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Abstract Background Resistant and refractory migraine are commonly encountered in specialized headache centers. Several comorbidities, mostly psychiatric conditions, have been linked to migraine worsening; however, there is little knowledge of the comorbidity profile of individuals with resistant and refractory migraine. Methods REFINE is a prospective observational multicenter international study involving individuals with migraine from 15 headache centers. Participants were categorized into three groups based on the European Headache Federation criteria: non-resistant and non-refractory (NRNRM), resistant (ResM), and refractory (RefM). We explored the prevalence of 20 comorbidities at baseline in the three groups. Results Of the 689 included patients (82.8% women), 262 (38.0%) had ResM, 73 (10.4%) had RefM and 354 (51.4%) NRNRM. A higher prevalence of psychiatric comorbidities, trigger points, temporomandibular joint disorders, thyroiditis, and cerebrovascular diseases was observed in the RefM group, followed by ResM and NRNRM. Multiple comorbidities were more common in the RefM group, followed by the ResM group and by the NRNRM group (41.6% vs. 24.5% vs. 14.1% respectively; p

Blinatumomab has remarkable efficacy in patients with relapsed/refractory (r/r) or measurable residual disease (MRD)-positive B-cell acute lymphoblastic leukemia (B-ALL). In many patients, blinatumomab treatment is followed by allogeneic hematopoietic stem cell transplantation (HSCT). However, the influence of blinatumomab on HSCT outcomes in children and young adults (YA) remains to be fully elucidated. We conducted a single-center, retrospective analysis on patients given blinatumomab as last treatment before HSCT. Seventy-eight pediatric and YA patients were evaluated. With a median follow-up of 23.23 months, the 2-year disease-free (DFS) and overall survival (OS) probability were 72.2% and 89.2%, respectively, with a 2-year cumulative incidence (CI) of non-relapse mortality (NRM) of 2.6%. A trend toward improved 2-year DFS, but not OS, was noted in patients transplanted in first complete remission (CR1) (92.9%) compared to those in second or greater remission (CR2/3) (68.5%, p=0.18) due to a lower CI of relapse (0% vs. 29.9%, p=0.05). Among CR2/3 patients, those receiving the sequential combination of inotuzumab and blinatumomab had a significantly lower CI of relapse as compared to those who did not receive inotuzumab (9.5% vs. 40.4%, p=0.023). Relapse after HSCT occurred in 16 patients, all exhibiting CD19-positive blasts; 10 of them received anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy and 2 inotuzumab as salvage therapy, leading to a 2-year post-relapse OS of 52.7%. Our results indicate that HSCT following blinatumomab in children and YA with B-ALL is highly effective, being associated with low NRM and not affecting the efficacy of subsequent salvage immunotherapies, including CAR-T cells.

Mucosal-associated invariant T (MAIT) cells are innate-like T-cells implicated in the response to fungal and bacterial infections. Their contribution to restoring T-cell immunity and influencing hematopoietic stem cell transplant (HSCT) outcomes remains poorly understood. We retrospectively studied MAIT-cell recovery in 145 consecutive children and young adults with hematological malignancies undergoing allo-HSCT, between April/2019 and May/2022, from unrelated matched donor (MUD, n=52), with standard graft-versus-host-disease (GvHD) prophylaxis, or HLA-haploidentical (Haplo, n=93) donor after in vitro αβT/CD19-cell depletion, without post-HSCT pharmacological prophylaxis. With a median follow-up of 33 months (12-49), overall survival (OS), disease-free survival (DFS) and non-relapse mortality (NRM) were 79.5%, 72% and 7%, respectively; GvHD-free, Relapse-free Survival (GRFS) was 63%, while cumulative incidence of relapse was 23%. While WWT-cells reconstituted 1-2 years post-HSCT, MAIT-cells showed delayed recovery and prolonged functional impairment, characterized by expression of activation (CD25, CD38), exhaustion (PD1, TIM3) and senescence (CD57) markers, and suboptimal ex vivo response. OS, DFS and NRM were not affected by MAIT-cells. Interestingly, higher MAIT-cells at day+30 correlated with higher incidence of grade II-IV acute GvHD (19% vs 7%, p=0.06). Furthermore, a greater MAIT-cell count tended to be associated with a higher incidence of chronic GvHD (17% vs 6%, p=0.07) resulting in lower GRFS (55% vs 73%, p=0.05). Higher MAIT-cells also correlated with greater cytomegalovirus (CMV) reactivation and lower late blood stream infections (BSI) (44% vs 24%, p=0.02 and 9% vs 18%, p=0.08, respectively). Future studies are needed to confirm the impact of early MAIT-cell recovery on cGvHD, CMV reactivation and late BSI.

