Medicine and Pharmacology

Abstract: Background/Objectives: Oxidative stress is a key pathogenic factor in gastric diseases (GDs). Nutraceuticals with antioxidant activity derived from macroalgae represent promising preventive strategies. However, Chilean macroalgae remains poorly explored in the context of GDs, particularly associated with oxidative stress. This study evaluated the antioxidant and cytoprotective properties of crude aqueous and ethanolic extracts from green, brown, and red macroalgae collected along the north-central coast of Chile. Methods: Crude extracts were prepared from green, brown, and red macroalgae and evaluated for antioxidant activity via ABTS, DPPH, and FRAP assays. Using hydrogen peroxide-induced oxidative stress in GES-1 gastric epithelial cells, we assessed cell viability (MTS assay), intracellular reactive oxygen species (ROS) levels (time-lapse confocal microscopy), and apoptosis (active caspase-3 detection). Results: All extracts exhibited antioxidant activity; the red macroalgae Gracilaria chilensis displayed the highest flavonoid content (up to 2.236 mg QE/g dw). Notably, extracts from G. chilensis, S. gaudichaudii, and M. canaliculata preserved GES-1 cell viability under hydrogen peroxide-induced stress, outperforming green and brown species, demonstrating the superior cytoprotective capacity of red macroalgae compared to other groups. Furthermore, G. chilensis extracts significantly reduced intracellular ROS levels and attenuated ROS-induced apoptosis. Conclusions: Red macroalgae extracts, particularly G. chilensis, exhibit strong antioxidant and cytoprotective effects. Our findings demonstrate that these species outperform green and brown macroalgae, addressing a gap in knowledge regarding Chilean marine resources. These results support their potential development as nutraceuticals for the prevention of oxidative stress-related gastric diseases and highlight red macroalgae as a valuable source of bioactive compounds for diet-based preventive strategies.

Abstract: Chronic migraine has traditionally been framed as a disabling but self-limited pain disorder. Recent large-scale epidemiology, Mendelian randomisation, and neuroimaging converge on a different reading: midlife chronic migraine, particularly with aura, precedes and predicts Alzheimer's dementia in a manner consistent with a causal direction rather than mere association. We propose a hierarchical model in which recurrent cortical spreading depression initiates a feed-forward network: transient glymphatic closure with stasis of amyloid-β and tau; brain insulin resistance and interictal energy failure; and sustained, TNF-α-centred neuroinflammation, with each level feeding back to lower the threshold for the others. Sleep, mood, and vascular comorbidities are repositioned as bidirectional amplifiers rather than independent confounders. We outline falsifiable predictions, discuss the ambiguous neurocognitive profile of CGRP-pathway blockade, and argue that midlife migraine prevention warrants evaluation as a candidate disease-modifying strategy for Alzheimer's dementia.

Abstract: BACKGROUND For patients with multivessel coronary artery disease (MVD) treated with coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI), we proposed novel pulmonary risk factors identified by machine learning (ML) that have impact on long-term revascularization outcomes. METHODS A total of 1035 consecutive patients with three-vessel disease (3-VD) and/or left main disease (LMD) treated with either CABG or PCI were followed up to 5 years in tertiary cardiovascular care centre that systematically screened their candidates for revascularization. Participants were stratified for the presence of absence of PH (pulmonary hypertension) and /or chronic obstructive pulmonary disease (COPD), and the impact of each on revascularization outcomes was examined. RESULTS Five-year mortality in overall cohort was 12.6%. A higher mortality was demonstrated for patients with diagnosis of COPD or PH (n=125) as compared with population who had neither COPD nor PH (n=910) [68.8% vs 4.8%, P< 0.001]. Among the 125 patients in COPD/PH population, a higher 5-year mortality was observed in those who underwent surgery as compared with PCI-group (85.2% vs 64.3%, P=0.04). We observed a significant interaction between COPD and revascularization strategy (P=0.014), but no association between PH and CABG/PCI was found. Cox regression analysis showed outstanding HRs of mortality for PH (6.01 [3.47-10.40]) and COPD (5.65 [3.21-9.96]) as compared with conventional risk factors. CONCLUSIONS In the overall cohort, novel pulmonary risk factors suggested by ML had a huge impact on 5-year mortality, hence a detailed diagnosis of pulmonary disease in the population with MVD has a paramount importance to predict long-term mortality.

