Humanitas University

Dopaminergic (DA) neurons of the olfactory bulb (OB) represent one of the largest forebrain DA populations, and increasing evidence highlights their role in shaping odor representations through presynaptic gain control, lateral inhibition, and circuit plasticity. These neurons are heterogeneous, comprising small, axonless cells generated throughout life and larger, axon-bearing cells whose generation is limited to embryonic and perinatal stages. Establishing functional distinctions between these subtypes has been hindered by limited tools for selective targeting. Here, we developed an adeno-associated viral (AAV) strategy using the tyrosine hydroxylase (TH) promoter to drive Cre recombinase expression (AAV-rTH-Cre), enabling temporally controlled labeling of OB DA neurons. Intracerebroventricular injections at embryonic day 14.5 preferentially enriched the targeted DA population in large cells, while adult injections predominantly targeted small DA neurons, consistent with their developmental origins. Neonatal injections yielded reduced specificity, likely reflecting developmental and technical constraints on TH promoter activity. To assess functional properties, we combined AAV-rTH-Cre with Cre-dependent GCaMP7s and performed two-photon calcium imaging in adult mice. Our data revealed significant heterogeneity in spontaneous activity, showing a negative correlation between soma size and both spiking probability and event frequency. Thus, smaller DA neurons exhibited higher spontaneous activity, whereas larger neurons were less active despite their higher intrinsic excitability reported previously. These findings validate AAV-rTH-Cre as a versatile tool for dissecting OB DA subtypes and provide direct in vivo evidence that their morphological diversity translates into distinct spontaneous activity patterns, supporting the hypothesis of complementary roles in olfactory processing.

Asthma is a chronic inflammatory airway disease characterized by variable airflow obstruction and bronchial hyperresponsiveness, affecting millions worldwide and showing heterogeneity in its endotype, clinical presentation, and severity. Following the principles of modern precision medicine, studying an asthmatic patient involves collecting various biomarkers that may assist in diagnosis, management, and characterization of the disease to predict clinical outcomes and treatment responses. Although systemic corticosteroid use should be limited to specific situations, this therapy still plays a crucial role in managing an asthmatic patient, especially during exacerbations. While it is known that steroids can affect biomarkers, the extent of this impact is often unclear. This remains an open issue, particularly in patients with severe asthma, where systemic steroids are more frequently used and biomarker measurement can deeply influence management and even access to therapy. Misinterpreting biomarkers can lead to over- or underestimating asthma severity, potentially resulting in serious consequences. In this comprehensive analysis, we have collected the available literature data on how systemic corticosteroids can affect different biomarkers used in clinical practice and research setting, categorizing them into humoral (eg, blood eosinophil count, total and specific IgE, alfa-1 antitrypsin, interleukins, eosinophil cationic protein, and thymic stromal lymphopoietin), instrumental (eg, spirometry, impulse oscillometry, fractional and multiple flow exhaled nitric oxide, and nasal nitric oxide), and clinical (ear-nose-throat and gastroenterological evaluation). The goal is to provide a practical and concise overview of this impact to assist clinicians in interpreting biomarkers independently of steroid therapy. Research should focus on developing predictive models that adjust individual biomarker readings for steroid dosage and duration, as well as markers less affected by corticosteroid interference. A detailed understanding of steroid-induced biomarker modulation is crucial for accurate asthma phenotyping, personalized treatment choices, and avoiding adverse outcomes caused by both under- and overtreatment. Going forward, integrating improved biomarker correction methods, enhancing patient education on steroid use, and continuing research into new inflammatory markers will be crucial for improving the accuracy and effectiveness of asthma management.

