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Abstract Objectives: Patients with post-traumatic stress disorder (PTSD) present a variety of symptoms, with different intensities, causing impairment in individual, social, and occupational functioning. The aim of this study was to understand the psychodynamic functioning of patients with PTSD, exploring relationships between symptom severity, quality of life, subjective suffering, conflicts, and psychic structure and sociodemographic characteristics, styles, and defensive mechanisms. Methods: This is a cross-sectional quantitative study with 60 participants. The following instruments were used: a sociodemographic questionnaire, the Operationalized Psychodynamic Diagnosis-2 (OPD-2), and the Defensive Style Questionnaire (DSQ-40). Results: Participants had moderate to high symptom severity, with significant subjective suffering and isolation. The main conflict was need for care vs. self-sufficiency and the level of total structure was moderate/low. Use of immature, neurotic, and mature defensive styles was observed. More primitive personality structures, more rigid defenses, and greater dependence were found in patients with history of past trauma. Other mental disorders were also associated. Conclusion: The OPD-2 was effective for assessment of the psychodynamic functioning characteristics of patients with PTSD. Therapeutic treatment should focus on the psychic structure and not only on symptom control. Prevention strategies should target vulnerability factors while strengthening protective factors.

The interest in terbium radionuclides, which can be used in nuclear medicine, has increased tremendously over the last decade. Several research studies have shown the potential of four terbium radionuclides 149,152,155,161Tb both for cancer diagnosis as well as therapy. The comparison of 161Tb and 177Lu showed 161Tb as the preferred candidate not only for standard radiotherapy, but also for the treatment of minimal residual disease. Nevertheless, among the terbium sisters, currently, only 161Tb has an established production protocol where its no-carrier-added form is obtained via neutron irradiation of enriched 160Gd targets. The other terbium radioisotopes face challenges related to production capacity and production yield, which currently restricts their use in nuclear medicine. The purpose of this review is to report on recent research on the production and separation of terbium sisters and to assess the prospects for upscaling their production for nuclear medicine applications.

Purpose: Although younger age has been negatively associated with persistence to adjuvant endocrine therapy (ET), factors contributing to non-persistence remain poorly understood. We assessed factors associated with non-persistence to ET and described the 5-year trajectories of quality of life (QoL) and symptoms in young women (≤40 years) with hormone receptor-positive breast cancer (BC). Methods: We retrieved data on clinical characteristics and non-persistence from the medical annual records in the European cohort of the “Helping Ourselves, Helping Others: The Young Women's BC Study” (IBCSG 43-09 HOHO). Women completed surveys at baseline, biannually for three years, and annually for another seven years. Data collection included sociodemographic information, QoL aspects assessed by the Cancer Rehabilitation Evaluation System-Short Form and symptoms assessed by the Breast Cancer Prevention Trial symptom scales. Cox regression models were applied to identify factors associated with non-persistence. Results: The cumulative risk of interrupting ET within 5 years was 27.7 % (95 % CI, 21.5–35.2). The QoL subscale scores remained stable over 5 years, with slight improvements in the physical subscale. Hot flashes decreased (p

Abstract Background Immune Checkpoint Inhibitors (ICIs) lead to durable response and a significant increase in long-term survival in patients with advanced malignant melanoma (MM) and Non-Small Cell Lung Cancer (NSCLC). The identification of serum cytokines that can predict their activity and efficacy, and their sex interaction, could improve treatment personalization. Methods In this prospective study, we enrolled immunotherapy-naïve patients affected by advanced MM and NSCLC treated with ICIs. The primary endpoint was to dissect the potential sex correlations between serum cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, GM-CSF, MCP-1, TNF-ɑ, IP-10, VEGF, sPD-L1) and the objective response rate (ORR). Secondly, we analyzed biomarker changes during treatment related to ORR, disease control rate (DCR), progression free survival (PFS) and overall survival (OS). Blood samples, collected at baseline and during treatment until disease progression (PD) or up to 2 years, were analyzed using Luminex xMAP or ELLA technologies. Results Serum samples from 161 patients (98 males/63 females; 92 MM/69 NSCLC) were analyzed for treatment response. At baseline, IL-6 was significantly lower in females (F) versus males (M); lower levels of IL-4 in F and of IL-6 in both sexes significantly correlated with a better ORR, while higher IL-4 and TNF-ɑ values were predictive of a lower ORR in F versus M. One hundred and sixty-five patients were evaluable for survival analysis: at multiple Cox regression, an increased risk of PD was observed in F with higher baseline values of IL-4, sPD-L1 and IL-10, while higher IL-6 was a negative predictor in males. In males, higher levels of GM-CSF predict a longer survival, whereas higher IL-1β predicts a shorter survival. Regardless of sex, high baseline IL-8 values were associated with an increased risk of both PD and death, and high IL-6 levels only with shorter OS. Conclusions Serum IL-1β, IL-4, IL-6, IL-10, GM-CSF, TNF-ɑ, and sPD-L1 had a significant sex-related predictive impact on ORR, PFS and OS in melanoma and NSCLC patients treated with ICIs. These results will potentially pave the way for new ICI combinations, designed according to baseline and early changes of these cytokines and stratified by sex.

