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Abstract This study sought to investigate the demographic and clinical characteristics of Sudanese men diagnosed with prostate cancer (PCa) to highlight differences in diagnosis among the three major ethnolinguistic groups. A total of 532 patients with confirmed PCa diagnosis through biopsy were enrolled from six medical centers in Sudan. The majority of patients, comprising 84.2% (448/532), were diagnosed with advanced-stage disease, with a Grade group above 3. There were no discernible differences in PCa aggressiveness among the ethnolinguistic groups. However, higher levels of prostate-specific antigen (PSA) were observed in the Niger-Congo group, where 55.2% had PSA values exceeding 50 ng/ml. Patients from this group were also diagnosed at a younger age. In contrast, 90.5% of Afro-Asiatic patients are over 60 years old. Further analysis conducted within an age-matched subgroup of patients (n = 273) revealed a higher incidence of perineural invasion in the Afro-Asiatic group. This research represents the first investigation of PCa across different African ethnic groups and associates a higher incidence of perineural invasion with a specific ethnic group. While recent efforts have been made to establish African-relevant risk models to mitigate PCa health disparities, there remains a need for further investigation into genetically distinct populations within the African continent.

Abstract Diabetes is a prevalent metabolic condition with substantial health and economic impacts. Therefore, effective and accessible indicators are essential for early detection and prevention. This study investigates the link between the waist-to-calf circumference ratio (WCR) and diabetes risk in a large cohort from the Longevity Check-Up (Lookup) 8+ Study. The present investigation is a retrospective cross-sectional study. Diabetes was defined either as self-reported diagnosis, or fasting plasma glucose equal to or greater than 126 mg/dL, or random plasma glucose equal to or greater than 200 mg/dL. The WCR was calculated by dividing waist circumference by calf circumference. A total population of 8900 participants (mean age 57.1 ± 14.8 years, 55% women) was included in the study. The prevalence of diabetes was 9.4%. Mean WCR displayed a significant trend (p for trend

Abstract The Coma Recovery Scale-revised (CRS-r) is the gold standard for the behavioral assessment of patients with Disorders of Consciousness (DoCs). However, the misdiagnosis rate is around 40%. For this reason, recent guidelines suggested enhancing the assessment with neurophysiological measures: among these, surface electromyography (sEMG) represents a convenient bedside solution. This work presents the use of the STRIVEfc system, a wearable device that allows CRS-r administration while recording four sEMG signals. STRIVEfc was employed in 40 sessions on 33 DoCs patients and the sEMG was analyzed to look for voluntary and consistent over threshold (OT) muscular activities. Their duration, amplitude, and number were retained and compared between patients in Unresponsive Wakefulness Syndrome (UWS) and Minimally Conscious State (MCS), revealing more numerous and significantly longer OTs in the latter group. Lastly, the EMG information was exploited to enrich the behavioral assessment by building the instrumented CRS-r score (ICRS-r). In 9/16 UWS sessions, the ICRS-r score suggested a higher-level functioning, not translated into a behavioral response, compatible with MCS diagnosis. Overall, the use of STRIVEfc allows to reveal hidden muscular patterns not detectable by the clinician, thus improving the characterization of DoCs patient’s functional capabilities and supporting the diagnostic process.

Abstract The abnormal biological activity of cytokines and their imbalance are implicated in developing rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Cytokine levels were measured in RA and SLE patients and compared to healthy controls using the Wilcoxon rank sum test and Kruskal–Wallis test. The relationship between cytokine levels and blood and clinical parameters was assessed using Spearman's correlation test. Compared to healthy controls, both RA and SLE patients exhibited elevated levels of GM-CSF, CX3CL1, IFN-α2, IL-12p70, IL-17A, TNF-α, IL-1β, and IFN-γ, which is evidence of their shared inflammatory signature. IL-2 levels were elevated exclusively in RA patients, while MCP-1 and IL-10 were uniquely increased in SLE patients. Notably, TNF-α showed the most significant increase in SLE patients. IL-4 was elevated in SLE patients with nephritis, correlating with IL-6, IL-10, sCD40L, and IL-8, suggesting B cell involvement in lupus nephritis. The negative correlation between CX3CL1 and TNF-α with HDL in RA and SLE respectively, highlights the potential association of these inflammatory markers with cardiovascular risk. These findings underscore the complex cytokine interplay in RA and SLE. CX3CL1 emerges as a potential therapeutic target for RA, while TNF-α and IL-4 show promise as therapeutic targets for SLE.

