Search

BackgroundAnkle instability results in sensory and motor impairments. Typically, health professionals recommend conservative treatment as the initial approach for individuals with this condition. One such treatment option is Electrical Stimulation (ES). This systematic review assesses the effects of ES techniques on postural control measures in cases of ankle instability.MethodWe systematically searched five electronic databases: ClinicalTrials.gov, PubMed, Scopus, SPORTDiscus, and Web of Science. To evaluate the quality of the included articles, we utilized the PEDro checklist. We extracted data on population, intervention, and outcomes and synthesized them narratively.ResultES decreased the time needed to stabilize the center of pressure, velocity, displacement, and area, thereby enhancing the performance of clinical tests. While postural stability indexes remained unaffected, the gait inversion angle increased with electrical stimulation.ConclusionThese results suggest that ES interventions are crucial in enhancing postural control in subjects with ankle instability compared to coordination exercises therapy alone. Stochastic resonance reduced A/P and M/L TTS, COP velocity, COP displacement, and COP area, resulting in enhanced postural control.

Abstract Huntington’s disease (HD) causes selective degeneration of striatal and cortical neurons, resulting in cell mosaicism of coexisting still functional and dysfunctional cells. The impact of non-cell autonomous mechanisms between these cellular states is poorly understood. Here we generated telencephalic organoids with healthy or HD cells, grown separately or as mosaics of the two genotypes. Single-cell RNA sequencing revealed neurodevelopmental abnormalities in the ventral fate acquisition of HD organoids, confirmed by cytoarchitectural and transcriptional defects leading to fewer GABAergic neurons, while dorsal populations showed milder phenotypes mainly in maturation trajectory. Healthy cells in mosaic organoids restored HD cell identity, trajectories, synaptic density, and communication pathways upon cell-cell contact, while showing no significant alterations when grown with HD cells. These findings highlight cell-type-specific alterations in HD and beneficial non-cell autonomous effects of healthy cells, emphasizing the therapeutic potential of modulating cell-cell communication in disease progression and treatment.

The Visceral Sensitivity Index (VSI) represents a significant advancement in the assessment of gastrointestinal-specific anxiety among patients with irritable bowel syndrome (IBS) and chronic inflammatory bowel diseases (IBD)—such as ulcerative colitis and Crohn’s disease. However, an Italian version of the instrument is not yet available for the Italian-speaking population. This study utilized a national sample of 500 individuals divided into four groups: (a) patients with Crohn’s disease, (b) patients with ulcerative colitis, (c) patients with IBS, and (d) healthy controls (individuals without any diagnoses) to test the validity and reliability of the Italian VSI. Using back-translation methodology to ensure translation fidelity, this research applied a questionnaire and the VSI through an online format to 500 participants. Confirmatory Factor Analysis (CFA) revealed that the Italian VSI had excellent psychometric properties, demonstrating high internal consistency (Cronbach’s α = 0.949) and construct validity. The scale proved sensitive in detecting significant differences in visceral sensitivity among groups, highlighting its utility as a clinical and research assessment tool. Specifically, the Italian VSI exhibited a unidimensional factorial structure and maintained a strong correlation with interoceptive awareness, type of disease, and gastrointestinal symptom severity, confirming its role in enhancing the understanding and management of IBD and IBS in Italy.

Abstract Extracellular vesicles (EVs) are a new mechanism of cellular communication, by delivering their cargo into target cells to modulate molecular pathways. EV-mediated crosstalk contributes to tumor survival and resistance to cellular stress. However, the role of EVs in B-cell Acute Lymphoblastic Leukaemia (B-ALL) awaits to be thoroughly investigated. We recently published that ActivinA increases intracellular calcium levels and promotes actin polymerization in B-ALL cells. These biological processes guide cytoskeleton reorganization, which is a crucial event for EV secretion and internalization. Hence, we investigated the role of EVs in the context of B-ALL and the impact of ActivinA on this phenomenon. We demonstrated that leukemic cells release a higher number of EVs in response to ActivinA treatment, and they can actively uptake EVs released by other B-ALL cells. Under culture-induced stress conditions, EVs coculture promoted cell survival in B-ALL cells in a dose-dependent manner. Direct stimulation of B-ALL cells with ActivinA or with EVs isolated from ActivinA-stimulated cells was even more effective in preventing cell death. This effect can be possibly ascribed to the increase of vesiculation and modifications of EV-associated microRNAs induced by ActivinA. These data demonstrate that ActivinA boosts EV-mediated B-ALL crosstalk, improving leukemia survival in stress conditions.

Non-alcoholic fatty liver disease (NAFLD), redefined as Metabolic Associated Fatty Liver Disease (MAFLD), is characterized by an extensive multi-organ involvement. MAFLD-induced systemic inflammatory status and peripheral metabolic alteration lead to an impairment of cerebral function. Herein, we investigated a panel of leptin-related inflammatory mediators as predictive biomarkers of neuroinflammation and evaluated the possible role of Bergamot Polyphenolic Fraction (BPF) in counteracting this MAFLD-induced inflammatory cascade. Male DIAMOND mice were randomly assigned to fed chow diet and tap water or high fat diet with sugar water. Starting from week 16, mice were further divided and treated with vehicle or BPF (50 mg/kg/day), via gavage, until week 30. Magnetic resonance imaging was performed at the baseline and at week 30. Correlation and regression analyses were performed to discriminate the altered lipid metabolism in the onset of cerebral alterations. Steatohepatitis led to an increase in leptin levels, resulting in a higher expression of proinflammatory mediators. The inflammatory biomarkers involved in leptin/CCL3-CCL4 axes were correlated with the altered thalamus energetic metabolism and the white matter degeneration. BPF administration restored leptin level, improved glucose and lipid metabolism, and reduced chronic low-grade inflammatory mediators, resulting in a prevention of white matter degeneration, alterations of thalamus metabolism and brain atrophy. The highlighted positive effect of BPF, mediated by the downregulation of the inflammatory biomarkers involved in leptin/CCL3-CCL4 axes, affording novel elements to candidate BPF for the development of a therapeutic strategy aimed at counteracting MAFLD-related brain inflammation.

