Search Results (1,435)

Background and Objectives: Peripheral vascular access in infants is a frequent but technically challenging procedure due to the anatomical characteristics of this population. Repeated failed attempts may increase complications and emotional stress for both patients and healthcare professionals. This systematic review aimed to evaluate the efficacy and safety of ultrasound-guided peripheral vascular cannulation compared to the conventional or “blind” technique in infants. Materials and Methods: A systematic review was conducted in accordance with PRISMA guidelines. The PubMed database was searched for studies published between 2017 and 2025. Studies comparing both techniques in infants under two years of age were selected, evaluating variables such as the number of punctures, first-attempt success, healthcare staff perception, associated stress, and the role of simulation in training. Results: Eleven studies were included, comprising clinical trials, observational studies, and training program assessments from different countries. Most reported a higher first-attempt success rate with the ultrasound-guided technique (often exceeding 85%), along with fewer punctures and complications, particularly among less-experienced professionals. Improvements in staff perception were also observed following structured training. The impact on stress experienced by patients and families was less frequently assessed directly, although some studies reported indirect benefits. Conclusions: Ultrasound-guided peripheral vascular cannulation appears to be more effective and safer than the conventional technique in infants, particularly in complex or critical care contexts. Its implementation requires specific training and appropriate resources but could significantly improve clinical outcomes and the pediatric patient experience. Full article

Background: It is estimated that in Italy, there were 364,000 new diagnoses of neoplasms each year and that the overall incidence of blood cancers was 10% of these. Leukemia and lymphomas represented the ninth and eighth places, respectively, among the causes of death from neoplasia. Hematopoietic stem cell transplantation represented an effective treatment option for many of these malignancies, and not only that: benign and congenital diseases could also be treated. Objective: To assess knowledge among the Apulian population regarding stem cell donation and factors that could influence this choice, focusing especially on the knowledge of the residents of Puglia, Italy on how stem cells were harvested and their functions, their reasons for joining the National Registry, and the reasons that hold them back from making such a choice. Study Design: An observational and cross-sectional study was conducted, through snowball sampling methodology, until data saturation. An online survey was conducted, which included several Italian associations. The questionnaire administered contained five main sections, such as sociodemographic data, knowledge of the existence of National Registries and their adherence, the nationwide presence of various associations that promote donation, knowledge with respect to the structure, use and functions of stem cells, sources of procurement, such as bone marrow, peripheral blood and umbilical cord, and related procedures, beliefs, attitudes, values, and opinions of the Italian population regarding the topic, and degree of information and education regarding bone marrow donation. Results: A total of 567 Apulian citizens were enrolled. Of these, 75.3% were female and 96.8% were aged between 18 and 65 years. Most of participants were single (46.9%) and married (47.3%) and had a diploma (44.4%), and less had a degree (35.8%). Significant differences were recorded between gender, singles, and married participants, and participants with a diploma or a degree and the items proposed. Conclusions: A true culture of donation in our region was not clearly spread. Although something has been accomplished in recent years in terms of deceased donor donation, still a great deal needs to be achieved for living donation, which encountered a great deal of resistance. It has been deemed necessary to seek winning solutions to this issue in terms of communication and information campaigns, raising awareness and empowering citizens to express consciously their concerns about organs and tissues and to stand in solidarity with those who suffered. Full article

