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Background: Multiple epiphyseal dysplasia (MED) is a clinically and genetically heterogeneous group of skeletal diseases characterized by epiphyseal abnormalities associated with mild short stature. The clinical variability is wide, and the first clinical manifestations still occur in childhood with joint pain and stiffness that evolve into degenerative joint disease. MED, caused by mutations in the Cartilage Oligomeric Matrix Protein (COMP) gene, is the most common form of the disease. COMP-MED usually shows significant involvement of the capital femoral epiphyses and irregular acetabulum; instead, COL9A1-, COL9A2-, and COL9A3-MED appear to have more severe knee involvement than hips, resulting in a milder presentation than COMP-MED cases. Other complications have been reported, in particular osteochondritis dissecans (OCD), which has been described in two large COL9A2-related MED families associated with myopathy. Methods: Here, we report the case of a 24-year-old man affected by COMP-MED with a positive family history for the disease and a clinical presentation that interestingly is characterized by the presence of multiple OCD. Results: To our knowledge, this is the first case of COMP mutations related to multiple OCD as the main clinical feature. Conclusions: This report can expand the clinical phenotype related to the pathogenic variants of the COMP gene, as it shows that multiple OCD can also be present in COMP-related MED as well as in COL9A2-related MED. [ABSTRACT FROM AUTHOR]

Microbial fermentation is a well-known strategy for enhancing the nutraceutical attributes of foods. Among the fermentation outcomes, bioactive peptides (BAPs), short chains of amino acids resulting from proteolytic activity, are emerging as promising components thanks to their bioactivities. Indeed, BAPs offer numerous health benefits, including antimicrobial, antioxidant, antihypertensive, and anti-inflammatory properties. This review focuses on the production of bioactive peptides during the fermentation process, emphasizing how different microbial strains and fermentation conditions influence the quantity and quality of these peptides. Furthermore, it examines the health benefits of BAPs from fermented foods, highlighting their potential in disease prevention and overall health promotion. Additionally, this review addresses the challenges and future directions in this field. This comprehensive overview underscores the promise of fermented foods as sustainable and potent sources of bioactive peptides, with significant implications for developing functional foods and nutraceuticals. [ABSTRACT FROM AUTHOR]

The need to develop synthetic bone substitutes with structures, properties, and functions similar to bone and capable of preventing microbial infections is still an ongoing challenge. This research is focused on the preparation and characterization of three-dimensional porous scaffolds based on hydroxyapatite (HA)-functionalized calcium carbonate loaded with silver nanoparticles and simvastatin (SIMV). The scaffolds were prepared using the foam replica method, with a polyurethane (PU) sponge as a template, followed by successive polymer removal and sintering. The scaffolds were then coated with poly(lactic-co-glycolic) acid (PLGA) to improve mechanical properties and structural integrity, and loaded with silver nanoparticles and SIMV. The scaffolds were characterized by X-ray powder diffraction (XRD), field emission scanning electron microscopy (FE-SEM), ATR FT-IR, and silver and SIMV loading. Moreover, the samples were analyzed by Brillouin and Raman microscopy. Finally, in vitro bioactivity, SIMV and silver release, and antimicrobial activity against Staphylococcus aureus and Staphylococcus epidermidis were evaluated. From the Brillouin spectra, samples showed characteristics analogous to those of bone tissue. They exhibited new hydroxyapatite growth, as evidenced by SEM, and good antimicrobial activity against the tested bacteria. In conclusion, the obtained results demonstrate the potential of the scaffolds for application in bone repair. [ABSTRACT FROM AUTHOR]

Mechanosensing and mechanotransduction pathways between the Extracellular Matrix (ECM) and cells form the essential crosstalk that regulates cell homeostasis, tissue development, morphology, maintenance, and function. Understanding these mechanisms involves creating an appropriate cell support that elicits signals to guide cellular functions. In this context, polymers can serve as ideal molecules for producing biomaterials designed to mimic the characteristics of the ECM, thereby triggering responsive mechanisms that closely resemble those induced by a natural physiological system. The generated specific stimuli depend on the different natural or synthetic origins of the polymers, the chemical composition, the assembly structure, and the physical and surface properties of biomaterials. This review discusses the most widely used polymers and their customization to develop biomaterials with tailored properties. It examines how the characteristics of biomaterials-based polymers can be harnessed to replicate the functions of biological cells, making them suitable for biomedical and biotechnological applications. [ABSTRACT FROM AUTHOR]

Background/Objectives: Urinary tract infections (UTIs) are infections that involve the urethra, bladder, and, in much more severe cases, even kidneys. These infections represent one of the most common diseases worldwide. Various pathogens are responsible for this condition, the most common being Escherichia coli (E. coli). Bromelain is a proteolytic complex obtained from the stem and stalk of Ananas comosus (L.) Merr. showing several beneficial activities. In addition to bromelain, N-acetylcysteine (NAC) has also been used. Methods: The purpose of this experiment was to evaluate the antibacterial, anti-motility, and anti-biofilm effects of a new polyenzymatic complex (DIF17BRO®) in combination with NAC (the Formulation) on various strains of E. coli isolated from patients with UTIs. Subsequently, the anti-inflammatory and antioxidant effects of the Formulation were studied in an ex vivo model of cystitis, using bladder samples from mice exposed to E. coli lipopolysaccharide (LPS). Results: Our results showed that the Formulation significantly affects the capability of bacteria to form biofilm and reduces the bacteria amount in the mature biofilm. Moreover, it combines the interesting properties of NAC and a polyenzyme plant complex based on bromelain in a right dose to affect the E. coli adhesion capability. Finally, the Formulation exhibited protective effects, as confirmed by the inhibitory activities on multiple inflammatory and oxidative stress-related pathways on bladder specimens exposed to LPS. Conclusions: This blend of active compounds could represent a promising and versatile approach to use to overcome the limitations associated with conventional therapies. [ABSTRACT FROM AUTHOR]

Checkpoint inhibitors (ICIs) have demonstrated substantial efficacy in the treatment of numerous solid tumors, including head and neck cancer. Their inclusion in the therapeutic paradigm in metastatic lines of treatment has certainly improved the outcomes of these patients. Starting from this assumption, numerous studies have been conducted on ICIs in other earlier disease settings, including studies conducted in patients in neoadjuvant settings. However, how many and which studies are truly significant? Can they lay concrete foundations for further future studies and therefore allow us to continue to have this interesting future perspective? Through a review of the existing literature, coupled with insights gleaned from clinical practice and from the main recently published studies, we aim to examine the therapeutic potential of ICIs in patients affected by head and neck cancer in a neoadjuvant treatment setting and encourage researchers to set up successful future clinical trials. [ABSTRACT FROM AUTHOR]

Breast milk is the natural source of nutrition for infants, but while it supports their health, it can also be a potential source of toxic inorganic particulate matter, and this applies to both breast milk and industrially produced milk. The aim of the present study was to evaluate the presence of nanoparticles in both breast milk and formula milk samples. We collected and analyzed, via a new electron scanning microscopic procedure, 19 samples of breast milk from Italian women and 19 formula milk samples produced by different companies. Organic–inorganic agglomerates were detected in 58% of formula and in 63% of breast milk samples, respectively. In addition, a significantly (p < 0.05) greater size of nanoparticles was observed in formula milk samples. The results, showing the presence of inorganic nanosized particles in breast and artificial milk, may lead to future studies aimed at investigating possible nanosized contamination of milk and identifying early prevention strategies for women and animals involved in the food chain. [ABSTRACT FROM AUTHOR]