Background: While many studies have explored the direct impact of psychosocial factors on affective experiences, there remains a gap in understanding the specific factors that mediate the relationships between social support and affective outcomes. Objective: The present study aimed to investigate the mediating role of self-esteem in the association between social support and affective experiences among a sample of Turkish undergraduate students. Method: The study utilized an online survey to recruit 300 participants, with a majority of female participants (59.33 %). The age of the participants ranged from 18 to 28 years (Mage = 21.15; SD = 1.86). Participants completed the Multidimensional Scale of Perceived Social Support (Zimet et al., 1988), the Rosenberg Self-Esteem Scale (Rosenberg, 1965), and the Scales of Positive and Negative Experiences (Diener et al., 2010). Results: The mediation model with bootstrapping technique analysis revealed that social support was significantly associated with self-esteem and positive affective experiences. Self-esteem was also significantly associated with both positive and negative affective experiences. Additionally, self-esteem was found to partially mediate the relationship between social support and both positive and negative affective experiences, indicating that self-esteem acted as a mediator in these associations. Conclusions: These findings contribute to our understanding of the association between social support, self-esteem, and affective experiences and have implications for the development and implementation of interventions aimed at enhancing the positive effects of social support and self-esteem on affective experiences among young adults.

The fear of being without a mobile phone, known as nomophobia, is a new psychological issue that has arisen with the widespread use of information and communication technologies. To understand this phenomenon, more research is needed. The present study aimed to assess the factor structure of the Moroccan dialect version of the Nomophobia Questionnaire (NMP-Q) among a sample of Moroccan university students. The study included 400 students selected by convenience sampling from two universities (Fez and Rabat). First, an Exploratory Factor Analysis (EFA) was conducted using the principal component method with Varimax rotation. Then, a Confirmatory Factor Analysis (CFA), and Exploratory Structural Equation Modeling (ESEM) were carried out. The results showed that a 20-item, four-factor model was the best fit for the data collected from the sample, indicating cross-cultural validity and the robustness of the NMP-Q's structure. This suggests that the Moroccan version of the NMP-Q is useful for assessing nomophobia behavior among Moroccan university students.

Background: To analyze the anatomical characteristics of a posterior area in the mandible localized distally to the second molars and extending in the vestibular direction toward the bony step, which we define as “buccal step”, in a patient with different skeletal patterns for mini-screw insertion. Methods: The sample included 85 CBCT (cone beam computed tomography) records selected from the digital archive. Analysis focused on the buccal step area. Sections were obtained in axial view using reference lines, and measurements of cortical and total bone were taken at specific points M0 (starting point, 6 mm apical from CEJc—cementoenamel junction crest), M2 (located 2 mm posterior to M0 in the apical direction), and M4 (positioned 4 mm posterior to M0 in the apical direction) in both directions. Six measurements were recorded for each scan root plane, assessing cortical and total bone depth. Results: The thickness of the bone increases toward the inside of the mouth at all tested sites (M0, M2, M4), which is good for placing mini-screws. Cortical bone thickness decreases toward the inside of the mouth, with no significant differences among the sites except for M0 vs. M4. People with a particular jaw shape (hypo-divergent) have a thicker cortical bone, indicating that facial structure affects bone thickness. Conclusions: The posterior buccal step insertion site has biomechanical advantages and reduces the risk of damaging roots during mini-screw insertions.

Abstract Objective The Education and Career Task Force of the Young Epilepsy Section‐Italy focuses on educational and career development needs of young Italian epileptologists. Two surveys were developed (pre‐ and post COVID‐19 pandemic) in order to identify the needs of members of the Lega Italiana Contro l'Epilessia under 40 years of age. Methods The first was distributed during the 42nd National Congress (Rome, June 5–7, 2019); the second during the 45th National Congress (Padova, June 8–10, 2022) and subsequently by e‐mail until July 9, 2022. Data from the 2019 survey were analyzed descriptively. Data from the 2022 survey were further analyzed with Pearson's chi‐square test to establish if gender, field of clinical practice, and professional role were associated with different needs. Results Sixty surveys were completed in 2019 and 69 in 2022. Attendance to courses and congresses as the preferred way to keep medical knowledge updated reduced between 2019 and 2022. The reason was different between trainees (mostly elevated costs) and early‐career consultants (mostly organizational issues) (p = 0.005). The main needs for improvement also diverged: trainees indicated differential diagnosis and diagnostic approach to the first seizure while consultants indicated diagnostic approach to genetic epilepsies (p = 0.004); in the genetic field, priority needs were selection of genetic investigations for trainees versus genotype–phenotype correlations for consultants (p = 0.022). The field of practice (pediatric vs. adult) also impacted on the main needs for improvement that is, acquisition of expertise in neuroradiology and drug therapy for pediatric versus genetics for adult neurology trainees or consultants (p = 0.018); in the clinical area, differential diagnosis and approach to the first seizure versus status epilepticus (p = 0.027); in the genetic field, precision medicine versus genotype–phenotype correlations (p = 0.034). No differences were found based on gender. Significance The surveys identified different needs based on professional role and discipline. Plain Language Summary The Education and Career Task Force of the Young Epilepsy Section‐Italy (YES‐I) launched two surveys among young Italian epileptologists. Our research shows that the educational and professional needs of young Italian epileptologists vary based on their job role and field of practice, but not on gender. Their preference for on‐site congresses and courses reduced after the pandemic, and the main reason is linked to financial constraints for trainees and to organizational issues for consultants. The main expectation toward YES‐I is to receive support for education and career development. Thus, we collected useful suggestions on how to organize our future YES‐I activities.

