Search Results (4,748)

Three targeted therapies are currently available for spinal muscular atrophy (SMA), which have dramatically changed the natural history of this severe and potentially fatal disease. More than 95% of SMA cases have a homozygous deletion of exon 7 of the SMN1 gene. Disease expression mainly depends on the copy number of SMN2, a hypomorphic copy of SMN1. Many countries in the world have implemented newborn screening (NBS) programs for early identification and treatment of children with SMA. We herein present the first two-year results of the SMA NBS program in Campania, a region with one of the highest birth rates in Italy. Genomic DNA was extracted from dried blood spots (DBS) and peripheral blood. For DBS, the SMN1 gene copy number was evaluated by quantitative polymerase chain reaction (qPCR) targeting SMN1 exon 7 and a reference gene (RPP30). In positive newborns and their parents, SMN1/SMN2 copies were evaluated by multiplex ligation probe amplification (MLPA). We analyzed 77,945 newborns and identified 11 positive children. Six patients had 2 copies of SMN2, but only one showed severe SMA-related signs at birth. Eligible newborns were treated with gene therapy within 20 days of birth. Notably, qPCR failed to amplify the reference RPP30 gene in 5/77,945 DBS. Despite this limitation, we observed that about 1/40 DBS had ΔCt values consistent with the presence of one SMN1 copy. The semi-automated procedure used for SMA NBS showed excellent performance in detecting the presence of homozygous deletion of SMN1 exon 7, with the exception of a few cases with the absence of amplification of the reference gene. By solving this limitation, the screening procedure has the potential to detect heterozygous carriers of the SMN1 deletion and, consequently, identify families at procreative risk of SMA. Full article

Pediatric asthma and allergic rhinitis are prevalent chronic inflammatory diseases ruled by complex interactions among genetic, environmental, and nutritional factors. Zinc, an essential trace element, plays a crucial role in immune modulation, oxidative stress regulation, and epithelial barrier maintenance, all of which are significant in the context of allergic airway diseases. This review aimed to explore and synthesize current evidence on the biological mechanisms and clinical implications of zinc in pediatric asthma and allergic rhinitis. A comprehensive literature search was conducted through PubMed and the Cochrane Library for studies published between 2015 and 2025. Eligible studies included observational and interventional research focused on zinc status or supplementation in children with asthma or allergic rhinitis. Numerous observational studies and meta-analyses indicated reduced circulating zinc levels in children with asthma, often correlating with poor symptom control, increased oxidative stress, and lower pulmonary function. In allergic rhinitis, zinc depletion in nasal mucosa was associated with elevated local inflammation, although paradoxical increases in zinc concentrations have been observed in nasal secretions during active disease. Interventional trials in pediatric asthma populations showed that zinc supplementation may improve clinical symptoms, reduce inflammation, and enhance lung function, although the results were inconsistent and limited by methodological variability. In conclusion, zinc plays a multifactorial role in modulating immune responses and maintaining mucosal health in pediatric allergic airway diseases. While zinc supplementation holds promise as a safe and accessible adjunctive therapy, further high-quality randomized controlled trials are needed to define its clinical utility and establish evidence-based guidelines. Full article

Seismo-stratigraphic data of the Gulf of Pozzuoli have been revised with the aim of identifying the tectonic structures controlling the area in more detail and to highlight the possible relationships of the morpho-structures with the new bradyseismic crisis, still in course. In particular, the relationships between the tectonic structures, consisting of both normal faults and folds, and the possible rising of fluids have been analyzed based on seismic interpretation. We hypothesize that the normal faults occurring in this area have possibly controlled the rising of fluids in these extensional structures. The fluid uprising could possibly be related to the increasing gas activity of the Solfatara–Pisciarelli area onshore during the active bradyseismic crisis (2024–2025). The proposed mechanism is controlled by the occurrence of a heat source, possibly a magmatic reservoir, in the continental crust and/or the mantle, genetically related to the presence of submerged hydrothermal discharges in the coastal areas of the Campania region. To achieve this objective, detailed seismo-stratigraphic sections of the Gulf of Pozzuoli have been constructed, focusing on the areas characterized by tectonic activity. Fluid uprising is mainly controlled by the tectonic setting of the Gulf of Pozzuoli, characterized by anticlines and synclines, representing important structural and stratigraphic traps. Full article

