Enhanced Antitumor Activity by the Combination of Dasatinib and Selinexor in Chronic Myeloid Leukemia.

BACKGROUND: Chronic myeloid leukemia is a hematological malignancy characterized by the abnormal proliferation of leukemic cells. Despite significant progress with tyrosine kinase inhibitors, such as Dasatinib, resistance remains a challenge. The aim of the present study was to investigate the potential of Selinexor, an Exportin-1 inhibitor, to improve TKI effectiveness on CML. METHODS: Human CML cell lines (LAMA84 and K562) were treated with Selinexor, Dasatinib, or their combination. Apoptosis, mitochondrial membrane potential, and mitochondrial mass were assessed using flow cytometry. Real-time RT-PCR was used to evaluate the expression of genes related to mitochondrial function. Western blot and confocal microscopy examined PINK and heme oxygenase-1 (HO-1) protein levels. RESULTS: Selinexor induced apoptosis and mitochondrial depolarization in CML cell lines, reducing cell viability. The Dasatinib/Selinexor combination further enhanced cytotoxicity, modified mitochondrial fitness, and downregulated HO-1 nuclear translocation, which has been associated with drug resistance in different models. CONCLUSIONS: In conclusion, this study suggests that Dasatinib/Selinexor could be a promising therapeutic strategy for CML, providing new insights for new targeted therapies.

Copper Micro-Flowers for Electrocatalytic Sensing of Nitrate Ions in Water.

The progressive increase in nitrate's (NO3-) presence in surface and groundwater enhances environmental and human health risks. The aim of this work is the fabrication and characterization of sensitive, real-time, low-cost, and portable amperometric sensors for low NO3- concentration detection in water. Copper (Cu) micro-flowers were electrodeposited on top of carbon screen-printed electrodes (SPCEs) via cyclic voltammetry (with voltage ranging from -1.0 V to 0.0 V at a scan rate of 0.1 V s-1). The obtained sensors exhibited a high catalytic activity toward the electro-reduction in NO3-, with a sensitivity of 44.71 µA/mM. They had a limit of detection of 0.87 µM and a good dynamic linear concentration range from 0.05 to 3 mM. The results were compared to spectrophotometric analysis. In addition, the devices exhibited good stability and a maximum standard deviation (RSD) of 5% after ten measurements; reproducibility, with a maximum RSD of 4%; and repeatability after 10 measurements with the RSD at only 5.63%.

Experience in Post-Bariatric Abdominoplasty for Patients with Significant Weight Loss: A Prospective Study.

BACKGROUND: Abdominoplasty is a critical aesthetic and functional procedure for individuals who have undergone massive weight loss. Numerous techniques have been proposed to optimize aesthetic results while minimizing complications. METHODS: This prospective study examined 500 patients who underwent abdominoplasty during body-contouring procedures between 1 January 2018 and 31 December 2021 at a tertiary center. The Skin-Adipose Tissue-Muscle (SAM) protocol was employed to analyze the operative strategies and complication rates and compare them with the existing literature. Furthermore, patient satisfaction and aesthetic outcomes were measured one year post-operation using a comprehensive four-point questionnaire evaluated by the patients themselves and two independent surgeons. RESULTS: Participants had an average age of 34.8 years and a mean BMI of 31.1 kg/m2. The surgeries included 328 full abdominoplasties and 172 T-inverted abdominoplasties. Notable complications included wound infection (4%), wound dehiscence (8.6%), tissue necrosis (0.6%), seroma (8.4%), and hematoma (2.6%). A higher BMI was correlated with an increased risk of complications and lower patient satisfaction. Data analysis was performed using Stata version 18 software. CONCLUSIONS: The increasing prevalence of obesity highlights an urgent need for more bariatric surgeries and subsequent abdominoplasties to mitigate the effects of massive weight loss. A crucial link between elevated BMI and a heightened risk of postoperative complications, emphasizing the necessity for standardized surgical protocols tailored to individuals with higher BMI, was noted. Innovatively, future studies must further investigate the intricate dynamics between BMI and surgical risks. Exploring and establishing uniform, adaptive surgical guidelines promise to revolutionize patient care by significantly reducing complications and enhancing recovery and satisfaction following abdominoplasty.