The REarranged during Transfection (RET) receptor tyrosine kinase plays a crucial role in the development of various anatomical structures during embryogenesis and it is involved in many physiological cellular processes. This protein is also associated with the initiation of various cancer types, such as thyroid cancer, non-small cell lung cancer, and multiple endocrine neoplasms. In breast cancer, and especially in the estrogen receptor-positive (ER+) subtype, the activity of RET is of notable importance. Indeed, RET seems to be involved in tumor progression, resistance to therapies, and cellular proliferation. Nevertheless, the ways RET alterations could impact the prognosis of breast cancer and its response to treatment remain only partially elucidated. Several inhibitors of RET kinase have been developed thus far, with various degrees of selectivity toward RET inhibition. These molecules showed notable efficacy in the treatment of RET-driven tumors, including some breast cancer cases. Despite these encouraging results, further investigation is needed to fully understand the potential role RET inhibition in breast cancer. This review aims to recapitulate the existing evidence about the role of RET oncogene in breast cancer, from its pathogenic and potentially prognostic role, to the clinical applications of RET inhibitors.

Background: Aging implies changes in terms of lung function, immune system, and respiratory and extra-respiratory comorbidities. Few studies have specifically addressed the relevance of age on severe asthma burden and control. We aimed to evaluate whether age acts as an independent determinant of asthma severity, in terms of clinical, functional, and inflammatory profile, and to explore potential cofactors that contribute to a more difficult disease control in different age groups. Methods: Patients from Severe Asthma Network Italy (SANI) registry were retrospectively divided in subgroups according to their age. Cutoffs for age were established according to quartiles in order to obtain a comparable number of patients for each group, and then rounded for the sake of simplicity. Results: Overall, 1805 severe asthma patients were analyzed. Lung function represented the most important age-related variable. On the opposite the level of asthma control was not differently distributed among age ranges. In young people the presence of atopy-related comorbidities (allergic rhinitis, atopic dermatitis) predominated, whilst systemic-metabolic and degenerative comorbidities such as diabetes, cardiovascular diseases, anxious-depressive syndrome, and osteoporosis prevailed in elderly. Bronchiectasis and sleep disturbances were significantly associated with age. Conclusions: Despite that it cannot be considered a treatable trait, our study suggests that age should be evaluated within a personalized approach to severe asthma patients, in order to provide a better clinical profiling and a more tailored treatment strategy.

Background and aim: Variation in practice has been observed among the prescribed diets for inpatients with acute, uncomplicated diverticulitis. This study aimed to observe outcomes (length of stay (LOS), re-presentations, and gastrointestinal symptoms) for acute, uncomplicated diverticulitis inpatients prescribed restricted or liberalised diets during usual care. Methods: Adult inpatients with acute, uncomplicated diverticulitis were prospectively enrolled from 2017 to 2019. Demographics, clinical data, and prescribed diets were collected from medical records. Patients were categorised as having restricted or liberalised diets. Primary outcomes were LOS, re-presentations related to diverticulitis, and gastrointestinal symptoms, collected from medical records and patient surveys. Descriptive statistics were used to characterise all variables. Adjusted regression analysis was used to determine the effect of diet prescription on primary outcomes. Results: Of the 81 included patients, 47% were prescribed restricted diets, and 53% were prescribed liberalised diets. Patients prescribed restricted diets had greater LOS (median 4.0 (IQR: 3.5–5.1) vs. 2.8 (IQR: 2.2–3.8) days, p < 0.001) and were more likely to re-present due to diverticulitis at six months (OR 8.1, 95% CI 1.3–51.0, p = 0.025) in adjusted models. No difference in gastrointestinal symptoms was observed 30-days post-admission. Conclusion: In patients hospitalised with uncomplicated diverticulitis, restricted diets may be associated with longer LOS and increased odds of re-presentation at 6 months compared to liberalised diets. No differences in post-discharge gastrointestinal symptoms were observed between restricted versus liberalised diets. Randomised controlled trials are needed to confirm the causal role of inpatient diet prescription on clinical outcomes, healthcare utilisation, and patient experience. Registration: prospectively registered; ANZCTR Number: ACTRN12616001378415.

As well known success in orthodontics is related to a correct diagnosis and to a carefull treatment planning. Our study aims to provide clinician with a reproducible and precise method, for orthodontic indirect bonding, thanks to CBCT images and due to a CAD-CAM process. Methods: A case of an orthodontic treatment plan, of a female patient, 37 years old, was selected. Plaster models were digitally acquired using the Extra-Oral scanner Maestro 3D and processed within the Studio Maestro 3D software. CBCT images in DICOM format were imported into the MIMICS software, in order to perform the segmentation of the dental elements, and to obtain a three-dimensional coronal-root dental arches model. The DICOM file thus processed was exported in an STL file, reworked with Meshmixer software to improve image quality, and imported into the 3D Maestro software to be superimposed on the digital model. In this way a three-dimensional real model of the dental arches was developed. After an accurate orthodontic virtual set-up, we proceeded to brackets positioning on the 3D model of the dental arches. Subsequently, a virtual transfer template was created, in order to carry out the digital printing of a thermo-printed mask necessary to perform an indirect bonding of the orthodontic appliance. Results: The original digital workflow proposed in this study allows the development of a real and non-ideal three-dimensional coronal-root model of the dental arches; this model can be used for indirect orthodontic bonding eliminating any errors in the expression of 1st, 2nd and 3rd order information of the pre-informed orthodontic appliance. Conclusions: Technological advancements in oral scanning and 3D printing will allow the achievement of an easy and reproducible ideal positioning of the orthodontic brackets.