Background: Reliable Human Papillomavirus (HPV) testing and genotyping are essential for quality assurance in HPV-based primary screening, disease management and for monitoring the impact of HPV vaccination. The clinical validation of HPV molecular diagnostic assays has significantly contributed to these objectives; however, little emphasis has been placed on assuring sample quality. This study aimed to evaluate the accuracy of sample cellularity assessment using the C-C Motif Chemokine Receptor 5 (CCR5) gene target as a marker of sample adequacy in molecular diagnostics. Methods: Jurkat cell line samples were counted using both a Thoma cell-counting chamber and Fluorescence-Activated Cell Sorting (FACS). Jurkat cell line samples at three different concentrations were subsequently evaluated using the OncoPredict HPV Quality Control (QC) real-time PCR assay, employing CCR5 for molecular cellularity quantification. Results: The cellularity values obtained were comparable across the three different methods for all dilutions of the cell line tested. Conclusions: The results obtained from this study show that CCR5 represents a promising molecular marker for the accurate quantification of sample cellularity, confirming its use as a reliable sample adequacy control, thus reducing the risk of "false-negative" results. [ABSTRACT FROM AUTHOR]

This review covers recent advancements in the use of zirconium phosphates and phosphonates (ZrPs) as catalysts or catalyst supports for a variety of reactions, including biomass conversion, acid–base catalysis, hydrogenation, oxidation, and C-C coupling reactions, from 2015 to the present. The discussion emphasizes the intrinsic catalytic properties of ZrPs, focusing on how surface acidity, hydrophobic/hydrophilic balance, textural properties, and particle morphology influence their catalytic performance across various reactions. Additionally, this review thoroughly examines the use of ZrPs as supports for catalytic species, ranging from organometallic complexes and metal ions to noble metals and metal oxide nanoparticles. In these applications, ZrPs not only enhance the dispersion and stabilization of active catalytic species but also facilitate their recovery and reuse due to their robust immobilization on the solid support. This dual functionality underscores the importance of ZrPs in promoting efficient, selective, and sustainable catalytic processes, making them essential to the advancement of green chemistry. [ABSTRACT FROM AUTHOR]

Objectives: This systematic review aimed to analyse the published evidence for the use of non-invasive methods for the early detection of oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs). Methods: The literature was systematically searched through several databases: PubMed, Cochrane Library, and Web of Science. Additional exploration was performed through cross-checks on the bibliographies of selected reviews. The inclusion criteria involved studies assessing the application of non-invasive tests on humans in the screening, diagnosis, or surveillance of OSCC or OPMDs and reporting sensitivity (SE) and specificity (SP). The Newcastle–Ottawa scale (NOS) was applied to assess the quality of the studies included. Results: The search strategy resulted in 8012 preliminary records. After a duplicate check, 116 titles remained. After abstract analysis, 70 papers remained. After full text analysis, only 54 of the 70 papers fit the inclusion criteria (28 were original articles and 26 were reviews). Those 26 reviews were used to manually search for further original articles. From this last search, 33 original articles were found. Thus, a total of 61 original studies were included and investigated. Findings from this systematic review indicate useful information, such as a description of the mechanisms, ease of use, limitations, and SE and SP values, to drive the choice of the optimal minimally invasive method to be utilized as an adjunctive tool to examine the suspicious lesions. Conclusions: Each of the analysed tools can be improved or implemented, considering their high SE and low SP. Despite advancements, incisional biopsy continues to be the gold standard for the definitive diagnosis of oral cancer and precancerous lesions. Further research and development are essential to improving the sensitivity, specificity, and reliability of non-invasive tools for widespread clinical application. [ABSTRACT FROM AUTHOR]

Coronary artery disease (CAD) is the leading global cause of mortality, accounting for approximately 30% of all deaths. It is primarily characterized by the accumulation of atherosclerotic plaques within the coronary arteries, leading to reduced blood flow to the heart muscle. Early detection of atherosclerotic plaques is crucial to prevent major adverse cardiac events. Notably, recent studies have shown that 15% of myocardial infarctions occur in patients with non-obstructive CAD, underscoring the importance of comprehensive plaque assessment beyond merely identifying obstructive lesions. Cardiac Computed Tomography Angiography (CCTA) has emerged as a cost-effective and efficient technique for excluding obstructive CAD, particularly in patients with a low-to-intermediate clinical likelihood of the disease. Recent advancements in CCTA technology, such as improved resolution and reduced scan times, have mitigated many technical challenges, allowing for precise quantification and characterization of both calcified and non-calcified atherosclerotic plaques. This review focuses on two critical physiological aspects of atherosclerotic plaques: the burden of calcifications, assessed via the coronary artery calcium score (CACs), and perivascular fat attenuation index (pFAI), an emerging marker of vascular inflammation. The CACs, obtained through non-contrast CT scans, quantifies calcified plaque burden and is widely used to stratify cardiovascular risk, particularly in asymptomatic patients. Despite its prognostic value, the CACs does not provide information on non-calcified plaques or inflammatory status. In contrast, the pFAI, derived from CCTA, serves as an indirect marker of coronary inflammation and has shown potential in predicting adverse cardiac events. Combining both CACs and pFAI assessment could offer a comprehensive risk stratification approach, integrating the established calcification burden with novel inflammatory markers to enhance CAD prevention and management strategies. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is the leading cause of traumatic death worldwide and is a public health problem associated with high mortality and morbidity rates, with a significant socioeconomic burden. The diagnosis of brain injury may be difficult in some cases or may leave diagnostic doubts, especially in mild trauma with insignificant pathological brain changes or in cases where instrumental tests are negative. Therefore, in recent years, an important area of research has been directed towards the study of new biomarkers, such as micro-RNAs (miRNAs), which can assist clinicians in the diagnosis, staging, and prognostic evaluation of TBI, as well as forensic pathologists in the assessment of TBI and in the estimation of additional relevant data, such as survival time. The aim of this study is to investigate the expression profiles (down- and upregulation) of a panel of miRNAs in subjects deceased with TBI in order to assess, verify, and define the role played by non-coding RNA molecules in the different pathophysiological mechanisms of brain damage. This study also aims to correlate the detected expression profiles with survival time, defined as the time elapsed between the traumatic event and death, and with the severity of the trauma. This study was conducted on 40 cases of subjects deceased with TBI (study group) and 10 cases of subjects deceased suddenly from non-traumatic causes (control group). The study group was stratified according to the survival time and the severity of the trauma. The selection of miRNAs to be examined was based on a thorough literature review. Analyses were performed on formalin-fixed, paraffin-embedded (FFPE) brain tissue samples, with a first step of total RNA extraction and a second step of quantification of the selected miRNAs of interest. This study showed higher expression levels in cases compared to controls for miR-16, miR-21, miR-130a, and miR-155. In contrast, lower expression levels were found in cases compared to controls for miR-23a-3p. There were no statistically significant differences in the expression levels between cases and controls for miR-19a. In cases with short survival, the expression levels of miR-16-5p and miR-21-5p were significantly higher. In cases with long survival, miR-21-5p was significantly lower. The expression levels of miR-130a were significantly higher in TBI cases with short and middle survival. In relation to TBI severity, miR-16-5p and miR-21-5p expression levels were significantly higher in the critical–fatal TBI subgroup. Conclusions: This study provides evidence for the potential of the investigated miRNAs as predictive biomarkers to discriminate between TBI cases and controls. These miRNAs could improve the postmortem diagnosis of TBI and also offer the possibility to define the survival time and the severity of the trauma. The analysis of miRNAs could become a key tool in forensic investigations, providing more precise and detailed information on the nature and extent of TBI and helping to define the circumstances of death. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) vaccination has been available for over four decades. However, a synthesis of the evidence regarding the effectiveness of this strategy on preventing hepatitis B infection in people who use drugs (PWUD) is lacking. A systematic search of the MEDLINE (via PubMed), SCOPUS, Web of Science, and Cochrane Library databases was conducted up to June 2024. Eight studies reported on the effectiveness of HBV vaccination, defined as a positive result for HBsAg or anti-Hbc in vaccinated versus non-vaccinated PWUD, with a pooled effect size of 52% (95% CI: 28.2–67.9) for HBsAg and 31.89% (95% CI: 14.8–45.5) for anti-Hbc. For sero-immunity, defined as the proportion of vaccinated PWUD with levels of anti-HBs ≥ 10 mIU/mL, we found that 66.2% (95% CI: 0.61–0.71; I2 = 94%) had protective levels of anti-HBs. The results of this meta-analysis indicate that the incidence of HBV infection is lower in vaccinated PWUD than in those who did not receive the vaccine. However, the effectiveness is lower than that observed in the general population. This highlights the need for a thorough review of the factors influencing the prevention of HBV infection in PWUD. [ABSTRACT FROM AUTHOR]