This paper addresses the problem of subsurface target localization from single-snapshot multimonostatic and multifrequency radar measurements. In this context, the use of subspace projection methods—known for their super-resolution capabilities—is hindered by the rank deficiency of the data correlation matrix and the lack of a Vandermonde structure, especially in near-field configurations and layered media. To overcome this issue, we propose a novel pre-processing strategy that transforms the measured data into the $\omega -k$ domain, thereby restoring the structural conditions required for subspace-based detection. The resulting algorithm, referred to as $\omega -k$ MUSIC, enables the application of subspace projection techniques in scenarios where traditional smoothing procedures are not viable. Numerical experiments in a 2-D scalar configuration demonstrate the effectiveness of the proposed method in terms of resolution and robustness under various noise conditions. A Monte Carlo simulation study is also included to provide a quantitative assessment of localization accuracy. Comparisons with conventional migration imaging highlight the superior performance of the proposed approach. Full article

Background/Objectives: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the BCR–ABL fusion gene, whose constitutive tyrosine kinase activity drives leukemogenesis. Although tyrosine kinase inhibitors (TKIs) have revolutionized treatment, drug resistance and leukemic stem cell persistence remain major challenges. Natural compounds such as polyphenols have shown potential in modulating key oncogenic pathways in CML. Results: Polyphenols such as resveratrol, quercetin, curcumin, and epigallocatechin gallate (EGCG) demonstrated significant antiproliferative and pro-apoptotic effects in CML cell lines, including imatinib-resistant models. These effects were mediated through the modulation of signaling pathways, including PI3K/Akt, STAT5, and MAPK; inhibition of BCR–ABL expression; induction of oxidative stress; and the enhancement of apoptosis via mitochondrial and caspase-dependent mechanisms. Some polyphenols also showed synergistic activity with TKIs, potentiating their efficacy and overcoming resistance. Conclusions: Preclinical evidence supports the role of polyphenols as potential adjuvants in CML therapy, particularly in drug-resistant contexts. Their pleiotropic molecular actions and low toxicity profile make them promising candidates for integrative oncology. Nonetheless, clinical translation requires further investigation through well-designed trials assessing efficacy, safety, and pharmacokinetics. Full article

Aims: The effect of sodium–glucose cotransporter 2 inhibitors (SGLT2is) in addition to optimal medical therapy (OMT) on right ventricular (RV) systolic function in patients with heart failure with reduced ejection fraction (HFrEF) is not well established. This study aimed to assess the impact of SGLT2is on RV function using advanced echocardiographic parameters in patients with HFrEF and type 2 diabetes (T2D). Methods: The real-world prospective, observational GLISCAR study enrolled 31 consecutive patients with T2D and HFrEF. All participants underwent clinical evaluation, laboratory testing, and comprehensive echocardiography at baseline and after 12 months of treatment with an SGLT2i. Results: After 12 months, statistically significant improvements in RV function were observed. Tricuspid annular plane systolic excursion (TAPSE) increased from 18.00 mm (SD ± 4.23; 95% confidence interval (CI): 16.51–19.49 mm) to 19.40 mm (SD ± 4.13; 95% CI: 17.95–20.85 mm) (p = 0.0346), and pulmonary artery systolic pressure (PASP) decreased from 35.23 mmHg (SD ± 14.61; 95% CI: 30.09–40.37 mm) to 30.89 mmHg (SD ± 7.77; 95% CI: 28.15–33.63 mm) (p < 0.001). These changes may suggest favorable RV remodeling and improved right ventricular–arterial coupling (RVAC). Conclusions: SGLT2i therapy was associated with improved RV function and RVAC in patients with HFrEF and T2D. While these findings are preliminary and drawn from a small, observational cohort, they support a potential role for SGLT2is in right heart remodeling. Further randomized, controlled studies are needed to confirm these effects and clarify their clinical implications. Full article