Growing epidemiological studies highlight a bi-directional relationship between depressive symptoms and diabetes mellitus. However, the detrimental impact of their co-existence on mental health suggests the need to treat this comorbidity as a separate entity rather than the two different pathologies. Herein, we characterized the peculiar mechanisms activated in mouse hippocampus from the concurrent development of hyperglycaemia, characterizing the different diabetes subtypes, and chronic stress, recognized as a possible factor predisposing to major depression. Our work demonstrates that kynurenine overproduction, leading to apoptosis in the hippocampus, is triggered in a different way depending on hyperglycaemia or chronic stress. Indeed, in the former, kynurenine appears produced by infiltered macrophages whereas, in the latter, peripheral kynurenine preferentially promotes resident microglia activation. In this scenario, QA, derived from kynurenine catabolism, appears a key mediator causing glutamatergic synapse dysfunction and apoptosis, thus contributing to brain atrophy. We demonstrated that the coexistence of hyperglycaemia and chronic stress worsened hippocampal damage through alternative mechanisms, such as GLUT-4 and BDNF down-expression, denoting mitochondrial dysfunction and apoptosis on one hand and evoking the compromission of neurogenesis on the other. Overall, in the degeneration of neurovascular unit, hyperglycaemia and chronic stress interacted each other as the partners of a “West Coast Swing” in which the leading role can be assumed alternatively by each partner of the dance. The comprehension of these mechanisms can open novel perspectives in the management of diabetic/depressed patients, but also in the understanding the pathogenesis of other neurodegenerative disease characterized by the compromission of hippocampal function.

Morphine is an important pain reliever employed in pain management, its extended utilize is hindered by the onset of analgesic tolerance and oxidative stress. Long-term morphine administration causes elevated production of reactive oxygen species (ROS), disrupting mitochondrial function and inducing oxidation. Sirtuin 3 (SIRT3), a mitochondrial protein, is essential in modulating ROS levels by regulating mitochondrial antioxidant enzymes as manganese superoxide dismutase (MnSOD). Our investigation focused on the impact of SIRT3 on hyperalgesia and morphine tolerance in mice, as evaluating the antioxidant effect of the polyphenolic fraction of bergamot (BPF). Mice were administered morphine twice daily for four consecutive days (20 mg/kg). On the fifth day, mice received an acute dose of morphine (3 mg/kg), either alone or in conjunction with BPF or Mn (III)tetrakis (4-benzoic acid) porphyrin (MnTBAP). We evaluated levels of malondialdehyde (MDA), nitration, and the activity of SIRT3, MnSOD, glutamine synthetase (GS), and glutamate 1 transporter (GLT1) in the spinal cord. Our findings demonstrate that administering repeated doses of morphine led to the development of antinociceptive tolerance in mice, accompanied by increased superoxide production, nitration, and inactivation of mitochondrial SIRT3, MnSOD, GS, and GLT1. The combined administration of morphine with either BPF or MnTBAP prevented these effects.

Peri-menopausal discomfort can have a detrimental effect on the physical health of women due to physiological and behavioral changes. Estrogen and progesterone-based hormone therapy can alleviate menopausal symptoms, but estrogen supplementation may have negative health effects. The effectiveness of hormone replacement therapy using natural compounds for peri-menopausal disorders is still uncertain. Evidence from in vivo experiments indicates that Ferula L. extract in ovariectomized rats leads to better sexual behavior. The effect seems to be linked to the phytoestrogenic properties of ferutinin, the primary bioactive compound in the extract. The purpose of this study was to assess the clinical impact of Ferula communis L. extract (titrated at 20% ferutinin, and given at doses of 100 mg/die for 90 days) on the quality of life of 64 menopausal women. The clinical trial was randomized, double-blind, and placebo controlled. Our data showed that Ferula communis L. extract reduced by 67 + 9% all symptoms associated to postmenopausal discomfort and enhanced significantly sexual behavior. In addition, the supplement led to a significant improvement of BMI and oxidative stress decrease in the women who received it, while also keeping platelet aggregation within normal levels. Overall, these results could point to the potential use of supplementation with Ferula communis L. extract to revert or mitigate menopause dysfunction.

Adhering to a healthy diet has a protective effect on human health, including a decrease in inflammatory diseases due to consuming fiber. The purpose of this manuscript was to obtain and compare two extracts based on fiber (BF and IF-C), derived from two plants particularly present in the Mediterranean region: bergamot (Citrus bergamia) and prickly pear (Opuntia ficus-indica). The parts used by these plants have been the “pastazzo” for the bergamot and the cladodes for the prickly pear. In addition to in vitro evaluations, the antioxidant activity was also measured on human neurons under inflammatory conditions. Furthermore, the extracts of interest were examined for their effects on the cell cycle and the regulation of pro-apoptotic proteins, caspase 9 and 3, induced by LPS. The results indicated that both extracts had a protective effect against LPS-induced damage, with BF consistently exhibiting superior functionality compared to IF-C. Moreover, the extracts can reduce inflammation, which is a common process of disease. By exploring this avenue, studying the consumption of dietary fiber could enhance our understanding of its positive effects, but additional experiments are needed to confirm this.