Vegetables and fruits grown in urban areas pose a potential threat to human health due to contamination with heavy metals (HMs). This study aimed to identify and quantify the concentrations of heavy metals (Fe, Mn, Zn, Cu, Pb, Cd) in tomatoes, leafy vegetables, and fruits collected from 16 allotment gardens (AGs) located in Warsaw. A total of 112 samples were analyzed (72 vegetable and 40 fruit samples). Vegetables from AGs accumulated significantly higher levels of HMs than fruits. Leafy vegetables, particularly those cultivated near high-traffic roads, exhibited markedly elevated levels of Pb, Cd, and Zn compared to those grown in peripheral areas. Lead concentrations exceeded permissible limits by six to twelve times, cadmium by one to thirteen times, and zinc by 0.7 to 2.4 times. Due to high levels of Pb and Cd, tomatoes should not be cultivated in urban environments. Regardless of location, only trace amounts of HMs were detected in fruits. The greatest health risk is associated with the consumption of leafy vegetables. Lettuce should be considered an indicator plant for assessing environmental contamination. The obtained Hazard Index (HI) values indicate that only the tested fruits are safe for consumption. Meanwhile, the values of the Hazard Quotient (HQ) indicate no health risk associated with the consumption of lettuce, cherries, and red currants. Among the analyzed elements, Pb showed a higher potential health risk than other metals. This study emphasizes the need for continuous monitoring of HM levels in urban soils and the establishment of baseline values for public health purposes. Remediation of contaminated soils and the implementation of safer agricultural practices are recommended to reduce the exposure of urban populations to the risks associated with the consumption of contaminated produce. In addition, the safety of fruits and vegetables grown in urban areas is influenced by the location of the AGs and the level of industrialization of the agglomeration. Therefore, the safety assessment of plant products derived from AGs should be monitored on a continuous basis, especially in vegetables. Full article

Human cytomegalovirus (HCMV) establishes lifelong latency in the host, with the bone marrow (BM) CD34+ cells serving as a key reservoir. To investigate tissue-specific immune responses to CMV, we analysed paired peripheral blood mononuclear cells (PBMCs) and bone marrow mononuclear cells (BMMNCs) from HCMV-seropositive donors using multiparametric flow cytometry and cytokine FluroSpot assays. We assessed immune cell composition, memory T cell subsets, cytokine production, cytotoxic potential, activation marker expression, and checkpoint inhibitory receptor (CIR) profiles, both ex vivo and following stimulation with lytic and latent HCMV antigens. BMMNCs were enriched in CD34+ progenitor cells and exhibited distinct T cell memory subset distributions. HCMV-specific responses were compartmentalised: IFN-γ responses predominated in PBMCs following lytic antigen stimulation, while IL-10 and TNF-α responses were more prominent in BMMNCs, particularly in response to latent antigens. US28-specific T cells in the BM showed elevated expression of CD39, PD-1, BTLA, CTLA-4, ICOS, and LAG-3 on CD4+ T cells and increased expression of PD-1, CD39, BTLA, TIGIT, LAG-3, and ICOS on CD8+ T cell populations, suggesting a more immunoregulatory phenotype. These findings highlight functional and phenotypic differences in HCMV-specific T cell responses between blood and bone marrow, underscoring the role of the BM niche in shaping antiviral immunity and maintaining viral latency. Full article

The objective of this study was to investigate the temporal effectiveness of repetitive peripheral magnetic stimulation (rPMS) on lower-limb motor skill performance in individuals with chronic stroke. In this sham-controlled crossover study, we hypothesized that individuals with stroke who received rPMS would demonstrate improved motor skill performance after the stimulation and maintain this enhanced performance at 30 and 60 min after the stimulation. Sixteen participants performed a visuomotor ankle-tracking task at multiple time points following either rPMS or sham stimulation. rPMS, delivered to the tibialis anterior muscle, did not result in statistically significant changes in spatiotemporal (p = 0.725) or spatial error (p = 0.566) metrics at any post-stimulation time point. These findings suggest that a single session of rPMS does not lead to measurable improvements in lower-limb motor skill performance in individuals with stroke, underscoring the need to refine stimulation parameters and target populations in future protocols. Full article

With the rapid advancement of urbanization, the increasing demand and insufficient supply of public service facilities for children have become urgent problems requiring resolution. This study employs the Shannon diversity index, the location entropy, spatial autocorrelation, and the Geographically Weighted Regression (GWR) to analyze the spatial distribution characteristics and influencing factors of children’s public service facilities in the central urban area of Shenyang. The findings of the study are as follows: (1) There are significant differences in the spatial distribution of children’s public service facilities. Higher quantity distribution and diversity index are observed in the core area and Hunnan District compared to the peripheral areas. The Gini coefficient of various facilities is below the fair threshold of 0.4, but 90.32% of the study units have location entropy values below 1, indicating a supply–demand imbalance. (2) The spatial distribution of various facilities exhibits significant clustering characteristics, with distinct differences between high-value and low-value cluster patterns. (3) The spatial distribution of facilities is shaped by four factors: population, transportation, economy, and environmental quality. Residential area density and commercial service facility density emerge as the primary positive drivers, whereas road density and average housing price act as the main negative inhibitors. (4) The mechanisms of influencing factors exhibit spatial heterogeneity. Positive driving factors exert significant effects on new urban areas and peripheral zones, while negative factors demonstrate pronounced inhibitory effects on old urban areas. Non-linear threshold effects are observed in factors such as subway station density and public transport station density. Full article

