomic activity in acute stroke patients, by means of heart rate variability analysis, in order to identify autonomic modifications that can predispose to delirium.Methods: Patients were consecutively enrolled from the stroke unit. Inclusion criteria were age ≥ 18 years and diagnosis of stroke with onset within the previous 72 h confirmed by neuroimaging. Exclusion criteria were atrial fibrillation, congestive heart failure, and conditions requiring intensive care unit. Patients were evaluated by means of Richmond Agitation Sedation Scale (RASS) and Confusion Assessment Method-Intensive Care Unit (CAM-ICU) at baseline, after 72 h, or when symptoms suggesting delirium occurred. For each patient, ECG was recorded at baseline assessment and HRV analysis was conducted on five consecutive minutes of artifact-free ECG traces.Results: Fifty-six ECGs were available for analysis. During the study period, 11 patients developed delirium. Patients with and without delirium did not differ for sex, age, severity of stroke, and comorbidities. The delirium group had greater standard deviation of the heart rate (DLR - :9.16 ± 8.28; DLR + : 14.36 ± 5.55; p = 0.026) and lower power spectral density of the HF component (DLR - : 38.23 ± 19.23 n.u.; DLR + : 25.75 ± 8.77 n.u.; p = 0.031).Conclusions: Acute non-cardioembolic stroke patients with increased variability of heart rate and decreased vagal control are at risk for delirium. [ABSTRACT FROM AUTHOR]

Introduction: Treatments other than topical and systemic antibiotics are needed to restore the dysbiosis correlated with acne onset and evolution. In this view, probiotics and botanical extracts could represent a valid adjunctive therapeutic approach. The purpose of this study was to test the efficacy of a dietary supplement containing probiotics (Bifidobacterium breve BR03 DSM 16604, Lacticaseibacillus casei LC03 DSM 27537, and Ligilactobacillus salivarius LS03 DSM 22776) and botanical extract (lupeol from Solanum melongena L. and Echinacea extract) in subjects with mild to moderate acne over an 8-week study period. Methods: Monocentric, randomized, double-blind, four-arm, placebo-controlled clinical study involving 114 subjects. Results: A significant (p < 0.05) effect on the number of superficial inflammatory lesions was reported over the study period in the subjects taking the study agent (group II) (−56.67%), the botanical extracts (group III) (−40.00%), and the probiotics (group IV) (−38.89%) versus placebo (−10.00%). A significant (p < 0.05) decrease in mean desquamation score, sebum secretion rate, and porphyrin mean count versus baseline was also reported, and the effect was most evident for group II. The analysis of log relative abundance after 4 and 8 weeks of treatment compared with baseline showed a significant (p < 0.01) decrease in Cutibacterium acnes and S. aureus, along with a contextually and significant (p < 0.05) increase in Staphylococcus epidermidis, especially in group II. No significant changes were reported for group I. Conclusion: The results from this study suggest that the administration of the dietary supplement under study was effective, safe, and well tolerated in subjects with mild to moderate acne and could represent a promising optional complement for the treatment of inflammatory acne as well as for control of acne-prone skin. [ABSTRACT FROM AUTHOR]

When reaching to grasp previously seen, now out-of-view objects, we rely on stored perceptual representations to guide our actions, likely encoded by the ventral visual stream. So-called memory-guided actions are numerous in daily life, for instance, as we reach to grasp a coffee cup hidden behind our morning newspaper. Little research has examined obstacle avoidance during memory-guided grasping, though it is possible obstacles with increased perceptual salience will provoke exacerbated avoidance maneuvers, like exaggerated deviations in eye and hand position away from obtrusive obstacles. We examined the obstacle avoidance strategies adopted as subjects reached to grasp a 3D target object under visually-guided (closed loop or open loop with full vision prior to movement onset) and memory-guided (short- or long-delay) conditions. On any given trial, subjects reached between a pair of flanker obstacles to grasp a target object. The positions and widths of the obstacles were manipulated, though their inner edges remained a constant distance apart. While reach and grasp behavior was consistent with the obstacle avoidance literature, in that reach, grasp, and gaze positions were biased away from obstacles most obtrusive to the reaching hand, our results reveal distinctive avoidance approaches undertaken depend on the availability of visual feedback. Contrary to expectation, we found subjects reaching to grasp after a long delay in the absence of visual feedback failed to modify their final fixation and grasp positions to accommodate the different positions of obstacles, demonstrating a more moderate, rather than exaggerative, obstacle avoidance strategy. [ABSTRACT FROM AUTHOR]

