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Abstract Recent research shows that emotional facial expressions impact behavioral responses only when their valence is relevant to the task. Under such conditions, threatening faces delay attentional disengagement, resulting in slower reaction times and increased omission errors compared to happy faces. To investigate the neural underpinnings of this phenomenon, we used functional magnetic resonance imaging to record the brain activity of 23 healthy participants while they completed two versions of the go/no-go task. In the emotion task (ET), participants responded to emotional expressions (fearful or happy faces) and refrained from responding to neutral faces. In the gender task (GT), the same images were displayed, but participants had to respond based on the posers’ gender. Our results confirmed previous behavioral findings and revealed a network of brain regions (including the angular gyrus, the ventral precuneus, the left posterior cingulate cortex, the right anterior superior frontal gyrus, and two face-responsive regions) displaying distinct activation patterns for the same facial emotional expressions in the ET compared to the GT. We propose that this network integrates internal representations of task rules with sensory characteristics of facial expressions to evaluate emotional stimuli and exert top-down control, guiding goal-directed actions according to the context.

Fault slip is a complex natural phenomenon involving multiple spatiotemporal scales from seconds to days to weeks. To understand the physical and chemical processes responsible for the full fault slip spectrum, a multidisciplinary approach is highly recommended. The Near Fault Observatories (NFOs) aim at providing high-precision and spatiotemporally dense multidisciplinary near-fault data, enabling the generation of new original observations and innovative scientific products. The Alto Tiberina Near Fault Observatory is a permanent monitoring infrastructure established around the Alto Tiberina fault (ATF), a 60 km long low-angle normal fault (mean dip 20°), located along a sector of the Northern Apennines (central Italy) undergoing an extension at a rate of about 3 mm yr−1. The presence of repeating earthquakes on the ATF and a steep gradient in crustal velocities measured across the ATF by GNSS stations suggest large and deep (5–12 km) portions of the ATF undergoing aseismic creep. Both laboratory and theoretical studies indicate that any given patch of a fault can creep, nucleate slow earthquakes, and host large earthquakes, as also documented in nature for certain ruptures (e.g., Iquique in 2014, Tōhoku in 2011, and Parkfield in 2004). Nonetheless, how a fault patch switches from one mode of slip to another, as well as the interaction between creep, slow slip, and regular earthquakes, is still poorly documented by near-field observation. With the strainmeter array along the Alto Tiberina fault system (STAR) project, we build a series of six geophysical observatory sites consisting of 80–160 m deep vertical boreholes instrumented with strainmeters and seismometers as well as meteorological and GNSS antennas and additional seismometers at the surface. By covering the portions of the ATF that exhibits repeated earthquakes at shallow depth (above 4 km) with these new observatory sites, we aim to collect unique open-access data to answer fundamental questions about the relationship between creep, slow slip, dynamic earthquake rupture, and tectonic faulting.

Summary: Our case report aims to highlight the multidisciplinary approach adopted for the avoidance of ICU-acquired weakness and the assessment of nutritional therapy in 16 weeks young pregnant with diagnosis of hyperemesis gravidarum complicated with central pontine myelinolysis, after the development of acute respiratory failure due to pneumonia.Thiamine and electrolytes were properly supplemented to minimize the high risk of developing refeeding syndrome. Due to severe nausea and vomiting, antiemetic therapy was started and a parenteral route was chosen during the first two days of non-invasive ventilation. On day three, the patient was intubated and mechanically ventilated due to severe respiratory failure, semi-elemental formula was started by enteral route while parenteral nutrition was supplemented and early rehabilitation was started. Antiemetic therapy was continued until day 28th when the pregnant woman was shifted to oral nutrition only. On day 87th the postpartum mother was transferred to the rehabilitation center for an intensive rehabilitative program based on the motor recovery of lower limb and swallowing recovery.

Abstract The purpose of this work is to provide the methodological and instrumental framework for the establishment of a new absolute gravity and height reference network in Sicily. The aim of the network is to contribute to the new reference systems in the Italian area, useful for the scientific and technological activities related to the gravity field and to the proper definition of a modern height system in this region. The network is composed of 5 stations, evenly distributed to form a large mesh, which roughly covers the entire Sicily. Since four of the five selected stations were measured also in the 1990s, it was also possible to evaluate whether long-term gravity changes occurred at these sites (basic requirement for a reference network) and check the long-term ground deformation patterns, using data from the closest GPS/GNSS stations. The observed gravity changes over a time interval of about 30 years at the absolute stations and in the surrounding areas, confirm the long-term stability of the selected areas/sites.

Background This study aims to examine whether the Edinburgh Postnatal Depression Scale (EPDS), excluding the self-harm item (EPDS-9), performs as effectively as the full EPDS in identifying depression among perinatal women.Methods A total of 3571 pregnant women and 3850 postpartum women participated in this observational study. Participants who scored ≥ 9 on the EPDS underwent further diagnostic evaluations by a clinical psychologist and/or psychiatrist.Results The EPDS-9 and full EPDS demonstrated a near-perfect correlation in both the antepartum (r = 0.996) and postpartum (r = 0.998) cohorts. EPDS-9 showed exceptional precision in identifying depression as screened by the full EPDS at cutoff points ranging 9–14, with areas under the curve ≥0.998. The sensitivity of EPDS-9 and full EPDS to detect depression that requires psychotropic medications was poor. The highest accuracy for both versions was at a cutoff score of 9: sensitivity of 0.579 for the full EPDS and 0.526 for the EPDS-9. At the cutoff point of 9, EPDS-9 performed adequately in predicting the response of the participants to the self-harm item.Conclusion The EPDS-9 represents a solid and effective replacement for the full EPDS in clinical settings. If the presence of suicidal thoughts needs to be assessed, specialized scales should be used.

Patient-reported outcomes (PROs) are essential for understanding the effects of MS and its treatments on patients’ lives; they play an important role in multiple sclerosis (MS) research and practice. We present the protocol for an observational study to prospectively assess the effect of cladribine tablets on PROs and their correlation to disability and physical activity in adults with highly active relapsing MS switching from a first disease modifying drug (DMD) to cladribine tablets in routine clinical practice at study sites in Italy. The primary objective will be to evaluate changes from baseline in the impact of highly active MS on self-assessed physical functioning 52 weeks after the switch to cladribine tablets using the Multiple Sclerosis Impact Scale-29 (MSIS-29). Secondary objectives will include self-assessed psychological impact of highly active MS in daily life and general health after the switch to cladribine tablets as well as changes in cognitive function, anxiety, and depression symptoms. Additional PRO measures will include the Hospital Anxiety and Depression Scale (HADS), the EuroQoL 5-Dimension 5-Level (EQ-5D-5L), the Work Productivity and Activity Impairment Questionnaire: Multiple Sclerosis (WPAI:MS), and the Patient-Reported Outcomes Measurement Information System (PROMIS). Wearable devices will acquire activity data (step counts, walking speed, time asleep, and energy expenditure). Additional clinical, radiological, and laboratory data will be collected when available during routine management. The findings will complement data from controlled trials by providing insight from daily clinical practice into the effect of cladribine tablets on the patient’s experience and self-assessed impact of treatment on daily life.

