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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.

Objectives: The foot and ankle complex is crucial in stability, propulsion, and musculoskeletal interactions. Optimizing orthotic interventions in this anatomical region is essential to improve motor outcomes. This systematic review investigates the impact of foot orthoses (FOs) with sensorimotor bars on gait, postural control, and muscle activity in healthy individuals and those with musculoskeletal disorders. Methods: We conducted an electronic search in January 2024 using the PubMed, Web of Science, and Scopus databases. The article identification, screening, and selection followed the PISMA (the preferred reporting items for systematic reviews and meta-analysis) guidelines. We conducted the quality assessment using the PEDro (the physiotherapy evidence database) checklist. Data extraction and synthesis were performed using the Cochrane handbook for systematic review of interventions. Results: FOs with sensorimotor bars can increase foot external rotation, dorsiflexion, and abduction while decreasing foot eversion. Additionally, they can reduce anteroposterior displacement of the hip, shoulder, and head. Furthermore, significant improvements have been observed in spatiotemporal parameters such as walking speed, stride length, stance time, swing time, and kinetic parameters such as plantar pressure. These orthoses can also impact clinical tasks and decrease center-of-pressure movements. Discussion: Sensorimotor bars have demonstrated beneficial effects on gait (kinematic, kinetic, and spatial-temporal measures), balance control (clinical performance and center of pressure displacement measures), and muscle activity recording.

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.

Abstract Several reports have described the autoimmune encephalitis' (AE) possible onset during pregnancy. In this systematic review, we summarize the available data on the diagnostic and therapeutic approach to AE during pregnancy, highlighting the associated maternal and fetal clinical outcomes. A systematic search of the literature was performed. The following databases were used: PubMed, Google Scholar, EMBASE, and CrossRef. The revision was registered on the PROSPERO platform (CRD42022336357). Forty‐nine patients were included. AE onset was mainly observed during the first and the second trimester of pregnancy with psychiatric manifestations and seizures as main onset symptoms. CSF analysis showed AE‐specific autoantibody positivity in 33 patients (anti‐NMDA receptor as the most frequent). EEG generally showed normal findings. MRI revealed pathological findings in less than half of patients. Tumor screening was positive in 14 cases. First‐line immunotherapy (single or combined) was generally employed while second line was administered in a minority of patients. Levetiracetam was the most used antiseizure medication. Cesarean section was performed in 18 women. Most of the women had an excellent early outcome after delivery but 22 showed persistent neurological deficits in long‐term follow‐up. Fetal outcome was positive in 33 cases, whereas 12 cases of fetal death were reported. A logistic regression showed that no variable significantly influenced the odds of good/bad maternal and fetal clinical outcome. Diagnosis and treatment of AE during pregnancy is challenging. The rate of miscarriage in women with AE seems to be higher than the general population. In addition, mothers may show long‐term neurological deficits.

Abstract Preprocessing is an essential task for the correct analysis of digital medical images. In particular, X-ray imaging might contain artifacts, low contrast, diffractions or intensity inhomogeneities. Recently, we have developed a procedure named PACE that is able to improve chest X-ray (CXR) images including the enforcement of clinical evaluation of pneumonia originated by COVID-19. At the clinical benchmark state of this tool, there have been found some peculiar conditions causing a reduction of details over large bright regions (as in ground-glass opacities and in pleural effusions in bedridden patients) and resulting in oversaturated areas. Here, we have significantly improved the overall performance of the original approach including the results in those specific cases by developing PACE2.0. It combines 2D image decomposition, non-local means denoising, gamma correction, and recursive algorithms to improve image quality. The tool has been evaluated using three metrics: contrast improvement index, information entropy, and effective measure of enhancement, resulting in an average increase of 35% in CII, 7.5% in ENT, 95.6% in EME and 13% in BRISQUE against original radiographies. Additionally, the enhanced images were fed to a pre-trained DenseNet-121 model for transfer learning, resulting in an increase in classification accuracy from 80 to 94% and recall from 89 to 97%, respectively. These improvements led to a potential enhancement of the interpretability of lesion detection in CXRs. PACE2.0 has the potential to become a valuable tool for clinical decision support and could help healthcare professionals detect pneumonia more accurately.