The focus of this article was to evaluate the link between obstructive sleep apnea syndrome (OSAS) and periodontitis, considering various hypotheses supporting the relationship between respiratory disorders and periodontitis. The literature review for this study was performed using the PubMed, Google Scholar, Cochrane library, and Proquest databases. The review process was guided by the PRISMA guidelines. The PECOS protocol (Population, Exposure, Control, Outcome, Study) was followed in developing the search strategy to ensure consistent and accurate selection of articles. To evaluate quality, cross-sectional studies were reviewed using the Joanna Briggs Institute (JBI) critical appraisal tool. Case-control studies were assessed with the Newcastle–Ottawa Scale (NOS). The research included a total of 10 studies, encompassing 88,040 participants. The meta-analysis observed a statistically significant association between OSAS and periodontitis, with an odds ratio OR = 2.4620 (95%-CI: 1.7345–3.4946 p ≤ 0.0001). The results suggest a potential association between OSA and periodontitis. Further investigations are warranted to confirm this association and elucidate its underlying mechanism.

Autophagy is a complex physiological pathway mediating homeostasis and survival of cells degrading damaged organelles and regulating their recycling. Physiologic autophagy can maintain normal lung function, decrease lung cellular senescence, and inhibit myofibroblast differentiation. It is well known that autophagy is activated in several chronic inflammatory diseases; however, its role in the pathogenesis of chronic obstructive pulmonary disease (COPD) and the expression of autophagy-related genes (ATGs) in lower airways of COPD patients is still controversial. The expression and localization of all ATG proteins that represented key components of the autophagic machinery modulating elongation, closure, and maturation of autophagosome membranes were retrospectively measured in peripheral lungs of patients with stable COPD (n = 10), control smokers with normal lung function (n = 10), and control nonsmoking subjects (n = 8) using immunohistochemical analysis. These results show an increased expression of ATG4 protein in alveolar septa and bronchiolar epithelium of stable COPD patients compared to smokers with normal lung function and non-smoker subjects. In particular, the genes in the ATG4 protein family (including ATG4A, ATG4B, ATG4C, and ATG4D) that have a key role in the modulation of the physiological autophagic machinery are the most important ATGs increased in the compartment of lower airways of stable COPD patients, suggesting that the alteration shown in COPD patients can be also correlated to impaired modulation of autophagic machinery modulating elongation, closure, and maturation of autophagosomes membranes. Statistical analysis was performed by the Kruskal–Wallis test and the Mann–Whitney U test for comparison between groups. A statistically significant increased expression of ATG4A (p = 0.0047), ATG4D (p = 0.018), and ATG5 (p = 0.019) was documented in the bronchiolar epithelium as well in alveolar lining for ATG4A (p = 0.0036), ATG4B (p = 0.0054), ATG4C (p = 0.0064), ATG4D (p = 0.0084), ATG5 (p = 0.0088), and ATG7 (p = 0.018) in patients with stable COPD compared to control groups. The ATG4 isoforms may be considered as additional potential targets for the development of new drugs in COPD.

Antibody-drug conjugates (ADCs) represent an effective class of agents for the treatment of several tumor types, including breast cancer (BC), featuring approved molecules such as trastuzumab-emtansine, trastuzumab-deruxtecan, and sacituzumab-govitecan. Immune-checkpoint inhibitors (ICIs) also showed activity in selected BC subtypes, and two agents, pembrolizumab and atezolizumab, are currently approved for the treatment of triple-negative BC patients. The potential synergy between ADCs and immunotherapy in BC remains an area of active investigation. Preclinical studies suggest that ADCs promote immune surveillance, modulating tumor microenvironment, inducing immunogenic cell death, and enhancing antitumor immunity. Translational evidence has shown potential predictive biomarkers for ADCs alone or in combination with immunotherapy, including expression of target antigen, oncogenic pathways, tumor-infiltrating lymphocytes, and neutrophil-to-lymphocyte ratio. Given this background, several clinical trials evaluated ADC-ICI combinations in BC patients, demonstrating promising outcomes with an overall manageable toxicity profile, and many studies are currently ongoing to confirm the efficacy and feasibility of this therapeutic approach. In the present review, we summarized the available evidence about the integration of ADCs and immunotherapy for the management of BC, emphasizing the need for further translational and clinical investigations to optimize this treatment strategy and elucidate predictive biomarkers, eventually improving patient outcomes.

The gut microbiota is a diverse bacterial community consisting of approximately 2000 species, predominantly from five phyla: Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, and Verrucomicrobia. The microbiota’s bacterial species create distinct compounds that impact the host’s health, including well-known short-chain fatty acids. These are produced through the breakdown of dietary fibers and fermentation of undigested carbohydrates by the intestinal microbiota. The main short-chain fatty acids consist of acetate, propionate, and butyrate. The concentration of butyrate in mammalian intestines varies depending on the diet. Its main functions are use as an energy source, cell differentiation, reduction in the inflammatory process in the intestine, and defense against oxidative stress. It also plays an epigenetic role in histone deacetylases, thus helping to reduce the risk of colon cancer. Finally, butyrate affects the gut–brain axis by crossing the brain–blood barrier, making it crucial to determine the right concentrations for both local and peripheral effects. In recent years, there has been a significant amount of attention given to the role of dietary polyphenols and fibers in promoting human health. Polyphenols and dietary fibers both play crucial roles in protecting human health and can produce butyrate through gut microbiota fermentation. This paper aims to summarize information on the key summits related to the negative correlation between intestinal microbiota diversity and chronic diseases to guide future research on determining the specific activity of butyrate from polyphenols and dietary fibers that can carry out these vital functions.