Abstract: Background/Objectives: Cephalometric analysis remains the principal tool for diagnosing sagittal jaw discrepancies. Its clinical reliability depends on the accuracy of landmark identification and the resulting horizontal and vertical dispersion in the Cartesian system. The aim of this study was to assess the inter-rater reliability of 12 cephalometric landmarks and of six measurements used for sagittal discrepancy assessment (ANB, Wits, Tau, Yen, Sar and W) across three skeletal classes. Methods: Twenty-four lateral cephalograms (eight per skeletal class) were assessed twice, seven days apart, by 15 orthodontists trained in a 5-hour calibration course. Landmark coordinates were normalized against a reference value derived from two expert raters. Reliability of horizontal (X) and vertical (Y) coordinates and of the resulting sagittal measurements was quantified using the intraclass correlation coefficient ICC(2,1). Between-class differences were tested with Fisher Z-transformed Z-tests; the Benjamini–Hochberg false-discovery-rate (FDR) procedure was applied to control for multiple comparisons. Results: Horizontal coordinates of all landmarks showed excellent inter-rater agreement (ICC 0.91-0.96) regardless of skeletal class. Vertical coordinates showed considerably greater variability (ICC 0.52-0.94). Among sagittal measurements, Wits demonstrated the highest reliability across all classes (ICC 0.87-0.90), followed by Yen (ICC 0.76-0.86). Tau, Sar and W reached near-perfect agreement only in Class III patients (ICC 0.93-0.95). The ANB angle showed the lowest reliability, particularly in Class I (ICC =0.55, 95% CI 0.32-0.84). Conclusions: Vertical and horizontal dispersion of cephalometric landmarks materially influences the diagnostic accuracy of sagittal measurements. Wits and Yen are the most reliable parameters across all skeletal classes, whereas Tau, Sar and W are particularly trustworthy in Class III. The traditional reliance on the ANB angle as a gold standard should be reconsidered, as it was the least reproducible measurement in our cohort.

Abstract: Despite the wide palette of clinically available investigative tools, not all deep molecular phenomena governing the cardiovascular system can be studied on living humans. Therefore, a reasonable alternative is to explore such phenomena on animal models, given that the two-circuits centered on a tetra chamber heart practically did not evolve since the crocodilians. This review presents our two decades-long experience with mouse, rat and dog models of Chagas disease, metabolic syndrome, post ischemic heart failure, and pulmonary hypertension. We studied also the transcriptomic consequences of cell treatment of Chagas and ischemic cardiomyopathies, genetic engineering, and exposure to hypobaric hypoxia, oxygen deprivation, low salt and high fructose diets. Among others, the investigations revealed heart transcriptomic sex dichotomy and inter-chamber differences, as well as changes in the subcellular localization of the heart rhythm determinants: connexin43, plakophilin-2, N-cadherin and plakoglobin during the female estrogen cycle. Use of these animal models considerably enriched our understanding of the cardiovascular system pathophysiology.

Abstract: Background: Borderline Personality Disorder (BPD) lacks approved pharmacological treatments despite a high symptom burden. Artificial intelligence (AI) offers new opportunities to accelerate drug discovery and model therapeutic effects. Objective: This study will outline an AI‑enabled framework for identifying and modelling a novel pharmacological agent for BPD, designed to meet five therapeutic goals: (1) reduce depression without increasing impulsivity and suicidality, (2) reduce suicidality without sedation, (3) limit side effects and weight gain, (4) reduce polypharmacy, and (5) provide combined antidepressant, anti-suicidal, mood‑stabilising, and antipsychotic effects.Methods: Three AI‑driven approaches will be piloted: (1) deep‑learning‑based compound generation, (2) natural‑language‑processing (NLP) evidence synthesis, and (3) predictive modelling of symptom trajectories. These methods will be used to design and characterise a hypothetical multimodal compound, BPD‑AI‑01, including its predicted 3D molecular structure and receptor binding profile. All analyses will use publicly available data and in silico simulations.Results: AI‑guided modelling will generate BPD‑AI‑01, a candidate molecule predicted to act as a partial agonist at 5‑HT1A receptors, a modulator at NMDA‑associated sites, and a weak antagonist at 5‑HT2A/D2 receptors, with low affinity for histaminergic and muscarinic receptors. Its 3D structure will be optimised to balance CNS penetration with reduced metabolic burden. Simulated trajectories will suggest potential antidepressant, anti-suicidal, mood‑stabilising, and antipsychotic‑like effects without marked sedation or weight gain. Conclusions: AI‑enabled pharmacological research may support the design of next‑generation medications for BPD that address multiple symptom domains within a single molecule. Empirical validation will be required before any clinical application.