Nitrite/nitrate poisoning is an emerging problem, with an ongoing escalation of reported self-administration with suicidal intent in several countries. Nitrites toxicity mainly consists of their interaction with hemoglobin (Hb), causing its oxidization to methemoglobin (MetHb). In order to give support to the correct procedures for the analysis of these cases, this study aims to evaluate spontaneous sample degradation and consequent MetHb formation in the typical storage conditions of a forensic toxicology laboratory. Two different types of samples have been used in this study: the first stage of our study consisted of a retrospective analysis of blood samples obtained by judicial autopsies already stored in the toxicology laboratory, collected over four years (2018–2021), while the samples used for the second stage were appositely collected during judicial autopsies. The data obtained by the application of a derivative spectrophotometry method on these samples suggest that there seems not to be a maximum threshold for MetHb formation within which it is possible to state with a sufficient grade of certainty that the concentration of MetHb found is consistent with an ante-mortem formation and is not the result of an artifact due to sample degradation and storage conditions. On the other hand, the results suggest that MetHb formation depends on the time passed between sample collection and analysis, so that a tempestive sample processing, performed as soon as the samples are received in the laboratory, is crucial to obtain the maximum reliability and diagnostic values from the data when MetHb quantitation is necessary. [ABSTRACT FROM AUTHOR]

Squamous cell carcinoma of the head and neck (SCCHN) is among the ten most common cancers worldwide, with advanced SCCHN presenting with a 5-year survival of 34% in the case of nodal involvement and 8% in the case of metastatic disease. Disease-free survival at 2 years is 67% for stage II and 33% for stage III tumors, whereas 12–30% of patients undergo distant failures after curative treatment. Previous treatments often hinder the success of salvage surgery and/or reirradiation, while the standard of care for the majority of metastatic SCCHN remains palliative chemo- and immuno-therapy, with few patients eligible for locoregional treatments. The aim of this paper is to review the characteristics of recurrent SCCHN, based on different recurrence sites, and metastatic disease; we will also explore the possibilities not only of salvage surgery and reirradiation but also systemic therapy choices and locoregional treatment for metastatic SCCHN. [ABSTRACT FROM AUTHOR]

Resource-intensive processes currently hamper the discovery of bioactive peptides (BAPs) from food by-products. To streamline this process, in silico approaches present a promising alternative. This study presents a novel computational workflow to predict peptide release, bioactivity, and bioavailability, significantly accelerating BAP discovery. The computational flowchart has been designed to identify and optimize critical enzymes involved in protein hydrolysis but also incorporates multi-enzyme screening. This feature is crucial for identifying the most effective enzyme combinations that yield the highest abundance of BAPs across different bioactive classes (anticancer, antidiabetic, antihypertensive, anti-inflammatory, and antimicrobial). Our process can be modulated to extract diverse BAP types efficiently from the same source. Here, we show the potentiality of our method for the identification of diverse types of BAPs from by-products generated from Solanum lycopersicum, the widely cultivated tomato plant, whose industrial processing generates a huge amount of waste, especially tomato peel. In particular, we optimized tomato by-products for bioactive peptide production by selecting cultivars like Line27859 and integrating large-scale gene expression. By integrating these advanced methods, we can maximize the value of by-products, contributing to a more circular and eco-friendly production process while advancing the development of valuable bioactive compounds. [ABSTRACT FROM AUTHOR]

Objective: The goal of this systematic review and meta-analysis was to assess whether there were clinically relevant differences in the treatment of edentulous areas comparing zirconia (Zr) and titanium (Ti) dental implants. The null hypothesis is that no differences can be observed in terms of the clinical parameters; the positive hypothesis I is that Zr implants have generally better results compared to Ti implants; and the positive hypothesis II is that Ti implants have a generally superior result than Zr implants. Methods: This review work was registered on the PROSPERO platform, and its development was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. The electronic search process was conducted on three databases (PubMed/Scopus/Web of Science), including randomized controlled trials (RCTs) from the past 10 years (up to April 2024). Identified articles were analyzed and included/excluded based on pre-defined selection and exclusion criteria. The quality assessment and risk of bias were evaluated using a Cochrane risk-of-bias assessment tool specifically designed for randomized trials (RoB2). A meta-analysis was conducted to correlate different treatment options based on the described outcomes; a random-effects model was used in the analysis of the variables. The analysis of heterogeneity was conducted by means of Cochran's Q-test and Higgins' I2 statistic. Results: Six RCTs were enrolled; 152 patients (90 males and 62 females) and 448 implants (267 Zr and 181 Ti) were included. Dental implant placement involved both the maxillary and mandibular arches. The implant sites showed heterogeneity in receiving Zr and Ti dental implants; in particular, 22 dental implants were placed in the mid-palatal region and 426 dental implants in the alveolar region (255 were in Zr and 171 in Ti). Regarding the success rate, it was better for Zr but with no statistical difference (p > 0.05); bleeding on probing had slight differences between Ti with 0.34% ± 0.42 and Zr with 0.26% ± 0.36 (p > 0.05); plaque score showed 0.46 ± 0.47 for Ti compared to 0.44 ± 0.49 for Zr (p > 0.05); no statistically significant difference was observed for pink esthetic score (PES). Statistically significant results were found for survival rate, which favored Ti implants (77.6%) compared to Zr (70.3%) (p < 0.05), and for marginal bone loss, which showed less loss in Ti implants (0.18 mm ± 0.47) compared to 0.42 mm ± 0.40 in Zr at 12 months (p < 0.001). Conclusions: The present systematic review and meta-analysis identified the positive hypothesis I and rejected the null and positive hypothesis II; it was possible to conclude that Ti dental implants have a better survival rate and less marginal bone loss than Zr dental implants after 1-year follow-up. [ABSTRACT FROM AUTHOR]

The interaction between oral bacteria and dental implant surfaces is a critical factor in the success and longevity of dental implants. With advancements in additive manufacturing technologies, selective laser melting (SLM) has emerged as a prominent method for producing titanium implants with highly controlled microstructures and porosities. These 3D printed titanium surfaces offer significant benefits, such as enhanced osseointegration and improved mechanical properties. However, the same surface features that promote bone cell attachment and proliferation may also provide favorable conditions for bacterial adhesion and biofilm formation. Understanding the dynamics of these interactions is essential for developing implant surfaces that can effectively resist bacterial colonization while promoting tissue integration. This narrative review explores the complex interplay between oral bacteria and SLM-produced titanium porous surfaces, examining current research findings and potential strategies for optimizing implant design to mitigate the risks of infection and ensure successful clinical outcomes. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide, with 20% of patients presenting with metastatic disease at diagnosis. TGF-β signaling plays a crucial role in various cellular processes, including growth, differentiation, apoptosis, epithelial-mesenchymal transition (EMT), regulation of the extracellular matrix, angiogenesis, and immune responses. TGF-β signals through SMAD proteins, which are intracellular molecules that transmit TGF-β signals from the cell membrane to the nucleus. Alterations in the TGF-β pathway and mutations in SMAD proteins are common in metastatic CRC (mCRC), making them critical factors in CRC tumorigenesis. This review first analyzes normal TGF-β signaling and then investigates its role in CRC pathogenesis, highlighting the mechanisms through which TGF-β influences metastasis development. TGF-β promotes neoangiogenesis via VEGF overexpression, pericyte differentiation, and other mechanisms. Additionally, TGF-β affects various elements of the tumor microenvironment, including T cells, fibroblasts, and macrophages, promoting immunosuppression and metastasis. Given its strategic role in multiple processes, we explored different strategies to target TGF-β in mCRC patients, aiming to identify new therapeutic options. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR) T cells represent a revolutionary immunotherapy that allows specific tumor recognition by a unique single-chain fragment variable (scFv) derived from monoclonal antibodies (mAbs). scFv selection is consequently a fundamental step for CAR construction, to ensure accurate and effective CAR signaling toward tumor antigen binding. However, conventional in vitro and in vivo biological approaches to compare different scFv-derived CARs are expensive and labor-intensive. With the aim to predict the finest scFv binding before CAR-T cell engineering, we performed artificial intelligence (AI)-guided molecular docking and steered molecular dynamics analysis of different anti-CD30 mAb clones. Virtual computational scFv screening showed comparable results to surface plasmon resonance (SPR) and functional CAR-T cell in vitro and in vivo assays, respectively, in terms of binding capacity and anti-tumor efficacy. The proposed fast and low-cost in silico analysis has the potential to advance the development of novel CAR constructs, with a substantial impact on reducing time, costs, and the need for laboratory animal use. [ABSTRACT FROM AUTHOR]