Lung cancer (LC) is one of the most prevalent cancers in both men and women and today is still characterized by high mortality and lethality. Several biomarkers have been identified for evaluating the prognosis of non-small cell lung cancer (NSCLC) patients and selecting the most effective therapeutic strategy for these patients. The introduction of innovative targeted therapies and immunotherapy with immune checkpoint inhibitors (ICIs) for the treatment of NSCLC both in advanced stages and, more recently, also in early stages, has revolutionized and significantly improved the therapeutic scenario for these patients. Promising evidence has also been shown by analyzing both micro-RNAs (miRNAs) and the lung/gut microbiota. MiRNAs belong to the large family of non-coding RNAs and play a role in the modulation of several key mechanisms in cells such as proliferation, differentiation, inflammation, and apoptosis. On the other hand, the microbiota (a group of several microorganisms found in human orgasms such as the gut and lungs and mainly composed by bacteria) plays a key role in the modulation of inflammation and, in particular, in the immune response. Some data have shown that the microbiota and the related microbiome can modulate miRNAs expression and vice versa by regulating several intracellular signaling pathways that are known to play a role in the pathogenesis of lung cancer. This evidence suggests that this axis is key to predicting the prognosis and effectiveness of ICIs in NSCLC treatment and could represent a new target in the treatment of NSCLC. In this review, we highlight the most recent evidence and data regarding the role of both miRNAs and the lung/gut microbiome in the prediction of prognosis and response to ICI treatment, focusing on the link between miRNAs and the microbiome. A new potential interaction based on the underlying modulated intracellular signaling pathways is also shown.

Arterial hypertension represents a leading cause of cardiovascular morbidity and mortality worldwide, and the identification of effective solutions for treating the early stages of elevated blood pressure (BP) is still a relevant issue for cardiovascular risk prevention. The pathophysiological basis for the occurrence of elevated BP and the onset of arterial hypertension have been widely studied in recent years. In addition, consistent progress in the development of novel, powerful, antihypertensive drugs and their appropriate applications in controlling BP have increased our potential for successfully managing disease states characterized by abnormal blood pressure. However, the mechanisms responsible for the disruption of endogenous mechanisms contributing to the maintenance of BP within a normal range are yet to be fully clarified. Recently, evidence has shown that several natural antioxidants containing active ingredients originating from natural plant extracts, used alone or in combination, may represent a valid solution for counteracting the development of arterial hypertension. In particular, there is evidence to show that natural antioxidants may enhance the viability of endothelial cells undergoing oxidative damage, an effect that could play a crucial role in the pathophysiological events accompanying the early stages of arterial hypertension. The present review aims to reassess the role of oxidative stress on endothelial dysfunction in the onset and progression of arterial hypertension and that of natural antioxidants in covering several unmet needs in the treatment of such diseases.

To date, the complex pathological interactions between renal and cardiovascular systems represent a real global epidemic in both developed and developing countries. In this context, renovascular hypertension (RVH) remains among the most prevalent, but also potentially reversible, risk factor for numerous reno-cardiac diseases in humans and pets. Here, we investigated the anti-inflammatory and reno-cardiac protective effects of a polyphenol-rich fraction of bergamot (BPF) in an experimental model of hypertension induced by unilateral renal artery ligation. Adult male Wistar rats underwent unilateral renal artery ligation and treatment with deoxycorticosterone acetate (DOCA) (20 mg/kg, s.c.), twice a week for a period of 4 weeks, and 1% sodium chloride (NaCl) water (n = 10). A subgroup of hypertensive rats received BPF (100 mg/kg/day for 28 consecutive days, n = 10) by gavage. Another group of animals was treated with a sub-cutaneous injection of vehicle (that served as control, n = 8). Unilateral renal artery ligation followed by treatment with DOCA and 1% NaCl water resulted in a significant increase in mean arterial blood pressure (MAP; p

Objectives: The persistence in therapy of rheumatoid arthritis drugs and particularly bDMARD is a limiting factor for their long-term use. The randomized controlled trials (RCTs) may not reflect real-world contexts due to strict inclusion and exclusion criteria. Baricitinib, which targets both JAK1 and JAK2, has been used in Italy for several years. The aim of this multi-center study is to assess the real world persistence on therapy of baricitinib in RA patients and to identify predictive factors of baricitinib's survival rate. Methods: This is a retrospective, multicentric, Italian, longitudinal study. All patients were enrolled according to the following criteria: a) age ≥ 18 years old; b) diagnosed with RA according 2010 ACR/EULAR classification criteria; c) treated with baricitinib. In order to describe baricitinib clinical efficacy, the survival rate was evaluated by The Kaplan–Meier curve. Then, predictive factors of drug retention rate were assessed by performing the Cox analysis, identifying which risk factors influenced treatment persistence. Results: Overall, we included 478 patients treated with baricitinib. Among them, 380 (79.5%) were females. Baricitinib's survival rate was 94.6% at 6 months, 87.9% at 12 months, 81.7% at 24 months and 53.4% at 48 months. The Cox analysis regression showed that a higher bDMARDs/tsDMARD line of therapy seems to be a negative prognostic factor for the drug retention rate (HR 1.26 CI 95% 1.07–1.49, p = 0.006. Conclusion: Real-life study confirms baricitinib effectiveness up to 4 years, but previous treatment with bDMARDs was a negative prognostic factor for its survival rate.