Several studies suggested a negative association between olive oil (OO) consumption and the risk of several chronic diseases. However, an attempt to systematically search, organize, and evaluate the existing evidence on all health outcomes associated with OO consumption is lacking. The objective of this review is to describe the multiple health outcomes associated with OO consumption. The Medline, Scopus, and Web of Science databases were searched through 5 April 2024. The selected studies met all of the following criteria: (1) a meta-analysis of both observational (case–control and cohort studies) and interventional studies (trials), (2) an evaluation of the association between OO consumption, mortality, and/or the incidence of non-communicable/chronic degenerative diseases, and (3) a study population ≥18 years old. Two independent reviewers extracted the relevant data and assessed the risk of bias of individual studies. The PRISMA statement and guidelines for the Integration of Evidence from Multiple Meta-Analyses were followed. The literature search identified 723 articles. After selection, 31 articles were included in this umbrella review. The primary health benefits of OO were observed in cardiovascular diseases and risk factors, cancer, mortality, diabetes, and specific biomarkers related to anthropometric status and inflammation. As a key component of the Mediterranean diet, OO can be considered a healthy dietary choice for improving positive health outcomes.

The presence of Salmonella spp. in dairy cattle farms poses a major risk to animal health and welfare. This study focused on Salmonella detection in dairy farms located in the Cremona and Mantua provinces (northern Italy) in samples collected and submitted to laboratories in 2021–2022. A total of 2710 samples from different sources, including calf carcasses/organs (n = 128), rectal swabs (n = 1937), feces (n = 390), bulk milk (n = 93), and overshoes/swabs (n = 127) for environmental sampling, were analyzed for the presence of Salmonella spp. and were included in the present study. Our results indicate that Salmonella was most commonly firstly identified from calf carcasses and organs (61.67%) and that the serotypes most frequently detected in dairies were S. Dublin (38.33%), S. Typhimurium (23.33%), and S. Typhimurium monophasic variant (14.17%). The most common pathological findings in calf carcasses were enteritis, hepatosplenomegaly, and pneumonia. The antimicrobial resistance pattern analyzed using the MIC assay of 51 Salmonella isolates revealed the presence of multi-resistant strains, which pose a major risk to public and animal health.

This article examines the misrecognition of climate refugees as a form of climate coloniality, through the lens of decolonial environmental justice (EJ). I address two research questions: (1) Why is climate refugeehood a matter of decolonial EJ? (2) How can decolonial EJ contribute to overcoming the colonial impasse that prevents the expansion of the notion of a refugee in international law? This case of climate coloniality is examined through the tripartite notion of the coloniality of power, knowledge, and being to decolonize the concept of refugeehood while rethinking the current model of responsibility and the subjects entitled to it.

The increased availability of genetic technologies has significantly improved the detection of novel germline variants conferring a predisposition to tumor development in patients with malignant disease. The identification of variants of uncertain significance (VUS) represents a challenge for the clinician, leading to difficulties in decision-making regarding medical management, the surveillance program, and genetic counseling. Moreover, it can generate confusion and anxiety for patients and their family members. Herein, we report a 5-year-old girl carrying a VUS in the Succinate Dehydrogenase Complex Subunit C (SHDC) gene who had been previously treated for high-risk neuroblastoma and subsequently followed by the development of secondary acute myeloid leukemia. In this context, we describe how functional studies can provide additional insight on gene function determining whether the variant interferes with normal protein function or stability.

This paper demonstrates an approach for sharing and safeguarding modelling expertise based on the use of Historic Building Information Modelling (HBIM). The approach involves the exchange of information between subjects involved in the creation of HBIM models, an exchange enhanced by Semantic Web Technologies.HBIM datasets usually contain rich and detailed information about historic buildings and their construction; this experiment, in a slightly unusual way, deals with another type of information regarding something that happens in the background during the definition of an HBIM model: the procedures that create the complex three-dimensional geometries typical of historical architecture. This kind of information does not usually live inside BIM models and is even less likely the subject of semantic enrichment. It is however beneficial to record and make available this kind of information for several reasons, discussed in the text.

Metal contamination is a waste-generating and serious issue in the synthesis of chemicals, in particular in the case of products with biological activity. The appropriate selection of operating conditions plays a crucial role in the abatement of metal leaching in solution and associated wastes. Herein we report a waste-minimized continuous flow process for the synthesis of 1,4-disubstituted β-keto 1,2,3-triazoles exploiting the use of a copper tube flow reactor (CTFR). The selection of the proper azeotropic mixture allowed an almost quantitative recovery of the reaction medium greatly influencing the E-factor of the protocol. A thorough understanding of the main parameters affecting the waste generation was given by calculation of the E-factor distribution for different work-up tested under batch and flow conditions. Furthermore, the measurement of different green metrics (AE: Atom Economy, SF: Stoichiometric Factor, RME: Reaction Mass Efficiency, and MRP: Mass Recover Parameter) clearly demonstrated the benefits of the flow scale-up that allowed to perform a low environmental footprint CuAAC reaction.

Abstract A pharmacokinetic/pharmacodynamic (PK/PD) model was developed to describe the time course of writhings after intraperitoneal injection of acetic acid in mice. The model was applied to investigate the antinociceptive effect of trazodone and gabapentin alone and in combination. Writhings time course was described by a transit compartment model with the delay due to the transit of the acetic acid being represented by a chain of intermediate compartments. In the drug‐treated animals, the number of writhings decreases according to a k2 factor linking drug concentration and antinociceptive effect. Compounds' potency parameters were 10.9 and 0.0459 L/μmoles/min for trazodone and gabapentin, respectively, indicating a much higher in vivo potency of trazodone in the PD writhing test. The PK/PD parameters were used to simulate the expected writhing counts in mice at combined doses without efficacy alone, assuming pharmacological additivity. Simulation results indicated that, at low dose combinations, experimental data were mostly below the simulated writhings median, suggesting possible synergic effect. Such hypothesis was tested by adding the γ parameter in the PK/PD model to represent the deviation from the assumption of no‐interaction, leading to a reduction of the objective function compared to the additive model. On this basis, several simulations were performed to identify possible starting dose combinations of trazodone and gabapentin in humans, by selecting doses yielding systemic exposures close to those being synergic in the mouse. Simulations indicated that doses of 50–100 mg trazodone could enhance gabapentin antinociceptive effect in humans, supporting the development of a low dose combination for optimal analgesia treatment.