Considering the health benefits of kombucha, already widely studied, the objective of this study was to develop kombucha beverages with the addition of an infusion of specialty arabica coffee from the first fermentation, varying the proportion of specialty coffee (2% to 13%), and evaluate their pH, volatile acidity, degree of alcohol, centesimal composition, sodium contents, and colour parameters to determine the acceptability of the beverages. Concerning the pH, all of the formulations conformed with the kombucha identity standard, but K3 (11% coffee) and K4 (13% coffee) were below the established minimum for volatile acidity. Except for K4, all of the other formulations were classified as alcoholic kombuchas, although their values were very close to the limit for non-alcoholic beverages. The formulations presented low sugar and sodium contents, which corroborated their low caloric value. Therefore, coffee-flavoured kombucha fermented for 18 days becomes an option for consumers looking for low-calorie, refreshing, and healthy drinks. The luminosity of the beverages decreased as the proportion of coffee increased, and consequently, the values for a* and b* increased, indicating a strong tendency for a yellowish-red colour. Sensorially, the formulations K4 and K3 were the most well accepted in all respects and can therefore be considered formulations with high commercialisation potential. [ABSTRACT FROM AUTHOR]

Background/Objectives: Childhood and adolescence are important stages of life for acquiring healthy habits. There is a high prevalence of sedentary lifestyles worldwide during these ages, which negatively impacts health. This is attributed, in part, to excessive time spent engaging in sedentary behaviors. The aim of this study was to assess the time spent on sedentary behaviors and their relationship with physical activity levels in children and adolescents in the Community of Madrid. Methods:A total of 26,729 participants aged 10–17 from various schools and institutes took part in this study. The International Physical Activity Questionnaire Short Form (IPAQ-SF) was used, and they were asked about the time they spent on different leisure time habits (specific sedentary behaviors and organized physical activity). A generalized linear model was used to analyze the association between the time spent in sedentary activities and the time spent in physical activity. Results: The results revealed that children and adolescents engage in low levels of physical activity and most of them spend considerable time in sedentary behaviors such as studying, watching television, or using social media. Completing school homework (Coef: 1.23, 95% CI: −0.51 to 2.97, p = 0.167) or using social media for more than 2 h (Coef: 1.29, 95% CI: −2.98 to 0.40, p = 0.133) compared to not dedicating time to them did not show a significant association with daily physical activity time. Watching television for more than 2 h was associated with a decrease of 2.60 min (95% CI: −4.41 to −0.78, p = 0.005). Thus, no or only irrelevant associations were found between time spent in sedentary activities and physical activity time. Conclusions: Despite the drawbacks of spending time engaging in sedentary behaviors, they seem to be compatible with physical activity levels. Therefore, it is important to continue research on physical activity adherence strategies to promote overall health and well-being. [ABSTRACT FROM AUTHOR]

Oxidative stress and high levels of reactive oxygen species (ROS) are linked to various age-related diseases and chronic conditions, including damage to oral tissues. Dexamethasone (DEX), a widely used glucocorticoid in dentistry, can have side effects like increased ROS production and delayed wound healing. Resveratrol (RSV) is known for its antioxidant properties, but its limited bioavailability hinders its clinical use. This study investigated the potential of two RSV derivatives (1d and 1h) to address these limitations. The antioxidant abilities of 1d and 1h (5 μM) against DEX-induced oxidative stress (200 μM) were evaluated in human gingival fibroblasts (hGFs) and osteoblasts (hOBs). The effects of these compounds on cell viability, morphology, ROS levels, SOD activity, gene expression, and collagen production were evaluated. RSV derivatives, under DEX-induced oxidative stress condition, improved cell growth at 72 h (191.70 ± 10.92% for 1d+DEX and 184.80 ± 13.87% for 1h+DEX), morphology, and SOD activity (77.33 ± 3.35 OD for 1d+DEX; 76.87 ± 3.59 OD for 1h+DEX at 1 h), while reducing ROS levels (2417.33 ± 345.49 RFU for 1d+DEX and 1843.00 ± 98.53 RFU at 4 h), especially in hOBs. The co-treatment of RSV or derivatives with DEX restored the expression of genes that were downregulated by DEX, such as HO-1 (1.76 ± 0.05 for 1d+DEX and 1.79 ± 0.01 for 1h+DEX), CAT (0.97 ± 0.06 for 1d+DEX and 0.99 ± 0.03 for 1h+DEX), NRF2 (1.62 ± 0.04 for 1d+DEX and 1.91 ± 0.05 for 1h+DEX), SOD1 (1.63 ± 0.15 for 1d+DEX and 1.69 ± 0.04 for 1h+DEX). In addition, 1d and 1h preserved collagen production (111.79 ± 1.56 for 1d+DEX and 122.27 ± 1.56 for 1h+DEX). In conclusion, this study suggests that the RSV derivatives 1d and 1h hold promise as potential antioxidant agents to counteract DEX-induced oxidative stress. These findings contribute to the development of novel therapeutic strategies for managing oxidative stress-related oral conditions. [ABSTRACT FROM AUTHOR]

In chaos control, one usually seeks to stabilize the unstable periodic orbits (UPOs) that densely inhabit the attractors of many chaotic dynamical systems. These orbits collectively play a significant role in determining the dynamics and properties of chaotic systems and are said to form the skeleton of the associated attractors. While UPOs are insightful tools for analysis, they are naturally unstable and, as such, are difficult to find and computationally expensive to stabilize. An alternative to using UPOs is to approximate them using cupolets. Cupolets, a name derived from chaotic, unstable, periodic, orbit-lets, are a relatively new class of waveforms that represent highly accurate approximations to the UPOs of chaotic systems, but which are generated via a particular control scheme that applies tiny perturbations along Poincaré sections. Originally discovered in an application of secure chaotic communications, cupolets have since gone on to play pivotal roles in a number of theoretical and practical applications. These developments include using cupolets as wavelets for image compression, targeting in dynamical systems, a chaotic analog to quantum entanglement, an abstract reducibility classification, a basis for audio and video compression, and, most recently, their detection in a chaotic neuron model. This review will detail the historical development of cupolets, how they are generated, and their successful integration into theoretical and computational science and will also identify some unanswered questions and future directions for this work. [ABSTRACT FROM AUTHOR]