The ongoing digital transformation is reshaping organizational and care delivery models in cardiology, positioning telemedicine as a pivotal tool to address increasing clinical and demographic complexity. This ANMCO position paper presents a comprehensive and critical overview of telemedicine applications in cardiovascular care, with a focus on its role in strengthening hospital-community integration, its deployment within hospital-based healthcare systems, and the associated regulatory and operational frameworks. The analysis encompasses the management of chronic cardiovascular conditions, such as heart failure and atrial fibrillation, through telemonitoring, telecontrol, televisit, and teleconsultation. Additionally, it explores the use of digital technologies in post-myocardial infarction follow-up, oral anticoagulation management, preoperative assessment, and care for elderly patients. The position paper also highlights the challenges and opportunities linked to digital infrastructure, interoperability, data protection, and healthcare professional training.

Chronic hand eczema (CHE) is associated with substantial functional impairment and reduced quality of life. Delgocitinib, a pan-Janus kinase (JAK) inhibitor, has emerged as a promising topical treatment for CHE. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to assess the efficacy and safety of topical delgocitinib 20-30 mg/g compared with vehicle in patients with CHE. PubMed, Embase, Cochrane Library, ClinicalTrials.gov, EU CTR, and WHO ICTRP were searched up to 15 February 2026. The primary outcome was treatment success at week 16, defined as clear or almost clear skin with a ≥ 2-point improvement on the Investigator's or Physician's Global Assessment (IGA/PGA). Secondary outcomes included treatment success at weeks 4 and 8, changes in Hand Eczema Symptom Diary (HESD) itch and pain scores, and safety outcomes. Relative risks (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated using random-effects models. Three publications reporting four RCTs involving 1154 patients were included, with 752 receiving delgocitinib and 402 receiving vehicle. At week 16, treatment success was significantly higher with delgocitinib (RR 3.17; 95% CI 1.78-5.65; p < 0.01), corresponding to an absolute risk difference of 16.9% and a number needed to treat (NNT) of 6 (95% CI 3-16). Similar results at weeks 4 and 8. Delgocitinib also led to significantly greater improvements in HESD itch and pain scores. No significant differences were found in overall adverse events (AEs), treatment-related AEs, or serious AEs. Discontinuation due to AEs was lower in the delgocitinib group. Delgocitinib 20-30 mg/g demonstrated greater efficacy than vehicle and a favourable safety profile, supporting its use as a topical treatment for CHE.

Breast surgery is a cornerstone of breast cancer (BC) treatment and has distinctive features that distinguish it from other subspecialties within general surgery. BC management requires multidisciplinary competencies, with specialized training and dedicated care shown to improve patient outcomes. Breast surgery training should become a critical priority within residency programs. We conducted a cross-sectional survey during the 2025 Italian Society of Breast Surgeon (ANISC) annual meeting, to explore the opinions of breast surgery consultants and residentsregarding the current state of breast surgery training, as well as future perspectives for its improvement. A total of 126 participants (77% consultants, 23% residents) completed the survey. Most of the participants (49.2%) worked in medium-volume Breast Units and had > 10 years of clinical practice (45.2%). Overall, 67.5% of respondents judged their training only partially satisfactory, while 23.8% were completely dissatisfied. The majority (58.7%) supported a hybrid model with three years of general surgery followed by two years exclusively dedicated to breast surgery. Most respondents endorsed mandatory training periods in complementary specialties (79.4%) and rotations in peripheral Breast Units (69.8%). Notably, 88.1% favored the development of a vertical breast surgeon profile, capable of independently managing both oncologic and reconstructive procedures. This is the first national survey exploring breast care professionals’ perspectives on surgical training in Italy. Only 8.7% considered the current system adequate to meet clinical needs. The strong demand for structured and specialized programs, together with the recognition of a vertical breast surgeon figure, highlights the urgent need to redefine breast surgery training pathway.