This explorative study aimed to assess the mutagenicity and genotoxicity of stored-cooked beef patties formulated with and without phenols (7.00 mg of phenols/80-g patty) extracted from olive vegetation water (OVW), as related to the formation of cholesterol oxidation products (COPs) and heterocyclic amines (HCAs). The patties were packaged in a modified atmosphere, sampled during cold storage (4 °C) for 9 days, and grilled at 200 °C. The genotoxicity was evaluated by the Comet assay. The patty extract was found to be genotoxic on primary peripheral blood mononuclear cells (PBMCs), while no mutagenicity was detected. The addition of OVW phenols significantly decreased the genotoxicity of the patty extract and reduced the total COPs content in stored-cooked patties (4.59 times lower than control); however, it did not affect the content of total HCAs (31.51–36.31 ng/patty) and the revertants’ number. Therefore, these results demonstrate that the OVW phenols were able to counteract the formation of genotoxic compounds in stored-cooked beef patties.

Este artículo representa un avance inicial de una tesis de maestría en Tecnología Educativa en curso, centrada en la formación de formadores para la integración de la Inteligencia Artificial Generativa (IAG) en la enseñanza universitaria. Se aborda el desarrollo de un marco teórico en construcción y se da cuenta de las indagaciones preliminares a docentes universitarios y expertos en el campo, resaltando los desafíos didácticos que la integración de estas tecnologías presentan para la enseñanza. Se subraya la necesidad de una reflexión crítica y propositiva sobre la inclusión de estas tecnologías en la enseñanza universitaria. Se dejan abiertos algunos interrogantes.

Background: Incidence rates of thyroid cancer have increased. Recent studies findings suggest that women who underwent a hysterectomy have an elevated relative risk of thyroid cancer. The aim of our meta-analysis is to summarize the evidence about the association between hysterectomy and thyroid cancer risk. Methods: PubMed, Web of Science, and Scopus database were searched for studies published up to 5 September 2023. The PRISMA statement was followed. Heterogeneity was explored with Q statistic and the I2 statistic. Publication bias was assessed with Begg's and Egger's tests. Results: Sixteen studies met the criteria. The pooled analysis showed a significantly 64% increment of thyroid cancer risk in association with any hysterectomy (OR 1.64, 95% CI 1.48–1.81; I2 = 28.68%, p = 0.156). Hysterectomy without oophorectomy was a stronger predictor of risk than hysterectomy with oophorectomy. The pooled analysis of data regarding hysterectomy without oophorectomy showed a statistically significant increment of thyroid cancer risk by 59%. Hysterectomy with oophorectomy was associated with an increase of thyroid cancer risk of 39% (OR 1.39, 95% CI 1.16–1.67; I2 = 42.10%, p = 0.049). Significant publication bias was not detected. Conclusions: Our findings help with decision making around these surgeries.

Abstract Introduction Headache is the most prevalent neurological manifestation in adults and one of the leading causes of disability worldwide. In children and adolescents, headaches are arguably responsible for a remarkable impact on physical and psychological issues, yet high-quality evidence is scarce. Material and methods We searched cross-sectional and cohort studies in Embase, Medline, Web of Science, and Cochrane databases from January 1988 to June 2022 to identify the prevalence of headaches in 8–18 years old individuals. The risk of bias was examined with the Joanna Briggs Institute (JBI) scale. A random-effects model was used to estimate the pooled prevalence of pediatric headache. Subgroup analyses based on headache subtypes were also conducted. Results Out of 5,486 papers retrieved electronically, we identified 48 studies that fulfilled our inclusion criteria. The pooled prevalence of primary headaches was 11% for migraine overall [95%CI: 9–14%], 8% for migraine without aura (MwoA) [95%CI: 5–12%], 3% for migraine with aura (MwA) [95%CI:2–4%] and 17% for tension-type headache (TTH) [95% CI: 12–23%]. The pooled prevalence of overall primary headache in children and adolescents was 62% [95% CI: 53–70%], with prevalence in females and males of 38% [95% CI: 16–66%] and 27% [95% CI: 11–53%] respectively. After the removal of studies ranked as low-quality according to the JBI scale, prevalence rates were not substantially different. Epidemiological data on less common primary headaches, such as trigeminal autonomic cephalalgias, were lacking. Conclusion We found an overall remarkably high prevalence of primary headaches in children and adolescents, even if flawed by a high degree of heterogeneity. Further up-to-date studies are warranted to complete the picture of pediatric headache-related burden to enhance specific public interventions.