Climate change has massive global impacts and affects a wide range of species. Threatened species such as the roan antelope (Hippotragus equinus) are particularly vulnerable to these changes because of their ecological requirements. Attempts to address concerns about the roan's vulnerability have not been well documented in South African protected areas. This study identifies the landscape use and distribution of the roan as well as habitat and forage suitability changes to help inform management decisions for the conservation of roan. We used fine- and broad-scale data from Mokala National Park, South Africa that includes roan occurrence data, vegetation condition indices, vegetation (structure and plant species composition), elevation and temperature differences, and precipitation strata to construct a suitability framework using the Maximum Entropy (Maxent) and Random Forest statistical package. In Mokala National Park, roan occurred in the Schmidtia pappophoroides–Vachellia erioloba sparse woodland, Senegalia mellifera–Vachellia erioloba closed woodland, Senegalia mellifera–Vachellia tortilis open shrubland, Vachellia erioloba–V. tortilis closed woodland and Rhigozum obovatum–Senegalia mellifera open shrubland. The veld (vegetation) condition index (VCI) improved from 2019 (VCI < 50%) to 2021 (VCI > 60%), with the proportion of palatable grass species (Schmidtia pappophoroides and Eragrostis lehmanniana) also increasing. This study identified four key climatic conditions affecting roan distribution, namely annual mean daily temperature range, temperature seasonality, minimum temperatures of the coldest month, and precipitation of the wettest month. These results suggest that the conservation of roan antelope should consider these key variables that affect their survival in preferred habitats and foraging areas in anticipation of changing ecological conditions. [ABSTRACT FROM AUTHOR]

The impact of soil fertilization with animal manure on the spread and persistence of antibiotic resistance in the environment is far from being fully understood. To add knowledge about persistence and correlations between antibiotic residues and antibiotic resistance genes (ARGs) in fertilized soil, a longitudinal soil mesocosm study was conducted. Soil samples were collected from the mesocosms immediately before spreading and then afterward at fifteen time points during a 320-day observation period. Eight ARGs (ermB, sul1, tetA, tetG, tetM, cfr, fexA, and optrA) and the class 1 integron-integrase gene, intI1, were determined in both pig slurry and soil, as well as residues of 36 antibiotics. Soil chemical and biochemical parameters were also measured. Twelve antibiotics were detected in the slurry in the range of 3 µg kg−1–3605 µg kg−1, with doxycycline, lincomycin, and tiamulin being the most abundant, whereas ermB, sul1, and tetM were the predominant ARGs. Before spreading, neither antibiotic residues nor ARGs were detectable in the soil; afterwards, their concentrations mirrored those in the slurry, with a gradual decline over the duration of the experiment. After about three months, the effect of the amendment was almost over, and no further evolution was observed. [ABSTRACT FROM AUTHOR]

Drug-induced liver disease (DILI) represents one of the main problems in the therapeutic field. There are several non-modifiable risk factors, such as age and sex, and all drugs can cause hepatotoxicity of varying degrees, including those for the treatment of inflammatory bowel diseases (IBD). The aim of this review is to illustrate the adverse effects on the liver of the various drugs used in the treatment of IBD, highlighting which drugs are safest to use based on current knowledge. The mechanism by which drugs cause hepatotoxicity is not fully understood. A possible cause is represented by the formation of toxic metabolites, which in some patients may be increased due to alterations in the enzymatic apparatus involved in drug metabolism. Various studies have shown that the drugs that can most frequently cause hepatotoxicity are immunosuppressants, while mesalazine and biological drugs are, for the most part, less associated with such complications. Therefore, it is possible to assume that in the future, biological therapies could become the first line for the treatment of IBD. [ABSTRACT FROM AUTHOR]

Simple Summary: Diffuse midline glioma (DMG), especially diffuse intrinsic pontine glioma (DIPG), is a deadly pediatric brain tumor that is difficult to diagnose and lacks any real treatment. These tumors often affect deep midline brain structures in young children, suggesting a connection to early brain development and differentiation. The H3K27M mutation triggers DIPG, impacting gene expression and brain development. Despite targeted drug interventions for gene mutations, the grim prognosis of the disease remains unaltered. DIPG patients typically succumb to the illness within 12 to 18 months post-diagnosis. Our review found over 85% of DIPG tumors have the K27M mutation in histone genes, driving abnormal growth. This mutation affects crucial brain processes, including the epithelial–mesenchymal transition pathway, potentially explaining differences between gliomas with and without K27M. The timing of these mutations is not known. One idea is that these mutations might have started during the early development of the brain before birth. Diffuse intrinsic pontine glioma (DIPG), now referred to as diffuse midline glioma (DMG), is a highly aggressive pediatric cancer primarily affecting children aged 4 to 9 years old. Despite the research and clinical trials conducted to identify a possible treatment for DIPG, no effective drug is currently available. These tumors often affect deep midline brain structures in young children, suggesting a connection to early brain development's epigenetic regulation targets, possibly affecting neural progenitor functions and differentiation. The H3K27M mutation is a known DIPG trigger, but the exact mechanisms beyond epigenetic regulation remain unclear. After thoroughly examining the available literature, we found that over 85% of DIPG tumors contain a somatic missense mutation, K27M, in genes encoding histone H3.3 and H3.1, leading to abnormal gene expression that drives tumor growth and spread. This mutation impacts crucial brain development processes, including the epithelial–mesenchymal transition (EMT) pathway, and may explain differences between H3K27M and non-K27M pediatric gliomas. Effects on stem cells show increased proliferation and disrupted differentiation. The genomic organization of H3 gene family members in the developing brain has revealed variations in their expression patterns. All these observations suggest a need for global efforts to understand developmental origins and potential treatments. [ABSTRACT FROM AUTHOR]

Background: In recent years, new technologies have been applied in cerebral palsy. Among these, immersive virtual reality is one with promising motor and cognitive effects along with the reduced costs of its application. The level of immersion of the subject in the illusional world gives the feeling of being a real part of the virtual environment. This study aims to investigate the safety and the efficacy of immersive virtual reality in children affected by cerebral palsy. Methods: PubMed, Embase, Cochrane Database of Systematic Reviews, RehabData, and Web of Science were screened up to February 2023 to identify eligible clinical studies. Results: Out of 788, we included 15 studies involving CP patients. There was high heterogeneity in the outcomes considered, and the results showed non-inferiority to conventional therapy and initial additional benefits in comparison with conventional rehabilitation. Conclusions: Immersive virtual reality emerges as a pivotal technological tool in rehabilitation, seamlessly integrating with conventional therapy within CP rehabilitation programs. Indeed, it not only enhances motivation but significantly increases children's functional capacity and abilities. [ABSTRACT FROM AUTHOR]

Chronic kidney disease poses a growing global health concern, as an increasing number of patients progress to end-stage kidney disease requiring kidney replacement therapy, presenting various challenges including shortage of care givers and cost-related issues. In this narrative essay, we explore innovative strategies based on in-depth literature analysis that may help healthcare systems face these challenges, with a focus on digital health technologies (DHTs), to enhance removal and ensure better control of broader spectrum of uremic toxins, to optimize resources, improve care and outcomes, and empower patients. Therefore, alternative strategies, such as self-care dialysis, home-based dialysis with the support of teledialysis, need to be developed. Managing ESKD requires an improvement in patient management, emphasizing patient education, caregiver knowledge, and robust digital support systems. The solution involves leveraging DHTs to automate HD, implement automated algorithm-driven controlled HD, remotely monitor patients, provide health education, and enable caregivers with data-driven decision-making. These technologies, including artificial intelligence, aim to enhance care quality, reduce practice variations, and improve treatment outcomes whilst supporting personalized kidney replacement therapy. This narrative essay offers an update on currently available digital health technologies used in the management of HD patients and envisions future technologies that, through digital solutions, potentially empower patients and will more effectively support their HD treatments. [ABSTRACT FROM AUTHOR]