Abstract Terbium-149 (T1/2 = 4.1 h, Eα = 3.98 MeV (16.7%), 28 µm range in tissue) is a radionuclide with potential for targeted alpha therapy. Due to the negligible emission of α-emitting daughter nuclides, toxicity to healthy tissue may be reduced in comparison with other α-particle emitters. In this study, terbium-149 was produced via 1.4 GeV proton irradiation of a tantalum target at the CERN-ISOLDE facility. The spallation products were mass separated and implanted on zinc-coated foils and, later, radiochemically processed. Terbium-149 was separated from the co-produced isobaric radioisotopes and the zinc coating from the implantation foil, using cation-exchange and extraction chromatographic techniques, respectively. At the end of separation, up to 260 MBq terbium-149 were obtained with > 99% radionuclidic purity. Radiolabeling experiments were performed with DOTATATE, achieving 50 MBq/nmol apparent molar activity with radiochemical purity > 99%. The chemical purity was determined by inductively coupled plasma–mass spectrometry measurements, which showed lead, copper, iron and zinc only at ppb level. The radiolabeling of the somatostatin analogue DOTATATE with [149Tb]TbCl3 and the subsequent in vivo PET/CT scans conducted in xenografted mice, showing good tumor uptake, further demonstrated product quality and its ability to be used in a preclinical setting.

Background: This study aimed to verify whether adding a combination of additives (blend) to the diet of dairy calves after weaning can improve animal performance and health and influence the profile of ruminal short-chain fatty acids and intestinal microbiota. Methods: We used 35 Holstein calves, males, with an average age of 70 days and an average body weight of 68 kg. The treatments used were negative control (T-0: without additive), positive control (T-Control: flavomycin + monensin), T-500 (500 g blend/ton), T-1000 (1000 g blend/ton), and T-1500 (1500 g blend/ton). The additives were classified as zootechnical (probiotics, prebiotics, and essential oils of cinnamon and oregano) and nutritional additive (minerals). Results: Weight gain and daily weight gain were higher for calves in the T-Control, T-500, and T-1000 groups. The concentration of heavy-chain immunoglobulins was higher in the blood of calves in the T-Control and T-500 groups when compared to the other groups. In the T-1500 groups, higher levels of reactive oxygen species were observed, while, in the T-0 and T-1500 groups, higher levels of TBARS and glutathione S-transferase activity were detected. The 15 abundant microorganisms in the calves’ feces, regardless of treatment, were Treponema suis, Treponema saccharophilum, Faecalibacterium prausnitzii, Pseudoflavonifractor sp., Roseburia faecis, Rikenellaceae, Enterobacteriaceae_f, Clostridium sp., Roseburia intestinalis, Aeromonadales_o, Prevotella copri, Treponema succinifaciens, Eubacterium sp., Treponema porcium, and Succinivibrio sp. The T-1000 group showed greater alpha diversity for the intestinal microbiota than T-Control, T-0, and T-500. The additive combination (T-1000) increased the bacterial activity in the ruminal fluid, and the animals of T-1000 had a higher concentration of short-chain fatty acids compared to T-0 and T-1500; this difference is because, in these calves, the production of acetic, butyric, and propionic acid increased. Conclusions: The combination of additives had positive effects on animal health, ruminal volatile fatty acid production, and intestinal microbiota, resulting in animals with more significant weight gain and feed efficiency.