In this manuscript we investigate the implications of adopting a double cyclic prefix in the orthogonal time-frequency space modulation. Our study first focuses on the analysis of the modulated signal and on the development of a useful model for the received signal in the presence of a doubly selective fading channel. On the one hand, our mathematical results allow us to accurately assess the impact of pulse shaping on the structure of the transmitted waveform and on its power spectral density, and to develop some simple rules for allocating multiple pilot symbols within each orthogonal time-frequency space symbol. On the other hand, they are exploited to develop a novel algorithm for pilot-aided channel estimation, whose output provides a detailed representation of the communication channel; for this reason, it can be used for sensing at the transmit side in integrated sensing and communication applications, or for channel equalization at the receive side in digital communications. Our numerical results evidence that our channel estimation & equalization algorithm outperforms the other related techniques available in the technical literature at the price of a limited increase in computational complexity.

Abstract Postoperative elevation of serum aminotransferase or alkaline phosphatase levels after liver and heart surgeries has been widely reported. The prevalence and clinical significance of hypertransaminasemia/liver dysfunction after thoracic surgery remains largely unknown. Significant differences in surgical procedures between thoracic and extra-thoracic surgeries may suggest different risks of liver dysfunction. We retrospectively analyzed data from 224 consecutive patients who underwent thoracic surgery. Liver function tests were recorded the day before surgery, 12 h, 1 day, 5, and 10 days after the surgical procedure. Patients were studied to identify the frequency of hypertransaminasemia and/or hyperbilirubinemia and/or increase of INR levels. 37,5% of patients showed an increase in serum alanine aminotransferase (ALT) level after thoracic surgery, whereas an increase in gamma glutamyl transferase (GGT) serum levels of any grade was observed in 53,6% of patients. Approximately 83% of patients who experienced an increase in the serum GGT or ALT levels showed a grade 1 or 2 change. Operative time was associated with hypertransaminasemia in the univariate and multivariate analyses, whereas the use of metformin was associated with a lower risk of ALT increase.

Background: Hydroxyurea (HU), also known as hydroxycarbamide, is an oral ribonucleotide reductase inhibitor. In 1999, the United States Food and Drug Administration (FDA) approved HU for the treatment of sickle cell disease (SCD). Since then, it has become the cornerstone in the management of SCD patients, helping to reduce vaso-occlusive crises, acute chest syndrome, the need for blood transfusions, hospitalizations and mortality. There is considerable variability among individuals in HU pharmacokinetic (Pk) parameters that can influence treatment efficacy and toxicity. The objective of this work is part of a clinical study aimed at investigating HU Pk and determining the optimal sampling time to estimate the Area Under the Curve (AUC) in SCD patients. Methods: HU plasma concentration in 80 patients at various time points (2, 4, 6, 24 h) following a 48-h drug washout was quantified using High-Pressure Liquid Chromatography (HPLC) coupled with an ultraviolet (UV) detection method previously described in the literature and adapted to new conditions with partial modifications. Results: The mean HU administered dose was 19.5 ± 5.1 mg/kg (range: 7.7–37.5 mg/kg). The median AUC quantified in plasma patients was 101.3 mg/L/h (Interquartile Range (IQR): 72.5–355.9) and it was not influenced by the weight-based dose. However, there was a strong positive correlation between AUC and Body Mass Index (BMI) as well as dose per Body Surface Area (BSA). Along with a three-point approach for AUC determination present in the literature, we show results obtained from a four-point sampling strategy, which is more useful and effective for better optimizing dose escalation to the maximum tolerated dose (MTD). Moreover, we observed that most patients achieved the maximum HU plasma concentration two hours after drug administration, regardless of age differences. Conclusions: HU treatment, which represents a milestone in the treatment of SCD due to its ability to reduce disease complications and improve patients’ quality of life, requires careful monitoring to optimize the individual dose for saving potential side effects and/or adverse events.

Endovascular aneurysm repair (EVAR) has become the preferred approach over open repair for abdominal aortic aneurysms (AAAs) due to its minimally invasive nature. The common femoral artery (CFA) is the main access vessel for EVAR, with both surgical exposure and percutaneous access being utilized. However, in emergent cases, percutaneous access can be challenging and may result in complications such as bleeding or dissection thrombosis, leading to the need for surgical conversion. This study aimed to share experiences in implementing a decision-making algorithm to reduce surgical conversions due to percutaneous access failures. A total of 74 aortic patients treated with EVAR in emergency settings were included in this retrospective study. This study focused on various outcomes such as perioperative mortality, morbidity, procedure time, surgical exposure time, and surgical conversion rate. After the implementation of the decision-making algorithm, decreases in surgical conversions and operating time were observed. Percutaneous access was found to be more challenging in cases with specific anatomical characteristics of the CFA, such as severe atherosclerosis or smaller vessel diameter. This study highlighted the importance of carefully assessing patient anatomical features and utilizing a decision-making algorithm to optimize outcomes in EVAR procedures. Further research is needed to continue improving practices for managing aortic aneurysms and reducing complications in femoral artery access approaches.

This paper addresses the growing importance of efficient street lighting management, driven by rising electricity costs and the need for municipalities to implement cost-effective solutions. Central to this study is the UNI 11248 Italian regulation, which extends the European EN 13201-1 standard introduced in 2016. These standards provide guidelines for designing, installing, operating, and maintaining lighting systems in pedestrian and vehicular traffic areas. Specifically, the UNI 11248 standard introduces the possibility to dynamically adjust light intensity through two alternative operating modes: (a) Traffic Adaptive Installation (TAI), which dims the light based solely on real-time traffic flow measurements; and (b) Full Adaptive Installation (FAI), which, in addition to traffic measurements, also requires evaluating road surface luminance and meteorological conditions. In this paper, we first present the general architecture and operation of an FAI-enabled lighting infrastructure, which relies on environmental sensors and a heterogeneous wireless communication network to connect intelligent, remotely controlled streetlights. Subsequently, we examine large-scale, in-field FAI infrastructures deployed in Vietnam and Italy as case studies, providing substantial measurement data. The paper offers insights into the measured energy consumption of these infrastructures, comparing them to that of conventional light-control strategies used in traditional installations. The measurements demonstrate the superiority of FAI as the most efficient solution.

Research on strawberry (Fragaria x ananassa Duch.) was carried out in greenhouse in 2022-2023, arranging a 4 x 2 factorial experiment, consisting of four levels of electrical conductivity of the nutrient solutions (1.2, 1.7, 2.2, and 2.7 dS m-1) and application of gypsum (without application – control and application). The plants were grown in coconut fibre substrate from late October to early June. The 2.2 dS m-1 ECsol resulted in the highest yield, whereas the highest values of dry matter and soluble solids were recorded under 2.7 dS m-1 ECsol. Gypsum application resulted in the increase of dry matter, soluble solids, firmness and colour components. The 2.2 and 2.7 dS m-1 ECsol led to the highest levels of hydrophilic and lipophilic antioxidant activities as well as polyphenols and vitamin C. From the research carried out on strawberry grown in coconut fibre, it arose that the 2.2 dS m-1 EC of the nutrient solution showed the best effect on yield, but it did not generally differ from 2.7 dS m-1 regarding the quality of the 'fruits'. Gypsum treatment represents an effective strategy to improve some important qualitative characteristics of strawberry 'fruits', under the perspective of sustainable management of crop systems.