The most frequent cause of periprosthetic infections (PJIs) is intraoperative contamination; hence, antibiotic prophylaxis plays a crucial role in prevention. Modifications to standard prophylaxis can be considered if there is a high incidence of microorganisms resistant to current protocols. To date, very few studies regarding microbial etiology have been published in Italy. In this single-center, retrospective study conducted at IRCCS Ospedale Galeazzi-Sant'Ambrogio in Milan, we analyzed hip, knee, and shoulder PJIs in patients undergoing first implantation between 1 January 17 and 31 December 2021. The primary aim was to derive a local microbiological case history. The secondary aim was to evaluate the adequacy of preoperative antibiotic prophylaxis in relation to the identified bacteria. A total of 57 PJIs and 65 pathogens were identified: 16 S. aureus, 15 S. epidermidis, and 10 other coagulase-negative staphylococci (CoNS), which accounted for 63% of the isolations. A total of 86.7% of S. epidermidis were methicillin-resistant (MRSE). In line with other case reports, we found a predominance of staphylococcal infections, with a lower percentage of MRSA than the Italian average, while we found a high percentage of MRSE. We estimated that 44.6% of the bacteria isolated were resistant to cefazolin, our standard prophylaxis. These PJIs could be prevented by using glycopeptide alone or in combination with cefazolin, but the literature reports conflicting results regarding the adequacy of such prophylaxis. In conclusion, our study showed that in our local hospital, our standard antibiotic prophylaxis is ineffective for almost half of the cases, highlighting the importance of defining specific antibiotic guidelines based on the local bacterial prevalence of each institution. [ABSTRACT FROM AUTHOR]

Background: Mental capacity is a fundamental aspect that enables patients to fully participate in various healthcare procedures. To assist healthcare professionals (HCPs) in assessing patients' capacity, especially in the mental health field, several standardized tools have been developed. These tools include the MacArthur Competence Assessment Tool for Treatment (MacCAT-T), the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR), and the Competence Assessment Tool for Psychiatric Advance Directives (CAT-PAD). The core dimensions explored by these tools include Understanding, Appreciation, Reasoning, and Expression of a choice. Objective: This meta-analysis aimed to investigate potential differences in decision-making capacity within the healthcare context among groups of patients with bipolar disorders (BD) and schizophrenia spectrum disorders (SSD). Methods: A systematic search was conducted on Medline/Pubmed, and Scopus. Additionally, Google Scholar was manually inspected, and a manual search of emerging reviews and reference lists of the retrieved papers was performed. Eligible studies were specifically cross-sectional, utilizing standardized assessment tools, and involving patients diagnosed with BD and SSD. Data from the studies were independently extracted and pooled using random-effect models. Hedges' g was used as a measure for outcomes. Results: Six studies were identified, with three studies using the MacCAT-CR, two studies the MacCAT-T, and one the CAT-PAD. The participants included 189 individuals with BD and 324 individuals with SSD. The meta-analysis revealed that patients with BD performed slightly better compared to patients with SSD, with the difference being statistically significant in the domain of Appreciation (ES = 0.23, 95% CI: 0.01 to 0.04, p = 0.037). There was no statistically significant difference between the two groups for Understanding (ES = 0.09, 95% CI:−0.10 to 0.27, p = 0.352), Reasoning (ES = 0.18, 95% CI: −0.12 to 0.47, p = 0.074), and Expression of a choice (ES = 0.23, 95% CI: −0.01 to 0.48, p = 0.60). In the sensitivity analysis, furthermore, when considering only studies involving patients in symptomatic remission, the difference for Appreciation also resulted in non-significant (ES = 0.21, 95% CI: −0.04 to 0.46, p = 0.102). Conclusions: These findings indicate that there are no significant differences between patients with BD and SSD during remission phases, while differences are minimal during acute phases. The usefulness of standardized assessment of capacity at any stage of the illness should be considered, both for diagnostic-therapeutic phases and for research and advance directives. Further studies are necessary to understand the reasons for the overlap in capacity between the two diagnostic categories compared in this study. [ABSTRACT FROM AUTHOR]

Purpose: Errors and incidents may occur at any point within radiotherapy (RT). The aim of the present retrospective analysis is to evaluate the impact of a customized ARIA Visual Care Path (VCP) on quality assurance (QA) for the RT process. Materials and Methods: The ARIA VCP was implemented in June 2019. The following tasks were customized and independently verified (by independent checks from radiation oncologists, medical physics, and radiation therapists): simulation, treatment planning, treatment start verification, and treatment completion. A retrospective analysis of 105 random and unselected patients was performed, and 945 tasks were reviewed. Patients' reports were categorized based on treatment years period: 2019–2020 (A); 2021 (B); and 2022–2023 (C). The QA metrics included data for timeliness of task completion and data for minor and major incidents. The major incidents were defined as incorrect prescriptions of RT dose, the use of different immobilization systems during RT compared to the simulation, the absence of surface-guided RT data for patients' positioning, incorrect dosimetric QA for treatment plans, and failure to complete RT as originally planned. A sample size of approximately 100 was able to obtain an upper limit of 95% confidence interval below 5–10% in the case of zero or one major incident. Results: From June 2019 to December 2023, 5300 patients were treated in our RT department, an average of 1300 patients per year. For the purpose of this analysis, one hundred and five patients were chosen for the study and were subsequently evaluated. All RT staff achieved a 100% compliance rate in the ARIA VCP timely completion. A total of 36 patients were treated in Period A, 34 in Period B, and 35 in Period C. No major incidents were identified, demonstrating a major incident rate of 0.0% (95% CI 0.0–3.5%). A total of 26 out of 945 analyzed tasks (3.8%) were reported as minor incidents: absence of positioning photo in 32 cases, lack of patients' photo, and absence of plan documents in 4 cases. When comparing periods, incidents were statistically less frequent in Period C. Conclusions: Although the present analysis has some limitations, its outcomes demonstrated that software for the RT workflow, which is fully integrated with both the record-and-verify and treatment planning systems, can effectively manage the patient's care path. Implementing the ARIA VCP improved the efficiency of the RT care path workflow, reducing the risk of major and minor incidents. [ABSTRACT FROM AUTHOR]

Antiphospholipid syndrome (APS) is a thromboinflammatory disorder caused by circulating antiphospholipid autoantibodies (aPL) and characterized by an increased risk of thrombotic events. The pathogenic mechanisms of these antibodies are complex and not fully understood, but disturbances in coagulation and fibrinolysis have been proposed to contribute to the thrombophilic state. This study aims to evaluate the role of an emerging hemostatic molecule, FXI, in the thrombotic risk of patients with aPL. Cross-sectional and observational study of 194 consecutive and unrelated cases with aPL recruited in a single center: 82 asymptomatic (AaPL) and 112 with primary antiphospholipid syndrome (APS). Clinical and epidemiological variables were collected. The profile of aPL was determined. Plasma FXI was evaluated by Western blotting and two coagulation assays (FXI:C). In cases with low FXI, molecular analysis of the F11 gene was performed. FXI:C levels were significantly higher in patients with APS than in patients with AaPL (122.8 ± 33.4 vs. 104.5 ± 27.5; p < 0.001). Multivariate analysis showed a significant association between symptomatic patients with aPL (APS) and high FXI (>150%) (OR = 11.57; 95% CI: 1.47–90.96; p = 0.020). In contrast, low FXI (<70%), mostly caused by inhibitors, was less frequent in the group of patients with APS compared to AaPL (OR = 0.17; 95%CI: 0.36–0.86; p = 0.032). This study suggests that FXI levels may play a causal role in the prothrombotic state induced by aPLs and holds the promise of complementary treatments in APS patients by targeting FXI. [ABSTRACT FROM AUTHOR]

Previous evidence associates insulin resistance with arterial stiffness in various pathologies, yet limited reports exist in healthy adults. Therefore, this study aims to estimate the association between insulin resistance and arterial stiffness in healthy adults. The cross-sectional EVasCu study enrolled 390 participants (42.05 ± 13.15 years). ANCOVAs, unadjusted (model 1) and adjusted (model 2), explored the association between arterial stiffness markers (aortic Pulse Wave Velocity [aPWV], Augmentation Index [AIx@75] and Cardio-Ankle Vascular Index [CAVI]), and insulin resistance markers (Homeostasis Model Assessment of Insulin Resistance [HOMA-IR], Quantitative Insulin Sensitivity Check Index [QUICKI] and Triglycerides-Glucose [TyG]). In model 1, all insulin resistance markers were associated with aPWV, HOMA-IR and QUICKI were associated with AIx@75, and the TyG index was associated with CAVI. In model 2, HOMA-IR and QUICKI increased aPWV by 0.179 and 0.156 m/s (p = 0.001 and p = 0.011), and AIx@75 by 4.17 and 5.39% (p = 0.009 and p = 0.003). The EVasCu study offers valuable insights into the relationship between insulin resistance and arterial stiffness in healthy adults, providing a deeper understanding of metabolic and cardiovascular health. By examining this influence, we embark on an intriguing exploration of how these factors interplay in the human body. [ABSTRACT FROM AUTHOR]