Objectives: Sickle Cell Disease (SCD) has a significant impact on the musculoskeletal system. The use of the Oxford Hip (OHS) and Shoulder score (OSS) as patient-reported outcome measures (PROMs) revealed a high rate of long-term impairment in joints with a pre-existing diagnosis of avascular necrosis (AVN). With this study, we aimed at detecting dysfunction in joints apparently not affected by AVN. Methods: This is a subgroup analysis of a previous core study assessing the OHS and OSS in 47 SCD patients with a pre-existing diagnosis of AVN. For this study, only patients with a pre-existing diagnosis of isolated AVN (only hip or only shoulder) were selected, and the OHS or OSS was measured in previously unaffected joints. Results: Among 37 patients with isolated AVN, 19 (51%) patients presented abnormal scores in the apparently unaffected joint; 16 (50%) patients with pre-existing isolated hip AVN had an abnormal OSS; and 9 (56%) had moderate to severe shoulder impairment. All patients with pre-existing isolated shoulder AVN had an abnormal OHS, with severe hip impairment in two out of three. As per clinical practice, patients with an abnormal score were prescribed joint magnetic resonance imaging (MRI) and/or X-rays. Only 10 out 19 (53%) performed imaging studies and all showed signs of AVN. Conclusions: Abnormal OHS and OSS values indicated a high rate of joint dysfunction in sites apparently not affected by AVN. The routine use of these PROMs should be applied to all SCD adults and subjects with a pathological score should have priority access to diagnostic radiological tests. Full article

Carbohydrate-based hydrogels represent a new advancement in the development of multifunctional biomedical systems, thanks to their intrinsic biocompatibility, structural versatility, and capacity for functional modification. This review examines the latest progress made in employing these materials as intelligent theranostic platforms, with a particular focus on their role as biosensors and therapeutic drug delivery devices. Engineered to interact dynamically with the biological environment, carbohydrate hydrogels enable the site-specific release of therapeutic agents while simultaneously supporting the monitoring of key physiological markers. Their dual functionality offers significant advantages in managing complex pathologies such as cancer, metabolic disorders, and chronic inflammation, where personalized treatment and real-time feedback are essential. By exploring their biological application, this review underscores the pivotal role played by carbohydrate hydrogels in advanced therapeutic technologies. Full article

Background/Objectives: Long non-coding RNAs (lncRNAs) play a crucial role in trophoblast invasion, immune tolerance, and placental angiogenesis. To delineate their diagnostic and pathological significance, we critically evaluated the evidence for correlations between circulating or placental lncRNA profiles with pregnancy complications. Methods: Five databases were searched from inception through September 2024. We included only the studies that assessed the expression of the lncRNA-complicated pregnancies versus a control group. Results: Three single-center case–control studies fulfilled the inclusion criteria. Eight serum lncRNAs that present <20 weeks of gestation were elevated in subsequent pregnancy-induced hypertension or preeclampsia. The three lncRNAs in intrahepatic cholestasis of pregnancy were consistently decreased with a negative correlation with bile acids. Gestational diabetes was characterized by the elevation of MALAT1. Conclusions: Different lncRNAs showed a potential for use as non-invasive markers as well as for risk stratification for pregnancy-induced hypertension or preeclampsia, metabolic, and hepatobiliary pregnancy complications. There is a need for large-scale, multi-ethnic, prospective cohorts to include lncRNA as screening or therapeutic targeting in obstetric practice. Full article