IntroductionOutcome research in eating disorders (EDs) is commonly focused on psychopathological dysfunction. However, Ryff’s model of psychological well-being (PWB) has shown promising—yet preliminary—results with ED patients. Additionally, despite substantial evidence highlighting the association between the therapeutic alliance and treatment outcome, findings in ED samples remain unclear. The present study aimed at exploring the direct effect of PWB dimensions and the early therapeutic alliance on ED patients’ individual treatment responses, as well as the mediating role played by the early therapeutic alliance in the relationship between PWB dimensions and overall pre-post symptom change.MethodsA sample of N = 165 ED patients assigned female at birth, who were receiving treatment in a residential program, completed the Psychological Well-Being Scale at treatment intake and the Working Alliance Inventory after the first four psychotherapy sessions. Patients also completed the Outcome Questionnaire-45.2 at the same time point and during the week prior to discharge.ResultsThe PWB dimensions of autonomy, positive relations, and self-acceptance were associated with clinically significant change, while the dimensions of personal growth and self-acceptance were associated with reliable change. The early therapeutic alliance showed both direct and indirect effects on therapy outcome, predicting clinically significant and reliable symptom reduction. It also emerged as a significant mediator in the relationship between all PWB dimensions and overall symptomatic change.ConclusionThe identification of individual, adaptive characteristics in ED patients that might influence their development of an early therapeutic alliance may help therapists to predict relationship ruptures and tailor their interventions to enhance treatment effectiveness.

IntroductionThe widespread use of surgical masks during the COVID-19 pandemic has posed challenges in interpreting facial emotions. As the mouth is known to play a crucial role in decoding emotional expressions, its covering is likely to affect this process. Recent evidence suggests that facial expressions impact behavioral responses only when their emotional content is relevant to subjects’ goals. Thus, this study investigates whether and how masked emotional faces alter such a phenomenon.MethodsForty participants completed two reaching versions of the Go/No-go task in a counterbalanced fashion. In the Emotional Discrimination Task (EDT), participants were required to respond to angry, fearful, or happy expressions by performing a reaching movement and withholding it when a neutral face was presented. In the Gender Discrimination Task (GDT), the same images were shown, but participants had to respond according to the poser’s gender. The face stimuli were presented in two conditions: covered by a surgical mask (masked) or without any covering (unmasked).ResultsConsistent with previous studies, valence influenced behavioral control in the EDT but not in the GDT. Nevertheless, responses to facial emotions in the EDT exhibited significant differences between unmasked and masked conditions. In the former, angry expressions led to a slowdown in participants’ responses. Conversely, in the masked condition, behavioral reactions were impacted by fearful and, to a greater extent, by happy expressions. Responses to fearful faces were slower, and those to happy faces exhibited increased variability in the masked condition compared to the unmasked condition. Furthermore, response accuracy to masked happy faces dramatically declined compared to the unmasked condition and other masked emotions.DiscussionIn sum, our findings indicate that surgical masks disrupt reactions to emotional expressions, leading people to react less accurately and with heightened variability to happy expressions, provided that the emotional dimension is relevant to people’s goals.

Abstract Recent research indicates that emotional faces affect motor control only when task-relevant. However, these studies utilized a single-face presentation, which does not accurately mirror real-life situations wherein we frequently engage with multiple individuals simultaneously. To overcome this limitation, we gave 40 participants two versions of a novel Flanker-Go/No-go task, where we presented three-face stimuli with a central target and two task-irrelevant flankers that could be congruent or incongruent with the target for valence and gender. In the Emotional Discrimination Task (EDT), participants had to respond to fearful or happy targets and refrain from moving with neutral ones. In the Gender Discrimination Task (GDT), the same images were shown, but participants had to respond according to the target's gender. In line with previous studies, we found an effect of valence only in EDT, where fearful targets increased reaction times and omission error rates compared to happy faces. Notably, the flanker effect, i.e., slower and less accurate responses in incongruent than congruent conditions, was not found. This likely stems from the higher perceptual complexity of faces than that of stimuli traditionally used in the Eriksen Flanker task (letters or signs), leading to a capacity limit in face feature processing.

Abstract Elevated impulsivity is a key component of attention-deficit hyperactivity disorder (ADHD), bipolar disorder and juvenile myoclonic epilepsy (JME). We performed a genome-wide association, colocalization, polygenic risk score, and pathway analysis of impulsivity in JME (n = 381). Results were followed up with functional characterisation using a drosophila model. We identified genome-wide associated SNPs at 8q13.3 (P = 7.5 × 10−9) and 10p11.21 (P = 3.6 × 10−8). The 8q13.3 locus colocalizes with SLCO5A1 expression quantitative trait loci in cerebral cortex (P = 9.5 × 10−3). SLCO5A1 codes for an organic anion transporter and upregulates synapse assembly/organisation genes. Pathway analysis demonstrates 12.7-fold enrichment for presynaptic membrane assembly genes (P = 0.0005) and 14.3-fold enrichment for presynaptic organisation genes (P = 0.0005) including NLGN1 and PTPRD. RNAi knockdown of Oatp30B, the Drosophila polypeptide with the highest homology to SLCO5A1, causes over-reactive startling behaviour (P = 8.7 × 10−3) and increased seizure-like events (P = 6.8 × 10−7). Polygenic risk score for ADHD genetically correlates with impulsivity scores in JME (P = 1.60 × 10−3). SLCO5A1 loss-of-function represents an impulsivity and seizure mechanism. Synaptic assembly genes may inform the aetiology of impulsivity in health and disease.

Graft steatosis has been associated with inferior outcomes after liver transplantation. Given the rising prevalence of obesity and fatty liver disease, strategies allowing safe and successful utilization of fatty liver grafts are needed. Liver preservation by normothermic machine perfusion (NMP) allows reducing ischemia-reperfusion injury, extending preservation time and assessing graft viability prior to implantation into the recipient. NMP can be initiated at the donor hospital using a transportable device (referred to as upfront NMP or normothermic machine preservation) or after a period of cold ischemia (known as back-to-base). In this report, we present the case of a graft from an HCV-positive DBD donor with 70% macrovesicular steatosis, which was successfully preserved and transplanted using upfront NMP. This approach was key to minimize initial injury to the graft and allowed assessing its viability before transplantation, while improving transplant logistics. Upfront NMP represents a promising approach to enhance the transplantation of fatty liver grafts.