Background/Objectives: Supernumerary teeth, or hyperdontia, refer to a developmental anomaly defined by the presence of additional teeth beyond the normal dentition. Hyperdontia may result in clinical complications including delayed eruption, crowding, and malocclusion. Despite its prevalence having been studied in various populations, data from geographically isolated or peripheral groups remain limited. This study aimed to investigate the prevalence and distribution of supernumerary teeth in a sample of children and adolescents from the island of Lesvos, Greece. Methods: A retrospective cross-sectional study was conducted using panoramic radiographs from 621 Caucasian children aged 9–16 years who attended orthodontic or general/pediatric dental clinics in Mytilini, Lesvos island, Greece. Radiographs were examined for the presence, number, type, and location of supernumerary teeth. The analysis included data to explore gender and arch distribution. Results: Supernumerary teeth were identified in 15 individuals, corresponding to a prevalence of 2.4%. A slightly higher occurrence was observed in males (1.4%) than in females (1%). The majority of supernumerary teeth were situated in the maxillary arch (1.9%). Mesiodens represented the most frequently observed type, followed by supernumerary lateral incisors, paramolars, and a single supernumerary central incisor. Conclusions: The prevalence of supernumerary teeth in this population is consistent with reported findings. Mesiodens was the most frequently observed type, with a predominance in the maxillary arch. Early detection of supernumerary teeth is crucial for accurate diagnosis and effective management. Full article

Background and Objectives: Arthrogenic muscle inhibition (AMI) is a key neurophysiological barrier to effective rehabilitation in individuals with chronic ankle instability (CAI). The primary objective of this narrative review is to explore the role of arthrogenic muscle inhibition (AMI) in chronic ankle instability (CAI) and to critically appraise neurophysiological and rehabilitative strategies targeting its resolution. Although peripheral strengthening remains a cornerstone of treatment, the roles of spinal and cortical modulation are increasingly recognised. Materials and Methods: A narrative review was conducted to examine recent clinical trials targeting AMI in CAI populations. A structured search of MEDLINE, Web of Science, Scopus, Cochrane Central, and PEDro was performed. Five studies were included, encompassing peripheral, spinal, and cortical interventions. The outcomes were grouped and analysed according to neurophysiological and functional domains. Results: Manual therapy combined with exercise improved pain, strength, and functional mobility. Fibular reposition taping transiently enhanced spinal reflex excitability, while transcranial direct current stimulation (tDCS) over the primary motor cortex significantly modulated corticospinal excitability and voluntary muscle activation. Improvements in subjective stability, dynamic balance, and neuromuscular responsiveness were observed in the majority of the five included studies, although methodological heterogeneity and short-term follow-ups limit generalisability. Conclusions: Multimodal interventions targeting different levels of the neuromotor system appear to be more effective than isolated approaches. Integrating manual therapy, sensorimotor training, and neuromodulation may optimise outcomes in CAI rehabilitation. Future trials should focus on standardised outcome measures and long-term efficacy. Full article

Peripheral artery disease (PAD) is a common vascular disorder in the elderly, often accompanied by frailty syndrome, which is associated with increased inflammation, oxidative stress, and functional decline. Nutritional strategies, particularly those involving bioactive compounds like flavonoids and omega-3 fatty acids, have been suggested as potential approaches to modulate these pathological processes. This narrative review summarizes current evidence regarding the anti-inflammatory and antioxidant effects of flavonoids and omega-3 fatty acids, and their possible roles in mitigating frailty syndrome in patients with PAD. We examine mechanistic pathways including NF-κB, AMPK, PI3K/Akt/mTOR, and Nrf2, which are implicated in chronic inflammation, endothelial dysfunction, and muscle wasting. Although studies in general and aging populations suggest beneficial effects of these compounds on vascular and muscle health, specific evidence in PAD patients remains limited. Flavonoids may reduce pro-inflammatory cytokine production and enhance antioxidant responses, while omega-3 fatty acids have shown potential in modulating inflammatory signaling and supporting vascular repair. Current data provide a basis for further investigation into the dietary modulation of frailty syndrome in PAD. Understanding the impact of these nutrients may offer insights into adjunctive strategies for improving patient outcomes. Full article

