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Background For infants exposed in utero to Toxoplasma gondii , current guidelines recommend monitoring the specific antibody titer until 12 months of age. In this study, we investigated the antibody titer decay in the mother-infant dyad. Methods This is a single center, population-based cohort study of neonates referred for prenatal exposure to Toxoplasma gondii from January 2014 to December 2020. All infants underwent clinical, laboratory, and instrumental investigation for at least 12 months. Results A total of 670 eligible neonates were referred to the Perinatal Infection Unit of the University Federico II of Naples. 636 (95%) completed the serological follow up until 12 months. Specific IgG antibodies negativization occurred in 628 (98.7%) within 5 months. At 9 and 12 months, all patients had negative IgG. An initial neonatal IgG antibody titer ≥ 200 IU/ml was associated with a longer time to negativization (184 [177.5;256] days when above threshold vs. 139.5 [101;179] days when below it; p  < 0.001). Maternal IgG antibody titer ≥ 200 IU/ml at childbirth was also associated to delayed time to negativization in the infant (179 [163;184] days above the threshold vs 125 [96.8;178] days below it; p  < 0.001). Specific antibody negativization was irreversible in all patients. Conclusions Lower anti- Toxoplasma antibody titers detected at birth in the mother-infant-dyad lead to an earlier and irreversible negativization. This information allows for customisation of the infant follow up program and avoids invasive and expensive tests.

The resurgence of syphilis and subsequent risk for newborns has been described worldwide; however, European data on this congenital infection is lacking. We report the activity of a multidisciplinary specialized unit assisting a large area in the Southern Italy. A retrospective cohort study has been conducted at the Perinatal and Pediatric Infectious Diseases Units of the Federico II University of Naples, enrolling all newborns and children referred from January 2010 to June 2022 exposed to Treponema pallidum in utero and/or congenitally infected. A total of 323 patients were included in the analysis. Twenty (6.2%) received a diagnosis of confirmed congenital syphilis (CS) and one died. Fifteen CS cases had typical clinical features. Since 2017, the number of referred neonates tripled while the rate of late maternal diagnoses did not significantly differ. When compared with mothers of exposed infants, mothers of CS cases were younger (25 ± 7.2 vs 29.9 ± 6 years, p  =  0.041 ), had less previous pregnancies (0.64 vs 1.11, p  =  0.044 ), and received a diagnosis of syphilis at a later stage of pregnancy (86% vs 20%, from third trimester or later on; p  < 0.001). Appropriate maternal therapy was protective against vertical transmission (− 1.2; − 1.4, − 1 95% CI; p  < 0.001). Paternal syphilis status was known in 36% of cases. Conclusion : CS has still a significant impact. Prevention should be implemented towards specific maternal risk profiles. A specialized unit is the preferable model to improve surveillance and healthcare for this neglected population. What is Known: • The resurgence of syphilis and subsequent risk for newborns has been described worldwide. • European data on this congenital infection is lacking. What is New: • Congenital syphilis has a significant impact still in Europe and prevention should be implemented towards specific maternal risk profiles.  • A specialized unit is the preferable model to improve surveillance and healthcare for this neglected population.

The first report on the antitumor effects of interferon α/β (IFN-I) in mice was published 50 years ago. IFN-α were the first immunotherapeutic drugs approved by the FDA for clinical use in cancer. However, their clinical use occurred at a time when most of their mechanisms of action were still unknown. These cytokines were being used as either conventional cytostatic drugs or non-specific biological response modifiers. Specific biological activities subsequently ascribed to IFN-I were poorly considered for their clinical use. Notably, a lot of the data in humans and mice underlines the importance of endogenous IFN-I, produced by both immune and tumor cells, in the control of tumor growth and in the response to antitumor therapies. While many oncologists consider IFN-I as “dead drugs”, recent studies reveal new mechanisms of action with potential implications in cancer control and immunotherapy response or resistance, suggesting novel rationales for their usage in target and personalized anti-cancer treatments. In this Perspectives Article, we focus on the following aspects: (1) the added value of IFN-I for enhancing the antitumor impact of standard anticancer treatments (chemotherapy and radiotherapy) and new therapeutic approaches, such as check point inhibitors and epigenetic drugs; (2) the role of IFN-I in the control of cancer stem cells growth and its possible implications for the development of novel antitumor therapies; and (3) the role of IFN-I in the development of cancer vaccines and the intriguing therapeutic possibilities offered by in situ delivery of ex vivo IFN-stimulated dendritic cells.

Here we report on the humoral and cellular immune response in eight volunteers who autonomously chose to adhere to the Italian national COVID-19 vaccination campaign more than 3 months after receiving a single-administration GRAd-COV2 vaccine candidate in the context of the phase-1 clinical trial. We observed a clear boost of both binding/neutralizing antibodies as well as T-cell responses upon receipt of the heterologous BNT162b2 or ChAdOx1-nCOV19 vaccines. These results, despite the limitation of the small sample size, support the concept that a single dose of an adenoviral vaccine may represent an ideal tool to effectively prime a balanced immune response, which can be boosted to high levels by a single dose of a different vaccine platform.