Performance and Safety of Amino-Acid- and Hydroxyapatite Enriched-Hyaluronic Acid Intradermal Gel in Facial Skin Defects.

Background and Objectives: The facial skin defects associated with aging are common concerns in the aging population. Hyaluronic-acid-based intradermal gels have established themselves as safe and effective treatments for addressing these concerns. Recently developed enriched products aim to enhance the efficacy of these gels, yet their effectiveness lacks thorough validation in the existing literature. Materials and Methods: In this retrospective analysis, we investigated the outcomes of intradermal gel treatments in 103 patients with soft tissue defects. This study included three groups: 35 patients received amino-acid-enriched hyaluronic acid gel, another 35 were treated with hydroxyapatite-enriched hyaluronic acid gel, and the remaining 33 underwent hyaluronic acid treatment only. The efficacy of the treatments was assessed using the Global Aesthetic Improvement Scale (GAIS) score, while patient satisfaction was gauged through a detailed questionnaire. Any adverse event was monitored. Results: The treatments demonstrated remarkable efficacy, as evidenced by mean GAIS scores of 1.714 points for those treated with amino acid-enriched hyaluronic acid gel, 1.886 points for individuals receiving hydroxyapatite-enriched hyaluronic acid gel, and 1.697 for those treated with hyaluronic acid alone, all showing statistical significance (p < 0.0001). Patient satisfaction was very high. Significantly, there were no recorded instances of major adverse events. Conclusions: Hyaluronic gels, particularly those enriched with amino acids and hydroxyapatite, are effective and safe interventions for addressing facial skin aging defects. They serve as valuable tools in mitigating age-related blemishes and contribute to the overall improvement of skin aesthetics.

Study of a Subcutaneous Lesion of the Shoulder: The Saint Paolino Tumor.

In certain small counties in southern Italy, traditional Catholic festivals are observed by erecting tall, large, and weighty wagons referred to as "lilies." These wagons are borne on the shoulders of several individuals known as "cradles." This practice has given rise to the emergence of a distinct subcutaneous neoformation on the shoulder. This study investigates the unique clinical and anatomopathological attributes of "Saint Paolino tumor" (named in honor of the Catholic patron of the widely celebrated lilies festival). This tumor presents as a posttraumatic intermittent chronic lesion occurring on the shoulder, necessitating differential diagnosis from other cutaneous and soft tissue lesions such as spontaneous lipomas, elastofibroma, Madelung disease, and liposarcoma.

Distinctive clinical traits of lupus-related myocarditis: a multicentre retrospective study.

OBJECTIVES: Cardiovascular involvement in systemic lupus erythematosus (SLE) is frequent but little is known about possible distinctive traits of SLE-related myocarditis (myoSLE) in comparison to patients with SLE (onlySLE) or myocarditis alone (onlyMyo). METHODS: A retrospective analysis was performed comparing patients with myoSLE (n = 25) from three centres with consecutive patients with onlySLE (n = 279) and onlyMyo (n = 88). SLE patients were dichotomised by disease duration ≤1 vs >1 year into recent onlySLE/early myoSLE vs longstanding onlySLE/late myoSLE. Further stratification into disease duration of 1-5, 5-10 and >10 years was also performed. SLE disease activity index 2000 (SLEDAI-2K) was used to estimate disease activity. Myocarditis was diagnosed through biopsy or magnetic resonance. RESULTS: Women were significantly more frequent among myoSLE than among onlyMyo (72% vs 43%; p= 0.013). Compared with onlyMyo, myoSLE patients had a higher frequency of conduction abnormalities (22% vs 5%; p= 0.046) and presented with numerically higher frequencies of left ventricular function compromise (48% vs 30%), along with higher pro-brain natriuretic peptide levels. Inflammation markers were higher in myoSLE compared with onlyMyo and to patients with onlySLE with >10 years of disease duration. SLEDAI-2K was significantly higher in late myoSLE than in longstanding onlySLE. Antiphospholipid syndrome was more frequent in myoSLE than in onlySLE. Multivariate analysis showed an association among myoSLE, anti-beta-2-glycoprotein I antibodies (aB2GPI, p= 0.014) and a higher number of involved British Isles Lupus Assessment Group domains in patient history (p= 0.003). CONCLUSION: myoSLE has unique clinical traits compared with other forms of myocarditis and is associated with aB2GPI and a more severe SLE course.