Introduction: Galectin-3 is a β-galactoside-binding lectin with several roles in the immune- inflammatory response. The aim of this systematic review and meta-analysis was to explain the prognostic value of Galectin-3 on COVID-19 severity and mortality from the existing literature. Methods: PubMed/MEDLINE, EMBASE, SCOPUS, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases were surveyed up to November 10, 2023, for studies reporting data on Galectin-3 levels and the severity and mortality of patients with COVID-19. We performed frequentist random-effects network meta-analysis and presented the standard mean difference (SMD) and 95% confidence interval (CI). Results: Galectin-3 levels among patients with and without COVID-19 varied with the following values: 15.73±13.03 vs. 8.72±5.82 pg/mL, respectively (SMD = 2.59; 95%CI: 1.52 to 3.67; p

Introduction: In recent years, there has been a growing focus on assessing life satisfaction among students, as a way of measuring their overall wellbeing. This study aims to investigate how positive feelings (PF) and negative feelings (NF) predict academic performance (AP) through time management (TM) as a mediator in this process. Methods: This cross-sectional study was conducted among Moroccan students from the University of Sidi Mohamed ben Abdullah in Fez. A total of 540 students (288 females, 53.3%; 252 males, 46.7%; with a mean age of 21.51 and a standard deviation of 3.86) completed a pencil and paper questionnaire. A questionnaire was adopted as a tool in this research. Positive emotions (Pe), Negative emotions (Ne), and Life satisfaction were measured on a five-rank scale for each variable (strongly agree = 5, strongly disagree = 1). Results: The results of using structural equation modeling showed that the life satisfaction factor, which includes two dimensions, PF and NF, has a significant influence on academic performance. Discussion: Creating a supportive and positive learning environment can enhance students' wellbeing and improve academic performance.

Chronic obstructive pulmonary disease (COPD) represents an independent risk factor for lung cancer development. Accelerated cell senescence, induced by oxidative stress and inflammation, is a common pathogenic determinant of both COPD and lung cancer. The post transcriptional regulation of genes involved in these processes is finely regulated by RNA-binding proteins (RBPs), which regulate mRNA turnover, subcellular localization, splicing and translation. Multiple pro-inflammatory mediators (including cytokines, chemokines, proteins, growth factors and others), responsible of lung microenvironment alteration, are regulated by RBPs. Several mouse models have shown the implication of RBPs in multiple mechanisms that sustain chronic inflammation and neoplastic transformation. However, further studies are required to clarify the role of RBPs in the pathogenic mechanisms shared by lung cancer and COPD, in order to identify novel biomarkers and therapeutic targets. This review will therefore focus on the studies collectively indicating the role of RBPs in oxidative stress and chronic inflammation as common pathogenic mechanisms shared by lung cancer and COPD.

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.

Red raspberries (Rubus idaeus L.) are often chosen by consumers for their flavour, taste, and health-promoting properties A relevant issue related to these fruits is their high perishability. The aim of this study was to investigate the effect of the ultraviolet C light-emitting diode (UVC-LED) treatment on soil-grown and pot-grown raspberries in extending their shelf-life, maintaining their high quality throughout the preservation period, and improving features related to their phenolic compound content. The UVC-LED treatment increased the total phenolic content (158 to 200 mg GAE/100 g) and ferric reducing antioxidant power (55.3 to 78.6 mmol Fe 2 +/kg) of the pot-grown raspberries when the UVC-LED treatment was followed by storage in a climate-controlled room (20°C). Total anthocyanin content did not increase significantly compared to the control samples. Contrary to expectations, no effect of reducing the microbial count after storage was observed due to the exposure of raspberries to the UVC-LED radiation. The positive outcomes derived from the analyses of bioactive compounds may be implemented in further studies on the same matrix to better manage the treatment and its conditions, such as the exposure time, the distance from the LED lamps, and the UVC-rays’ dose, in order to find the best combination in terms of efficacy and efficiency.