We present the analysis of new, deep Chandra observations (130 ks) of the galaxy cluster A2495. This object is known for the presence of a triple offset between the peaks of the intracluster medium (ICM), the brightest cluster galaxy (BCG), and the warm gas glowing in H α line. The new Chandra data confirm that the X-ray emission peak is located at a distance of ∼6.2 kpc from the BCG, and at ∼3.9 kpc from the H α emission peak. Moreover, we identify two generations of X-ray cavities in the ICM, likely inflated by the central radio galaxy activity. Through a detailed morphological and spectral analysis, we determine that the power of the active galactic nucleus (AGN) outbursts ( P _cav = 4.7 ± 1.3 × 10 ^43 erg s ^−1 ) is enough to counterbalance the radiative losses from ICM cooling ( L _cool = 5.7 ± 0.1 × 10 ^43 erg s ^−1 ). This indicates that, despite a fragmented cooling core, A2495 still harbors an effective feedback cycle. We argue that the offsets are most likely caused by sloshing of the ICM, supported by the presence of spiral structures and a probable cold front in the gas at ∼58 kpc east of the center. Ultimately, we find that the outburst interval between the two generations of X-ray cavities is of the order of the dynamical sloshing timescale, as already hinted from the previous Chandra snapshot. We thus speculate that sloshing may be able to regulate the timescales of AGN feedback in A2495, by periodically fueling the central AGN.

Abstract Migraine is a complex condition in which genetic predisposition interacts with other biological and environmental factors determining its course. A hyperresponsive brain cortex, peripheral and central alterations in pain processing, and comorbidities play a role from an individual biological standpoint. Besides, dysfunctional psychological mechanisms, social and lifestyle factors may intervene and impact on the clinical phenotype of the disease, promote its transformation from episodic into chronic migraine and may increase migraine-related disability. Thus, given the multifactorial origin of the condition, the application of a biopsychosocial approach in the management of migraine could favor therapeutic success. While in chronic pain conditions the biopsychosocial approach is already a mainstay of treatment, in migraine the biomedical approach is still dominant. It is instead advisable to carefully consider the individual with migraine as a whole, in order to plan a tailored treatment. In this review, we first reported an analytical and critical discussion of the biological, psychological, and social factors involved in migraine. Then, we addressed the management implications of the application of a biopsychosocial model discussing how the integration between non-pharmacological management and conventional biomedical treatment may provide advantages to migraine care.

Abstract Trazodone is approved for the treatment of major depressive disorders, marketed as immediate release (IR), prolonged release, and once a day (OAD) formulation. The different formulations allow different administration schedules and may be useful to facilitate patients’ compliance to the antidepressant treatment. A previously verified physiologically‐based pharmacokinetic model based on in vitro and in vivo information on trazodone pharmacokinetics was applied, aiming at predicting brain receptor occupancy (RO) after single and repeated dosing of the IR formulation and repeated dosing of the OAD formulation in healthy subjects. Receptors included in the simulations were selected using static calculations of RO based on the maximum unbound brain concentration (Cmax,brain,u) of trazodone for each formulation and dosing scheme, resulting in 16 receptors being simulated. Seven receptors were simulated for the IR low dose formulation (30 mg), with similar tonset and duration of coverage (range: 0.09–0.25 h and 2.1–>24 h, respectively) as well as RO (range: 0.64–0.92) predicted between day 1 and day 7 of dosing. The 16 receptors evaluated for the OAD formulation (300 mg) showed high RO (range: 0.97–0.84 for the receptors also covered by the IR formulation and 0.73–0.48 for the remaining) correlating with affinity and similar duration of time above the target threshold to the IR formulation (range: 2–>24 h). The dose‐dependent receptor coverage supports the multimodal activity of trazodone, which may further contribute to its fast antidepressant action and effectiveness in controlling different symptoms in depressed patients.

High-resolution surveying of historical floors is a very common practice in both research and everyday life. The type of floors typically concerned are made of mosaic, marble and stone. Because of their intrinsic characteristics, their survey typically requires very high-resolution results, to ensure excellent support for restoration, as well as in-depth knowledge of the artifact. In these cases, the focus must be kept on both geometric and radiometric content, to enable accurate metric representation and a rendering of colour and surfaces as close as possible to reality. In this research we propose a prototype of a photogrammetric acquisition system (under development) which tries to optimise the floor survey in terms of both geometric and colour documentation. In particular, the prototype makes use of the cross-polarisation technique with the aim of eliminating reflections from the images. The principle behind the prototype is the creation of a movable laboratory, a segregated space that allows excellent photographic acquisition even in difficult environmental conditions, which cannot always be controlled optimally. First tests showed its suitability and usefulness to reach the goal of a high resolution survey of historic floors.

Adjunctive treatment of bacterial endophthalmitis with intravitreal steroids is a topic of controversy among many ophthalmologists. The objective of this study is to evaluate the effects of intravitreal dexamethasone on the visual outcomes of patients with acute bacterial endophthalmitis through a systematic review and meta-analysis. A literature search of PubMed, Scopus, and Cochrane Library databases was performed to include studies on the visual outcomes of adjuvant intravitreal dexamethasone in patients with acute bacterial endophthalmitis. The review is based on the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) protocol. A total of 1545 articles met our search criteria and after further review, two randomized controlled trials and three retrospective case series were included in the final analysis. A total of 126 eyes were treated with intravitreal dexamethasone combined with antibiotics, and another 139 eyes were treated with antibiotics alone. All cases of endophthalmitis were post-operative or post-intravitreal injection, with pooled results demonstrating no visual benefit with supplementation of intravitreal dexamethasone. Our meta-analysis does not show any visual benefit from steroid supplementation and yet, considering a relatively small number of patients included in each study, larger randomized controlled trials are required to further clarify the role of steroids in the treatment of acute bacterial endophthalmitis.