Loris Cacciatore,1 Angelo Territo,2 Antonio Minore,1 Antonio Testa,1 Guglielmo Mantica,3 Francesco Esperto1 1Department of Urology, Fondazione Policlinico Universitario Campus Bio-Medico Di Roma, Rome, Italy; 2Department of Urology, Fundació Puigvert, Autonoma University of Barcelona, Barcelona, Spain; 3Department of Surgical and Diagnostic Integrated Sciences (DISC), University of Genova, Genoa, ItalyCorrespondence: Loris Cacciatore, Department of Urology, Fondazione Policlinico Universitario Campus Bio-Medico di Roma, Rome, Italy, Email loris.cacciatore@unicampus.itAbstract: Bladder pain Syndrome presents a multifaceted challenge in contemporary urological practice, marked by LUTS, negative behavioural, sexual, or emotional experiences, and the potential for sexual dysfunction. We meticulously explored the existing literature of conservative, non-invasive and invasive interventions, aiming to provide clinicians with a nuanced understanding of available options for comprehensive BPS management. We delve into the effectiveness and safety profiles from behavioural approaches through lifestyle changes and physical therapy, to oral or intravesical medications, until the definitive surgical treatment. The best option evaluated is the involvement of a multidisciplinary team, including urologists, urotherapists, gynaecologists, pain specialists, primary care physicians and psychologists, educating those patients regarding the condition and its chronic course and tailoring the perfect treatment for each person. Despite this, BPS remains a challenge for urologists. Indeed, our objective is to contribute to the evolving landscape of BPS management, fostering informed decision-making and personalized care for individuals grappling with this challenging condition.Keywords: bladder pain syndrome, interstitial cystitis, lower urinary tract symptoms, females, continence, therapy, conservative treatment

Only a very few studies to date have comprehensively assessed children's knowledge of sexuality. In this study, we examined the level of sexual knowledge among children aged 3-6 years in Finland. We analysed children's explanations of what they saw in drawings related to genital naming, conception and childbirth, safety skills, and adult sexual activity. Levels of knowledge were generally low. The largest number of correct answers were given for genital naming and safety skills. Knowledge increased with age. Children's gender was not related to their total level of knowledge. There was a correlation between children's ability to name their genitals and their knowledge of safety skills. The results suggest that only what is known about can be protected. Building on the findings of this study, age-appropriate sexuality education should be provided to all children.

Background: Poor sleep quality may contribute to sarcopenia, but evidence remains sparse. This retrospective cross-sectional study investigated the association between subjective sleep quality and probable sarcopenia in a cohort of community-dwelling older adults enrolled in the Longevity Check-Up 8+ study. Methods: Participants were asked about their sleep quality over the past month, with four possible options (“very good”, “quite good”, “quite bad”, very bad”). For the analysis, participants were grouped into good or bad sleep quality categories. Probable sarcopenia was operationalized according to handgrip strength values < 27 kg for men and

The primary objective of this paper is to examine, both theoretically and empirically, two distinct approaches through which artistic research intersects with academia. This examination is undertaken to critically evaluate the paradigmatic tensions arising from the juxtaposition of unfettered artistic exploration and the escalating pressures for demonstrable outcomes, accountability, and process transparency inherent in managerial contexts. Consequently, the theoretical underpinnings of artistic interventions within organizational settings will be explicated, emphasizing the academic community’s exploration and application of such modes of artistic inquiry. Conversely, the approach of art-based research will be delineated, emphasizing its utilization of artistic modalities to investigate phenomena through a scientific lens. Moreover, prominent theories positing academic research as constraining artistic experimentation will be outlined. Finally, drawing upon four case reports conducted within academic environments, a novel method will be proposed to mitigate the encroachment of increasingly institutionalized approaches towards the arts.