Background and aimsFast-track care have been proved to reduce the short-term risk of stroke after transient ischemic attack (TIA). We aimed to investigate stroke risk and to characterize short- and long-term stroke predictors in a large cohort of TIA patients undergoing fast-track management.MethodsProspective study, enrolling consecutive TIA patients admitted to a Northern Italy emergency department from August 2010 to December 2017. All patients underwent fast-track care within 24 h of admission. The primary outcome was defined as the first stroke recurrence at 90 days, 12 and 60 months after TIA. Stroke incidence with 95% confidence interval (CI) at each timepoint was calculated using Poisson regression. Predictors of stroke recurrence were evaluated with Cox regression analysis. The number needed to treat (NNT) of fast-track care in preventing 90-day stroke recurrence in respect to the estimates based on baseline ABCD2 score was also calculated.ResultsWe enrolled 1,035 patients (54.2% males). Stroke incidence was low throughout the follow-up with rates of 2.2% [95% CI 1.4–3.3%] at 90 days, 2.9% [95% CI 1.9–4.2%] at 12 months and 7.1% [95% CI 5.4–9.0%] at 60 months. Multiple TIA, speech disturbances and presence of ischemic lesion at neuroimaging predicted stroke recurrence at each timepoint. Male sex and increasing age predicted 90-day and 60-month stroke risk, respectively. Hypertension was associated with higher 12-month and 60-month stroke risk. No specific TIA etiology predicted higher stroke risk throughout the follow-up. The NNT for fast-track care in preventing 90-day stroke was 14.5 [95% CI 11.3–20.4] in the overall cohort and 6.8 [95% CI 4.6–13.5] in patients with baseline ABCD2 of 6 to 7.ConclusionOur findings support the effectiveness of fast-track care in preventing both short- and long-term stroke recurrence after TIA. Particular effort should be made to identify and monitor patients with baseline predictors of higher stroke risk, which may vary according to follow-up duration.

Abstract Objective Examining the size and reactivity of the pupils of traumatic brain injury coma patients is fundamental in the Neuro‐intensive care unit (ICU). Pupil parameters on admission predict long‐term clinical outcomes. However, little is known about the dynamics of pupillary parameters and their potential value for outcome prediction. Methods This study applied a time‐course analysis of pupillary signals (size and photo‐reactivity) in acute traumatic brain injury coma patients (n = 20) to predict outcome at 6 months. Results The time course of pupillary signals was informative in discriminating favorable (F) versus unfavorable (U) outcomes, with the highest correlation within the 1st week notwithstanding pharmacological sedation. Patients with favorable outcome at 6 months showed more consistent in time isochoric and photo‐reactive pupils. In contrast, patients with an unfavorable outcome showed more variable measures that tended to stabilize toward pathological values. Interpretation Time‐dependent tracking of pupils' size and reactivity is a promising application for ICU monitoring and long‐term prognosis. These findings support the usefulness of automatic tools for the dynamic, quantitative, and objective measurements of pupils.

The focus of this paper is on analyzing the role and the choice of parameters in sociophysics diffusion models by leveraging the potentialities of sociophysics from a mathematical programming perspective. We first present a generalised version of Galam’s opinion diffusion model. For a given selection of the coefficients in our model, this proposal yields the original Galam’s model. The generalised model suggests guidelines for possible alternative selection of its parameters that allow it to foster diffusion. Examples of the parameters selection process as steered by numerical optimisation, taking into account various objectives, are provided.

IntroductionThe COVID-19 pandemic has prompted global research efforts to reduce infection impact, highlighting the potential of cross-disciplinary collaboration to enhance research quality and efficiency.MethodsAt the FMUSP-HC academic health system, we implemented innovative flow management routines for collecting, organizing and analyzing demographic data, COVID-related data and biological materials from over 4,500 patients with confirmed SARS-CoV-2 infection hospitalized from 2020 to 2022. This strategy was mainly planned in three areas: organizing a database with data from the hospitalizations; setting-up a multidisciplinary taskforce to conduct follow-up assessments after discharge; and organizing a biobank. Additionally, a COVID-19 curated collection was created within the institutional digital library of academic papers to map the research output.ResultsOver the course of the experience, the possible benefits and challenges of this type of research support approach were identified and discussed, leading to a set of recommended strategies to enhance collaboration within the research institution. Demographic and clinical data from COVID-19 hospitalizations were compiled in a database including adults and a minority of children and adolescents with laboratory confirmed COVID-19, covering 2020–2022, with approximately 350 fields per patient. To date, this database has been used in 16 published studies. Additionally, we assessed 700 adults 6 to 11 months after hospitalization through comprehensive, multidisciplinary in-person evaluations; this database, comprising around 2000 fields per subject, was used in 15 publications. Furthermore, thousands of blood samples collected during the acute phase and follow-up assessments remain stored for future investigations. To date, more than 3,700 aliquots have been used in ongoing research investigating various aspects of COVID-19. Lastly, the mapping of the overall research output revealed that between 2020 and 2022 our academic system produced 1,394 scientific articles on COVID-19.DiscussionResearch is a crucial component of an effective epidemic response, and the preparation process should include a well-defined plan for organizing and sharing resources. The initiatives described in the present paper were successful in our aim to foster large-scale research in our institution. Although a single model may not be appropriate for all contexts, cross-disciplinary collaboration and open data sharing should make health research systems more efficient to generate the best evidence.