Beyond its immunological role, colostrum has emerged as a promising, non-invasive source of bioactive factors, including mesenchymal stem/stromal cells (MSCs). This study represents the first attempt to isolate and characterize MSCs from equine colostrum (C-MSCs) to assess their potential use in veterinary regenerative medicine. Colostrum (n = 6) was collected from mares immediately after their delivery and centrifuged, and the recovered cells were cultured under standard conditions. The C-MSCs displayed plastic adherence and a heterogeneous morphology, including spindle-shaped and epithelial-like cells. The population doubling time (PDT) values varied among the samples, and four out of six showed rapid proliferation (<2 days). Colony-forming unit (CFU) assays confirmed their clonogenic potential, though significant inter-sample variability was observed (p < 0.05). Spheroid formation assays revealed differences in cell–cell adhesion: four out of six samples formed stable spheroids within four days. A migration assay showed significant variability (p < 0.05): one out of six achieved complete wound closure within 72 h, whereas five out of six reached ~30% at 96 h. All samples were positive for adipogenic, chondrogenic, and osteogenic differentiation as shown via staining. RT-PCR confirmed MSC marker expression, while hematopoietic markers were absent. MHC-I expression was weak in five out of six samples, whereas MHC-II was consistently negative. These findings support equine colostrum as a viable MSC source, though its variability requires further validation with larger samples. Additional research is needed to investigate C-MSCs’ immunomodulatory properties and therapeutic potential.

AimTo analyse the choriocapillaris (CC) flow status in the area that subsequently showed geographic atrophy (GA) expansion secondary to age-related macular degeneration (AMD) during 1-year follow-up, matching optical coherence tomography angiography (OCT-A) and fundus autofluorescence (FAF).MethodsIn this prospective longitudinal observational study, 30 eyes of 20 consecutive patients with GA secondary to AMD (mean age 75.5±7.4 years) were included. All patients underwent OCT-A and FAF at baseline and 1-year follow-up. Main outcome measures included analysis of perfusion density (PD) in the ‘area surrounding GA margin’ (between the GA border and 500 µm distance) in comparison with the ‘control area’ (area outside the 500 µm line), and of the ‘expansion area’ (area that subsequently developed GA expansion during 1-year follow-up).ResultsDuring the 1-year follow-up, visual acuity significantly decreased from 0.34±0.38 Logarithm of the Minimum Angle of Resolution (LogMAR) to 0.39±0.40 LogMAR (p<0.001), and mean GA area increased from 6.82±5.47 mm2 to 8.76±6.28 mm2 (p<0.001). CC PD of the area surrounding the GA margin revealed a significant flow impairment compared with control area (PD 0.679±0.076 and 0.734±0.057, respectively (p<0.001)). Furthermore, the PD of the expansion area showed a greater CC flow impairment in comparison to the remaining area surrounding GA margin (p<0.001).ConclusionsWe reported a greater CC impairment in the area that subsequently developed GA expansion, suggesting that the CC flow impairment could predict the enlargement of GA lesion. The CC impairment could be considered as a new a risk factor for GA progression and a biomarker to be measured to determine efficacy of new interventions aiming to slow progression of GA.

Background: some consensus guidelines include C-reactive protein (CRP) in the diagnostic workup of early-onset neonatal sepsis (EOS), but its routine use remains debated due to variable diagnostic performance. The experiences and data from individual centers can help clarify its clinical utility and inform local practice. Methods: Retrospective analysis at a level III center assessing the impact of discontinuing routine C-reactive protein (CRP) testing for suspected early-onset sepsis (EOS). Laboratory use, antibiotic therapy, and outcomes in neonates of all gestational ages were compared before (2021–2022) and after (2024–2025) the policy change. Results: A total of 638 neonates were included (period 1, n = 348; period 2, n = 290). CRP testing decreased markedly (218/348 in period 1 vs. 40/290 in period 2; p < 0.001), alongside a significant reduction in the number of complete blood counts performed (285/348 vs. 214/290; p = 0.02). Concurrently, both the proportion of short antibiotic courses (≤48 h) initiated within the first 3 days of life (98/181 vs. 88/133) and the median duration of antibiotic therapy (48.0 h vs. 40.0 h; p < 0.001) decreased without worsening outcomes. The duration of antibiotic therapy was even shorter in infants born before 34 weeks’ gestation (48.0 h vs. 37.5 h; p < 0.001). Conclusions: Restricting the use of CRP in the evaluation of EOS was associated with a reduction in unnecessary antibiotic exposure. This strategy may be considered a core component of neonatal antibiotic stewardship programs.

