Topology optimization of multi-story buildings under fully non-stationary stochastic seismic ground motion

Topology optimization has been mainly addressed for structures under static loads using a deterministic setting. Nonetheless, many structural systems are subjected to uncertain dynamic loads, and thus efficient approaches are required to evaluate the optimal topology in such kind of applications. Within this framework, the present paper deals with the topology optimization of multi-story buildings subjected to seismic ground motion. Because of the inherent randomness of the earthquakes, the uncertain system response is determined through a random vibration-based approach in which the seismic ground motion is described as filtered white Gaussian noise with time-varying amplitude and frequency content (i.e., fully non-stationary seismic ground motion). The paper is especially concerned with the assessment of the dynamic response sensitivity for the gradient-based numerical solution of the optimization problem. To this end, an approximated construction of the gradient is proposed in which explicit, exact derivatives with respect to the design variables are computed analytically through direct differentiation for a sub-assembly of elements (up to a single element) resulting from the discretization of the optimizable domain. The proposed strategy is first validated for the simpler case of stationary base excitation by comparing the results with those obtained using an exact approach based on the adjoint method, and its correctness is ultimately verified for the more general case of non-stationary seismic ground motion. Overall, this validation demonstrates that the proposed approach leads to accurate results at low computational effort. Further numerical investigations are finally presented to highlight to what extent the features of the non-stationary seismic ground motion influence the optimal topology

Durum Wheat in Conventional and Organic Farming: Yield Amount and Pasta Quality in Southern Italy

Five durum wheat cultivars were grown in a Mediterranean area (Southern Italy) under conventional and organic farming with the aim to evaluate agronomic, technological, sensory, and sanitary quality of grains and pasta. The cultivar Matt produced the best pasta quality under conventional cropping system, while the quality parameters evaluated were unsatisfactory under organic farming. The cultivar Saragolla showed the best yield amount and pasta quality in all the experimental conditions, thus proving to be the cultivar more adapt to organic farming. In all the tested experimental conditions, nivalenol (NIV) and deoxynivalenol (DON) occurrence was very low and the other mycotoxins evaluated were completely absent. These data confirm the low risk of mycotoxin contamination in the Mediterranean climate conditions. Finally, it has been possible to produce high-quality pasta in Southern Italy from durum wheat grown both in conventional and organic farming

PEERS’ ANATOMY: teaching among students as an original approach to learning anatomy – a project made in Alma Mater

Anatomy is an ancient discipline which benefited greatly from technological improvements. Those very same technologies, along with a shift towards more clinically relevant topics, might be endangering anatomy’s central role as a cornerstone of medical education. A review of local realities showed anatomy to be quite uniformly taught by means of lectures alone. On the basis of our own experience, and comforted by references in literature (Day et al. [1]), we propose a revaluation of the teaching approach to anatomy, which includes an integration between different available resources and, above all, introduces peer-to-peer activity. Over the course of the last decade, based on a proposal from the Anatomy Department, more and more medical students took part to gross anatomy workshops abroad, thus consolidating what today is a large group of tutors. Working in parallel with the lectures, back home these students organize activities where notions are not a mere tool to pass the exam, but are aimed at giving younger students solid foundations on which to build their future competence. On the grounds of the experiences acquired in these years, we managed to divide the tutoring activities into six areas: surface and topographic anatomy, muscles and skeleton, heart and thorax, neuroanatomy, abdomen and pelvis, didactic coordination. Each group is based on the equal division of tasks and on respecting each tutor’s expertise, attitudes and skills. These workshops have proved to be highly effective both for students, as a chance to experience anatomy “hands-on”, and for tutors, as an opportunity of mastering the subject. Being appointed a tutor outlines a shift from a deductive learning method, typical of the pre-exam phase, to an inductive one, more useful in the future as medicine doctors. To sum up, the availability of adequate facilities for cadaveric dissection certainly enhances the teaching of anatomy; what our experience shows, however, is that only direct involvement of students as tutors brings out the full potential of these activities. We therefore propose abandoning a pure “learning-to-do” approach, in favour of a more effective “learning-by- doing” strategy

CRISPR/Cas9 Ablation of Integrated HIV-1 Accumulates Proviral DNA Circles with Reformed Long Terminal Repeats