Vibrio cholerae represents diverse species and includes pathogenic and non-pathogenic variants. Particularly serogroups O1 and O139 are related to cholera epidemics, while non-O1/O139 serogroups (NOVC) in general are non-pathogenic or asymptomatic colonizers in humans, but also can cause different diseases. Vibrio albensis, a non-O1/non-O-139 serogroup, is rarely implicated in human infections. Only a few cases of human pathology related to this species are described in the literature. We present the menagement of V. albensis gastroenteritis in a a 47-year-old woman and discuss clinical presentation, diagnosis and treatement.

Maize ear fasciation originates from excessive or abnormal proliferation of the ear meristem and usually manifests as flattened multiple-tipped ear and/or disordered kernel arrangement. Ear prolificacy expresses as multiple ears per plant or per node. Both ear fasciation and prolificacy can affect grain yield. The genetic control of the two traits was studied using two recombinant inbred line populations (B73 × Lo1016 and Lo964 × Lo1016) with Lo1016 and Lo964 as donors of ear fasciation and prolificacy, respectively. Ear fasciation-related traits, number of kernel rows (KRN), ear prolificacy and number of tillers were phenotyped in multi-year field experiments. Ear fasciation traits and KRN showed relatively high heritability (h2 > 0.5) except ratio of ear diameters. For all ear fasciation-related traits, fasciation level positively correlated with KRN (0.30 ≤ r ≤ 0.68). Prolificacy and tillering were not correlated and their h2 ranged from 0.41 to 0.78. QTL mapping identified four QTLs for ear fasciation, on chromosomes 1 (two QTLs), 5 and 7, the latter two overlapping with QTLs for number of kernel rows. Notably, at these QTLs, the Lo1016 alleles increased both ear fasciation and KRN across populations, thus showing potential breeding applicability. Four and five non-overlapping QTLs were mapped for ear prolificacy and tillering, respectively. Two ear fasciation QTLs, qFas1.2 and qFas7, overlapped with fasciation QTLs mapped in other studies and spanned compact plant2 and ramosa1 candidate genes. Our study identified novel ear fasciation loci and alleles positively affecting grain yield components, and ear prolificacy and tillering loci which are unexpectedly still segregating in elite maize materials, contributing useful information for genomics-assisted breeding programs.

Abstract Background Transcranial direct current stimulation (tDCS) could counteract the pathophysiological triggers of migraine attacks by modulating cortical excitability. Several pilot randomized controlled trials (RCTs) assessed the efficacy of tDCS for migraine prevention. We reviewed and summarized the state of the art of tDCS protocols for migraine prevention, discussing study results according to the stimulations parameters and patients’ populations. Main body We combined the keywords ‘migraine’, ‘headache’, ‘transcranial direct current stimulation’, and ‘tDCS’ and searched Pubmed, Scopus, and Web of Science, from the beginning of indexing to June 22, 2021. We only included RCTs comparing the efficacy of active tDCS with sham tDCS to decrease migraine frequency, intensity, and/or acute drug utilization. The risk of bias of each RCT was assessed by using the RoB-2 tool (Cochrane Collaboration). Thirteen RCTs (from 2011 to 2021) were included in the review. The included patients ranged from 13 to 135. RCTs included patients with any migraine (n=3), chronic migraine (n=6), episodic migraine (n=3) or menstrual migraine (n=1). Six RCTs used cathodal and five anodal tDCS, while two RCTs compared the efficacy of both cathodal and anodal tDCS with that of sham. In most of the cathodal stimulation trials, the target areas were the occipital regions, with reference on central or supraorbital areas. In anodal RCTs, the anode was usually placed above the motor cortical areas and the cathode on supraorbital areas. All RCTs adopted repeated sessions (from 5 to 28) at variable intervals, while the follow-up length spanned from 1 day up to 12 months. Efficacy results were variable but overall positive. According to the RoB-2 tool, only four of the 13 RCTs had a low risk of bias, while the others presented some concerns. Conclusions Both anodal and cathodal tDCS are promising for migraine prevention. However, there is a need for larger and rigorous RCTs and standardized procedures. Additionally, the potential benefits and targeted neurostimulation protocols should be assessed for specific subgroups of patients.

The aim of the study was to determine the activity concentration of the natural radionuclides (226Ra, 210Po, 228Ra and 40K) and artificial radionuclide 137Cs in the muscle of the marine fish species most consumed in the city of São Paulo and to evaluate the annual effective dose due to the consumption of the fish. Samples were collected in the supermarket chain Extra and Carrefour and in the distribution center CEAGESP. Six fish species were selected among the most available and consumed in São Paulo city: anchovy, tuna, dogfish, croaker, hake and sardine. After the sample preparation procedures, the determination of 226Ra, 228Ra, 40K and 137Cs was carried out by gamma spectrometry and the determination of 210Po by alpha spectrometry. The results obtained for all the species studied are below the limits adopted by the Brazilian Standards for 137Cs and, therefore, their consumption offers no risk due to the ingestion of this radionuclide. The concentration obtained for the radionuclides 226Ra, 210Po, 228Ra and 137Cs in the fish samples analized are low and of the same order of magnitude as data from literature. The results obtained for the doses, for all the species studied, showed that their consumption offers no risk of exposure due to the ingestion of the analyzed radionuclides.

