Abstract: Endogenous hypercortisolism, also known as Cushing syndrome, is a multisystemic disease characterized by a wide range of clinical signs and symptoms. The diverse and heterogeneous presentation can lead to significant diagnostic delays, often extending up to 10 years. The consequences of delayed diagnosis can be severe, in that prolonged exposure to excess cortisol can contribute to increased cardiometabolic abnormalities such as diabetes. When diabetes remains hard to control (unresponsive or only partially responsive to standard-of-care treatment with known effective medications), it is crucial to consider hypercortisolism as its potential underlying driver. Despite the risks associated with prolonged cortisol excess, guidance on identifying and managing hypercortisolism in patients with hard-to-control diabetes remains limited. We present a case series involving 10 patients from a single practice who were screened for hypercortisolism due to hard-to-control diabetes despite standard-of-care treatment, substantial medication burdens with multiple antihyperglycemic and antihypertensive drugs, and additional comorbidities (obesity, hypertension, and renal impairment). Hypercortisolism was diagnosed based on biochemical evaluations, imaging, and the patient’s comorbidities. All patients were treated for hypercortisolism with mifepristone, a competitive glucocorticoid receptor antagonist, which resulted in significant clinical improvements including weight loss, better glycemic control, and reduced medication needs. We review the clinical characteristics of these patients to identify those at high risk for hypercortisolism and share our clinical insights on diagnosing, treating, and managing this condition for optimal patient outcomes. This real-world case series highlights the importance of recognizing hypercortisolism as a differential diagnosis and a potential contributing factor to hard-to-control diabetes despite standard-of-care therapies. Addressing hypercortisolism with mifepristone can result in substantial clinical benefits, including improved glycemic control and a reduced need for medications.

Abstract: During the COVID-19 pandemic, the availability of cardiac rehabilitation (CR) was lim-ited. On the other hand, during that period of epidemic hazard, patients after acute cor-onary syndromes (ACS) required careful control and ensuring their improvement after the coronary event. The aim of this study was to assess whether CR conducted during the epidemic threat in a remote mode ensured similar improvement in physical per-formance as CR conducted in a centre-based mode before the COVID-19 pandemic. Material and methods: In this one-centre study, we compared the demographic and clinical profiles of patients after ACS who completed inpatient CR before the COVID-19 era with those of patients who completed telerehabilitation during the COVID-19 pan-demic. We assessed the workload on the initial and final exercise tests (ExT) obtained by patients and compared the values of the differences between the final and initial ExT. The study included 359 patients (pts) participating in inpatient CR before October 2020 (the suspension of centre-based CR) and 60 pts who took part in telerehabilitation after July 2021 (the introduction of the tele-CR programme). Both inpatient and tele- CR were performed according to the guidelines of the Working Group for Cardiac Rehabil-itation of the National Cardiac Society. A telemedic platform was used to control ECG, blood pressure and body mass of the pts participating in telerehabilitation. Statistical analysis included the Mann-Whitney U test, Student’s t-test and chi-square test. Results: The improvement of physical performance did not differ significantly between the two groups. The pts who completed telerehabilitation were significantly older than those who completed inpatient CR. The values of other parameters, such as the percentage of females, BMI, the percentage of pts with arterial hypertension and type 2 diabetes mellitus, as well as left ventricular ejection fraction did not differ significantly between the compared groups. Nor did the results of initial ExT expressed in METs, the results of final ExT and the improvement of workload understood as the difference between the final and initial results of ExT differ significantly – they were 7,7±3,06 vs 7,89±2,98 with p=0,82; 9,08±,29 vs 8,98±3,48 with p=0,84, and 1[0-2,2] vs 1,2[0-1,8] with p=0,17, respec-tively. Conclusions: In our centre, telerehabilitation after acute coronary syndrome guaranteed an equally good improvement in physical capacity as that observed in inpatient CR pa-tients, regardless of the difference in the age profile of the compared groups. These re-sults encourage the popularization of the cardiac rehabilitation mode with the remote monitoring of the ECG, blood pressure and body mass.