Abstract Background Migraine is a disabling and chronic neurovascular headache disorder. Trigeminal vascular activation and release of calcitonin gene-related peptide (CGRP) play a pivotal role in the pathogenesis of migraine. This knowledge has led to the development of CGRP(-receptor) therapies. Yet, a substantial proportion of patients do not respond to these treatments. Therefore, alternative targets for future therapies are warranted. The current narrative review provides a comprehensive overview of the pathophysiological role of these possible non-CGRP targets in migraine. Findings We covered targets of the metabotropic receptors (pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP), amylin, and adrenomedullin), intracellular targets (nitric oxide (NO), phosphodiesterase-3 (PDE3) and -5 (PDE5)), and ion channels (potassium, calcium, transient receptor potential (TRP), and acid-sensing ion channels (ASIC)). The majority of non-CGRP targets were able to induce migraine-like attacks, except for (i) calcium channels, as it is not yet possible to directly target channels to elucidate their precise involvement in migraine; (ii) TRP channels, activation of which can induce non-migraine headache; and (iii) ASICs, as their potential in inducing migraine attacks has not been investigated thus far. Drugs that target its receptors exist for PACAP, NO, and the potassium, TRP, and ASIC channels. No selective drugs exist for the other targets, however, some existing (migraine) treatments appear to indirectly antagonize responses to amylin, adrenomedullin, and calcium channels. Drugs against PACAP, NO, potassium channels, TRP channels, and only a PAC1 antibody have been tested for migraine treatment, albeit with ambiguous results. Conclusion While current research on these non-CGRP drug targets has not yet led to the development of efficacious therapies, human provocation studies using these targets have provided valuable insight into underlying mechanisms of migraine headaches and auras. Further studies are needed on these alternative therapies in non-responders of CGRP(-receptor) targeted therapies with the ultimate aim to pave the way towards a headache-free future for all migraine patients.

Liquid biopsy is expected to become widespread in the coming years thanks to point of care devices, which can include label-free biosensors. The surface functionalization of biosensors is a crucial aspect that influences their overall performance, resulting in the accurate, sensitive, and specific detection of target molecules. Here, the surface of a microring resonator (MRR)-based biosensor was functionalized for the detection of protein biomarkers. Among the several existing functionalization methods, a strategy based on aptamers and mercaptosilanes was selected as the most highly performing approach. All steps of the functionalization protocol were carefully characterized and optimized to obtain a suitable protocol to be transferred to the final biosensor. The functionalization protocol comprised a preliminary plasma treatment aimed at cleaning and activating the surface for the subsequent silanization step. Different plasma treatments as well as different silanes were tested in order to covalently bind aptamers specific to different biomarker targets, i.e., C-reactive protein, SARS-CoV-2 spike protein, and thrombin. Argon plasma and 1% v/v mercaptosilane were found as the most suitable for obtaining a homogeneous layer apt to aptamer conjugation. The aptamer concentration and time for immobilization were optimized, resulting in 1 µM and 3 h, respectively. A final passivation step based on mercaptohexanol was also implemented. The functionalization protocol was then evaluated for the detection of thrombin with a photonic biosensor based on microring resonators. The preliminary results identified the successful recognition of the correct target as well as some limitations of the developed protocol in real measurement conditions.

PurposeTo systematically review the existing literature that examines the relationship between cognition, hearing, and language in children using cochlear implants and hearing aids.MethodThe review has been registered in Prospero (Registration: CRD 42020203974). The review was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis and examined the scientific literature in VHL, MEDLINE, CINAHL, Scopus, WOS, and Embase. It included original observational studies in children using hearing aids and/or cochlear implants who underwent cognitive and auditory and/or language tests. Data were extracted from the studies and their level of evidence was graded with the Oxford Center for Evidence-Based Medicine: Levels of Evidence. Meta-analysis could not be performed due to data heterogeneity. Outcomes are described in narrative and tables synthesis.ResultsThe systematic search and subsequent full-text evaluation identified 21 studies, conducted in 10 different countries. Altogether, their samples comprised 1,098 individuals, aged 0.16–12.6 years. The studies assessed the following cognitive domains: memory, nonverbal cognition, reasoning, attention, executive functions, language, perceptual-motor function, visuoconstructive ability, processing speed, and phonological processing/phonological memory. Children with hearing loss using cochlear implants and hearing aids scored significantly lower in many cognitive functions than normal hearing (NH) children. Neurocognitive functions were correlated with hearing and language outcomes.ConclusionMany cognitive tools were used to assess cognitive function in children with hearing devices. Results suggest that children with cochlear implants and hearing aids have cognitive deficits; these outcomes are mainly correlated with vocabulary. This study highlights the need to understand children’s cognitive function and increase the knowledge of the relationship between cognition, language, and hearing in children using cochlear implants and hearing aids.