It has been observed that novel strains of Clostridioides difficile can rapidly emerge and move between animal and human hosts. The aim of this study was to investigate the prevalence of C. difficile in pigs and dairy cattle in northern Italy and to characterize and compare C. difficile animal strains with those from patients from the same geographical area. The C. difficile strains were isolated from animals from farms and slaughterhouses (cross-sectional studies) and from neonatal animals with enteric disorders in routine diagnostic investigations (passive surveillance). Samples positive for C. difficile were found in 87% of the pig farms and in 40% of the cattle farms involved in the cross-sectional studies, with a 20% prevalence among suckling piglets and 6.7% prevalence in neonatal calves, with no significant difference between animals with and without diarrheal symptoms. The prevalence of C. difficile in older animal categories was significantly lower. This result suggests that young age is an important risk factor for C. difficile colonization. In cross-sectional studies at slaughterhouses, in both the heavy pigs and dairy cows examined, only 2% of the intestinal content samples were positive for C. difficile and no contamination was found on the surface of the carcasses. Considering passive surveillance, the prevalence rates of positive samples were 29% in piglets and 1.4% in calves. Overall, 267 strains of animal origin and 97 from humans were collected. In total, 39 ribotypes (RTs) were identified, with RT 078 and RT 018 being predominant among animals and humans, respectively. Several RTs overlapped between animals and patients. In particular, RT 569 was identified as an emergent type in our country. Resistance to erythromycin and moxifloxacin was widely diffused among C. difficile strains, regardless of origin. This study supports C. difficile as a pathogen of one-health importance and highlights the need for a collaborative approach between physicians and veterinarians to control and prevent infections that are able to cross species and geographical barriers.

Ilena Pochiero,1 Fabrizio Calisti,1 Alessandro Comandini,1 Alessandra Del Vecchio,1 Isabella Costamagna,1 Maria Teresa Rosignoli,1 Agnese Cattaneo,1 Sasikiran Nunna,2 Ilaria Peduto,3 Franca Heiman,3 Hsiu-Ching Chang,2 Chi-Chang Chen,2 Christoph Correll4– 6 1Angelini Regulatory, Research & Development, Angelini Pharma S.p.A., Rome, Italy; 2IQVIA, Plymouth Meeting, PA, USA; 3IQVIA Solutions Italy S.r.l., RWS, Milan, Italy; 4Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany; 5Department of Psychiatry, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, NY, USA; 6Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USACorrespondence: Ilena PochieroAngelini Pharma S.p.A., Viale Amelia 70, Rome, ItalyEmail ilena.pochiero@angelinipharma.comPurpose: The primary objectives were to describe weight changes following initiation of lurasidone versus other antipsychotics and estimate the risk of clinically relevant (≥ 7%) weight changes.Patients and Methods: This retrospective, longitudinal comparative cohort study was based on electronic medical records (EMRs) of United States (US) adult patients with schizophrenia who were prescribed lurasidone or other antipsychotics as monotherapy between 1 April 2013 and 30 June 2019.Results: Overall, the study included 15,323 patients with a diagnosis of schizophrenia; 6.1% of patients received lurasidone, 60.4% received antipsychotics associated with a medium-high risk of weight gain (clozapine, olanzapine, quetiapine, risperidone, paliperidone) and 33.5% received antipsychotics with a low risk of weight gain (aripiprazole, first-generation antipsychotics, ziprasidone). Lurasidone was associated with the smallest proportion of patients experiencing clinically relevant weight gain and the greatest proportion of patients with clinically relevant weight loss. The risk of clinically relevant weight gain was numerically higher with all antipsychotics versus lurasidone and was statistically significant for olanzapine (hazard ratio [HR]=1.541; 95% confidence interval [CI]=1.121; 2.119; p=0.0078) versus lurasidone. The likelihood of ≥ 7% weight loss was significantly greater with lurasidone versus all antipsychotics (p< 0.05), except ziprasidone.Conclusion: This real-world study suggests that lurasidone has a lower risk of clinically relevant weight gain and a higher likelihood of clinically relevant weight loss than other commonly used antipsychotics.Keywords: retrospective studies, weight gain, real world clinical trials

Ablative and locoregional treatment options, such as radiofrequency, ethanol injection, microwave, and cryoablation, as well as irreversible electroporation, are effective therapies for early-stage hepatocellular carcinoma (HCC). Hepatocyte death caused by ablative procedures is known to increase the release of tumor-associated antigen, thus enhancing tumor immunogenicity. In addition, the heat ablative resection induces pyroptotic cell death accompanied by the release of several inflammatory factors and immune-related proteins, including damage-associated molecular patterns (DAMPs), heat shock proteins (HSPs), ficolin 3, ATP, and DNA/RNA, which potentiate the antitumoral immune response. Surgical approaches that enhance tumor necrosis and reduce hypoxia in the residual liver parenchyma have been shown to increase the disease-free survival rate by reducing the host’s immunosuppressive response. Scalpel devices and targeted surgical approach combined with immune-modulating drugs are an interesting and promising area to maximize therapeutic outcomes after HCC ablation.