Gene editing may be used to excise the human immunodeficiency virus type 1 (HIV-1) provirus from the host cell genome, possibly eradicating the infection. Here, using cells acutely or latently infected by HIV-1 and treated with long terminal repeat (LTR)-targeting CRISPR/Cas9, we show that the excised HIV-1 provirus persists for a few weeks and may rearrange in circular molecules. Although circular proviral DNA is naturally formed during HIV-1 replication, we observed that gene editing might increase proviral DNA circles with restored LTRs. These extrachromosomal elements were recovered and probed for residual activity through their transfection in uninfected cells. We discovered that they can be transcriptionally active in the presence of Tat and Rev. Although confirming that gene editing is a powerful tool to eradicate HIV-1 infection, this work highlights that, to achieve this goal, the LTRs must be cleaved in several pieces to avoid residual activity and minimize the risk of reintegration in the context of genomic instability, possibly caused by the off-target activity of Cas9. IMPORTANCE The excision of HIV-1 provirus from the host cell genome has proven feasible in vitro and, to some extent, in vivo. Among the different approaches, CRISPR/Cas9 is the most promising tool for gene editing. The present study underlines the remarkable effectiveness of CRISPR/Cas9 in removing the HIV-1 provirus from infected cells and investigates the fate of the excised HIV-1 genome. This study demonstrates that the free provirus may persist in the cell after editing and in appropriate circumstances may reactivate. As an episome, it might be transcriptionally active, especially in the presence of Tat and Rev. The persistence of the HIV-1 episome was strongly decreased by gene editing with multiple targets. Although gene editing has the potential to eradicate HIV-1 infection, this work highlights a potential issue that warrants further investigation

Grain Yield, Quality and Deoxynivalenol (DON) Contamination of Durum Wheat (Triticum Durum Desf.): Results of National Networks in Organic and Conventional Cropping Systems

This work shows the results of trials carried out over three years (2006-2008) within the national networks of durum wheat grown under conventional and organic cropping systems in six representative locations of the main cultivation areas of Italy. The main aspects of grain yield and grain quality were analyzed, particularly assessing the hygienic health status of the grain in relation to the possible presence of deoxynivalenol (DON) contamination. DON is considered the most common trichothecene mycotoxin found in the wheat grain, causing significant reductions in grain yield and adverse effects for human or animal consumption. In the studied period the average grain yields were quite interesting both in conventional samples (5.85 t ha-1) and in organic ones (4.91 t ha-1). As expected, the organic yields were significantly different(-16%). However, in the southern locations the same differences were lower (-5%), thus emphasizing the limited impact of the higher inputs of the conventional cropping in these environments. The reduced nitrogen input is notoriously the most critical point of organic wheat, because the protein content is the most sensitive parameter of grain quality. The protein content was significantly different among year, fields location and cropping system, but not among their interactions. Grain protein content in organic wheat was lower than in conventional one all over the three years; anyway, differences were somewhat limited (only about 1% in the southern locations and 0.5% in central Italy). Among cultivars no significant differences in the protein content were recorded. Mean levels of DON contamination during the study period were generally lower, with only a sample exceeding the legal limit of 1750 ppb. Among the main factors, year and location (and their interaction) had a strong influence on DON contamination, accounting for 75% of the observed variability. DON levels in 2008 at Papiano-PG were dramatically high; the strong influence of the year-location interaction may be due to this fact. Cropping system and cultivar, although significant, had a low influence; however, their interaction accounted for 13% of total variance. Cropping system – location interaction accounted for 5% of the total variability. Very low levels of DON were detected in the southern locations with both cropping systems; the lower levels were recorded in organic wheat samples. In the central Italy areas DON could represent a potential hazard, but even in these organically cropped environments wheat gave the best results. Lower concentrations of DON were detected in organic wheat samples, either in less favourable years for the occurrence of Fusarium (2006 and 2007) and in the more favourable one (2008). Regarding the role of the varietal choice, Creso revealed to be the less susceptible to DON contamination, probably as it is the best adapted to the areas of the Central Italy, where Fusarium is more widespread

Amyotrophic lateral sclerosis stratification: unveiling patterns with virome, inflammation, and metabolism molecules

Amyotrophic lateral sclerosis (ALS) is an untreatable and clinically heterogeneous condition primarily affecting motor neurons. The ongoing quest for reliable biomarkers that mirror the disease status and progression has led to investigations that extend beyond motor neurons' pathology, encompassing broader systemic factors such as metabolism, immunity, and the microbiome. Our study contributes to this effort by examining the potential role of microbiome-related components, including viral elements, such as torque tenovirus (TTV), and various inflammatory factors, in ALS. In our analysis of serum samples from 100 ALS patients and 34 healthy controls (HC), we evaluated 14 cytokines, TTV DNA load, and 18 free fatty acids (FFA). We found that the evaluated variables are effective in differentiating ALS patients from healthy controls. In addition, our research identifies four unique patient clusters, each characterized by distinct biological profiles. Intriguingly, no correlations were found with site of onset, sex, progression rate, phenotype, or C9ORF72 expansion. A remarkable aspect of our findings is the discovery of a gender-specific relationship between levels of 2-ethylhexanoic acid and patient survival. In addition to contributing to the growing body of evidence suggesting altered peripheral immune responses in ALS, our exploratory research underscores metabolic diversity challenging conventional clinical classifications. If our exploratory findings are validated by further research, they could significantly impact disease understanding and patient care customization. Identifying groups based on biological profiles might aid in clustering patients with varying responses to treatments