Abstract Background Specialized diets enriched with immune nutrients could be an important supplement in patients (pts) with acute traumatic brain injury (TBI). Omega-3 and arginine may interact with immune response and microbiota. No data are available about the role of the specialized diets in modulating the lung microbiota, and little is known about the influence of lung microbiota structure in development of ventilator-associated pneumonia (VAP) in TBI pts. The aims of this study are to evaluate the impact of specific nutrients on the lung microbiota and the variation of lung microbiota in TBI pts developing VAP. Methods A cohort of 31 TBI pts requiring mechanical ventilation in ICU was randomized for treatment with specialized (16pts) or standard nutrition (15pts). Alpha and beta diversity of lung microbiota were analyzed from bronco Alveolar Lavage (BAL) samples collected at admission and 7 days post-ICU admission in both groups. A further analysis was carried out on the same samples retrospectively grouped in VAP or no VAP pts. Results None developed VAP in the first week. Thereafter, ten out of thirty-one pts developed VAP. The BAL microbiota on VAP group showed significant differences in beta diversity and Staphylococcus and Acinetobacter Genera were high. The specialized nutrition had influence on beta diversity that reached statistical significance only in Bray–Curtis distance. Conclusion Our data suggest that TBI patients who developed VAP during ICU stay have different structures of BAL microbiota either at admission and at 7 days post-ICU admission, while no correlation has been observed between different enteral formulas and microbiota composition in terms of richness and evenness. These findings suggest that targeting the lung microbiota may be a promising approach for preventing infections in critically ill patients.

OBJECTIVES:. In patients with COVID-19 respiratory failure, controlled mechanical ventilation (CMV) is often necessary during the acute phases of the disease. Weaning from CMV to pressure support ventilation (PSV) is a key objective when the patient’s respiratory functions improve. Limited evidence exists regarding the factors predicting a successful transition to PSV and its impact on patient outcomes. DESIGN:. Retrospective observational cohort study. SETTING:. Twenty-four Italian ICUs from February 2020 to May 2020. PATIENTS:. Mechanically ventilated ICU patients with COVID-19-induced respiratory failure. INTERVENTION:. The transition period from CMV to PSV was evaluated. We defined it as “failure of assisted breathing” if the patient returned to CMV within the first 72 hours. MEASUREMENTS AND MAIN RESULTS:. Of 1260 ICU patients screened, 514 were included. Three hundred fifty-seven patients successfully made the transition to PSV, while 157 failed. Pao2/Fio2 ratio before the transition emerged as an independent predictor of a successful shift (odds ratio 1.00; 95% CI, 0.99–1.00; p = 0.003). Patients in the success group displayed a better trend in Pao2/Fio2, Paco2, plateau and peak pressure, and pH level. Subjects in the failure group exhibited higher ICU mortality (hazard ratio 2.08; 95% CI, 1.42–3.06; p < 0.001), an extended ICU length of stay (successful vs. failure 21 ± 14 vs. 27 ± 17 d; p < 0.001) and a longer duration of mechanical ventilation (19 ± 18 vs. 24 ± 17 d, p = 0.04). CONCLUSIONS:. Our study emphasizes that the Pao2/Fio2 ratio was the sole independent factor associated with a failed transition from CMV to PSV. The unsuccessful transition was associated with worse outcomes.

IntroductionThe hemodynamic management of septic patients involves initial fluid therapy, followed by the use of vasoconstrictors in case of treatment failure. The latest Surviving Sepsis Campaign guidelines suggest the synergistic use of argipressin in addition to norepinephrine when hemodynamic optimization is not achieved with norepinephrine alone.MethodsIn our single-center retrospective observational study, the primary endpoint is the safety of initial norepinephrine-argipressin association treatment, assessed through a reduction in Resistance Index. Our secondary endpoint includes the efficacy of this combination, measured by an increase in Mean Arterial Pressure and a reduction in Resistance Index as an indicator of organ perfusion. The Resistance Index (RI) is evaluated through Power Doppler ultrasound. RI is crucial for assessing multi-district vascular tone and multiorgan perfusion. Patients were categorized into three groups based on their treatment. In Group 1, we analyzed patients treated with norepinephrine alone in incremental doses; in Group 2, we analyzed patients receiving the initial norepinephrine-argipressin association treatment (norepinephrine 0.05 mcg/kg/min-argipressin 0.03 IU/min); in the third group (Group 3), we analyzed patients given argipressin (0.03 IU/min) after norepinephrine ( 65 mmHg). RI measurements were taken in the Renal Artery (ARE), Radial Artery (AR), Central Retinal Artery (CRA), and Superior Mesenteric Artery (AMS) at four different time points: T0 before vasopressor therapy, T1 at 1 h, T2 at 24 h, and T3 at 48 h after vasopressor infusion.ResultsA total of 48 patients were divided into three groups: 17 patients in Group 1, 16 in Group 2, and 15 in Group 3. In Group 1, an increase in Mean Arterial Pressure (MAP) was observed, but there was an increase in RIs in the right CRI and left ARE. In Group 2, there was an improvement in MAP and a reduction in RIs in the right/left CRI, left ARE, AMS, and right AR. In Group 3, there was an increase in MAP and a reduction in RIs in the right/left CRI, left ARE, AMS, and right AR.ConclusionEarly norepinephrine-argipressin association treatment appears to be a valid strategy for hemodynamic optimization in this patient population.

Abstract Background Papillary thyroid carcinoma (PTC) is a common neoplasia with multiple variants. One of these extremely rare and poorly described variants is PTC with fibromatosis-like stroma (PTC-FMS), a peculiar entity distinguished by its predominant mesenchymal component. This paper reviews the literature, discusses the diagnostic challenges, and the clinical and surgical implications of this type of tumor which has fewer than 30 cases reported in the literature. Case presentation We reported a case of PTC-FMS found in a 41-year-old Italian woman, who came to our Institute with a recent growth in the form of a mass on the neck. Further immunohistochemical examination showed β-catenin aberrant staining both in the nuclei and cytoplasm of the mesenchymal cells. The patient underwent total thyroidectomy and received radioactive iodine (RAI) 2 months after surgery. Conclusion Given the possibility of recurrence of PTC-FMS and the ineffectiveness of RAI therapy, complete surgical resection represents the main treatment for this type of tumor. Despite the fact that the specific nature of these lesions has yet to be determined, guidelines for classical PTC should be followed.

In patients with end-stage renal failure requiring hemodialysis, autogenous arteriovenous fistula (AVF) is preferred over tunneled dialysis catheters due to lower complications and costs. However, AVF maturation failure remains a common issue due to small vein size, multiple venipunctures, and other factors. Guidelines recommend using vessels of >2 mm for forearm AVFs and >3 mm for upper arm AVFs. This study investigates the use of intraoperative Doppler ultrasound (DUS)-guided Balloon-Assisted Maturation (BAM) with drug-eluting balloons (DEB) during initial AVF creation. Data from 114 AVF procedures, of which 27.2% underwent BAM, were analyzed. BAM was performed in 25 distal radio-cephalic and 6 proximal brachio-cephalic AVFs. With DUS guidance, vein stenosis was identified and treated using DEB. Technical success was achieved in all cases, with no early mortality. Early BAM-related complications were minimal, and no AVF thrombosis occurred. AVF maturation time was 15 days (SD: 3), and no further complications were reported during a mean follow-up of 10.38 months. Using BAM with DEB during AVF creation led to successful maturation and dialysis use without the need for secondary procedures. This study emphasizes the importance of identifying AVF failure risk early and utilizing DUS-guided procedures to enhance AVF outcomes. A more liberal use of intraoperative BAM could limit reinterventions in patients undergoing AVFs.