Digital three-dimensional assessment of free gingival graft remodeling over 12 months.

OBJECTIVE: To digitally evaluate the three-dimensional (3D) remodelling of FGG used to treat RT2 gingival recessions and lack of keratinized tissue on mandibular incisor teeth. METHODS: Data from 45 patients included in a previous multicentric RCT were analyzed. Silicone impressions were taken before (baseline) and 3, 6 and 12 months after standardized FGG placement. Casts were scanned and images were superimposed, using digital software, to obtain measurements of estimated soft tissue thickness (eTT; 1, 3, and 5 mm apical to baseline gingival margin). In addition, soft tissue volume (STV) and creeping attachment (CA) were assessed. RESULTS: All patients exhibited postoperative eTT and STV increases, at all time points. The greatest mean thickness gain was observed at eTT3 (1.0 ± 0.4 mm) at 12 months. At 12 months, STV was 52.3 ± 21.1 mm3, without relevant changes compared to the 3- and 6-month follow-up. CA, which was observed as early as six months postoperatively, was evident in ∼85 % of teeth at 12 months. CONCLUSIONS: Application of FGG was an effective phenotype modification therapy, as shown by the significantly increased tissue thickness postoperatively. Despite the use of FGG technique not aiming for root coverage, digital 3D assessment documented the early and frequent postoperative occurrence of CA, which helped improve recession treatment outcomes. CLINICAL SIGNIFICANCE: The use of 3D assessment methodology allows precise identification of the tissue gain obtained with FGG, which, regardless of technique, results in predictable phenotype modification and frequent occurrence of creeping attachment.

Is parental overcontrol a specific form of child maltreatment? Insights from a resting state EEG connectivity study.

INTRODUCTION: Recent studies suggest that parental overcontrol could be considered a specific form of childhood trauma (CT). Although previous research has shown that CT alters the functional and structural architecture of large-scale networks in the brain, the neural basis associated with parental overcontrol has not been sufficiently explored. Therefore, the main aim of the current study was to investigate the relationship between parental overcontrol and electroencephalography (EEG) triple network (TN) functional connectivity during the resting state (RS) condition in a non-clinical sample (N = 71; 39 females, mean age 23.94 ± 5.89 SD). METHODS: EEG was recorded during 5 min of RS with eyes closed. All participants were asked to self-report maternal and paternal overcontrol, CT and general psychopathology. All EEG analyses were performed using the exact low-resolution electromagnetic tomography software (eLORETA). RESULTS: Our results showed a significant positive correlation between maternal overcontrol and theta connectivity between the salience network and the central executive network. This connectivity pattern was independently associated with maternal overcontrol even when controlling for relevant confounding variables, including the severity of CT and the general level of psychopathology. This neurophysiological pattern may reflect a predisposition to detect and respond to potentially threatening stimuli in the environment, which is typically associated with excessive overcontrol. CONCLUSIONS: Our findings support the hypothesis that parental overcontrol should be considered a form of CT in all respects independent of the forms traditionally studied in the literature (i.e., emotional abuse, physical abuse, sexual abuse, and physical and emotional neglect).

Clinical outcomes of ruxolitinib treatment in 595 intermediate-1 risk patients with myelofibrosis: The RUX-MF Real-World Study.