Abstract: Background/Objectives: Buccal mucosa graft (BMG) is increasingly utilized in reconstructive urological surgeries due to its versatility, robust integration, histological characteristics and low morbidity at the donor site. Initially employed in urethral surgery, BMG use has expanded to complex ureteral and penile reconstructive procedures. This narrative review examines BMG applications in various urological surgeries, comparing its outcomes to other graft types, with a focus on surgical techniques and patient outcomes. Methods: A narrative review was conducted using PubMed and Scopus to identify relevant studies published over the last three decades on the use of BMG in urological reconstructive surgery. Articles in English addressing BMG harvesting, applications, and functional outcomes were analyzed. Results: BMG has demonstrated high success rates in every field of its application, especially in urethral reconstruction with an 83-91% efficacy rate in intermediate follow-up. Studies have also reported positive outcomes in complex ureteral and penile curvature surgeries, with patient satisfaction rates reaching up to 85%. Conclusions: BMG is an adaptable tissue graft for urological reconstructive surgeries, offering favorable outcomes with minimal morbidity. Although current results are encouraging, larger prospective studies with standardized protocols are necessary to fully validate its long-term efficacy and optimize treatment approaches for complex urological reconstructions.

Abstract: Metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) in pregnancy represent two distinct cardiometabolic populations, each potentially necessitating alternative clin-ical management. However, the understanding of the unique physiological effects of uncomplicated MHO or MUO on fetoplacental growth and metabolism remains limited. This study aimed to identify changes in placental morphology and metabolites concerning maternal obesity, inde-pendent of pregnancy-related cardiometabolic complications. Placentae from women with a pre-pregnancy body mass index (BMI) <25 kg/m² (control; n = 15) and women with MHO (pre-pregnancy BMI >30 kg/m² with no cardiometabolic diseases; n = 15) were analysed for indices of placental growth and untargeted metabolomics. Complementary measures of pro-inflammatory and antioxidant genes, as well as antioxidant proteins, enzymes, and lipid peroxidation markers were conducted. A clear placentomegaly without histopathological changes was observed in un-complicated MHO pregnancies. The metabolite 3-aminoisobutanoic acid emerged as the top-ranked feature distinguishing MHO from control placentae, and cysteine, methionine, and vitamin B6 metabolism pathways were among the most distinct signatures identified. These findings illustrate an altered placental morphology and metabolomic profile specific to uncomplicated MHO, offering new insights into how obesity without cardiometabolic complications influences fetoplacental growth and metabolism. They also represent a crucial first step towards marker identification for MHO pregnancies and underscore the importance of alternative care pathways when obesity is present but metabolic comorbidities are absent.

Abstract: Very few studies, all employing surveys, have investigated the perceptions of community pharmacists regarding antimicrobial stewardship (AMS). A qualitative inquiry exploring factors affecting community pharmacists’ participation in AMS may assist in the implementation of AMS in the primary care setting. This study aimed to explore the perceived barriers and enablers of community pharmacists’ participation in AMS. One-on-one semi-structured telephone interviews were conducted with a sample of community pharmacists from across Australia. Interviews were transcribed verbatim and analysed using the Framework Analysis. Method. Twenty community pharmacists (70% female), representing urban, regional, and remote areas of Australia participated in the study. Pharmacists identified a discord between clinical needs of patients and practice policies as the primary source of excessive prescribing and dispensing of antibiotics. The fragmented nature of the primary health care system in Australia was seen as limiting information exchange between community pharmacists and general practitioners about antibiotic use, that was encouraging inappropriate and, at times, unsupervised use of antibiotics. The existing community pharmacy funding model in Australia, where individual pharmacists do not benefit from any financial incentives associated with clinical interventions, was also discouraging their participation in AMS. Pharmacists suggested restricting default antibiotic repeat supplies, reducing legal validity of antibiotic prescriptions to less than the current 12 months, and adopting a treatment duration-based approach to antibiotic prescribing instead of the ‘quantity-based’ approach, where the quantity prescribed is linked to the available pack size of the antibiotic. Structural changes in the way antibiotics are prescribed, dispensed, and funded in the Australian primary care setting are urgently needed to discourage their misuse by the public. Modifications to the current funding model for pharmacist-led cognitive services are needed to motivate pharmacists to participate in AMS initiatives.