A few cases of multiple sclerosis (MS) onset after COVID-19 vaccination have been reported, although the evidence is insufficient to establish causality. The aim of this study is to compare cases of newly diagnosed relapsing–remitting MS before and after the outbreak of the COVID-19 pandemic and the impact of COVID-19 vaccination. Potential environmental and genetic predisposing factors were also investigated, as well as clinical patterns. This is a single-centre retrospective cohort study including all patients who presented with relapsing–remitting MS onset between January 2018 and July 2022. Data on COVID-19 vaccination administration, dose, and type were collected. HLA-DRB1 genotyping was performed in three subgroups. A total of 266 patients received a new diagnosis of relapsing–remitting MS in our centre, 143 before the COVID-19 pandemic (until and including March 2020), and 123 during the COVID-19 era (from April 2020). The mean number of new MS onset cases per year was not different before and during the COVID-19 era and neither were baseline patients’ characteristics, type of onset, clinical recovery, or radiological patterns. Fourteen (11.4%) patients who subsequently received a new diagnosis of MS had a history of COVID-19 vaccination within one month before symptoms onset. Patients’ characteristics, type of onset, clinical recovery, and radiological patterns did not differ from those of patients with non-vaccine-related new diagnoses of MS. The allele frequencies of HLA-DRB1*15 were 17.6% and 22.2% in patients with non-vaccine-related disease onset before and during the COVID-19 era, respectively, while no case of HLA-DRB1*15 was identified among patients with a new diagnosis of MS post-COVID-19 vaccine. In contrast, HLA-DRB1*08+ or HLA-DRB1*10+ MS patients were present only in this subgroup. Although a causal link between COVID-19 vaccination and relapsing–remitting MS cannot be detected, it is interesting to note and speculate about the peculiarities and heterogeneities underlying disease mechanisms of MS, where the interactions of genetics and the environment could be crucial also for the follow-up and the evaluation of therapeutic options.

Background and Objectives: Paragangliomas (PGLs) are rare neuroendocrine extra-adrenal tumors that could be secreting mass. The symptoms are the typical triad of paroxysmal headache, hypertension and sweating, but could also be accompanied by symptoms involving multiple organs. Surgery is the gold standard treatment for both PGLs and pheochromocytomas (PHEOs). Material and Methods: We used a computerized endocrine surgery registry to record the demographic and clinical data of 153 patients who underwent surgery for PPGL between 2010 and 2023 at our hospital. Results: Thirteen patients (8.43%) with paragangliomas underwent surgery at our institute. Five patients presented symptomatic syndrome. Preoperative investigations included enhanced abdominal CT (nine patients) and enhanced MRI (seven patients). In cases of suspicious mass, we performed 131I-MIBG scans (two patients) or 68GA-DOTATOC PET-CT scans (11 patients). Laparoscopic approach was used in four cases (30.7%) and abdominal laparotomy in the other nine (69.3%). Biochemical tests were performed on all patients. Conclusions: In this retrospective study, we discuss the multidisciplinary management in our institute of this rare disease, from its challenging diagnosis to the surgical strategy for PGLs. Laparoscopic surgery is the gold standard, but a tailored approach should be adopted for each patient.

Mandibular fractures are very common in maxillofacial trauma surgery. While previous studies have focused on possible risk factors related to post-operative complications, none have tried to identify pre-existing conditions that may increase the risk of mandibular fractures. We hypothesized, through clinical observation, that anatomical conditions involving poor dental contacts, such as malocclusions, may increase the risk of mandibular fractures. This work was subdivided into two parts. In the first part, Digital Imaging and Communications in Medicine (DICOM) data of four healthy patients characterized by different dentoskeletal occlusions (class I, class II, class III, and anterior open bite) have been used to develop four finite element models (FEMs) that accurately reproduce human bone structure. A vertical and lateral impact have been simulated at increasing speed on each model, analyzing the force distribution within the mandibular bone. Both vertical and lateral impact showed higher level of stress at the impact point and in the condylar area in models characterized by malocclusion. Specifically, the class III and the open bite models, at the same speed of impact, had higher values for a longer period, reaching critical stress levels that are correlated with mandibular fracture, while normal occlusion seems to be a protective condition. In the second part of this study, the engineering results were validated through the comparison with a sample of patients previously treated for mandibular fracture. Data from 223 mandibular fractures, due to low-energy injuries, were retrospectively collected to evaluate a possible correlation between pre-existing malocclusion and fracture patterns, considering grade of displacement, numbers of foci, and associated CFI score. Patients were classified, according to their occlusion, into Class I, Class II, Class III, and anterior open bite or poor occlusal contact (POC). Class I patients showed lower frequencies of fracture than class II, III, and open bite or POC patients. Class I was associated with displaced fractures in 16.1% of cases, class II in 47.1%, class III in 48.8% and open bite/POC in 65.2% of cases (p-value < 0.0001). In class I patients we observed a single non-displaced fracture in 51.6% of cases, compared to 12.9% of Class II, 19.5% of Class III and 22.7% of the open bite/POC group. Our analysis shows that class I appears to better dissipate forces applied on the mandible in low-energy injuries. A higher number of dental contacts showed a lower rate of multifocal and displaced fractures, mitigating the effect of direct forces onto the bone. The correlation between clinical data and virtual simulation on FEM models seems to point out that virtual simulation successfully predicts fracture patterns and risk of association with different type of occlusion. Better knowledge of biomechanics and force dissipation on the human body may lead to the development of more effective safety devices, and help select patients to plan medical, orthodontic/dental, and/or surgical intervention to prevent injuries.

Orexins A (OXA) and B (OXB) and their specific receptors, receptor 1 (OX1R) and 2 (OX2R) for orexins, are hypothalamic peptides involved in orchestrating several functions in the central nervous system and peripheral organs, including sleep, excitement, nutrition, reward, circadian rhythm, anxiety, cognition, and reproduction. The aim of this narrative review is, in particular, to speculate the role of orexins in the male genital tract of animal species and human beings. The experimental evidence collected in recent years assumed that in the testes of the animal species here described, orexins are directly involved in steroidogenesis and spermatogenesis regulation. In the epididymis, these peptides are locally synthesized, thus suggesting their role governing the fertilizing capability of the immature male gamete. In addition to playing a physiological role, orexins are involved in numerous inflammatory and/or neoplastic pathologies too. The expression of the orexinergic system in prostate cancer suggests that they might play a potential therapeutic function. Overall, the future directions of this literature review allow us to hypothesize a role of the orexinergic complex not only as a marker for the diagnosis of certain tumors affecting the male genital tract but also for the treatment of hypo/infertility condition.