The growing interest in functional foods is driven by the exploration of new foods with positive health effects. Pleasant sensory features are essential for consumer acceptance. In this work, we investigated the composition of the bioactive compounds, antioxidant activity, and aroma profiles of four edible flowers: Cucurbita moschata Duchesne, Dianthus chinensis L., Fuchsia regia (Vand. ex Vell.) Munz., and Viola cornuta L. For the first time, we quantified the water-soluble group of B vitamins. Significant variations in the content of soluble sugars, vitamins, and secondary metabolites were observed. V. cornuta showed the highest concentration of vitamin C and carotenoids, while C. moschata had the highest content of vitamin B and flavonoids. F. regia stood out for its exceptionally high content of total phenolics, while D. chinensis surpassed the other flowers in soluble sugar content. The aroma profile analysis revealed a diverse array of volatile organic compounds, with each species having its own unique composition. C. moschata was characterized by p-dimethoxybenzene and D. chinensis by non-terpene compounds; F. regia displayed high amounts of decanal and nonanal, while V. cornuta was rich in myrcene and α-farnesene. These findings provide valuable insights into the secondary metabolites and aroma profiles of these flowers, enhancing our understanding of their bioactive compounds and potential health benefits. [ABSTRACT FROM AUTHOR]

Background: Spasticity is a motor disorder characterised by exaggerated movements of the tendons and accompanied by hyperreflexia and hypertonia. Extracorporeal shock wave therapy (ESWT) is used as a treatment for spasticity, although more evidence is needed on the effectiveness of this therapy in the treatment of spasticity. Therefore, the aim of this study was to assess the effectiveness ESWT in the treatment of upper and lower limbs spasticity in both children and adults through different aetiologies. Methods: A systematic search was performed in different databases from inception to December 2023. Random-effects meta-analysis was used to estimate the efficacy of ESWT on spasticity using the Modified Ashworth Scale. Results: Sixteen studies were included in the systematic review and meta-analysis. The effect of ESWT on spasticity measured with the Modified Ashworth Scale shows a significant decrease in spasticity in the upper limbs and in the lower limbs in adults with chronic stroke and in children with cerebral palsy, is more effective immediately after application, and maintains its effect up to 12 weeks post treatment. Conclusions: These findings are important for clinical practice since they show evidence that ESWT is effective in reducing spasticity in both children and adults. [ABSTRACT FROM AUTHOR]

(1) Background: the scientific literature has shown that students' active involvement in the teaching–learning process significantly improves their learning outcomes. (2) Methods: this study shows the perceptions of seven researchers on the process of inquiring about the effects of the combined use of virtual reality (VR) and a practice teaching style in physical education in secondary educational institutions. (3) Results: the results obtained from the researchers' diaries and the focus group, through qualitative design, are arranged in the following categories: difficulties in data collection before, during, and after the intervention; perceived differences between VR interventions in laboratory situations and educational contexts; and the perceived transferability of the use of VR devices in the educational context. (4) Conclusions: more research is needed on the use of VR in the educational context, although the results obtained indicate that the teaching–learning process can be enriched by overcoming the difficulties inherent to the use of this technology in a variable context such as education. [ABSTRACT FROM AUTHOR]

Quality control testing of vaccines, including potency assessment, is critical to ensure equivalence of clinical lots. We developed a potency assay to support the clinical advancement of Nous-209, a cancer vaccine based on heterologous prime/boost administration of two multivalent viral vector products: GAd-209 and MVA-209. These consist of a mix of four Adeno (Great Ape Adenovirus; GAd) and four Modified Vaccinia Ankara (MVA) vectors respectively, each containing a different transgene encoding a synthetic polypeptide composed of antigenic peptide fragments joined one after the other. The potency assay employs quantitative Reverse Transcription PCR (RT-Q-PCR) to quantitatively measure the transcripts from the four transgenes encoded by each product in in vitro infected cells, enabling simultaneous detection. Results showcase the assay's robustness and biological relevance, as it effectively detects potency loss in one component of the mixture comparably to in vivo immunogenicity testing. This report details the assay's setup and validation, offering valuable insights for the clinical development of similar genetic vaccines, particularly those encoding synthetic polypeptides. [ABSTRACT FROM AUTHOR]

Thermal bridges significantly influence the energy performance of buildings. However, their impact varies depending on the type of thermal bridge, climate conditions, construction methodologies, and geometric characteristics of the building. On the Spanish Mediterranean coast, buildings with large balconies are predominant. Nevertheless, the Spanish energy efficiency regulations do not adequately specify the thermal bridges at the junctions of balconies with facades, leading to a lack of consideration for their influence in the majority of architectural projects. The objective of this study is to qualitatively and quantitatively assess the impact of such thermal bridges on the energy efficiency of buildings in a dry Mediterranean climate (BShs) within a warm semi-arid climate (BSh). As a case study, the influence of this thermal bridge is analyzed in two residential buildings located on the Mediterranean coast of southeastern Spain. The study also examines the modification of various construction parameters of this thermal bridge and determines the optimal design parameters to reduce its thermal transmittance. The results demonstrate that the energy needs caused by thermal bridges account for approximately 40% of the total annual energy needs of the studied residential buildings. Balcony thermal bridges account for 25% to 40% of the energy needs caused by all thermal bridges. The lack of differentiation in Spanish standards between balcony–facade and facade–slab edge junctions causes an imprecision in calculations equivalent to 12% of the total annual energy needs of dwellings. The novelty of this research lies in highlighting that current regulations and calculation programs need improvement to better characterize balcony thermal bridges and enhance the accuracy of building energy efficiency calculations. [ABSTRACT FROM AUTHOR]

Millet, a gluten-free cereal, has received attention for its environmental friendliness and higher protein content than other grains. It represents a staple food in many African countries, where fermentation is traditionally used for preserving food products and preparing different cereal-based products. This study aimed to assess the impact of sourdough fermentation on bioactive compounds and antioxidant and anti-inflammatory properties of pearl millet from Burkina Faso. Phenolic compounds were investigated spectrophotometrically and by HPLC-DAD. The antioxidant activity of unfermented (MF) and fermented (FeMF) millet was evaluated in vitro by spectrophotometric and fluorometric assays and ex vivo on oxidized human erythrocytes for hemolysis inhibition. Finally, the potential anti-inflammatory effect of FeMF and MF was evaluated on human adenocarcinoma cell line (HT-29) exposed to TNF-α inflammatory stimulus. Results revealed significantly higher levels of polyphenols, flavonoids, and in vitro antioxidant activity following millet fermentation. Notable differences in phenolic composition between FeMF and MF are observed, with fermentation facilitating the release of bioactive compounds such as gallic acid, quercetin, and rutin. A dose-dependent protection against oxidative hemolysis was observed in both FeMF- and MF-pretreated erythrocytes. Similarly, pretreatment with FeMF significantly reduced the levels of inflammatory markers in TNF-α-treated cells, with effects comparable to those of MF. Fermentation with sourdough represents a simple and low-cost method to improve the bioactive compounds content and in vitro antioxidant activity of millet flour with promising nutraceutical potential. [ABSTRACT FROM AUTHOR]