Abstract: Liposomal delivery of drugs and nanocarrier platforms are now revolutionized platforms for today's therapeutics, including better drug solubility, sustained circulation, and site-directed targeting. History and overview of liposomal drug delivery is addressed here, its formation, its types, and how it becomes functionalized. Advances in stealth technology and commercial FDA-approved formulations such as Doxil®, illustrate their place in cancer chemotherapy as well as general therapeutics. Comparison with micellar nanocarriers, solid lipid nanoparticles (SLNs), polymeric nanoparticles, and hybrid vesicular systems provides a scenario of the pros and cons of liposomes.Despite their advantages, liposomal systems are faced with targeting specificity, large-scale manufacture, and stability. The paper also identifies some of the up-and-coming trends in nanomedicine such as stimuli-responsive liposomes and hybrid carrier systems that aim at enhanced drug encapsulation, release kinetics, and therapeutic efficacy. All these have promising prospects for the future of liposomal technology in next-generation therapeutics to unlock improved drug delivery strategies with higher efficacy and fewer side effects.

Abstract: Background/Objective: Vancomycin, a hydrophilic glycopeptide antibiotic with bactericidal activity against gram-positive microorganisms, is one of the most used antibiotics at the intensive care units (ICU). Different efforts have been done to achieve therapeutically effective plasma concentration of vancomycin by using loading and subsequent maintenance doses on an individual basis, but this remains on the debate. Our objective was to individualize a dosage regimen in a Chilean ICU to optimize the pharmacological treatment of vancomycin by using a population pharmacokinetic model. Methods: A quantitative-descriptive study was carried out in 51 patients at the adult ICU, San Borja Arriarán Clinical Hospital in Santiago, Chile. The dose of vancomycin was calculated by using a population pharmacokinetic software, the Antibiotic Kinetics®, which was subsequently validated with plasma levels of the drug through a patient’s sample. Results: The most prescribed loading dose was 1,500 mg and the most used maintenance dose was 1,000 mg, 3 times a day. The measured blood plasma concentrations of each patient (16.98 ± 5.423 g/mL) were compared with the concentrations calculated through the population pharmacokinetic model (14.33 ± 4.630 g/mL, p&lt;0.05). Besides, a correlation was made between the software calculated trough concentration versus the measured trough concentration for vancomycin, where a positive correlation between both variables established (R2=0.65; p&lt;0.0001). No renal side effects were observed in the treated-patient group. Conclusions: In the present study, a vancomycin dosing model for critically ill patients, based on a population pharmacokinetic model, was successfully implemented for routine clinical practice.

Abstract: Background: Mesenchymal stem cell (MSC) therapy has garnered increasing attention as a novel therapeutic strategy for type 2 diabetes mellitus (T2DM), owing to its immunomodulatory and regenerative properties. However, the long-term efficacy of a single intravenous MSC infusion on glycemic control remains insufficiently explored. Objective: This study aimed to evaluate the long-term impact of a single intravenous infusion of MSCs on HbA1c reduction in patients with moderate and severe T2DM and to investigate potential dose- dependent responses. Methods: A total of 61 patients diagnosed with T2DM (HbA1c ≥6.2%) were enrolled. Patients received a single intravenous infusion of MSCs derived from umbilical cord tissue, bone marrow, or adipose tissue, with doses ranging from 100 million to 2 billion cells, tailored to individual clinical conditions. Patients were categorized into moderate (HbA1c 6.2–8%) and severe (HbA1c >8%) diabetes groups. Follow-up assessments were conducted over a median duration of 35 months (range: 6–68 months), with primary endpoints including changes in HbA1c levels. Statistical analyses were performed using paired t-tests, and correlation analyses evaluated the relationship between MSC dose and glycemic outcomes. Results: The mean baseline HbA1c level was 7.49%, which significantly decreased to 6.7% post- treatment (p < 0.0001). In the moderate diabetes group, the mean HbA1c reduction was 0.58% (p < 0.0000002), while the severe diabetes group exhibited a more pronounced mean reduction of 1.55% (p = 0.0122). Subgroup analysis suggested a trend toward greater HbA1c reduction in patients receiving higher MSC doses (≥1 billion cells), though this did not reach statistical significance. No serious adverse events were reported during the follow-up period. Conclusion: A single intravenous infusion of MSCs resulted in significant and sustained HbA1c reduction, particularly in patients with severe diabetes, with effects persisting for over three years. These findings highlight the potential of MSC therapy as a disease-modifying intervention in T2DM management. Further randomized controlled trials are warranted to validate these results and optimize dosing strategies.