To date, robotic surgery has gained much popularity, impacting deeply on surgical fields such as genitourinary system branches, general surgery, and cardiac surgery. We aim to outline the landscape of robotic surgery, focusing on design improvements, which have improved both the technical skills of surgeons and the outcomes of minimally invasive technique for patients. A thorough narrative literature review was conducted on PubMed/MEDLINE, employing keywords such as “robotic surgical system”, “robotic surgical device”, and “robotics AND urology”. Furthermore, the reference lists of the retrieved articles were scrutinized. The analysis focused on urological surgical systems from the 2000s to the present day. Beginning with the daVinci® Era in the 2000s, new robotic competitors, including Senhance®, Revo-I®, Versius®, Avatera®, Hi-notori®, and HugoTM RAS, have entered the medical market. While daVinci® has maintained a high competitiveness, even more new platforms are now emerging in the medical market with new intriguing features. The growing competition, driven by unique features and novel designs in emerging robotic technologies, has the potential to improve application fields, enhance diffusion, and ameliorate the cost effectiveness of procedures. Since the impact of these new surgical technologies on different specialties and healthcare systems remains unclear, more experience and research are required to define their evolving role.

Muscle tone represents a foundational property of the motor system with the potential to impact musculoskeletal pain and motor performance. Muscle tone is involuntary, dynamically adaptive, interconnected across the body, sensitive to postural demands, and distinct from voluntary control. Research has historically focused on pathological tone, peripheral regulation, and contributions from passive tissues, without consideration of the neural regulation of active tone and its consequences, particularly for neurologically healthy individuals. Indeed, simplistic models based on the stretch reflex, which neglect the central regulation of tone, are still perpetuated today. Recent advances regarding tone are dispersed across different literatures, including animal physiology, pain science, motor control, neurology, and child development. This paper brings together diverse areas of research to construct a conceptual model of the neuroscience underlying active muscle tone. It highlights how multiple tonic drive networks tune the excitability of complex spinal feedback circuits in concert with various sources of sensory feedback and in relation to postural demands, gravity, and arousal levels. The paper also reveals how tonic muscle activity and excitability are disrupted in people with musculoskeletal pain and how tone disorders can lead to marked pain and motor impairment. The paper presents evidence that integrative somatic methods address the central regulation of tone and discusses potential mechanisms and implications for tone rehabilitation to improve pain and performance.

In the field of medicinal chemistry, the versatility of the thiosemicarbazone scaffold makes it a promising platform for the development of next-generation pharmaceuticals. In this paper the thiosemicarbazone scaffold was explored to obtain novel series of derivatives: a) thiosemicarbazones 15–31, and 33 containing a linear thiosemicarbazone scaffold, b) 34–38 and 44–64 containing pyrazoline ring, and c) 39–43 containing the dihydropyrimidine cycle. Among these, compounds 21, 23, 26, 33–35, 37, 38, 44, 57, 61, and 62 demonstrated no significant cytotoxic effects on HDFa cells at concentrations up to 500 μg/mL. Importantly, compounds 21, 23, 26, 33, 34, 35, and 37 exhibited significant protective effects against neurotoxicity induced by beta-amyloid peptide (1-42) in differentiated SHSY-5Y cell cultures. Enzymatic assays targeting BACE1 and AChE revealed modest inhibitory activity in compounds 21, 23, and 34, 37, respectively. The identification of compounds with inhibitory effects and neuroprotective activity against beta-amyloid peptide (1-42) offers a platform for further optimization and refinement of these compounds to enhance their potency and selectivity.

Purpose Orthostatic hypotension (OH) may predispose older adults to health complications leading to functional impairment. Despite the central role of the kidney in blood pressure control, the contribution of renal function in orthostatic hypotension is poorly investigated. To verify the association between Chronic Kidney Disease (CKD) and OH a population of hospitalised elderly patients with comorbidities was studied.Materials and methods 174 patients were consecutively admitted to Acute Geriatric Wards. On admission, patients underwent postural systolic (SBP) and diastolic (DBP) blood pressure evaluation by automatic oscillometric device after 10 min rest in lying position, and in standing position at time 0, 1, 3 and 5 min. CKD was assumed for estimated glomerular filtration rate (e-GFR) less than 60 mL/min/1.73 m2.Results The mean age of the population enrolled was 74.4 ± 7.0. OH was found in 46.0% and CKD in 56.3% of patients, respectively. A lower e-GFR was observed in patients with (56.1 ± 16.7 mL/min/1.73 m2) than in those without OH (61.1 ± 15.9 mL/min/1.73 m2) (p