Abstract Bimetallic decoration of semiconductor electrodes typically improves catalytic and sensing performances because of a well-claimed synergistic effect. A microscopic and quantitative investigation of such an effect on energy bands of semiconductor can be really useful for further exploitation. Au, Pd and Au@Pd (core@shell) nanoparticles (10–20 nm in size) were synthesized through chemical reduction method and characterized with scanning and transmission microscopy, Rutherford backscattering spectrometry, cyclic voltammetry electrochemical impedance spectroscopy and Mott–Schottky analysis. The nanoparticles have been used to decorate Ni-based nanostructured electrodes with the aim to quantitatively investigate the effect of decoration with mono or bimetallic nanoparticles. Decorated electrodes show higher redox currents than bare ones and a shift in redox peaks (up to 0.3 V), which can be ascribed to a more efficient electron transport and improved catalytic properties. These effects were satisfactorily modeled (COMSOL) employing a nano Schottky junction at the nanoparticle–semiconductor interface, pointing out large energy band bending (up to 0.4 eV), space charge region and local electric field (up to $${10}^{8}\mathrm{ V }{\mathrm{m}}^{-1}$$ 10 8 V m - 1 ) in bimetallic decoration. Sensing test of glucose and H2O2 by decorated Ni oxide electrodes were performed to consolidate our model. The presence of bimetallic nanoparticles enhances enormously the electrochemical performances of the material in terms of sensitivity, catalytic activity, and electrical transport. The modification of energy band diagram in semiconductor is analyzed and discussed also in terms of electron transfer during redox reactions.

In this manuscript, the problem of detecting multiple targets and jointly estimating their spatial coordinates (namely, the range, the Doppler and the direction of arrival of their electromagnetic echoes) in a colocated multiple-input multiple-output radar system employing orthogonal frequency division multiplexing is investigated. It is well known its optimal solution, namely the joint maximum likelihood estimator of an unknown number of targets, is unfeasible because of its huge computational complexity. Moreover, until now, sub-optimal solutions have not been proposed in the technical literature. In this manuscript a novel approach to the development of reduced complexity solutions is illustrated. It is based on the idea of separating angle estimation from range-Doppler estimation, and of exploiting known algorithms for solving these two sub-problems. A detailed analysis of the accuracy and complexity of various detection and estimation methods based on this approach is provided. Our numerical results evidence that one of these methods is able to approach optimal performance in the maximum likelihood sense with a limited computational effort in different scenarios.

In this manuscript, we analyze the most relevant classes of deterministic signal processing methods currently available for the detection and the estimation of multiple targets in a joint communication and sensing system employing orthogonal frequency division multiplexing. Our objective is offering a fair comparison of the available technical options in terms of required computational complexity and accuracy in both range and Doppler estimation. Our numerical results, obtained in various scenarios, evidence that distinct algorithms can achieve a substantially different accuracy-complexity trade-off.

The role of sedation in patients with acute respiratory failure in the intensive care unit is crucial for improving the adaptation to mechanical ventilation, avoiding lung injury, and reducing stress related to the over-stimulated sympathetic tone. The drug class alpha 2 agonists, alone or in synergic association, can help the clinician achieve these goals. Understanding the principles of pharmacology and applying them to the alpha 2 agonists, clonidine and dexmedetomidine, can lead to different pharmaceutical choices to adapt various sedative approaches to the different stages of acute respiratory failure. A scheme is proposed using these two drugs as a pharmacological continuation for an early weaning and recovery from the intensive care unit.

Abstract Hydrogeological perturbations in response to earthquakes are widely described worldwide. In carbonate aquifers, a post-seismic discharge increase is often attributed to an increase of bulk permeability due to co-seismic fracturing and the attention on the role of faults to explain the diversion of groundwater is increasing. We focus on the reaction of carbonate hydrogeological basins to extensional seismicity, taking as an example the effects of the Central Italy 2016–2017 seismic sequence, on the Basal aquifer of the Sibillini Mountains area. Geo-structural, seismological and ground deformation data were collected and merged with artificial tracer tests results and with a 4-years discharge and geochemical monitoring campaign. The main NNW-directed groundwater flow was diverted to the west and a discharge deficit was observed at the foot-wall of the activated fault system with a relevant discharge increase, accompanied by geochemical variations, at the fault system hanging-wall. The observed variations are consistent with the combined action of a permeability increase along the activated fault systems, which modified the predominant pre-seismic along-strike regional flow, and with hydraulic conductivity increase due to fracturing, determining a fast aquifers emptying. We show that the prevailing mechanism depends on the aquifer systems position with respect to the activated faults.

Abstract Objective Staphylococcus epidermidis is a skin colonizer and a major cause of nosocomial infections that can lead to sepsis. It causes opportunistic infections by forming biofilms on medical devices, which are hard to control with conventional antibiotics. In an attempt to develop its biofilm inhibitors, the culture supernatant (CS) of Pseudomonas fluorescens was assessed. This study examined the effect of the CS on S. epidermidis 1457 biofilm formation, the characteristics of inhibitors in the CS, and the differential gene expression of S. epidermidis when treated with the CS. Results P. fluorescens CS specifically targeted the maturation stage of S. epidermidis biofilm formation while not affecting planktonic growth. RT-qPCR analysis revealed that P. fluorescens CS significantly downregulated S. epidermidis ica genes and upregulated an ica repressor, tcaR. This indicates that the CS reduced polysaccharide intercellular adhesin synthesis, a major component of the S. epidermidis 1457 biofilm matrix. Further studies are required to elucidate the specific inhibitory components in the CS and their mechanism of action. Our results indicate that inhibitors in the P. fluorescens CS may have a significant value for inhibiting S. epidermidis biofilm. Combinations of specific inhibitors from the CS and antibiotics against staphylococci may provide an effective measure to control S. epidermidis biofilm formation while avoiding antibiotic resistance and compensating the attenuated effectiveness of antibiotics on biofilms.