AimTo analyse quantitative optical coherence tomography angiography (OCTA) parameters of choriocapillaris (CC) at the foveal, perifoveal and parafoveal regions in healthy subjects of different age.MethodsIn this observational cross-sectional study, consecutive healthy subjects underwent swept source OCTA (PLEX Elite 9000, Carl Zeiss Meditec, USA). 3×3 mm and 6×6 mm scans centred on the fovea were acquired analysed and postprocessed with thresholding and binarisation processes. The main outcome measures included CC quantitative OCTA features (perfusion density (PD), vessel length density (VLD) and vessel diameter index (VDI)) at the foveal, perifoveal and parafoveal regions, and their relationship with age.ResultsSeventy-two eyes (72 patients, mean age 47.4±19.2 years, mean axial length 24.0±0.7 mm) were included. The mean PD was statistically lower in the foveal region compared with the parafoveal region in 3×3 mm scans (p=0.009). In subjects aged 70–80, PD of the foveal region was significantly reduced compared with the perifoveal region in 6×6 mm scans (p=0.008). A strong negative correlation was found between PD and ageing in the foveal, parafoveal and perifoveal regions (p<0.001 in all analyses). Furthermore, PD in the nasal-perifoveal region was significantly lower than the temporal-perifoveal region (p=0.005). No significant correlation was found between VLD and age in all regions, whereas VDI was strictly correlated with age (p<0.001).ConclusionsWe reported in vivo a strong negative correlation between PD and ageing in the CC of healthy subjects. This reduction seems related to a reduced diameter, and not to a reduced number, of capillaries. The age-related changes were higher in the central area compared with the perifoveal area.

Background Cutaneous squamous cell carcinoma (cSCC) is a common age-related cancer, with a subset prone to recurrence and metastasis. Currently, no useful diagnostic biomarkers for high-risk cSCC are available. Based on our previous findings, indicating that age-related changes in the neurotrophin receptor tyrosine kinase-2 (TrkB) axis may promote skin tumorigenesis, this study aims to identify novel cSCC biomarkers and therapeutic targets. Methods A retrospective analysis was conducted on specimens from patients with in situ or invasive cSCCs using immunohistochemistry to assess the expression of TrkB and specific downstream proteins (i.e., E-cadherin, Yap1, and Notch1). Statistical and machine learning analyses were applied to identify biomarkers that distinguish cSCC subtypes and patient risk groups. In vitro studies involved treating SCC cells, cancer-associated fibroblasts (CAFs), and three-dimensional (3D) SCC models with the TrkB inhibitor ANA-12. Gene and protein expression were analyzed via RTqPCR, immunoblotting, and immunoassays. Functional assays evaluated cell proliferation, migration, and invasion. Secretomes were profiled using cytokine arrays. Results Protein expression levels mainly correlated with cSCC types. Our findings indicated that the ‘TrkB, E-cadherin, Yap1, Notch1’ signature can be a relevant biomarker for both cSCC subtype classification and identification of high-risk cases. Despite the limited sample size, machine learning models demonstrated promising accuracy in differentiating between cSCC classes. Our analysis also highlighted the added value of including stromal markers for classifying high-risk patients. Furthermore, TrkB blockade suppressed tumorigenic traits in TP53 -mutant SCC cells, including proliferation, EMT, migration, invasiveness, and disruption of the IL-6/STAT3 signaling loop, while promoting differentiation and senescence through modulation of key players such as p63, Yap1, Notch1, and p21. Data are consistent with a tumor-suppressive effect, thereby promoting tissue homeostasis, especially in physiologically relevant 3D models. Inhibiting TrkB reprogrammed primary CAFs into a less proliferative, migratory, inflammatory, and fibrotic phenotype by simultaneously suppressing key activating pathways, such as β-catenin, Yap1, and Notch1. This aligns with a reduction in their tumor-supportive functions. Conclusions Our findings provide a basis for improved high-risk patient stratification by highlighting a TrkB-based signature and generating prototype predictive models. Furthermore, they offer promising therapeutic avenues for developing combined targeted interventions to overcome resistance in high-risk patients. Graphical abstract

Objectives: To investigate clinical and imaging predictors of short- and long-term outcomes in patients with posterior circulation stroke (PCS), with particular focus on infarct topography and ischemic burden. Methods: We conducted a retrospective multicenter observational study including 251 consecutive patients with acute PCS. All patients underwent CT angiography within 24 h and follow-up CT/MRI at 48–72 h. Clinical data, vascular risk factors, stroke severity (NIHSS), and functional outcome assessed by modified Rankin Scale (mRS), were collected. Short-term outcome was defined as mRS at discharge and long-term outcome as mRS at 3 months. Favorable outcome was defined as independence, graded as mRS 0–1. Imaging analysis included pc-ASPECTS, collateral scores, and quantitative ischemic volume assessment. Multivariable logistic regression was performed to identify independent predictors of outcome. Results: Among 251 patients, 105 (41.8%) had LVO. Patients with LVO presented with higher NIHSS scores, larger infarct volumes, and more frequent multiregional involvement. Basilar artery occlusion was associated with the most severe clinical and radiological profile. Infarct location, ischemic volume, baseline NIHSS, and pre-stroke mRS were independently associated with short-term outcome. For long-term outcome, age, infarct location, diabetes, and pre-stroke mRS remained significant predictors. LVO status and treatment variables were not independently associated with outcome. Conclusions: In PCS, outcome is primarily influenced by infarct topography and clinical factors rather than LVO status alone. Multiregional involvement and baseline disability are key determinants of prognosis. These findings underscore the need for PCS-specific prognostic models and highlight the importance of detailed imaging assessment beyond vessel occlusion.