Abstract: Pain is a fundamental yet highly complex biological and psychosocial phenomenon. While acute pain functions as a defence mechanism, alerting the body to tissue damage or injury, chronic pain loses this protective role and becomes a persistent, independent problem. Chronic pain in the elderly is of significant clinical importance, as it impacts not only physical health but also severely affects mental well-being, quality of life, and social participation. Diagnosing pain in older adults is particularly challenging due to its subjective nature, which is influenced by cognitive decline, comorbidities, and diminished communication abilities. As such, both objective scales and subjective self-assessment tools are essential in pain evaluation. Managing chronic pain in the elderly requires a multidisciplinary approach combining pharmacological and non-pharmacological therapies. Analgesic use, including non-steroid-antiinflammatory drugs (NSAIDs) and opioids, should match pain type and intensity. Age-related pharmacokinetic and pharmacodynamic changes, like reduced renal function and slower metabolism, impact drug efficacy and side effects, raising complication risks. Non-pharmacological therapies, such as physiotherapy, psychological interventions and complementary techniques (e.g., acupuncture), can also be effective, particularly for long-term pain relief. These methods aim to reduce pain perception and contribute to maintaining physical activity, psychological well-being, and social engagement. Developing and continuously revising personalized pain management plans are essential for preserving patients' quality of life. Nurses are crucial in alleviating chronic pain in the elderly, extending beyond patient monitoring to emotional support and multidisciplinary care coordination. Adequate training and access to essential tools are vital for effective pain management.

Abstract: Nanoparticles (NPs) have revolutionized biomedical and pharmaceutical applications due to their unique physicochemical properties. However, their widespread use has raised concerns regarding their potential toxicity, particularly through oxidative stress mechanisms. Oxidative stress, primarily driven by reactive oxygen species (ROS) overproduction, plays a central role in NP-induced toxicity, leading to cellular dysfunction, inflammation, apoptosis, and genotoxicity. Zebrafish (Danio rerio) has emerged as a powerful in vivo model for nanotoxicology, offering advantages such as genetic similarity to humans, rapid development, and optical transparency, allowing real-time monitoring of oxidative damage. This review synthesizes current findings on NP-induced oxidative stress in zebrafish, highlighting key toxicity mechanisms and case studies involving metallic (gold, silver, copper), metal oxide (zinc oxide, titanium dioxide, iron oxide), polymeric, and lipid-based NPs. The influence of NP physicochemical properties, such as size, surface charge, and functionalization on oxidative stress responses is explored. Additionally, experimental approaches used to assess ROS generation, antioxidant enzyme activity, and oxidative damage biomarkers in zebrafish models are examined. In addition to toxicity concerns, pharmaceutical applications of antioxidant-modified NPs are evaluated, particularly their potential in drug delivery, neuroprotection, and disease therapeutics. Challenges in zebrafish-based nanotoxicology, the need for standardized methodologies, and future directions for optimizing NP design to minimize oxidative stress-related risks are also discussed. By integrating insights from toxicity mechanisms, case studies, and pharmaceutical strategies, this review supports the development of safer and more effective nanoparticle-based therapies while addressing the challenges of oxidative stress-related toxicity.

Abstract: Azvudine (FNC) is a novel cytidine analogue widely used in the treatment of AIDS and COVID-19 infectious disease. Previous studies have demonstrated its anticancer activity in various cancer cell lines, including non-Hodgkin’s lymphomas and lung adenocarcinoma cell lines. However, its effects on hepatocellular carcinoma (HCC) and the underlying mechanisms remain unclear. This study aimed to investigate the anti-epithelial-mesenchymal transition (anti-EMT) activity of FNC and evaluate its potential application in HCC treatment. We found that FNC significantly inhibits the migration of the liver cancer cell line Huh7 by downregulating key EMT markers, such as matrix metalloproteinases (MMPs) and E-cadherin, at both transcriptional and protein expression levels. Notably, we found that FNC inhibits HEY proteins, particularly HEY1, a transcriptional regulator of the Notch signalling pathway that is overexpressed in approximately 50% of HCC patients. To identify the primary target of FNC, microscale thermophoresis (MST) and molecular dynamics (MD) simulations were performed, revealing that FNC directly binds to Jagged1. This study provides valuable insights into the therapeutic potential of FNC in HCC treatment and elucidates its underlying mechanisms.