Genetic defects of the gene encoding the ubiquitin ligase UBE3A cause a severe neurodevelopmental disorder, the Angelman syndrome (AS). The pathophysiology of AS remains unclear, hindering the development of effective therapies. Using AS animal models, we show here that UBE3A controls the development of excitatory and distinct subtypes of inhibitory synapses in cortical pyramidal neurons through cell-autonomous mechanisms, ultimately leading to alteration of synaptic transmission and hyperexcitability. Replacing endogenous Ube3a with individual isoforms, we demonstrate that their uneven nuclear (hUBE3A isoform 1) and cytosolic (hUBE3A isoforms 2/3) distribution is critical for regulating distinct aspects of synaptic development. We also define the molecular requirements underpinning this regulation, showing that: (i) both nuclear and cytosolic UBE3A rely on their ubiquitin ligase activity to ensure proper assembly of synapses; (ii) in addition to the nucleus, UBE3A isoform 1 is also localized in the cytosol, where it is functionally interchangeable with UBE3A isoform 3. Our findings identify a subcellular distribution-dependent mechanism by which UBE3A coordinates cortical circuit development and suggest pathogenic mechanisms of AS.

To compare in vitro performance of phacoemulsification platforms during critical surgical phases including aspiration, occlusion and occlusion break. Five phacoemulsification platforms (Alcon Centurion, Bausch & Lomb PC Stellaris, BVI Virtuoso, DORC Eva Nexus and Zeiss Quatera) underwent standardized testing including controlled occlusion within a collapsible test chamber. Tests were conducted with 21G tips, infusion pressure presets 30 and 55 mmHg, flow-rate 30 ml/min and vacuum range 200–600 mmHg. Outcome measures included Intraocular Pressure (IOP) at rest, during aspiration, occlusion and standardized occlusion break as well as chamber volume loss and time to regain 90% of IOP after/during occlusion break. All devices kept target IOP at rest. During aspiration, IOP changed significantly (p < 0.01): Stellaris showed the greatest IOP reduction, Quatera had small decrease, Virtuoso maintained preset, Centurion and Eva Nexus slightly overcompensated. During occlusion, Eva Nexus and Stellaris PC exceeded the preset 55 mmHg (p < 0.05) whereas other machines remained on target. Upon occlusion break, volume loss ranged 35-200μL (p < 0.001) and recovery time to 90% of preset IOP varied between 0.30–2 s (p < 0.001) with Centurion and Virtuoso outperforming others at 30 mmHg IOP and Centurion, Quatera and Virtuoso at 55 mmHg IOP. Phacoemulsifiers exhibited distinct behaviour under standardized conditions and fluidic settings significantly influenced performance. Surgeon must understand machines’ fluidic to master different platforms. What is known What is new

Background/Objectives: Cardiac magnetic resonance (CMR) imaging at 7 Tesla provides a substantially higher intrinsic signal-to-noise ratio compared with conventional 1.5 T and 3 T systems, potentially enabling higher spatial resolution, improved tissue contrast, and advanced metabolic imaging. However, clinical translation remains limited by technical challenges associated with ultra-high-field operation. This systematic review aimed to synthesize current human in vivo evidence on the feasibility, applications, and methodological limitations of 7-T cardiovascular MRI. Methods: A PRISMA-guided systematic search of PubMed, Cochrane Library, Web of Science, and Scopus was conducted from database inception through January 2025. Studies reporting human in vivo cardiovascular MRI at 7 Tesla were included. Data regarding study design, sample characteristics, imaging applications, feasibility, quantitative findings, and reported limitations were extracted and qualitatively synthesized. Results: Sixty-five studies met inclusion criteria, predominantly small prospective cohorts (mean sample size = 13), largely involving healthy volunteers. Across diverse applications-including coronary MR angiography, cine imaging, valvular assessment, vascular imaging, flow quantification, myocardial tissue characterization, and multinuclear (31P, 23Na, 39K) imaging-7-T CMR was consistently feasible and capable of producing high-quality images. Quantitative ventricular and vascular measurements were generally concordant with lower field strengths. Incremental benefits were most apparent in high-resolution structural imaging and metabolic applications, whereas routine functional and flow assessments showed limited additional advantages. No serious adverse events were reported. Conclusions: Human cardiovascular MRI at 7 Tesla represents a technically feasible research and early translational platform with selective advantages over established field strengths. Further advances in radiofrequency technology, protocol harmonization, and larger disease-focused studies are required to clarify its potential clinical role.