Apathy is a highly prevalent symptom of dementia. Despite its association with faster cognitive and functional decline, decreased quality of life and increased mortality, no therapies are currently approved to treat apathy. The objective of this review was to summarize the drugs that have been studied for apathy treatment in patients with dementia (specifically Alzheimer's disease [AD], Huntington's disease [HD] and Parkinson's disease [PD] dementia; dementia with Lewy bodies [DLB]; vascular dementia [VaD]; and frontotemporal dementia [FTD]) based on their putative mechanisms of action. A search for relevant studies was performed using ClinicalTrials.gov and PubMed. Eligible studies were randomized controlled trials that were available in English and included at least one drug intervention and an apathy measure scale. A total of 52 studies that included patients with AD (n = 33 studies), PD (n = 5), HD (n = 1), DLB (n = 1), FTD (n = 3), VaD (n = 1), VaD and AD (n = 4), VaD and mixed dementia (n = 1), and AD, VaD and mixed dementia (n = 3) were eligible for inclusion. These studies showed that methylphenidate, olanzapine, cholinesterase inhibitors, choline alphoscerate, citalopram, memantine, and mibampator are the only beneficial drugs in AD-related apathy. For PD-related apathy, only methylphenidate, rotigotine and rivastigmine showed benefits. Regarding FTD- and DLB-related apathy, initial studies with agomelatine and rivastigmine showed benefits, respectively. As for HD- and only-VaD-related apathy, no drugs demonstrated benefits. With regards to mixed populations, memantine, galantamine and gingko biloba showed effects on apathy in the AD plus VaD populations and nimodipine in the VaD plus mixed dementia populations. Of the drugs with positive results, some are already prescribed to patients with dementia to target other symptoms, some have characteristics—such as medical contraindications (e.g., cardiovascular) and adverse effects (e.g., gastrointestinal disturbances)—that limit their clinical use and some require further study. Future studies should investigate apathy as a primary outcome, making use of appropriate sample sizes and study durations to ensure durability of results. There should also be a consensus on using scales with high test/retest and interrater reliabilities to limit the inconsistencies between clinical trials. In conclusion, there are currently no US FDA-approved drugs that target apathy in dementia, so there is an ongoing need for the development of such drugs. [ABSTRACT FROM AUTHOR]

Oxidative stress has been known to be the underlying cause in many instances of cancer development. The new aspect of cancer genesis that has caught the attention of many researchers worldwide is its connection to non-coding RNAs (ncRNAs). ncRNAs may not be protein coding, but in light of the more recent discovery of their wide range of functions, the term 'dark matter of the genome' has been rendered inapplicable. There is an extensive mention of colon cancer as an example, where some of these ncRNAs and their manipulations have seen significant progress. As of now, the focus is on discovering a non-invasive, cost-effective method for diagnosis that is easier to monitor and can be conducted before visible symptoms indicate cancer in a patient, by which time it may already be too late. The concept of liquid biopsies has revolutionized recent diagnostic measures. It has been possible to detect circulating parts of the cancer genome or other biomarkers in the patients' bodily fluids, resulting in the effective management of the disease. This has led these ncRNAs to be considered effective therapeutic targets and extrinsic modifications in several tumor types, proven to be effective as therapy. However, there is a vast scope for further understanding and pertinent application of our acquired knowledge and expanding it in enhancing the utilization of ncRNAs for a better prognosis, quicker diagnosis, and improved management of cancer. This review explores the prognosis of cancer and related mutations by scrutinizing small ncRNAs in the disease. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the present cross-sectional study is to investigate the role of perceived COVID-19-related organizational demands and threats in predicting emotional exhaustion, and the role of organizational support in reducing the negative influence of perceived COVID-19 work-related stressors on burnout. Moreover, the present study aims to add to the understanding of the role of personal resources in the Job Demands-Resources model (JD-R) by examining whether personal resources—such as the professionals' orientation towards patient engagement—may also strengthen the impact of job resources and mitigate the impact of job demands. Methods: This cross-sectional study involved 532 healthcare professionals working during the COVID-19 pandemic in Italy. It adopted the Job-Demands-Resource Model to study the determinants of professional's burnout. An integrative model describing how increasing job demands experienced by this specific population are related to burnout and in particular to emotional exhaustion symptoms was developed. Results: The results of the logistic regression models provided strong support for the proposed model, as both Job Demands and Resources are significant predictors (OR = 2.359 and 0.563 respectively, with p < 0.001). Moreover, healthcare professionals' orientation towards patient engagement appears as a significant moderator of this relationship, as it reduces Demands' effect (OR = 1.188) and increases Resources' effect (OR = 0.501). Conclusions: These findings integrate previous findings on the JD-R Model and suggest the relevance of personal resources and of relational factors in affecting professionals' experience of burnout. [ABSTRACT FROM AUTHOR]

For both spiritual and cultural reasons, churches are an essential part of the historical heritage of several countries worldwide, including Europe, Americas and Australasia. The extreme damage that occurred during the 2016–2017 Central Italy seismic swarm highlighted once again the noteworthy seismic vulnerability of unreinforced masonry churches, which exhibited several collapses and caused uncountable losses to the Italian artistic heritage. The seismic performance of 158 affected buildings was analyzed in the aftermath of the main shocks. The failure modes activated by the earthquakes were identified making reference to the local mechanisms currently considered in Italy for post-seismic assessment of churches. The structural damage of the investigated buildings, related to 21 mechanisms rather than to an overall global response, was explained resorting to empirical statistical procedures taking into account ground motion intensity and structural details that can worsen or improve the seismic performance. Finally, parametric fragility curves were derived selecting those structural details that mostly influence the damage by means of the likelihood-ratio test. Developed models can be used in future territorial-scale scenario or risk analyses. [ABSTRACT FROM AUTHOR]