Abstract Background Since January 2020, coronavirus disease 19 (COVID-19) has rapidly spread all over the world. An early assessment of illness severity is crucial for the stratification of patients in order to address them to the right intensity path of care. We performed an analysis on a large cohort of COVID-19 patients (n=581) hospitalized between March 2020 and May 2021 in our intensive care unit (ICU) at Policlinico Riuniti di Foggia hospital. Through an integration of the scores, demographic data, clinical history, laboratory findings, respiratory parameters, a correlation analysis, and the use of machine learning our study aimed to develop a model to predict the main outcome. Methods We deemed eligible for analysis all adult patients (age >18 years old) admitted to our department. We excluded all the patients with an ICU length of stay inferior to 24 h and the ones that declined to participate in our data collection. We collected demographic data, medical history, D-dimers, NEWS2, and MEWS scores on ICU admission and on ED admission, PaO2/FiO2 ratio on ICU admission, and the respiratory support modalities before the orotracheal intubation and the intubation timing (early vs late with a 48-h hospital length of stay cutoff). We further collected the ICU and hospital lengths of stay expressed in days of hospitalization, hospital location (high dependency unit, HDU, ED), and length of stay before and after ICU admission; the in-hospital mortality; and the in-ICU mortality. We performed univariate, bivariate, and multivariate statistical analyses. Results SARS-CoV-2 mortality was positively correlated to age, length of stay in HDU, MEWS, and NEWS2 on ICU admission, D-dimer value on ICU admission, early orotracheal intubation, and late orotracheal intubation. We found a negative correlation between the PaO2/FiO2 ratio on ICU admission and NIV. No significant correlations with sex, obesity, arterial hypertension, chronic obstructive pulmonary disease, chronic kidney disease, cardiovascular disease, diabetes mellitus, dyslipidemia, and neither MEWS nor NEWS on ED admission were observed. Considering all the pre-ICU variables, none of the machine learning algorithms performed well in developing a prediction model accurate enough to predict the outcome although a secondary multivariate analysis focused on the ventilation modalities and the main outcome confirmed how the choice of the right ventilatory support with the right timing is crucial. Conclusion In our cohort of COVID patients, the choice of the right ventilatory support at the right time has been crucial, severity scores, and clinical judgment gave support in identifying patients at risk of developing a severe disease, comorbidities showed a lower weight than expected considering the main outcome, and machine learning method integration could be a fundamental statistical tool in the comprehensive evaluation of such complex diseases.

HPV (Human papillomavirus) affects 600,000 people worldwide each year. Almost all cervical cancers are associated with a past HPV infection. In particular, the positivity to the high-risk type HPV16 is detected in most of the invasive cervical cancers. FDA has approved prophylactic vaccines that protect against new HPV16 infections, but do not induce immunity in those patients with established infections or neoplasms. To date, no therapeutic vaccine targeting HPV16-associated lesions has been authorized. We have developed an mRNA-based vaccine against the HPV16 late oncoproteins E6 and E7, which are abundantly and exclusively expressed in high-grade squamous intraepithelial lesions (HSILs), a stage of the cervical disease that precedes the progression to carcinoma. Our in vitro and in vivo studies demonstrated that the translated mRNA is functional and elicits an antigen-specific adaptive immune response. Upon immunization with the vaccine, mice with HPV16+ lesions exhibited tumor growth inhibition, extension of lifespan, and development of a protective immune memory. In light of these results and the remarkable clinical success of mRNA vaccines against SARS-CoV2, we believe that our mRNA-based therapeutic vaccine has the potential to offer a non-invasive treatment alternative to the current standard of care for HPV16+ HSILs.

Efficient and sustainable materials are requested to overcome the actual major issues related to green energy production. Ni/NiO nanoparticles (NPs, 2–4 nm in size) produced by Pulsed Laser Ablation in Liquid (PLAL) are reported as highly efficient and stable electrocatalysts for oxygen evolution reaction (OER) in water splitting applications. Ni/NiO NPs dispersions are obtained by ablating a Ni target immersed in deionized water with an Nd:YAG nanosecond pulsed laser. NPs size and density were driven by laser energy fluence (ranging from 8 to 10 J cm−2) and shown to have an impact on OER performance. Ni/NiO NPs were characterized by scanning and transmission electron microscopy, x-ray diffraction, photoemission spectroscopy, and Rutherford back-scattering spectrometry. By drop-casting onto graphene paper, anode electrodes were fabricated for electrochemical water splitting in alkaline electrolytes. The extrinsic and intrinsic catalytic performances for OER have been quantified, achieving an overpotential of 308 mV (at a current density of 10 mA cm−2) and unprecedented mass activity of more than 16 A mg−1, using NPs synthesized with the highest and lowest laser energy fluence, respectively. The impact of NPs’ size and density on OER performances has been clarified, opening the way for PLAL synthesis as a promising technique for highly efficient nano-electrocatalysts production.

ObjectivesThe dynamics of the memory B cell (MBC) repertoire after SARS-CoV-2 vaccination is crucial for assessing long-term immunity. We compare spike-specific MBC responses between SARS-CoV-2 unexposed and recovered individuals, and their impact on breakthrough infections during follow-up.MethodsSpike-specific MBC and T cells were quantified at inclusion and after two doses of mRNA vaccine in a longitudinal cohort of 85 naïve and 64 recovered participants (47 with positive serology and 17 with negative serology after infection).ResultsAt inclusion, there was minimal spike-specific MBC in naïve SARS-CoV-2 individuals. After the second vaccine dose, MBCs were significantly boosted in naïve individuals, but reached a significantly lower level than that observed even in unvaccinated SARS-CoV-2 convalescents (p

Background: Most patients with testicular germ cell tumors (GCTs) are treated with cisplatin (CP)-based chemotherapy. However, some of them may develop CP resistance and therefore represent a clinical challenge. Cyclin-dependent kinase 5 (CDK5) is involved in chemotherapy resistance in different types of cancer. Here, we investigated the possible role of CDK5 and other CDKs targeted by dinaciclib in nonseminoma cell models (both CP-sensitive and CP-resistant), evaluating the potential of the CDK inhibitor dinaciclib as a single/combined agent for the treatment of advanced/metastatic testicular cancer (TC). Methods: The effects of dinaciclib and CP on sensitive and resistant NT2/D1 and NCCIT cell viability and proliferation were evaluated using MTT assays and direct count methods. Flow cytometry cell-cycle analysis was performed. The protein expression was assessed via Western blotting. The in vivo experiments were conducted in zebrafish embryos xenografted with TC cells. Results: Among all the CDKs analyzed, CDK5 protein expression was significantly higher in CP-resistant models. Dinaciclib reduced the cell viability and proliferation in each cell model, inducing changes in cell-cycle distribution. In drug combination experiments, dinaciclib enhances the CP effect both in vitro and in the zebrafish model. Conclusions: Dinaciclib, when combined with CP, could be useful for improving nonseminoma TC response to CP.

Enteroendocrine cells (EECs) constitute only a small proportion of Villin-1 (Vil1)-expressing intestinal epithelial cells (IECs) of the gastrointestinal tract; yet, in sum, they build the largest endocrine organ of the body, with each of them storing and releasing a distinct set of peptides for the control of feeding behavior, glucose metabolism, and gastrointestinal motility. Like all IEC types, EECs are continuously renewed from intestinal stem cells in the crypt base and terminally differentiate into mature subtypes while moving up the crypt–villus axis. Interestingly, EECs adjust their hormonal secretion according to their migration state as EECs receive altering differentiation signals along the crypt–villus axis and thus undergo functional readaptation. Cell-specific targeting of mature EEC subtypes by specific promoters is challenging because the expression of EEC-derived peptides and their precursors is not limited to EECs but are also found in other organs, such as the brain (e.g., Cck and Sst) as well as in the pancreas (e.g., Sst and Gcg). Here, we describe an intersectional genetic approach that enables cell type-specific targeting of functionally distinct EEC subtypes by combining a newly generated Dre-recombinase expressing mouse line (Vil1-2A-DD-Dre) with multiple existing Cre-recombinase mice and mouse strains with rox and loxP sites flanked stop cassettes for transgene expression. We found that transgene expression in triple-transgenic mice is highly specific in I but not D and L cells in the terminal villi of the small intestine. The targeting of EECs only in terminal villi is due to the integration of a defective 2A separating peptide that, combined with low EEC intrinsic Vil1 expression, restricts our Vil1-2A-DD-Dre mouse line and the intersectional genetic approach described here only applicable for the investigation of mature EEC subpopulations.