To describe a technique for managing acute corneal hydrops in eyes with keratoconus using dome stromal drainage with intracameral air injection under real-time three-dimensional (3D) microscope-integrated optical coherence tomography (OCT) guidance. We describe a retrospective case series of six eyes from six patients with keratoconus who developed acute corneal hydrops. All eyes underwent intracameral air injection with controlled dome puncture for stromal fluid drainage, without the use of sutures. The procedure was performed using a 3D visualization system that enables integrated and simultaneous viewing of the surgical field and intraoperative OCT scan (a 3D digitally assisted visualization system that displayed a split-screen view of the surgical field and OCT cross-sections simultaneously). Postoperative resolution of edema and improvement in clarity were documented. The resolution of corneal edema allowed for subsequent mushroom-shaped penetrating keratoplasty performed with a femtosecond laser in four eyes of four patients. All six eyes showed significant resolution of corneal edema within 2 to 4 weeks. Stromal clefts collapsed rapidly after drainage. In each case, the thick edema was reduced to a confined leucoma. No intraoperative or postoperative complications were observed. All four eyes that underwent a femtosecond laser-assisted mushroom-shaped penetrating keratoplasty showed optimal anatomical and functional success. Air-assisted dome drainage, combined with simultaneous 3D and OCT visualization, is a safe and effective technique for treating acute corneal hydrops. This technology enables real-time decision-making and enhances surgical precision, opening the door to advanced procedures that are otherwise limited by corneal opacity. Full article

Background: Bone loss management is a tough challenge in orthopedic and trauma surgery that is generally treated using graft or substitute. Bone is the second most common transplanted tissue behind blood. Autologous bone graft represents the gold standard, while allograft is generally used as a secondary option, considering their impressive osteoconductive and osteoinductive properties. However, both allograft and autograft sources are limited. Therefore, synthetic bone substitutes gained popularity due to their low cost and ease of application. β-tri-Calcium phosphate (β-TCP) is a promising material implemented as a bone substitute. One of the limits of bone substitutes is related to their three-dimensional organization, which rarely replicates that of the normal bone. b.Bone™ is a novel bone substitute derived from rattan wood with a unique 3D structure that mimics the architecture of the human bone. This study aims to objectively evaluate the osteointegration of b.Bone™ in complex clinical settings. Methods: We retrospectively evaluated eight patients who underwent surgeries requiring filling bone loss through the use of b.Bone™. Osteointegration of the bone substitute was evaluated radiologically using a modified Van Hemert classification. Results: Eight patients were enrolled into this study: five females and three males with a mean age of 53,75 years old. b.Bone™ was applied in the following shapes: granules in four cases, cylinders in three cases and a prism in one. In four patients, the osteointegration reached a grade Van Hemert 4, three a grade 3, and only one a grade 2. Conclusions: β-TCP-based bone substitutes, such as those derived from rattan, appear to facilitate successful osteointegration in various clinical settings. Future studies with larger cohorts and longer follow-ups are necessary to evaluate the long-term efficacy of this promising substitute. Full article

Technological innovation has significantly transformed the field of statistics, not only in data analysis but also in data collection. Traditional methods based on direct observation have evolved into hybrid approaches that combine passively collected data (e.g., from GPS or accelerometers) with active user input through digital interfaces. This evolution has led to Smart Surveys—next-generation tools that leverage smart devices, such as smartphones and wearables, to collect data actively (via questionnaires or images) and passively (via embedded sensors). Smart Surveys offer strategic value in industrial contexts by enabling real-time data collection on worker behavior, environments, and operational conditions. However, the heterogeneity of such data poses challenges in management, integration, and quality assurance. This study proposes a modular system architecture incorporating gamification elements to enhance user participation, particularly among hard-to-reach worker segments, such as mobile or shift workers. By leveraging motivational strategies and interactive feedback mechanisms, the system seeks to foster greater engagement while addressing critical data security and privacy concerns within industrial Internet of Things (IoT) environments. Full article