Simple Summary: In this review, we will analyze the main mutations predominant in the various histotypes of salivary gland carcinomas, we will discover whether they behave as driver mutations, and finally we will make hypotheses relating to the best targeted therapy to be used in salivary gland carcinomas, apart from polychemotherapy. Salivary gland carcinomas (SGCs) are rare neoplasms, representing less than 10% of all head and neck tumors, but they are extremely heterogeneous from the histological point of view, their clinical behavior, and their genetics. The guidelines regarding their treatment include surgery in most cases, which can also play an important role in oligometastatic disease. Where surgery cannot be used, systemic therapy comes into play. Systemic therapy for many years has been represented by polychemotherapy, but recently, with the affirmation of translational research, it can also count on targeted therapy, at least in some subtypes of SGCs. Interestingly, in some SGC histotypes, predominant mutations have been identified, which in some cases behave as "driver mutations", namely mutations capable of governing the carcinogenesis process. Targeting these driver mutations may be an effective therapeutic strategy. Nonetheless, it is not always possible to have drugs suitable for targeting driver mutations—and targeting driver mutations is not always accompanied by a clinical benefit. In this review, we will analyze the main mutations predominant in the various histotypes of SGCs. [ABSTRACT FROM AUTHOR]

This mixed-method study examined the impact of combining virtual reality (VR) and gamification (GAM) with the practice teaching style (PTS) on students' motor skills and perceived effort in physical education. Participants (n = 75) were divided into three groups: PTS (control), PTS + GAM and PTS + GAM + VR. Each group had two one-hour sessions per week for six weeks. Participants' motor skills and perceived effort were evaluated quantitatively and qualitatively using tests such as the SportComp Motor, flamingo and plate-tapping tests, as well as the handgrip strength test and the Pictorical Children's Effort Rating Table. The results indicate that the PTS group reported a higher perceived effort compared to the other groups (p < 0.001). All study groups exhibited improvements in the handgrip strength (p < 0.001) and flamingo (p < 0.05) tests, while lateral jump test improvements were observed only in the two GAM groups (p < 0.001). The VR group showed an improvement in the plate-tapping tests (p < 0.001), while the PTS group exhibited a decline in the displacement with support test (p < 0.05). Participant perceptions suggest that the activity nature, motivation from competition and rewards influenced the perceived effort and motor skills. In conclusion, GAM techniques are effective in reducing perceived effort in physical education programs, and combining GAM with VR enhances improvements in motor skills. [ABSTRACT FROM AUTHOR]

Chagas disease and leishmaniasis are among the most widespread neglected tropical diseases, and their current therapies have limited efficacy and several toxic side effects. The present study reports the chemical and antikinetoplastid profiles of extracts from five Salvadoran Celastraceae species against the Trypanosoma cruzi epimastigotes stage and Leishmania amazonensis and Leishmania donovani promastigote forms. The phytochemical profile evinced the presence of flavonoids, tannins, sterols, and triterpenes as the main components in all plant species, whereas quinonemethide triterpenoids (QMTs) were restricted to the root bark of the studied species. Antikinetoplastid evaluation highlights the root bark extracts from Zinowewia integerrima, Maytenus segoviarum, and Quetzalia ilicina as the most promising ones, exhibiting higher potency against T. cruzi (IC50 0.71–1.58 µg/mL) and L. amazonensis (IC50 0.38–2.05 µg/mL) than the reference drugs, benznidazole (IC50 1.81 µg/mL) and miltefosine (IC50 2.64 µg/mL), respectively. This potent activity was connected with an excellent selectivity index on the murine macrophage J774A.1 cell line. These findings reinforce the potential of QMTs as antikinetoplastid agents for the development of innovative phytopharmaceuticals and the plant species under study as a source of these promising lead compounds. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the ability of photodynamic therapy, based on the use of a gel containing 5% delta aminolaevulinic acid (ALAD) for 45′ followed by irradiation with 630 nm LED (PDT) for 7′, to eradicate Candida albicans strains without damaging the gingiva. C. albicans oral strains and gingival fibroblasts (hGFs) were used to achieve these goals. The potential antifungal effects on a clinical resistant C. albicans S5 strain were evaluated in terms of biofilm biomass, colony forming units (CFU/mL) count, cell viability by live/dead analysis, and fluidity membrane changes. Concerning the hGFs, viability assays, morphological analysis (optical, scanning electronic (SEM), and confocal laser scanning (CLSM) microscopes), and assays for reactive oxygen species (ROS) and collagen production were performed. ALAD-mediated aPDT (ALAD-aPDT) treatment showed significant anti-biofilm activity against C. albicans S5, as confirmed by a reduction in both the biofilm biomass and CFUs/mL. The cell viability was strongly affected by the treatment, while on the contrary, the fluidity of the membrane remained unchanged. The results for the hGFs showed an absence of cytotoxicity and no morphological differences in cells subjected to ALAD-aPDT expected for CLSM results that exhibited an increase in the thickening of actin filaments. ROS production was augmented only at 0 h and 3 h, while the collagen appeared enhanced 7 days after the treatment. [ABSTRACT FROM AUTHOR]

Organs-on-a-chip (OoCs) are microfluidic devices constituted by PDMS or hydrogel in which different layers of cells are separated by a semipermeable membrane. This technology can set many parameters, like fluid shear stress, chemical concentration gradient, tissue–organ interface, and cell interaction. The use of these devices in medical research permits the investigation of cell patterning, tissue–material interface, and organ–organ interaction, mimicking the complex structures and microenvironment of human and animal bodies. This technology allows us to reconstitute in vitro complex conditions that recapitulate in vivo environments. One of the main advantages of these systems is that they represent a very realistic model that, in many cases, can replace animal experimentation, eliminating costs and related ethical issues. Organ-on-a-chip can also contain bacteria or cancer cells. This technology could be beneficial in dentistry for testing novel antibacterial substances and biomaterials, performing studies on inflammatory disease, or planning preclinical studies. A significant number of publications and reviews have been published on this topic. Still, to our knowledge, they mainly focus on the materials used for fabrication and the different patterns of the chip applied to the experimentations. This review presents the most recent applications of organ-on-a-chip models in dentistry, starting from the reconstituted dental tissues to their clinical applications and future perspectives. [ABSTRACT FROM AUTHOR]

Hydrogen fuel-cell systems are one of the alternatives for the decarbonization of the transportation sector. In such systems, the usage of O 2 -enriched air has the potential to improve fuel cell performance as well as to reduce degradation phenomena linked to local O 2 starvation. However, the production of an O 2 -enriched air stream implies energy consumption that needs to be evaluated in the overall system efficiency. In this study, the potential of a system including polymeric membranes for O 2 -N 2 separation to produce O 2 -enriched air was evaluated theoretically. First, the balance of plant, including the O 2 -N 2 separation membrane and a two-stage boosting system, was considered. Two sources of energy recovery were identified: a high-pressure H 2 stream and retentate flow (N 2 -rich) at the outlet of the separation membrane. Then, the efficiency of the system was evaluated for different levels of O 2 enrichment, with sensitivities to the main operational and design parameters, i.e., cathode excess O 2 ratio, turbomachinery efficiency, essure ratios. The results show the potential for an O 2 -enriched system if the energy recovered reaches approximately 25% of the additional power consumption induced by the separation membrane. [ABSTRACT FROM AUTHOR]

The present paper describes the preparation and characterization of novel microbeads from alginate filled with nanoclay such as halloysite nanotubes (HNTs). HNTs were used as support for the growth of layered double hydroxide (LDH) crystals producing a flower-like structure (HNT@LDH). Such nanofiller was loaded with grapefruit seed oil (GO), an active compound with antimicrobial activity, up to 50% wt. For comparison, the beads were also loaded with HNT and LDH separately, and filled with the same amount of GO. The characterization of the filler was performed using XRD and ATR spectroscopy. The beads were analyzed through XRD, TGA, ATR and SEM. The functional properties of the beads, as nanocarriers of the active compound, were investigated using UV-vis spectroscopy. The release kinetics were recorded and modelled as a function of the structural characteristics of the nanofiller. [ABSTRACT FROM AUTHOR]