Abstract Disease lesion mimic (DLM) or necrotic mutants display necrotic lesions in the absence of pathogen infections. They can show improved resistance to some pathogens and their molecular dissection can contribute to revealing components of plant defense pathways. Although forward‐genetics strategies to find genes causal to mutant phenotypes are available in crops, these strategies require the production of experimental cross populations, mutagenesis, or gene editing and are time‐ and resource‐consuming or may have to deal with regulated plant materials. In this study, we described a collection of 34 DLM mutants in barley (Hordeum vulgare L.) and applied a novel method called complementation by sequencing (CBS), which enables the identification of the gene responsible for a mutant phenotype given the availability of two or more chemically mutagenized individuals showing the same phenotype. Complementation by sequencing relies on the feasibility to obtain all induced mutations present in chemical mutants and on the low probability that different individuals share the same mutated genes. By CBS, we identified a cytochrome P450 CYP71P1 gene as responsible for orange blotch DLM mutants, including the historical barley nec3 locus. By comparative phylogenetic analysis we showed that CYP71P1 gene family emerged early in angiosperm evolution but has been recurrently lost in some lineages including Arabidopsis thaliana (L.) Heynh. Complementation by sequencing is a straightforward cost‐effective approach to clone genes controlling phenotypes in a chemically mutagenized collection. The TILLMore (TM) collection will be instrumental for understanding the molecular basis of DLM phenotypes and to contribute knowledge about mechanisms of host–pathogen interaction.

BackgroundMigraine is a recurrent headache disorder that has a still unclear pathophysiology, involving several circuits of both the central and peripheral nervous system. Monoclonal antibodies acting on the calcitonin gene-related (CGRP) pathway (CGRP-MAbs) are the first drugs specifically designed for migraine; those drugs act peripherally on the trigeminal ganglion without entering the blood-brain barrier. Conversely, neuromodulation techniques such as transcranial direct current stimulation (tDCS) act centrally by increasing or decreasing the neuronal firing rate of brain cortical areas. The aim of the study will be to evaluate whether tDCS, in addition to CGRP-MAbs, is an effective add-on treatment in reducing headache frequency, intensity and acute medication use in patients with migraine. To demonstrate the biological effects of tDCS, the electroencephalographic (EEG) power changes after tDCS will be assessed.MethodsWe will include patients with migraine on treatment with CGRP-MAbs and reporting ≥8 monthly migraine days. During a prospective 28-day baseline period, patients will fill in a headache diary and questionnaires to evaluate migraine-related disability, anxiety and depressive symptoms, sleep quality, and health-related quality of life. Subjects will be randomly assigned in a 1:1 ratio to active or sham tDCS. The stimulation protocol will consist in five daily sessions, the cathodes will be applied bilaterally above the occipital areas, with the reference anode electrodes positioned above the primary motor areas. Before the first, and immediately after the last stimulation session, patients will perform a 10-min resting EEG recording. During a 28-day follow-up period following tDCS, patients will have to fill in a headache diary and questionnaires identical to those of the baseline period.DiscussionThis trial will evaluate the efficacy of an add-on treatment acting on the brain in patients with migraine, who are already treated with peripherally acting drugs, showing how tDCS acts in restoring the dysfunctional brain networks typical of the migraine patient.Clinical Trial RegistrationNCT05161871.

All biota is exposed to natural radiation, the soil being the major source of radionuclides. Phosphogypsum is classified as a NORM residue of the phosphate fertilizer industry, often used in agriculture, as a soil conditioner. This residue is stored in stacks by the phosphate industries, potentially posing environmental risks. The aim of this study is to compare the risk for the terrestrial and aquatic biota arising from the storage of PG residue in the environment with that arising from its reuse as soil amendment. For this purpose, typical Brazilian soils amended with PG and PG itself were leached with distilled water. The concentration of natural radionuclides in the soil samples were used to evaluate the risk for terrestrial and aquatic biota, using the ERICA Tool. The results for terrestrial biota exposed to soils amended with phosphogypsum showed a risk reduction of about 85%, when compared to the exposure arising from phosphogypsum stacks. Considering the aquatic biota, the results showed a risk reduction of about 46% when comparing to radionuclide concentrations in leachates from phosphogypsum and from the soils amended with phosphogypsum. A new risk reduction assessment was performed to determine exclusively the contribution of the application of PG to the soil using the soil without PG, the risk reduction for terrestrial biota was of 99% and aquatic biota was a 74% reduction. Finally, it can be concluded that the addition of phosphogypsum in soils reduces the risk quotient related to the exposure of terrestrial and aquatic biota, showing that this is a safe practice.