BACKGROUND: Ruxolitinib (RUX) is a JAK1/2 inhibitor approved for the therapy of myelofibrosis (MF) based on clinical trials including only intermediate2-high risk (INT2/HIGH) patients. However, RUX is commonly used in intermediate-1 (INT1) patients, with scarce information on responses and outcome. METHODS: The authors investigated the benefit of RUX in 1055 MF patients, included in the "RUX-MF" retrospective study. RESULTS: At baseline (BL), 595 (56.2%) patients were at INT1-risk according to DIPSS (PMF) or MYSEC-PM (SMF). The spleen was palpable at <5 cm, between 5 and 10 cm, and >10 cm below costal margin in 5.9%, 47.4%, and 39.7% of patients, respectively; 300 (54.1%) were highly symptomatic (total symptom score ≥20). High-molecular-risk (HMR) mutations (IDH1/2, ASXL-1, SRSF2, EZH2, U2AF1Q157) were detected in 77/167 patients. A total of 101 (19.2%) patients had ≥1 cytopenia (Hb < 10 g/dL: n.36; PLT <100 x 109/L: n = 43; white blood cells <4 x 109/L: n = 40). After 6 months on RUX, IWG-MRT-defined spleen and symptoms response rates were 26.8% and 67.9%, respectively. In univariate analysis, predictors of SR at 6 months were no HMR mutations odds ratio [OR], 2.0, p = .05], no cytopenia (OR, 2.10; p = .01), and blasts <1% (OR, 1.91; p = .01). In multivariate analysis, absence of HMR maintained a significant association (OR, 2.1 [1.12-3.76]; p = .01). CONCLUSIONS: In INT1 patients, responses were more frequent and durable, whereas toxicity rates were lower compared to INT2/high-risk patients. Presence of HMR mutations, cytopenia, and peripheral blasts identified less-responsive INT1 patients, who may benefit for alternative therapeutic strategies.

Miniaturizable Chemiluminescence System for ATP Detection in Water.

We present the design, fabrication, and testing of a low-cost, miniaturized detection system that utilizes chemiluminescence to measure the presence of adenosine triphosphate (ATP), the energy unit in biological systems, in water samples. The ATP-luciferin chemiluminescent solution was faced to a silicon photomultiplier (SiPM) for highly sensitive real-time detection. This system can detect ATP concentrations as low as 0.2 nM, with a sensitivity of 79.5 A/M. Additionally, it offers rapid response times and can measure the characteristic time required for reactant diffusion and mixing within the reaction volume, determined to be 0.3 ± 0.1 s. This corresponds to a diffusion velocity of approximately 44 ± 14 mm2/s.

Clarifying Glycerol Electrooxidation Studies on Pd-Based Catalysts: Insights Into Catalytic Performance and Practical Challenges.

Escalating biodiesel production led to a surplus of glycerol, prompting its exploration as a valuable resource in industrial applications. Electrochemical systems have been studied, specifically employing noble metal catalysts like palladium for glycerol electrooxidation. Despite numerous studies on Pd-based catalysts for glycerol electrooxidation, a comprehensive analysis addressing critical questions related to the economic feasibility, global sourcing of Pd, and the thematic cohesion of publications in this field is lacking. Moreover, a standardized framework for comparing the results of various studies is absent, hindering progress on glycerol technologies. This critical overview navigates the evolution of Pd-based catalysts for glycerol electrooxidation, examining catalytic activity, stability, and potential applications. It critically addresses the geographical sources of Pd, the motivation behind glycerol technology exploration, thematic coherence in existing publications, and the meaningful comparison of results. It correlates the use of Pd-based catalysts with the natural source of Pd and the origin of glycerol derived from biodiesel. The proposed standardized approach for comparing electrochemical parameters and establishing experimental protocols provides a foundation for meaningful study comparisons. This critical overview underscores the need to address fundamental questions to accelerate the transition of glycerol technologies from laboratories to practical applications.

Prophylactic Venous Supercharging in Deep Inferior Epigastric Artery Perforator Flap Surgery: A Retrospective Dual-Center Study.