IntroductionCardiovascular diseases (CVDs) are the most important cause of premature death and disability worldwide. Environmental degradation and cardiovascular diseases are two keys to health challenges, characterized by a constant evolution in an industrialized world that exploits natural resources regardless of the consequences for health. The etiological risk factors of CVDs are widely known and include dyslipidemia, obesity, diabetes, and chronic cigarette consumption. However, one component that is often underestimated is exposure to heavy metals. The biological perspective explains that different metals play different roles. They are therefore classified into essential heavy metals, which are present in organisms where they perform important vital functions, especially in various physiological processes, or non-essential heavy metals, with a no biological role but, nonetheless, remain in the environment in which they are absorbed. Although both types of metal ions are many times chemically similar and can bind to the same biological ligands, the attention given today to nonessential metals in several eukaryotic species is starting to raise strong concerns due to an exponential increase in their concentrations. The aim of this systematic review was to assess possible correlations between exposure to nonessential heavy metals and increased incidence of cardiovascular disease, reporting the results of studies published in the last 5 years through March 2023.MethodsThe studies includes reviews retrieved from PubMed, Medline, Embase, and Web of Science databases, in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement and following the PICO (Population Intervention Comparison Outcome Population) framework.ResultsEight reviews, including a total of 153 studies, were identified. Seven of these review enlighted the association between CVDs and non-essential heavy metals chronic exposure.DiscussionIt is evident that exposure to heavy metals represent a risk factor for CVDs onset. However, further studies are needed to better understand the effects caused by these metals.

Raman spectroscopy plays a pivotal role in spectroscopic investigations. The small Raman scattering cross-section of numerous analytes, however, requires enhancement of the signal through specific structuring of the electromagnetic and morphological properties of the underlying surface. This enhancement technique is known as surface-enhanced Raman spectroscopy (SERS). Despite the existence of various proposed alternatives, the approach involving Fabry–Pérot cavities, which constitutes a straightforward method to enhance the electromagnetic field around the analyte, has not been extensively utilized. This is because, for the analyte to experience the maximum electric field, it needs to be embedded within the cavity. Consequently, the top mirror of the cavity will eventually shield it from the external laser source. Recently, an open-cavity configuration has been demonstrated to exhibit properties similar to the classic Fabry–Pérot configuration, with the added advantage of maintaining direct accessibility for the laser source. This paper showcases how such a simple yet innovative configuration can be effectively utilized to achieve remarkable Raman enhancement. The simple structure, coupled with its inexpensive nature and versatility in material selection and scalability, makes it an ideal choice for various analytes and integration into diverse Raman apparatus setups.

Opuntia ficus-indica (L.) Mill. belongs to the Cactaceae family and the genus Opuntia; it is a succulent plant that adapts to extreme climatic conditions. The aerial part of the plant consists of the cladodes, morphological changes of branches that appear green, are covered with thorns, and are essential to reduce excessive perspiration of water. The composition of cladodes is very varied, and the main constituents are water, fibers, polysaccharides, proteins, fatty acids, vitamins, sterols, minerals, and polyphenols. Polyphenols are responsible for many beneficial activities for human health, such as antioxidant, anti-inflammatory, anticancer, and nutritional properties. The purpose of this manuscript was to compare the properties of cladodes belonging to the same plant but with different stages of maturity. Relative extracts were tested both in vitro and on a cell line and antioxidant and anti-apoptotic properties were found. The antioxidant activity was tested by the Oxygen Radical Absorbance Capacity (ORAC) test, the 1,1-diphenyl-2-picrylhydrazil (DPPH) test, and the measurement of cellular accumulation of reactive oxygen species (ROS). Anti-apoptotic activity was evaluated by the annexin/PI assay and measurement of caspases 9 and 3 expression. The results obtained showed that the extracts considered possess antioxidant and anti-apoptotic properties. However, the different stages of maturity of cladodes are essential for the performance of both functions. In addition, important variations were made in the dissolution of the extracts that brought greater safety in their use. In conclusion, this manuscript provides further information on cladodes of Opuntia ficus-indica, which can be used as adjuvants in many human pathologies.

Background: The aim of this study was to propose a new 3D printing method for attachment production and compare the reproduction accuracy of traditional attachments with the proposed 3D-printed attachments. Methods: A standardized 3D model attachment was created with the dimensions of 3, 2, and 2 mm for the apico-coronal, mesio-distal, and vestibulo-lingual dimensions, respectively. A 3D ideal model of the maxillary arch was used to apply four standardized attachments on the vestibular surface of selected teeth. The obtained model with placed attachments was used to reproduce composite attachments via the conventional method. A transfer template was used to bond with the flow composite resin 3D-printed attachment on a new arch model without attachments. The models with traditional attachments and 3D-printed attachments were scanned and overlapped with the original CAD model with attachments. To assess the attachment precision, vertical and horizontal cutting planes were used on the overlapped models. The outcome selection focused on puff analysis (excess composite material evaluation) and shape analysis (attachment accuracy evaluation). Results: The results indicated that the 3D-printed attachments showed significant differences (p < 0.05) compared to the traditional attachments. The descriptive statistics showed the higher discrepancies compared to the CAD model of the traditionally created attachments in the shape (0.85 mm) and puff dimension (1.02 mm). Conclusion: Custom 3D-printed attachment production is an effective method for achieving greater attachment precision.