Normal Pressure Hydrocephalus (iNPH) typically affects the elderly and can cause cognitive decline, resulting in its differential diagnosis with other neurodegenerative conditions. Moreover, it is probably underdiagnosed; such under- and misdiagnosis prevents the patient from receiving the right treatment and significantly affects the quality of life and life expectancy. This investigation is an in-depth analysis of the actual incidence of iNPH in the population of the province served by our hospital (circa 580,000 individuals). The first phase of this study was conducted by visualizing a total of 1232 brain CT scans performed in the Emergency Departments of the four hospitals of our network on patients who were admitted for different complaints yet screened as suspicious for iNPH. Subsequently, corresponding Emergency Department medical records were investigated to understand the medical history of each patient in search of elements attributable to an alteration of CSF dynamics. The cohort of positive CT scans, according to the radiological and clinical inclusion criteria, included 192 patients. Among the reasons to require acute medical care, “Fall” was the most common. The cumulative incidence of CT scans suggestive of iNPH among the patients undergoing CT scans was as high as 15.58%, and the period prevalence calculated for the total amount of patients accessing the Emergency Departments was 1.084%. The real incidence of iNPH in the population may be underestimated, and the social burden linked to the assistance of patients suffering from such untreated conditions could be significantly relieved.

Abstract Background Implantation of radiopaque markers during aortic root surgery might possibly facilitate upcoming coronary angiography or transcatheter aortic valve implantation. Aim of this study was to report the impact of surgically placed radiopaque markers on procedural characteristics and on angiographic outcomes. Methods We retrospectively analyzed baseline characteristics, preoperative and postoperative data as well as procedural findings. In addition, a subgroup analysis of all patients who underwent coronary angiography after aortic root surgery was performed to report radiation time and contrast media used. Results A total of 469 patients underwent aortic root surgery between January 2008 and April 2020. Patients were divided into two groups: group w/ markers (n = 182) and group w/o markers (n = 287). A propensity score matching was performed resulting in a total of 28 patients w/ markers and 28 patients w/o markers. Aortic cross-clamp time did not differ statistically significantly between the group w/o markers and the group w/ markers (124.0 [96.0–150.0] versus 123.0 [110.0–149.0] min, p = 0.09). There was no increased probability for requirement of postoperative angiography in the group w/o markers compared to the group w/ markers (11.8% versus 15.4%, p = 0.27). There was no statistically significant difference in the radiation time 5.5 [3–6.5] versus 5 [2.5–7.5] min, p = 0.62) nor in the amount of contrast media used (85 [77.5–100] versus 80 [60–90] ml, p = 0.07). Conclusions Surgically placed radiopaque markers during aortic root surgery do not increase operative risk and have the potential for facilitating secondary diagnostic and therapeutic interventions.

Objective: Chronic obstructive pulmonary disease (COPD) is one of the main causes of morbidity and mortality in the United States. Oxidative stress due to cigarette smoking seems to be one of the major driving mechanisms in COPD pathogenesis. Since the scavenger receptor B1 (SR-B1) appears to play a key role in med iating the uptake for ɑ-tocopherol and other antioxidants in lung tissue, we aimed to investigate its role in COPD pathogenesis. Methods: Lung tissue biopsies were obtained from 12 subjects; 6 of these had a diagnosis of COPD in a stable clinical state, the others 6 were current (n = 1) or ex-smokers (n = 5) with normal lung function (controls). 4-Hydroxynonenal (4-HNE)–SR-B1 adducts were detected by immunoprecipitation. ɑ-tocopherol concentration was determined by HPLC. Results: SR-B1 levels were lower in COPD patients and these results par allel with lower levels of vitamin E in lung tissue found in COPD patients . This effect can be the consequence of oxidative posttranslational modifications, confirmed by the binding of the peroxidation product 4-HNE to SR-B1 possibly leading to its degradation. Conclusions: The loss of SR-B1 may be involved in lung ɑ-tocopherol content decrease with the consequence of making lung tissue more susceptible to oxidative damage as suggested by the SR-B1–4-HNE adduct formation, and more prone to COPD development. Thus, our findings suggest a novel role of SR-B1 in pathomechani sms underlying COPD. Significance statement Chronic obstructive pulmonary disease (COPD) is one of the main causes of morbidity and mortality in the United States. Oxidative stress has been suggested to be the major driving mechanism in COPD pathogenesis. Loss of scavenger receptor BI (SR-B1) significantly decreases tocopherol lung content making lung tissue more susceptible to oxidative damage. The results of our study show that SR-B1 levels were lower in COPD patients and these results parallel with lower levels of vitamin E in lung tissue. Our findings suggest a novel role of SR- B1 in pathomechanisms underlying COPD.