BACKGROUND: Deep inferior epigastric artery perforator (DIEP) flap is nowadays considered the gold standard in breast reconstruction. However, venous congestion is still a leading cause of free flap failure. Despite the conspicuous articles regarding the use of a secondary venous anastomosis, there is a lack in the literature regarding the prophylactic use of a secondary venous route to reduce the incidence of complications during breast reconstruction. METHODS: A double-center retrospective study based on women undergoing DIEP breast reconstruction was conducted, dividing patients into case group (DIEP flaps with double venous anastomosis) and control group (DIEP flaps with single venous anastomosis). Demographic and surgical data and complications were compared and statistically analyzed, and a reconstructive algorithm was proposed to improve the flap insetting. RESULTS: In total, 154 patients were included in the study, divided into case group (74 patients) and control group (80 patients). The median age at the time of surgery was 49.09 years (range: 29-68 years), slightly lower in group 1 when compared with group 2. The mean body mass index (BMI) was 25.52 kg/m2 (range: 21.09-29.37 kg/m2), in particular 25.47 kg/m2 (range: 23.44-28.63 kg/m2) in group 1 and 25.58 kg/m2 (range: 21.09-29.37 kg/m2) in group 2. No statistical differences were found between groups in terms of BMI and smoking and comorbidities history. The average operative times were 272.16 minutes (range: 221-328 minutes) in group 1 and 272.34 minutes (range: 221-327 minutes) in group 2, with no significant difference between groups, as well as ischemia time (44.4 minutes in group 1 [range: 38-56 minutes] and 49.12 minutes in group 2 [range: 41-67 minutes]). Statistical analysis showed a reduction in short-term complications and a statistically significant reduction for take-backs in the two groups. CONCLUSIONS: Our study suggests that venous supercharging of DIEP flap by performing dual venous anastomosis can be routinely and safely done prophylactically, and thus not only after intraoperative assessment of venous congestion, to avoid flap venous congestion and decrease the rates of re-exploration.

A Comprehensive Investigation of Methanol Electrooxidation on Copper Anodes: Spectroelectrochemical Insights and Energy Conversion in Microfluidic Fuel Cells.

Here, we comprehensively investigated methanol electrooxidation on Cu-based catalysts, allowing us to build the first microfluidic fuel cell (µFC) equipped with a Cu anode and a metal-free cathode that converts energy from methanol. We applied a simple, fast, small-scale, and surfactant-free strategy for synthesizing Cu-based nanoparticles at room temperature in steady state (ST), under mechanical stirring (MS), or under ultrasonication (US). The morphology evaluation of the Cu-based samples reveals that they have the same nanoparticle (NP) needle-like form. The elemental mapping composition spectra revealed that pure Cu or Cu oxides were obtained for all synthesized materials. In addition to having more Cu2O on the surface, sample US had more Cu(OH)2 than the others, according to X-ray diffractograms and X-ray photoelectron spectroscopy. The sample US is less carbon-contaminated because of the local heating of the sonic bath, which also enhances the cleanliness of the Cu surface. The activity of the Cu NPs was investigated for methanol electrooxidation in an alkaline medium through electrochemical and spectroelectrochemical measurements. The potentiodynamic and potentiostatic experiments showed higher current densities for the NPs synthesized in the US. In situ FTIR experiments revealed that the three synthesized NP materials eletcrooxidize methanol completely to carbonate through formate. Most importantly, all pathways were led without detectable CO, a poisoning molecule not found at high overpotentials. The reaction path using the US electrode experienced an additional round of formate formation and conversion into carbonate (or CO2 in the thin layer) after 1.0 V (vs. Ag/Ag/Cl), suggesting improved catalysis. The high activity of NPs synthesized in the US is attributed to effective dissociative adsorption of the fuel due to the site's availability and the presence of hydroxyl groups that may fasten the oxidation of adsorbates from the surface. After understanding the surface reaction, we built a mixed-media µFC fed by methanol in alkaline medium and sodium persulfate in acidic medium. The µFC was equipped with Cu NPs synthesized in ultrasonic-bath-modified carbon paper as the anode and metal-free carbon paper as the cathode. Since the onset potential for methanol electrooxidation was 0.45 V and the reduction reaction revealed 0.90 V, the theoretical OCV is 0.45 V, which provides a spontaneous coupled redox reaction to produce power. The µFC displayed 0.56 mA cm-2 of maximum current density and 26 µW cm-2 of peak power density at 100 µL min-1. This membraneless system optimizes each half-cell individually, making it possible to build fuel cells with noble metal-free anodes and metal-free cathodes.

Electrolytes for Sodium Ion Batteries: The Current Transition from Liquid to Solid and Hybrid systems.