Abstract: Portal vein thrombosis (PVT) is a partial or complete obstruction of blood flow through the portal vein (PV) due to an intraluminal thrombus. Neoplastic portal vein thrombosis is a common complication in cases of hepatocellular carcinoma (HCC), and it is a sign of a poor prognosis. Diagnosing HCC and tumor PVT is usually performed using non-invasive radiological imaging and measuring tumor marker blood levels. Sometimes, a PVT is present without any detectable liver tumor mass or conclusive findings. In cases like these, a tumor PVT biopsy is performed for confirmation. In the available literature, tumor PVT biopsy is performed either percutaneous or endoscopic, as fine-needle aspiration biopsy (FNAB). Only a single publication was regarding PVT CORE needle biopsy (CNB). At this moment, we present three cases of percutaneous transhepatic ultrasound-guided biopsy. For the patients in question, the single method remained for diagnostic, staging, and pathohistological verification due to the insufficient sensitivity of the performed radiological imaging. In all three cases, the diagnosis of HCC was confirmed. All three procedures have been carried out without any complications.

Abstract: Background: Von Hippel-Lindau (VHL) disease, a hereditary cancer syndrome, is characterized by mutations in the VHL gene, which result in the stabilization of hypoxia-inducible factors (HIF)-1α and -2α, ultimately leading to the development of highly vascularized tumors, such as hemangioblastomas of central nervous system (CNS-HBs). The standard treatment for these brain tumors is neurosurgical resection. However, multiple surgeries are often required due to tumor recurrence, increasing the risk of neurological sequelae. Therefore, developing pharmacological therapies is essential for reducing the need for repeated surgeries and offering alternatives for unresectable CNS-HBs. Belzutifan (Welireg™), a selective HIF-2α inhibitor and the only FDA-approved non-surgical option, has shown limited efficacy in CNS-HBs, highlighting the need for alternative therapeutic strategies. Results: In this study, 9 primary cell cultures were successfully established and characterized from CNS-HB tissue samples of 11 VHL patients, revealing a composition predominantly of stromal cells and pericytes, and a lower proportion of endothelial cells. Most primary HB cells showed significantly higher positivity (45–90%) for both HIF-1α and HIF-2α isoforms compared to primary glioblastoma cells. This overexpression was subsequently confirmed at both mRNA and protein levels, where HIF-1α showed a slight predominance. Furthermore, the therapeutic potential of acriflavine (ACF), a simultaneous HIF-1α/HIF-2α inhibitor with proven antitumor effects against glioblastoma, was evaluated in these patient-derived primary HB cells. ACF treatment markedly decreased HB cell proliferation and viability, induced G2/M cell cycle arrest, and mainly triggered necrotic cell death. Conclusions: These results suggest that inhibiting both HIF-1α and HIF-2α simultaneously may be more effective in controlling CNS hemangioblastoma progression than targeting HIF-2α alone. Our study provides new insights into the molecular mechanisms driving VHL-associated hemangioblastoma growth and supports the potential clinical application of targeting both HIF-α isoforms as a promising non-invasive therapeutic strategy.

Abstract: Hepatocellular carcinoma remains one of the leading contributors to global cancer mortality, frequently stemming from chronic liver conditions, such as viral hepatitis, non-alcoholic fatty liver disease, and alcohol-induced cirrhosis. While antiviral treatments have made significant strides, the rising prevalence of hepatocellular carcinoma linked to non-infectious causes underscores the pressing demand for more effective diagnostic tools and therapeutic interventions. Advances in imaging and liquid biopsy technologies have facilitated early detection and diagnosis, and treatment strategies are diversifying: immune checkpoint inhibitors, tyrosine kinase inhibitors, and interventional therapies. Translational therapies for advanced hepatocellular carcinoma have improved surgical opportunities and patient survival. Artificial intelligence has played a transformative role in the diagnosis and treatment of hepatocellular carcinoma, in terms of image analysis, histopathologic classification, drug development, and targeted therapy. The future of hepatocellular carcinoma lies in precision oncology and the collaboration of multidisciplinary teams as well as in early detection. The ultimate goal is to keep patients alive longer and reduce the global burden of this complex malignancy.