This study examines the impact of the Beijing–Tianjin–Hebei (BTH) coordinated development policy on the regional industrial network structure, with a focus on the significance of electricity consumption data in social network analysis (SNA). Utilizing a gravity model integrated with electricity consumption data, this research employs centrality analysis and Lambda analysis to compare changes in the steel industry network before and after policy implementation. The findings reveal that traditional models relying solely on indicators such as population and Gross Domestic Product (GDP) fail to comprehensively capture regional economic linkages, whereas incorporating electricity consumption data enhances the model’s accuracy in identifying core nodes and latent connections. Post policy implementation, the centrality of Beijing and Tianjin increased significantly, reflecting their transition from production hubs to centers for research and development (R&D) and management, while Shijiazhuang’s pivotal role diminished. This study also uncovers a “core–periphery” structure in the BTH urban network, where core cities (Beijing, Tianjin, and Shijiazhuang) dominate resource allocation and information flow, while peripheral cities exhibit uneven development. These results provide a scientific basis for optimizing regional coordinated development policies and underscore the critical role of electricity consumption data in refining regional economic analysis. Incorporating electricity consumption data into the gravity model significantly enhances its explanatory power by capturing hidden economic ties and improving policy evaluation, offering a more accurate and dynamic assessment of regional industrial linkages. Full article

Peripheral artery disease (PAD) is associated with an elevated risk of major adverse cardiovascular events (MACE). Despite this, few reliable biomarkers exist to identify patients at heightened risk of MACE. Growth differentiation factor 15 (GDF15), a stress-responsive cytokine implicated in inflammation, atherosclerosis, and thrombosis, has been broadly studied in cardiovascular disease but remains underexplored in PAD. This study aimed to evaluate the prognostic utility of GDF15 for predicting 2-year MACE in PAD patients using explainable statistical and machine learning approaches. We conducted a prospective analysis of 1192 individuals (454 with PAD and 738 without PAD). At study entry, patient plasma GDF15 concentrations were measured using a validated multiplex immunoassay. The cohort was followed for two years to monitor the occurrence of MACE, defined as stroke, myocardial infarction, or death. Baseline GDF15 levels were compared between PAD and non-PAD participants using the Mann–Whitney U test. A machine learning model based on extreme gradient boosting (XGBoost) was trained to predict 2-year MACE using 10-fold cross-validation, incorporating GDF15 and clinical variables including age, sex, comorbidities (hypertension, diabetes, dyslipidemia, congestive heart failure, coronary artery disease, and previous stroke or transient ischemic attack), smoking history, and cardioprotective medication use. The model’s primary evaluation metric was the F1 score, a validated measurement of the harmonic mean of the precision and recall values of the prediction model. Secondary model performance metrics included precision, recall, positive likelihood ratio (LR+), and negative likelihood ratio (LR-). A prediction probability histogram and Shapley additive explanations (SHAP) analysis were used to assess model discrimination and interpretability. The mean participant age was 70 ± SD 11 years, with 32% (n = 386) female representation. Median plasma GDF15 levels were significantly higher in PAD patients compared to the levels in non-PAD patients (1.29 [IQR 0.77–2.22] vs. 0.99 [IQR 0.61–1.63] pg/mL; p < 0.001). During the 2-year follow-up period, 219 individuals (18.4%) experienced MACE. The XGBoost model demonstrated strong predictive performance for 2-year MACE (F1 score = 0.83; precision = 82.0%; recall = 83.7%; LR+ = 1.88; LR− = 0.83). The prediction histogram revealed distinct stratification between those who did vs. did not experience 2-year MACE. SHAP analysis identified GDF15 as the most influential predictive feature, surpassing traditional clinical predictors such as age, cardiovascular history, and smoking status. This study highlights GDF15 as a strong prognostic biomarker for 2-year MACE in patients with PAD. When combined with clinical variables in an interpretable machine learning model, GDF15 supports the early identification of patients at high risk for systemic cardiovascular events, facilitating personalized treatment strategies including multidisciplinary specialist referrals and aggressive cardiovascular risk reduction therapy. This biomarker-guided approach offers a promising pathway for improving cardiovascular outcomes in the PAD population through precision risk stratification. Full article