Sodium-ion batteries (NIBs) have recently garnered significant interest in being employed alongside conventional lithium-ion batteries, particularly in applications where cost and sustainability are particularly relevant. The rapid progress in NIBs will undoubtedly expedite the commercialization process. In this regard, tailoring and designing electrolyte formulation is a top priority, as they profoundly influence the overall electrochemical performance and thermal, mechanical, and dimensional stability. Moreover, electrolytes play a critical role in determining the system's safety level and overall lifespan. This review delves into recent electrolyte advancements from liquid (organic and ionic liquid) to solid and quasi-solid electrolyte (dry, hybrid, and single ion conducting electrolyte) for NIBs, encompassing comprehensive strategies for electrolyte design across various materials, systems, and their functional applications. The objective is to offer strategic direction for the systematic production of safe electrolytes and to investigate the potential applications of these designs in real-world scenarios while thoroughly assessing the current obstacles and forthcoming prospects within this rapidly evolving field.

Decision-making on peri-implant mucositis management and treatment approaches.

Peri-implant mucositis is characterised by inflammation of soft tissues surrounding a dental implant without associated bone loss beyond initial remodelling. Early detection and timely intervention are critical to prevent its progression to peri-implantitis. This paper focuses on various treatment options for treating peri-implant mucositis. The cornerstone of professional treatment lies in the mechanical disruption and removal of microbial biofilms around the implant. This can be achieved through careful use of manual or powered instruments, such as ultrasonic scalers or air polishing devices. However, there is a need for further research to determine the most effective single approach for treating peri-implant mucositis. Current evidence does not support the combination of mechanical debridement with locally administered antibiotics. Contrarily, evidence strongly supports the removal, cleaning, and modifications of prostheses to improve both self-performance and professional cleanability. The use of adjunctive therapies like photodynamic therapy and diode laser, in conjunction with mechanical instrumentation, is not currently recommended due to the limited strength of available evidence. Preventive measures emphasise the importance of comprehensive oral hygiene care, encompassing professional guidance and at-home practices, to manage biofilms effectively. This encompasses oral hygiene instruction, regular debridement, and maintenance care. Supporting peri-implant therapy is also vital for ongoing implant monitoring, preventing the recurrence of mucositis, and halting its progression to peri-implantitis. This multifaceted approach is key to effectively managing and treating peri-implant mucositis.

EEG functional connectivity as a Riemannian mediator: An application to malnutrition and cognition.

Mediation analysis assesses whether an exposure directly produces changes in cognitive behavior or is influenced by intermediate "mediators". Electroencephalographic (EEG) spectral measurements have been previously used as effective mediators representing diverse aspects of brain function. However, it has been necessary to collapse EEG measures onto a single scalar using standard mediation methods. In this article, we overcome this limitation and examine EEG frequency-resolved functional connectivity measures as a mediator using the full EEG cross-spectral tensor (CST). Since CST samples do not exist in Euclidean space but in the Riemannian manifold of positive-definite tensors, we transform the problem, allowing for the use of classic multivariate statistics. Toward this end, we map the data from the original manifold space to the Euclidean tangent space, eliminating redundant information to conform to a "compressed CST." The resulting object is a matrix with rows corresponding to frequencies and columns to cross spectra between channels. We have developed a novel matrix mediation approach that leverages a nuclear norm regularization to determine the matrix-valued regression parameters. Furthermore, we introduced a global test for the overall CST mediation and a test to determine specific channels and frequencies driving the mediation. We validated the method through simulations and applied it to our well-studied 50+-year Barbados Nutrition Study dataset by comparing EEGs collected in school-age children (5-11 years) who were malnourished in the first year of life with those of healthy classmate controls. We hypothesized that the CST mediates the effect of malnutrition on cognitive performance. We can now explicitly pinpoint the frequencies (delta, theta, alpha, and beta bands) and regions (frontal, central, and occipital) in which functional connectivity was altered in previously malnourished children, an improvement to prior studies. Understanding the specific networks impacted by a history of postnatal malnutrition could pave the way for developing more targeted and personalized therapeutic interventions. Our methods offer a versatile framework applicable to mediation studies encompassing matrix and Hermitian 3D tensor mediators alongside scalar exposures and outcomes, facilitating comprehensive analyses across diverse research domains.

Structural basis for the broad antigenicity of the computationally optimized influenza hemagglutinin X6.