Abstract: Liposomal drug delivery systems are a novel phenomenon in pharmaceutical sciences with increased bioavailability of the drug, reduced toxicity, and targeted delivery. Historical perspective of liposomes, constitution, and classification are discussed in this paper. Encapsulation mechanisms, loading efficiency, and controlled release are examined in relation to parameters that affect retention of the drug and therapeutic response. Stealth liposomes, nanocarriers, and regulation are discussed to highlight their evolving role in contemporary medicine.Therapeutic uses of liposomal products for cancer chemotherapy, treatment of infectious diseases, and antibiotics delivery are discussed, and how their site-specific action and capacity to overcome drug resistance render them promising. At the same time, in spite of all these advantages, some limitations in terms of stability issues, complexity of production on a large scale, and regulatory issues still restrict widespread clinical application. The paper outlines novel alternatives and solutions, which are written as polymer-coated liposomes and hybrid lipid systems, that have been designed to address the stability issue and scalability issue.With continuous innovations, liposomal drug delivery will be the focus of personalized medicine and targeted therapy. Resolution of current limitations by the aid of advanced nanotechnological techniques and regulatory improvements will be key to the realization of the true potential of liposomal formulations. This review is a detailed overview of current developments, challenges, and future directions of liposomal drug delivery, making it the focus of contemporary pharmaceutical science.

Abstract: Alterations in sympathetic nervous activity are evident in response to changes in body weight. Sympathetic nervous activity and sympathetic responses to weight change are regionalized, with alterations in end organ function dependent on the changes occurring in brain regulatory pathways invoked and in the effector organs engaged. Obesity-induced activation of the sympathetic nervous system likely contributes to the initiation and worsening of cardiometabolic risk factors, including elevated blood pressure, cardiac dysfunction, dyslipidaemia, increased fasting blood glucose, insulin resistance and non-alcoholic steatohepatitis. Unintended weight loss, as occurs in cachexia, is driven, at least in part, by activation of sympathetic nervous-stimulated thermogenesis. The complexity of sympathetic nervous regulation renders the use of global measures of sympathetic activity problematic and the development of targeted therapies difficult, but not without promise or precedent. Knowledge of the central and peripheral pathways involved in sympathetic nervous regulation has opened opportunities for pharmacological, surgical and device-based approaches to mitigate the burden of disease development and progression. In this narrative review, we elaborate on sympathetic activity in response to changes in body weight, the brain pathways involved, and the cardiovascular and metabolic risks associated with perturbations in regional sympathetic activity.

Abstract: Background/Objectives: Elevated human epididymis protein 4 (HE4) expression has been observed in breast cancer and is linked to cancer progression; however, its role in ductal carcinoma in situ (DCIS) remains unclear. This study evaluated HE4 levels in DCIS serum and tissue and their correlation with clinicopathological features. Methods: Preoperative serum HE4 levels were measured in 59 DCIS patients. HE4 mRNA and protein expression were assessed in DCIS and adjacent normal tissues via RNAscope in situ hybridization and immunohistochemistry. An independent tissue microarray of 41 DCIS cases was also analyzed, and the BreastMark database was applied to explore the prognostic relevance of HE4. Results: Serum HE4 levels (mean ± SD: 39.4 ± 11.9 pmol/L) were within the normal range and did not significantly correlate to clinicopathological parameters except menopause status. HE4 expression was significantly higher in DCIS tissues than in adjacent normal tissues, with mRNA and protein levels positively correlated (r = 0.771, p < 0.001). High HE4 mRNA and protein expression was associated with ER positivity, HER2 negativity, low stromal tumor-infiltrating lymphocyte density, and HR+/HER2- subtypes but did not predict DCIS recurrence. High HE4 expression in breast cancer patients correlated with better survival outcomes. Conclusions: While serum HE4 is not elevated in DCIS, high HE4 expression in tissues is linked to favorable clinicopathological characteristics; thus, further research is warranted on its potential prognostic role.