Dark chocolate intake positively modulates gut permeability in elite football athletes. A randomized controlled study

: Gut barrier disruption can lead to enhanced intestinal permeability, which allows endotoxins, pathogens, and other proinflammatory substances to move through the intestinal barrier into circulation. Intense exercise over a prolonged period increases intestinal permeability, which can be further worsened by the increased production of reactive oxygen species (ROS) and pro-inflammatory cytokines. The aim of this study was to assess the degree of intestinal permeability in elite football players and to exploit the effect of cocoa polyphenols on intestinal permeability induced by intensive physical exercise. Biomarkers of intestinal permeability, such as circulating levels of zonulin, a modulator of tight junctions, occludin, a tight junction protein, and LPS translocation, were evaluated in 24 elite football players and 23 amateur athletes. Moreover, 24 elite football players were randomly assigned to either a dark chocolate (>85% cocoa) intake (n = 12) or a control group (n = 12) for 30 days in a randomized controlled trial. Biochemical analyses were performed at baseline and after 30 days of chocolate intake. Compared to amateur athletes, elite football players showed increased intestinal permeability as indicated by higher levels of zonulin, occludin, and LPS. After 30 days of dark chocolate intake, decreased intestinal permeability was found in elite athletes consuming dark chocolate. In the control group, no changes were observed. In vitro, polyphenol extracts significantly improved intestinal damage in the human intestinal mucosa cell line Caco-2. These results indicate that chronic supplementation with dark chocolate as a rich source of polyphenols positively modulates exercise-induced intestinal damage in elite football athletes

Hematopoietic reconstitution dynamics of mobilized- and bone marrow-derived human hematopoietic stem cells after gene therapy

Mobilized peripheral blood is increasingly used instead of bone marrow as a source of autologous hematopoietic stem/progenitor cells for ex vivo gene therapy. Here, we present an unplanned exploratory analysis evaluating the hematopoietic reconstitution kinetics, engraftment and clonality in 13 pediatric Wiskott-Aldrich syndrome patients treated with autologous lentiviral-vector transduced hematopoietic stem/progenitor cells derived from mobilized peripheral blood (n = 7), bone marrow (n = 5) or the combination of the two sources (n = 1). 8 out of 13 gene therapy patients were enrolled in an open-label, non-randomized, phase 1/2 clinical study (NCT01515462) and the remaining 5 patients were treated under expanded access programs. Although mobilized peripheral blood- and bone marrow- hematopoietic stem/progenitor cells display similar capability of being gene-corrected, maintaining the engineered grafts up to 3 years after gene therapy, mobilized peripheral blood-gene therapy group shows faster neutrophil and platelet recovery, higher number of engrafted clones and increased gene correction in the myeloid lineage which correlate with higher amount of primitive and myeloid progenitors contained in hematopoietic stem/progenitor cells derived from mobilized peripheral blood. In vitro differentiation and transplantation studies in mice confirm that primitive hematopoietic stem/progenitor cells from both sources have comparable engraftment and multilineage differentiation potential. Altogether, our analyses reveal that the differential behavior after gene therapy of hematopoietic stem/progenitor cells derived from either bone marrow or mobilized peripheral blood is mainly due to the distinct cell composition rather than functional differences of the infused cell products, providing new frames of references for clinical interpretation of hematopoietic stem/progenitor cell transplantation outcome.</p

Gender differences in outcomes after left atrial appendage closure with Watchman FLX device: insights from the Italian-FLX registry

IntroductionRecent studies have shown gender differences in cardiovascular outcomes after left atrial appendage closure (LAAC), highlighting different complication rates and adverse events, particularly in short-term assessments. As a result, there remains a significant knowledge gap on how these differences directly impact the efficacy and safety of LAAC procedures. The aim of this retrospective study was to investigate the clinical outcomes of LAAC in women and men using the Watchman FLX device.MethodsThis retrospective, multicenter study analyzes gender-specific outcomes in 650 patients who underwent LAAC with the Watchman FLX device between March 2019 and May 2022, drawn from the ITALIAN-FLX registry.ResultsThe results show comparable rates of all-cause mortality, stroke, transient ischemic attack and major bleeding in men and women 12 months after the procedure. Notably, no significant gender differences were found for periprocedural complications.ConclusionIn conclusion, this study shows that LAAC with the Watchman FLX device has comparable clinical outcomes between genders at both short-term and long-term follow-up