Influenza causes significant morbidity and mortality. As an alternative approach to current seasonal vaccines, the computationally optimized broadly reactive antigen (COBRA) platform has been previously applied to hemagglutinin (HA). This approach integrates wild-type HA sequences into a single immunogen to expand the breadth of accessible antibody epitopes. Adding to previous studies of H1, H3, and H5 COBRA HAs, we define the structural features of another H1 subtype COBRA, X6, that incorporates HA sequences from before and after the 2009 H1N1 influenza pandemic. We determined structures of this antigen alone and in complex with COBRA-specific as well as broadly reactive and functional antibodies, analyzing its antigenicity. We found that X6 possesses features representing both historic and recent H1 HA strains, enabling binding to both head- and stem-reactive antibodies. Overall, these data confirm the integrity of broadly reactive antibody epitopes of X6 and contribute to design efforts for a next-generation vaccine.

Targeted Metabolomics Highlights Dramatic Antioxidant Depletion, Increased Oxidative/Nitrosative Stress and Altered Purine and Pyrimidine Concentrations in Serum of Primary Myelofibrosis Patients.

To date, little is known concerning the circulating levels of biochemically relevant metabolites (antioxidants, oxidative/nitrosative stress biomarkers, purines, and pyrimidines) in patients with primary myelofibrosis (PMF), a rare form of myeloproliferative tumor causing a dramatic decrease in erythropoiesis and angiogenesis. In this study, using a targeted metabolomic approach, serum samples of 22 PMF patients and of 22 control healthy donors were analyzed to quantify the circulating concentrations of hypoxanthine, xanthine, uric acid (as representative purines), uracil, ß-pseudouridine, uridine (as representative pyrimidines), reduced glutathione (GSH), ascorbic acid (as two of the main water-soluble antioxidants), malondialdehyde, nitrite, nitrate (as oxidative/nitrosative stress biomarkers) and creatinine, using well-established HPLC method for their determination. Results showed that PMF patients have dramatic depletions of both ascorbic acid and GSH (37.3- and 3.81-times lower circulating concentrations, respectively, than those recorded in healthy controls, p < 0.0001), accompanied by significant increases in malondialdehyde (MDA) and nitrite + nitrate (4.73- and 1.66-times higher circulating concentrations, respectively, than those recorded in healthy controls, p < 0.0001). Additionally, PMF patients have remarkable alterations of circulating purines, pyrimidines, and creatinine, suggesting potential mitochondrial dysfunctions causing energy metabolism imbalance and consequent increases in these cell energy-related compounds. Overall, these results, besides evidencing previously unknown serum metabolic alterations in PMF patients, suggest that the determination of serum levels of the aforementioned compounds may be useful to evaluate PMF patients on hospital admission for adjunctive therapies aimed at recovering their correct antioxidant status, as well as to monitor patients' status and potential pharmacological treatments.

Psychometric Properties of the Detachment and Compartmentalization Inventory (DCI) in an Italian Community Sample.

The Detachment and Compartmentalization Inventory (DCI) is a valid and reliable self-report instrument that assesses these two distinct forms of dissociative symptoms. However, there is limited research on the cross-cultural validation of the DCI. Therefore, this study aimed to develop an Italian translation of the DCI and examine its internal structure and psychometric properties (including internal consistency, convergent validity, and test-retest reliability) within an Italian-speaking community sample. The sample consisted of 1276 adults (887 females; mean age: 29.57 ± 10.96 years), who completed the DCI and other self-report measures evaluating dissociative experiences and childhood trauma. Confirmatory factor analyses supported the original two-factor model (χ2169 = 1312.80, RMSEA = 0.073, 95%CI 0.069-0.077; CFI = 0.94; TLI = 0.94; SRMR = 0.04). Additionally, the DCI exhibited good internal consistency, test-retest reliability, and convergent validity with another measure of dissociation. The study also confirmed the association between DCI scores and the severity of childhood trauma. Finally, a Receiver Operating Characteristic (ROC) curve analysis demonstrated that the DCI effectively distinguishes individuals who screened positively for dissociative disorders. Overall, these findings indicate that the Italian translation of the DCI possesses satisfactory psychometric properties, suggesting its utility as a screening tool for assessing detachment and compartmentalization experiences.