Abstract Senna comprises about 350 species worldwide, of which 80 species occur in Brazil. This work brings an update taxonomic treatment of Senna species in the state of Minas Gerais, the second most diverse state for the genus, through the morphological analysis of about 2,348 specimens from herbaria and fieldwork. Thirty-six species and 29 varieties were recognized, including 34 native species and 2 cultivated species. Of the 39 species reported in literature for the state, but 4 species were excluded from the list produced. The occurrence of Senna acuruensis was confirmed; S. macranthera var. striata and S. pilifera var. tubata are new records, and S. hirsuta var. acuminata is endemic to Minas Gerais. There are 28 species in the Cerrado, 26 species in the Atlantic Forest and 20 species in the Caatinga. The distribution of Senna pentagonia var. pentagonia is extended to include the Atlantic Forest. Identification keys, descriptions, illustrations, taxonomic comments and geographic distribution are provided for the species and varities.

Over the past few decades, the number of available structural bioinformatics pipelines, libraries, plugins, web resources and software has increased exponentially and become accessible to the broad realm of life scientists. This expansion has shaped the field as a tangled network of methods, algorithms and user interfaces. In recent years PyMOL, widely used software for biomolecules visualization and analysis, has started to play a key role in providing an open platform for the successful implementation of expert knowledge into an easy-to-use molecular graphics tool. This review outlines the plugins and features that make PyMOL an eligible environment for supporting structural bioinformatics analyses.

Museums perform various tasks such as collecting, cataloguing and preserving the cultural heritage (CH). In addition, they have an institutional task, which is to disseminate the heritage, discovering the most efficient tools to tell how a monument to the origin could have looked. In this process of knowledge and dissemination, digital technologies play an important role. In fact, they allow building a digital archive in which virtual copies of found objects are available to scholars for more or less in-depth analysis. Digital archives of this type also allow the dissemination of scientific data, constituting, if published, databases accessible everywhere. The role of the digital archive is also to preserve the characteristics of the finds, which are often already deteriorated, without worsening the situation through their continuous manipulation or movement. Of course, the construction of digital copies must be done in the most rigorous way so as to guarantee scholars the truthfulness of the data being analysed, and building procedures as standardized as possible to allow their use even by unskilled personnel. Moreover, museums have the very complex task of communicating the heritage, which envisages two steps: reconstruction and communication. The first phase, reconstruction, is a very complex operation, especially in the archaeological field, where there are few documents and the hypotheses are based on principles of similarity. Since no direct reference is available, the reconstruction takes place through comparison with similar objects from the same period, the same area and with the same function. Communication, then, has the task of disseminating the results and the hypotheses made, with the most appropriate tools. 3D printing allows to build three-dimensional models of reality, and therefore immediately comprehensible, even of complex forms, not always achievable with the traditional tools of modelling tools. This article describes this complex process, and its application to the funerary aediculae monument at the Museo Archeologico di Mantova, on the occasion of the refurbishment of the museum and its exhibits. In this experience, the use of new technologies is being investigated in combination with more traditional methods of representation, the maquette, but not less effective.

Planned conservation approach requires a sustained, long-term action to better manage the cultural heritage assets during their life cycle. Together with programmed conservation and local interventions, there is a large amount of information related to the building; it emerges the need for an appropriate tool in which to store all data. Historic Building Information Modelling (HBIM) can be an appropriate way to address this issue. In this context, the lack of automatic tools (to speed up the project) and the need for data interpretation in the process are noticeable, especially for cultural heritage items. In this paper we present a practical case study. Starting from an integrated survey of Mantua Cathedral (located in Northern Italy) we developed a HBIM model of its façade. Particular emphasis is given to data interpretation both from geometrical survey and from historical sources. The resulting model is consistent and coherent with reality. As a result, we state that the development of a HBIM model is not an automatized process. In the process, from the survey to the final model, there is the need for a deep knowledge and a deep understanding of the building, not only in term of geometrical survey but also of its historical phases, its changes in time, its materials and the construction techniques. HBIM can be a useful instrument for planned conservation, which strongly requires a coherent model to be effective and useful. A proper model, working as an integrated archive, can increase the effectiveness of planned conservation.

There are many causes for hypertension, but among the modifiable factors, inadequate lifestyle is related to the higher prevalence of the disease. Therefore, the objective of this study was to evaluate the association between macro and micronutrient intake and blood pressure levels with the degree of food processing. Sixty-four adults from the rural area of ??Viçosa, Minas Gerais, Brazil were evaluated. Food consumption was assessed by a dietary recall using AVANUTRI Software, and the foods consumed were classified into three groups: in natura or minimally processed, processed and ultra-processed. Blood pressure was measured using an automatic inflation monitor. The data were analyzed in the Stata Software by means of the Student’s T test. Most of the sample consisted of female adults (64.1%) and the mean systolic and diastolic blood pressure was 122.8 mmHg (±17.1) and 77.7 mmHg (±10.9), respectively. The group of in natura or minimally processed food was responsible for the largest contribution (85.2%) of the average caloric intake (1,793.1 kcal/day), while the consumption of ultra-processed foods was only 7.7%. In addition, there was a higher intake of carbohydrate, lipid, cholesterol, polyunsaturated fat, vitamin E, potassium and sodium among individuals who consumed only in natura or minimally processed foods. Individuals who did not consume ultra-processed foods had higher intakes of vitamin E and sodium. It was concluded that there was an association between the degree of food processing and nutrient intake, however, no association was found among blood pressure levels.