Background: Patients undergoing head and neck surgery with free flap reconstruction are at a high risk for postoperative respiratory complications, including hypoxemia. Conventional oxygen therapy (COT) and non-invasive ventilation (NIV) may be poorly tolerated or contraindicated due to anatomical limitations. High-Flow Nasal Cannula (HFNC) therapy represents a promising alternative, offering better humidification, comfort, and oxygenation. Methods: This retrospective single-center study included 50 adult patients admitted to the ICU after head and neck oncologic surgery with flap reconstruction from January 2022 to November 2024. All patients received HFNC immediately after extubation. Hypoxemia was defined as a PaO₂/FiO₂ (P/F) ratio of < 300 mm Hg. The primary outcome was the incidence of postoperative hypoxemia. Secondary outcomes included reintubation rates and patient compliance. Data were collected at 1, 6, 12, and 24 h following HFNC initiation. Results: Out of 59 patients screened, 9 were excluded per predefined criteria. Among the 50 included, only 2 patients (4%) developed hypoxemia, with P/F ratios remaining above 250. No patients required reintubation. The respiratory rate–oxygenation index (ROX index) improved steadily during the first 24 h. HFNC was well tolerated; only three patients required minor adjustments due to discomfort. Conclusions: HFNC use in the immediate postoperative period after head and neck surgery was associated with a low incidence of hypoxemia and no reintubations. These findings suggest that HFNC is a safe and effective strategy for postoperative respiratory support in this high-risk population. Further prospective studies are warranted to confirm the benefit of HFNC in reducing hypoxemia and preventing reintubation in high-risk surgical populations. Full article

Ricin, a type 2 ribosome-inactivating protein, is a lethal toxin found in castor bean seeds. Although the systemic toxicity of ricin has been extensively studied, its localized effect on the gastrointestinal tract remains a critical concern, particularly in the case of oral ingestion. This study investigates the cytotoxic effects of ricin on human intestinal epithelial cell lines and its impact on epithelial barrier integrity. Ricin cytotoxicity was assessed on the intestinal-derived HT29 and Caco-2 cell lines using dose– and time–response assays, while the epithelial integrity was evaluated via Trans-Epithelial Electrical Resistance (TEER) measurements in Caco-2 monolayers. Cell death was determined through flow cytometry analysis, and the protective effects of cell death inhibitors and antioxidant scavengers were investigated on ricin-intoxicated cells. Ricin showed high cytotoxicity on HT29 and Caco-2 cells, with EC₅₀ values in the nM range after 24–72 h of intoxication. Moreover, ricin strongly reduced TEER values in Caco-2 cells at 0.1–1 nM after 24 h of treatment. At a 1 nM concentration, ricin cytotoxicity can be significantly prevented by pre-incubating cells with the cell death inhibitors Z-VAD or necrostatin-1 and the antioxidant scavenger catalase, butylated hydroxyanisole or sodium pyruvate, demonstrating the involvement of apoptosis/necroptosis and oxidative stress in ricin cell death pathways and mechanisms. Full article

Short-term channel adjustments are a research topic of great relevance in the framework of fluvial geomorphology, but studies on this topic have been quite scarce in Southern Italy, at least since the 2010s, notwithstanding the fact that this area is strongly representative of a much wider morphoclimatic context, i.e., the Mediterranean area, which particularly suffers from the effects of current climate change. Currently, different interpretations still exist about the type and role of controlling factors, and a common morphoevolutionary trend is quite far from being defined; so, new case studies are needed. In this paper, the geomorphological changes experienced by the Sabato R. (Southern Italy) over a period of ~150 years were investigated. A reach-scale geomorphological analysis in a GIS environment of raster data, consisting of four topographic maps (from 1870, 1909, 1941 and 1955) and five sets of orthophotos (from 1998, 2004, 2008, 2011 and 2014), was carried out, integrated with field-surveyed data. Land-use changes, in-channel anthropic disturbances, floods and rainfall variations were selected as possible controlling factors. The study highlighted four morphoevolutionary phases of the studied river. Phase 1 (1870s–1910s) was characterized by a relative channel stability in terms of both mean width and pattern, while channel widening dominated during Phase 2 (1910s–1940s). In contrast, Phase 3 (1940s–1990s) was characterized by intense and diffuse narrowing. Finally, during Phase 4 (from the 1990s onward), an alternation in channel narrowing and flood-induced widening was detected. During all phases, changes in both channel pattern and riverbed elevation were less evident than those in channel width. Land-use changes and, later, floods, in addition to in-channel human disturbances at a local scale, were the main controlling factors. The obtained results have profound implications for rivers located outside Italy as well, as they provide new insights into the role played by the considered controlling factors in the geomorphological evolution of a typical Mediterranean river. Understanding this role is fundamental in regional-scale river management, hazard mitigation and environmental planning, as proved by the vast pre-existing scientific literature. Full article