Cyclin-dependent kinase 9 (CDK9) and cytochrome P450 3A4 (CYP3A4) have emerged as promising targets in the development of anticancer drugs, presenting a consistent challenge in the quest for potent inhibitors. CDK9 inhibitors can selectively target fast-growing cancer cells by disrupting transcription elongation, which in turn hinders the production of proteins essential for cell cycle progression and survivaŚ. Understanding how CYP3A4 metabolizes specific chemotherapy drugs allows for personalized treatment plans, optimizing drug dosages according to a patient’s metabolic profile. Since many cancer patients undergo combination therapies, and CYP3A4 is vital in drug metabolism, its inhibition or induction by one drug can alter the plasma levels of others, potentially leading to treatment failure or increased toxicity. Therefore, managing CYP3A4 activity is critical for effective cancer treatment. Employing a range of computational methodologies, this study systematically investigated the binding mechanisms of pyrimidine derivatives against CDK9 and CYP3A4. The field-based model demonstrated high R2 values (0.99), with Q2 (0.66), demonstrating its ability to predict in silico inhibitory activity against the target of this study. The screening process followed in this work led to the discovery of powerful new inhibitor compounds. Of the 15 new compounds designed, three have a high affinity with the target (ranging from −8 to −9 kcal/mol kcal/mol) and were singled out through docking filtration for more detailed investigation. As well as, a reference compound with a substantial pIC50 value of 8.4, serving as the foundation for the development of the new compounds, was included for comparative analysis. To elucidate the essential features of CDK9 and CYP3A4 inhibitor design, a comparative analysis was conducted between 3D-QSAR-generated contours and molecular docking conformations of ligands. Molecular dynamics simulations were carried out for a duration of 100 ns on selected docked complexes, specifically those involving novel compounds with CDK9 and CYP3A4 enzymes. Additionally, the binding free energy for these complexes was assessed using the MM/PBSA method, which evaluates the free energy landscape of protein-ligand interactions. The results of MM/PBSA highlighted the strength of the new compounds in enhancing interactions with the target protein, which favors the results of molecular docking and MD simulation. These insights contribute to a deeper understanding of the mechanisms underlying CDK9 and CYP3A4 inhibition, offering potential avenues for the development of innovative and effective CDK9 inhibitors.

Background/Objectives: Over the past 25 years, numerous biological molecules, like recombinant lysosomal enzymes, neurotrophins, receptors, and therapeutic antibodies, have been tested in clinical trials for neurological diseases. However, achieving significant success in clinical applications has remained elusive. A primary challenge has been the inability of these molecules to traverse the blood–brain barrier (BBB). Recognizing this hurdle, our study aimed to utilize niosomes as delivery vehicles, leveraging the “molecular Trojan horse” technology, to enhance the transport of molecules across the BBB. Methods: Previously synthesized memantine derivatives (MP1–4) were encapsulated into niosomes for improved BBB permeability, hypothesizing that this approach could minimize peripheral drug toxicity while ensuring targeted brain delivery. Using the human neuroblastoma (SH-SY5Y) cell line differentiated into neuron-like structures with retinoic acid and then exposed to amyloid beta 1–42 peptide, we established an in vitro Alzheimer’s disease (AD) model. In this model, the potential usability of MP1–4 was assessed through viability tests (MTT) and toxicological response analysis. The niosomes’ particle size and morphological structures were characterized using scanning electron microscopy (SEM), with their loading and release capacities determined via UV spectroscopy. Crucially, the ability of the niosomes to cross the BBB and their potential anti-Alzheimer efficacy were analyzed in an in vitro transwell system with endothelial cells. Results: The niosomal formulations demonstrated effective drug encapsulation (encapsulation efficiency: 85.3% ± 2.7%), controlled release (72 h release: 38.5% ± 1.2%), and stable morphology (PDI: 0.22 ± 0.03, zeta potential: −31.4 ± 1.5 mV). Among the derivatives, MP1, MP2, and MP4 exhibited significant neuroprotective effects, enhancing cell viability by approximately 40% (p < 0.05) in the presence of Aβ1-42 at a concentration of 47 µg/mL. The niosomal delivery system improved BBB permeability by 2.5-fold compared to free drug derivatives, as confirmed using an in vitro bEnd.3 cell model. Conclusions: Memantine-loaded niosomes provide a promising platform for overcoming BBB limitations and enhancing the therapeutic efficacy of Alzheimer’s disease treatments. This study highlights the potential of nanotechnology-based delivery systems in developing targeted therapies for neurodegenerative diseases. Further in vivo studies are warranted to validate these findings and explore clinical applications.