Nowadays, old-generation pesticides are released into ecosystems alongside new formulations, giving rise to pharmacological interactions (additive, synergistic, and antagonistic effects). The aim of this study was to evaluate the impact that simultaneous exposure to DMT and FLU doses has on bee health. Groups of twenty honeybees were housed in cages to compose six macro-groups. One group consisted of experimental replicates treated orally with a toxic dose of deltamenthrin (DMT 21.6 mg/L); two other groups were subjected to the oral administration of two toxic doses of flupyradifurone (FLU 50 mg/L and FLU 100 mg/L); and two other groups were intoxicated with a combination of the two pesticides (DMT 21.6 + FLU 50 and DMT 21.6 + FLU 100). The consequences of the pesticides’ interactions were highlighted by measuring and comparing data on survival, food consumption, and abnormal behavior. Generally speaking, antagonism between the two pesticides has been demonstrated. The bees were able to survive for up to three days at the lowest dosage of FLU (50 mg/L), with 46% of the subjects still alive; however, the maximum dose (100 mg/L) caused all treated animals to die as early as the second day. When DMT and FLU 50 were administered together, the group that received DMT alone had a lower survival rate. When comparing the survival rates produced by the DMT and FLU 50 combination to those of the group receiving FLU 50 alone, the same was clearly visible. While there was no statistically significant improvement observed when the survival indices of the DMT and FLU 100 combination were compared to those of the group intoxicated with DMT alone, an improvement in survival indices was observed when these were compared with the group intoxicated with FLU 100 alone.

Opuntia ficus-indica (L.) Miller is a plant belonging to the Cactaceae family adapted to live in environments characterized by long periods of drought and arid or desert climates. This plant is characterized by an aerial part composed of structures transformed by branches, called “cladodes”, which are essential to reduce excessive perspiration of water and appear covered with thorns. The composition of the cladodes includes water, polysaccharides, fiber, proteins, vitamins, fatty acids, sterols, polyphenols, and minerals. The main purposes of this scientific work are (a) to compare the insoluble fiber (IF) extracted from the cladodes of O. ficus-indica belonging to the same plant but collected in different seasonal periods (winter and summer) and develop new extraction protocols that are able to improve the yield obtained and (b) evaluate the antioxidant potential of the fiber and study possible variations as a result of the extraction protocol chosen. The first objective was achieved (1) by measuring the amount of IF extracted from cladodes harvested in winter and summer (CW and CS, respectively) and (2) by modifying three variables involved in the fiber extraction protocol. To achieve the second objective, the following experiments were carried out: (1) measurement of the antioxidant potential of IF in CW and CS; (2) measurement of cellular reactive oxygen species; (3) measurement of the activity of some antioxidant enzymes; and (4) comparison of the polyphenol content in CW and CS. In conclusion, the results obtained showed that the IF extraction process can be improved, achieving a uniform yield regardless of seasonality; the antioxidant effect may vary depending on the extraction protocol.

Flupyradifurone (FLU) is a butenolide insecticide that has come onto the market relatively recently. It is used in agriculture to control aphids, psyllids, and whiteflies. Toxicity studies have decreed its low toxicity to honeybees. However, recent research has challenged these claims; oral exposure to the pesticide can lead to behavioral abnormalities and in the worst cases, lethal phenomena. Compounds with antioxidant activity, such as flavonoids and polyphenols, have been shown to protect against the toxic effects of pesticides. The aim of this research was to evaluate the possible protective effect of the bergamot polyphenolic fraction (BPF) against behavioral abnormalities and lethality induced by toxic doses of FLU orally administered to honeybees under laboratory conditions. Honeybees were assigned to experimental groups in which two toxic doses of FLU, 50 mg/L and 100 mg/L were administered. In other replicates, three doses (1, 2 and 5 mg/kg) of the bergamot polyphenolic fraction (BPF) were added to the above toxic doses. In the experimental groups intoxicated with FLU at the highest dose tested, all caged subjects (20 individuals) died within the second day of administration. The survival probability of the groups to which the BPF was added was compared to that of the groups to which only the toxic doses of FLU were administered. The mortality rate in the BPF groups was statistically lower (p < 0.05) than in the intoxicated groups; in addition, a lower percentage of individuals exhibited behavioral abnormalities. According to this research, the ingestion of the BPF attenuates the harmful effects of FLU. Further studies are needed before proposing BPF incorporation into the honeybees’ diet, but there already seem to be beneficial effects associated with its intake.

As well known success in orthodontics is related to a correct diagnosis and to a carefull treatment planning. Our study aims to provide clinician with a reproducible and precise method, for orthodontic indirect bonding, thanks to CBCT images and due to a CAD-CAM process. Methods: A case of an orthodontic treatment plan, of a female patient, 37 years old, was selected. Plaster models were digitally acquired using the Extra-Oral scanner Maestro 3D and processed within the Studio Maestro 3D software. CBCT images in DICOM format were imported into the MIMICS software, in order to perform the segmentation of the dental elements, and to obtain a three-dimensional coronal-root dental arches model. The DICOM file thus processed was exported in an STL file, reworked with Meshmixer software to improve image quality, and imported into the 3D Maestro software to be superimposed on the digital model. In this way a three-dimensional real model of the dental arches was developed. After an accurate orthodontic virtual set-up, we proceeded to brackets positioning on the 3D model of the dental arches. Subsequently, a virtual transfer template was created, in order to carry out the digital printing of a thermo-printed mask necessary to perform an indirect bonding of the orthodontic appliance. Results: The original digital workflow proposed in this study allows the development of a real and non-ideal three-dimensional coronal-root model of the dental arches; this model can be used for indirect orthodontic bonding eliminating any errors in the expression of 1st, 2nd and 3rd order information of the pre-informed orthodontic appliance. Conclusions: Technological advancements in oral scanning and 3D printing will allow the achievement of an easy and reproducible ideal positioning of the orthodontic brackets. [ABSTRACT FROM AUTHOR]