Abstract: (1) Background: Meningioma-related epilepsy (MRE) is observed in approximately 30% of patients. Although studies focus on identifying risk factors related to pre- and postoperative MRE, there is no clear evidence regarding the timing for discontinuing antiseizure medications (ASM) after surgical resection. (2) Methods: We retrospectively collected data from a series of naïve supratentorial meningiomas treated with surgical resection. Preoperative MRI was used to calculate the meningioma and peritumoral edema (PE) volumes through a voxel-based system. We analyzed the frequency of pre-and postoperative epilepsy in the group of meningiomas with and without perile-sional edema (PE > 1 cm3 as the cut-off); (3) Results: From a clinical series of 507 patients, we included 128 who underwent surgical resection in our Center, between January 2020 and December 2022, with a mean follow-up of 30.1 ± 19.8 months. Surgical treatment had a curative effect on MRE (41.4% pre- vs. 19.5% postoperative; p=0.0001). We observed a statistically significant reduction in the seizure rate in cases with preoperative PE (45.3% pre- vs. 18.9% postoperative; p=0.0002) and a non-statistically significant reduction in cases without PE (32.5% pre- vs. 21.4% postoperative; p=0.24). We observed ASM con-tinuation in 37.8% of Engel IA patients; (4) Conclusions: PE increases the likelihood of MRE resolution with surgery. Our results show that surgical resection directly impacts MRE and ASM discontinuation in the presence of preoperative PE. The PE is a reas-suring factor in decision-making regarding the timing of ASM discontinuation after surgery.

Abstract: Background: Adequate nutrition in early childhood is crucial for growth and development. Picky eating behaviors are common and contribute to undernutrition. Growth milk, a fortified milk product, has been suggested to address nutritional gaps, but its effectiveness remains uncertain. Methods: This clustered randomized controlled trial aimed to assess the effects of growth milk on nutritional status, immune resilience, appetite, and cognitive function of children aged 2-5 years in Kampung Melayu, East Jakarta. The intervention lasted three months, with 49 participants from two clusters randomly assigned to either the growth milk group or the control group, which received only nutritional education. Nutritional status was assessed monthly. Illness incidence, visual analog scale (VAS) for appetite, Child Eating Behavior Questionnaire (CEBQ) for food fussiness, and Brigance for cognitive function were assessed at baseline and endline. Results: Children in the intervention group showed significant improvements in weight (0.41 kg), height (1.93 cm), and head circumference (0.81 cm) (p &lt; 0.001). Z-scores for height-for-age from -1.65 to -1.58 and BMI also increased, suggesting positive effects on growth. The intervention group showed notable physical growth, but no significant differences were observed between groups in illness incidence, appetite, food fussiness, or cognitive function. Both groups had similar levels of appetite and reported similar cognitive development outcomes, with language scores slightly declining for both groups. Conclusions: Growth milk supplementation resulted in improved growth parameters, but its impact on overall health and cognitive development was minimal. Longer studies and the inclusion of younger children may provide a better understanding of its broader benefits.

Abstract: Individuals diagnosed with substance use disorders (SUD) exhibit notable deficits in executive function (EFs). In the context of substance abuse, the pro-inflammatory cytokine interleukin-6 (IL-6) appears to contribute to these cognitive impairments significantly. Background/Objectives: However, the specific neuropsychological parameters most affected by executive dysfunction remain poorly understood. Methods: In this study, sixteen patients diagnosed with SUD in the withdrawal phase were compared to twenty age-matched control subjects to ascertain which aspects of EFs were most adversely impacted. Plasma levels of IL-6 were quantified using enzyme-linked immunosorbent assay (ELISA). Data were analyzed using the Confidence Interval-Based Estimation of Relevance (CIBER) model to determine the most sensitive executive performance indicators. Results: Findings from the CIBER analysis revealed that the Wisconsin Card Sorting Test yielded the most pronounced cognitive discrepancies between males with and without SUD diagnoses. Elevated levels of IL-6 and associated executive dysfunction were observed to persist in males with SUD throughout the withdrawal phase. Conclusions: Notably, cognitive flexibility emerged as the most sensitive parameter indicative of executive dysfunction, suggesting its potential utility in tailoring clinical interventions for SUD patients during this critical recovery period.