Background and Objectives: Thyroid nodules are a common endocrine disorder, with 10–15% exhibiting malignancy. Accurate differentiation of malignant and benign nodules is crucial for optimizing treatment outcomes. Current diagnostic tools, such as the Bethesda classification and fine-needle aspiration biopsy (FNAB), are limited in sensitivity and specificity, particularly in indeterminate cases. Tumor-infiltrating immune cells (TIICs) in the tumor microenvironment (TME) play a significant role in thyroid cancer progression. CD66b⁺ neutrophil-like monocytes constitute a novel subset of myeloid cells that are implicated in the modulation of anti-tumor immune responses, but their role in thyroid cancer remains unclear. Materials and Methods: Peripheral blood and thyroid nodule tissue samples were obtained from 24 patients with papillary thyroid carcinoma, and from 10 patients who underwent surgery for symptoms of tracheal compression due to benign thyroid nodules. Myeloid cell populations were assayed by flow cytometric immunophenotyping with CD45, HLA-DR, CD14, and CD66b. The data were statistically analyzed with the clinical properties of the patients. Results: The neutrophil-like monocytes, which were determined as HLA-DR⁺CD14⁺CD66b⁺ cells, found in the circulation (11.9 ± 2.4% of total mononuclear immune cells) of the patients with papillary thyroid carcinoma, were significantly elevated (p < 0.001). Accordingly, these cells were more frequently detected in tumor tissues (21.1 ± 2.1% of total tumor-infiltrating immune cells) compared to non-tumor thyroid tissues (p = 0.0231). The infiltration levels of neutrophil-like monocytes were significantly higher in malignant nodules as well as in the peripheral blood of the papillary thyroid carcinoma patients compared to the samples obtained from the patients with benign nodules. The tumor tissues exhibited increased immune cell infiltration and harbored CD66b-expressing neutrophil-like HLA-DR⁺CD14⁺ monocytic cells, which indicates an inflammatory milieu in malignant thyroid cancer. Conclusions: This study identifies neutrophil-like monocytes as a potential biomarker for differentiating malignant and benign thyroid nodules. Elevated levels of this novel subtype of immune cells in malignant tissues suggest their role in tumor progression and their utility in enhancing diagnostic accuracy. Incorporating these findings into clinical practice may refine surgical decision-making and improve outcomes through personalized diagnostic and therapeutic strategies, particularly for radioiodine-refractory thyroid cancer. Full article

Background: Charcot-Marie-Tooth (CMT) disease is a hereditary motor and sensory neuropathy that affects foot morphology and gait patterns, potentially leading to abnormal plantar pressure distribution. This systematic review synthesizes the existing literature examining plantar pressure characteristics in CMT patients. Methods: A comprehensive search was conducted across PubMed, Scopus, and Web of Science databases. Risk of bias was assessed using the Newcastle–Ottawa Scale. Results: Six studies comprising 146 patients were included. Four studies employed dynamic baropodometry, and two used in-shoe pressure sensors to evaluate the main plantar pressure parameters. The findings were consistent across different populations and devices, with a characteristic plantar-pressure profile of marked midfoot off-loading with peripheral overload at the forefoot and rearfoot, often accompanied by a lateralized center-of-pressure path and a prolonged pressure–time exposure. These alterations reflect both structural deformities and impaired neuromuscular control. Interventional studies demonstrated a load redistribution of pressure after corrective surgery, though residual lateral overload often persists. Conclusions: Plantar pressure mapping seems to be a valuable tool to identify high-pressure zones of the foot in order to personalize orthotic treatment planning, to objectively monitor disease progression, and to evaluate therapeutic efficacy. Further longitudinal studies with standardized protocols are needed to confirm these results. Full article