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.

Introduction: People encounter many events across their life span. However, some life experiences cause negative psychological outcomes. One of them is earthquakes. Therefore, in this study, it was aimed to examine the mediating role of peritraumatic distress in the relationship between childhood psychological maltreatment and optimism and pessimism among earthquake survivors. Methods: Using a snowball sampling technique with a cross-sectional research design, the sample comprised 311 adults who survived earthquake survivors in Turkey. Participants ranged in age between 18 and 61 years (mean age = 27.57±8.03). Of the participants, 231 (74.3%) were females and 80 (25.7%) were males, and they completed the Psychological Maltreatment Questionnaire–Short Form, Peritraumatic Distress Inventory, and Optimism and Pessimism Questionnaire. Results: The findings showed that childhood psychological maltreatment was positively related to peritraumatic distress and pessimism, and negatively related to optimism. Similarly, peritraumatic distress was positively related to pessimism and negatively related to optimism. More importantly, peritraumatic distress mediated the relationship between childhood psychological maltreatment and optimism and pessimism. These findings highlight the importance of addressing peritraumatic distress as an important factor in improving individuals’ perspectives on life. Discussion: Implementing tailored interventions to mitigate peritraumatic distress could lead to a more optimistic mindset and reduced levels of pessimism. By providing individuals with effective coping strategies and support systems, such interventions may empower them to overcome the challenges posed by stressful situations and cultivate a more positive outlook on life.

Introduction: To investigate the role of environmental conditions, knowledge, attitudes, and control measures of preventive behaviors in cutaneous leishmaniasis (CL) based on the BASNEF model in patients who were referred to the health care centers of cities hit by earthquakes, including Sarpol-Zahab and Qasr-Shirin located in Kermanshah province, Western Iran, in 2021. Method: In this descriptive cross-sectional study, 128 individuals who visited rural and urban health centers were randomly selected, then they were asked to fill in a structured questionnaire with questions about their demographic information, environmental conditions, knowledge, attitude, and preventive behavior regarding CL. Results: Approximately 89.1% of the individuals used urban water supply networks, while 68% of the participants had access to the wastewater collection system. The most influential people in preventive behaviors (control actions) were family members (72.4%). Pearson’s correlation test showed that preventive behaviors positively correlated with understudy variables in the BASNEF model (p

Background: Amidst the COVID-19 pandemic and the implementation of home confinement measures, understanding the psychological well-being of individuals has become crucial. Aim: This study examines the irregular effects of gender, age, marital status, and educational level on the psychological well-being of the Moroccan population during COVID-19 home confinement. Design: A cross-sectional study design was utilized. Setting: The study was conducted online, with participants residing in Morocco. Population: The study included individuals from the Moroccan population (n=1.051) who experienced home confinement during the COVID-19 pandemic. Methods: Data was gathered through an anonymous psychological well-being scale administered online. Results: Data analysis revealed three underlying traits: The first is the unexpected impact of age, gender, education levels, and marital status on certain well-being parameters. The second is the varied impact of gender, specifically in its interaction with age and marital status. The varied impact was also reflected in the participants’ mean scores across the well-being parameters. The third indicator revealed the nonlinear impact of the education level on some well-being parameters. Conclusion: The study drew the attention of public health decision-makers to the need to include different scenarios in the elaboration of anticipatory plans in the case of a new pandemic and to avoid sticking to regular models based on regular scenarios only.