Background: In Awake Craniotomy (AC), α2-agonists and remifentanil (clonidine and dexmedetomidine) are used in the preoperative phase and throughout the procedure to combine monitored anesthesia care and local anesthesia. The study aims were to specify the key role of α2-agonists administered and to evaluate complication presence/absence in anesthesiologic management. Methods: 42 patients undergoing AC in 3 different centers in the south of Italy (Foggia, San Giovanni Rotondo, and Bari) were recruited. Our protocol involves analgo-sedation by administering Dexmedetomidine and Remifentanil in continuous intravenous infusion, allowing the patient to be sedated and in comfort but contactable and spontaneously breathing. During pre-surgery, the patient is premedicated with intramuscular clonidine (2 µg/kg). In the operating setting, Dexmedetomidine in infusion and Remifentanil in Target Controlled Infusion for effect are started. At the end of the surgical procedure, the infusion of drugs was suspended. Results: There were no intraoperative side effects. The mean duration of interventions was 240 ± 62 min. The average quantity of Remifentanil and Dexmedetomidine infused during interventions were 4.2 ± 1.3 mg and 1.0 ± 0.3 mg, respectively. No significant side effects were described in the post-operative phase. A total of 86% of patients and 93% of surgeons were totally satisfied. Conclusions: Synergy between opioid drugs and α2 agonists plays a fundamental role in ensuring procedure success.

Analytical methods for the early detection of the neurodegenerative biomarker for Parkinson’s disease (PD), α-synuclein, are time-consuming and invasive, and require skilled personnel and sophisticated and expensive equipment. Thus, a pain-free, prompt and simple α-synuclein biosensor for detection in plasma is highly demanded. In this paper, an α-synuclein electrochemical biosensor based on hierarchical polyglutamic acid/ZnO nanowires decorated by gold nanoparticles, assembled as nanostars (NSs), for the determination of α-synuclein in human plasma is proposed. ZnO NSs were prepared by chemical bath deposition (CBD) and decorated with electrodeposited Au nanoparticles (Au NPs). Then, electro-polymerized glutamic acid was grown and functionalized with anti-α-synuclein. A synergistic enhancement of electrode sensitivity was observed when Au NPs were embedded into ZnO NSs. The analytical performance of the biosensor was evaluated by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), using the Fe(II)(CN)64−/Fe(III)(CN)63− probe. The charge transfer resistance after α-synuclein recognition was found to be linear, with a concentration in the range of 0.5 pg·mL−1 to 10 pg·mL−1, a limit of detection of 0.08 pg·mL−1, and good reproducibility (5% variation) and stability (90%). The biosensor was also shown to reliably discriminate between healthy plasma and PD plasma. These results suggest that the proposed biosensor provides a rapid, quantitative and high-sensitivity result of the α-synuclein content in plasma, and represents a feasible tool capable of accelerating the early and non-invasive identification of Parkinson’s disease.

There is growing evidence by the literature that the unbalance between androgens and estrogens is a relevant condition associated with a common canine reproductive disorder known as cryptorchidism. The role of estrogens in regulating testicular cell function and reproductive events is supposedly due to the wide expression of two nuclear estrogen receptors (ERs), ER-alpha and ER-beta and a trans-membrane G protein-coupled estrogen receptor (GPER) in the testis. In this study, immunohistochemistry, Western blotting and qRT-PCR were used to assess the distribution and expression of GPER in the testis–epididymal complex in the normal and cryptorchid dog. ER-alpha and ER-beta were also evaluated to better characterize the relative abundances of all three receptors. In addition, in these tissues, the expression level of two proteins as SOD1 and Nrf2 normally associated with oxidative stress was investigated to evaluate a possible relationship with ERs. Our data revealed changes in the distribution and expression of the GPER between the normal and cryptorchid dog. In particular, dogs affected by cryptorchidism showed an upregulation of GPER at level of the examined reproductive tract. Also considering the obtained result of a modulation of SOD1 and Nrf2 expression, we could hypothesize the involvement of GPER in the cryptorchid condition. Further studies are, however, necessary to characterize the role of GPER and its specific signaling mechanisms.

Neurosarcoidosis is an uncommon and multiform clinical entity. Its presentation as an isolated longitudinal extensive transverse myelitis (LETM) is rare and challenging to identify. We report a case of LETM in a 60-year-old patient with no significant systemic symptoms nor relevant medical history. The peculiar spinal magnetic resonance imaging finding characterized by a posterior and central canal subpial contrast enhancement, the so-called “trident sign,” together with chest computed tomography scan and lymph node biopsy led to the diagnosis of sarcoidosis. We also discuss the main differential diagnoses of LETM and therapeutic options for sarcoidosis-related myelitis.

The Futurist book was instrumental in the circulation of Futurist ideas and represents a very experimental phase in book production, paving the way for the book object, the artist’s book, advertising and design. The purpose of this article is to produce a survey of the Italian Futurist collections held at the British Library. The survey, arranged by date of acquisition, is a tool for studying the circulation of Italian Futurist books in the UK.

The implementation of architectural heritages' information systems to collect a huge amount of data using BIM and GIS constitutes a relatively recent field of research. However, the potentiality of such an approach is clear: the systemic application of these tools to the sites belonging to the UNESCO World Heritage would allow the building of easily accessible databases to support the heritage sites' management and preservation. As part of the collaboration between the Municipality and the University of Bergamo, an information system has been designed to support the Preservation Program of the Venetian Fortress of Bergamo. The geometrical simplicity of its elements makes the complex a suitable case study for the development of a data digitization procedure, allowing an efficient management of ordinary maintenance and, where needed, a detailed representation of the state of conserva- tion, structural instabilities, and stratigraphic relationships, which can also be proposed in other contexts.

COVID-19 in immunocompromised patients is difficult to treat. SARS-CoV-2 interaction with the host immune system and the role of therapy still remains only partly understood. There are no data regarding the use of monoclonal antibodies and the combination of two antivirals in fighting viral replication and disease progression. We report the cases of two patients, both treated with rituximab for non-Hodgkin lymphoma and granulomatosis with polyangiitis, respectively, and both hospitalized for COVID-19 with positive SARS-CoV-2 RNAemia, who were successfully treated with a salvage combination therapy with sotrovimab, remdesivir and nirmatrelvir/ritonavir.