T-cell receptors (TCRs) exhibit degeneracy, enabling individual TCRs to recognize multiple altered peptide ligands (APLs) derived from a single cognate antigen. This characteristic has been involved in the pathogenesis of autoimmune diseases through cross-reactivity between microbial and self-antigens. Cytotoxic T lymphocytes (CTLs), which recognize peptide–MHC class I complexes via TCRs, play a critical role in the immune response against viral infections. However, the extent to which TCR degeneracy within a population of virus-specific CTLs contributes to effective viral control remains poorly understood. In this study, we investigated the magnitude and functional relevance of TCR degeneracy in CTLs targeting an immunodominant epitope of human T-cell leukemia virus type 1 (HTLV-1) in patients with HTLV-1-associated myelopathy (HAM). Using peripheral blood mononuclear cells (PBMCs) from these patients, we quantified TCR degeneracy at the population level by comparing CTL responses to a panel of APLs with responses to the cognate epitope. Our findings demonstrated that increased TCR degeneracy, particularly at the primary TCR contact residue at position 5 of the antigen, was inversely correlated with HTLV-1 proviral load (p = 0.038, R = −0.40), despite similar functional avidity across patient-derived CTLs. Viral sequencing further revealed that CTLs with high TCR degeneracy exerted stronger selective pressure on the virus, as indicated by a higher frequency of nonsynonymous substitutions within the epitope-encoding region in patients with highly degenerate TCR repertoires. Moreover, TCR degeneracy was positively correlated with the recognition rate of epitope variants (p = 0.018, R = 0.76), suggesting that CTLs with high TCR degeneracy exhibited enhanced recognition of naturally occurring epitope variants compared to those with low TCR degeneracy. Taken together, these results suggest that virus-specific CTLs with high TCR degeneracy possess superior antiviral capacity, characterized by broadened epitope recognition and more effective suppression of HTLV-1 infection. To our knowledge, this is the first study to systematically quantify TCR degeneracy in HTLV-1-specific CTLs and evaluate its contribution to viral control in HAM patients. These findings establish TCR degeneracy as a critical determinant of antiviral efficacy and provide a novel immunological insight into the mechanisms of viral suppression in chronic HTLV-1 infection. Full article

Peripheral arterial disease (PAD) is a macrovascular diabetic complication, characterized by atherosclerotic plaque formation due to hyperglycemia and dyslipidemia. The molecular mechanisms involved in PAD-T2DM pathogenesis will help in understanding and early prognosis; therefore, we aim to evaluate FABP4 levels and Nrf2 single-nucleotide polymorphisms (SNPs) among PAD-T2DM patients. In a case-control study, 123 samples (healthy control HC, T2DM, and PAD-T2DM; n = 41 each) were collected from the diabetic foot clinic at Mayo Hospital, Lahore. Baseline and biochemical data were collected. PAD diagnosis was established by measuring the ankle-brachial index with color Doppler ultrasound. Serum FABP4 levels were measured using an ELISA. Nrf2 SNP rs35652124 analysis was performed by restriction fragment length polymorphism. PAD-T2DM prevalence was higher among male subjects (61.1%). Fasting plasma glucose levels (p = 0.02), total cholesterol (p < 0.0001), and LDL-cholesterol (p = 0.01) were significantly higher in PAD-T2DM as compared to T2DM. SNP association analysis showed that homozygous genotype TT (OR: 3.85, 95% (CI): 1.22–12.11, p = 0.02) and T-allele (OR: 1.31, 95% (CI): 1.31–4.67, p = 0.005) were significantly associated with PAD-T2DM. FABP4 levels were higher in the PAD-T2DM group as compared to T2DM (p < 0.0001) and were significantly associated with Nrf2 SNP genotype TT (p < 0.001) and CT (p = 0.01) in PAD-T2DM. Our results showed, for the first time, that the Nrf2 SNP is significantly associated with PAD-T2DM and FABP4 levels compared to T2DM. Full article