Abstract: Neuroendocrine differentiation in tumors of the female genital tract is an uncommon but diagnostically consequential finding. Its interpretation is challenging because neuroendocrine marker expression does not necessarily define a neuroendocrine neoplasm. Focal or aberrant staining for synaptophysin, chromogranin A, CD56 or INSM1 may occur in otherwise conventional gynecologic carcinomas, whereas true poorly differentiated neuroendocrine carcinomas represent aggressive tumors with distinct prognostic and therapeutic implications. This narrative review examines neuroendocrine differentiation across the cervix, endometrium, ovary, vagina and vulva from an integrated clinicopathologic perspective. We emphasize that neuroendocrine differentiation should be approached as a diagnostic and biological spectrum, ranging from incidental immunophenotypic expression to carcinoma with neuroendocrine differentiation, mixed neuroendocrine/non-neuroendocrine tumors, well-differentiated neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas. Morphology remains the diagnostic anchor, while immunohistochemistry, molecular context and clinicoradiologic correlation refine classification and help exclude mimics or metastatic disease. Site-specific interpretation is essential: cervical neuroendocrine car-cinoma is commonly HPV-associated and clinically aggressive; endometrial tumors require integration with p53, mismatch repair, POLE and SWI/SNF-related contexts; ovarian lesions demand distinction between primary well-differentiated neuroendocrine tumors, poorly differentiated carcinomas and metastases; and vaginal or vulvar tumors require careful exclusion of adjacent extension, cutaneous mimics and extragenital primaries. We propose a practical diagnostic framework that separates incidental marker expression from clinically meaningful neuroendocrine differentiation and links this distinction to reporting, prognosis and treatment. The central diagnostic question is not whether neuroendocrine markers are expressed, but whether their expression defines a morphologically, biologically and clinically meaningful tumor category.

Abstract: Background/Objectives: Clinical management of uterine fibroids in the context of infertility is characterised by significant heterogeneity. The aim of our study was to record the participants’ views and clinical practices regarding minimally invasive, fertility-sparing management of fibroids, focusing on fertility outcomes. Methods: Online survey distributed to members of the European Society of Gynecology (ESG), using a questionnaire comprising 27 questions. Questions 1 to 5 related to the participants’ background, while questions 6 to 27 related to the clinical management of fibroids. Results: 98 participants completed the survey, 83% (n=82) of which practice in European countries. 43% (n=42) had completed specialist training in minimally invasive gynecological surgery. For FIGO 0–II fibroids, 94% of participants recommended hysteroscopic removal in infertile patients. 50% may use anti-adhesion agents after hysteroscopic removal of FIGO 0–II fibroids. For FIGO III fibroids, 57% of participants (n=56) believe they have a detrimental impact on fertility while, for FIGO IV fibroids, 51% (n=50) believe the same. 48% of participants (n=49) stated that the distance between the inner portion of an intramural, non-cavity distorting fibroid and the junctional zone does not affect their decision for removal in infertile patients, and 51% (n=50) stated that it does, with variable cut-off values given. The majority of participants favour minimal access approaches over traditional laparotomy; however, the use of robot-assisted laparoscopy was limited. Conclusions: Our results confirm the significant variation in clinical practice associated with fibroid management and underline the need for standardised care, based on high-quality evidence.

Abstract: Peripheral nerve regeneration remains one of the most difficult clinical problems in neuropathy management, and no currently approved treatment reliably restores nerve structure once damage has occurred. Low-frequency pulsed magnetic fields (LFPMFs) have attracted interest primarily as an analgesic modality, culminating in FDA clearance of a magnetic peripheral nerve stimulation (mPNS) device for painful diabetic neuropathy. However, accumulating preclinical data suggest that LFPMFs may act on the biological determinants of nerve repair, not merely on pain transmission. This review organizes those mechanisms chronologically. Early effects center on the endoneurial microvasculature: LFPMF exposure promotes release of FGF-2 and VEGF from endothelial cells, drives arteriolar dilation, and stimulates capillary neogenesis, restoring oxygen delivery to ischemic nerve segments. These vascular changes are especially relevant in diabetic neuropathy and peripheral vascular disease, where endoneurial ischemia drives progressive fiber loss. Later effects involve Schwann cell proliferation, downregulation of neuroinflammatory cytokines, upregulation of BDNF, NGF, and GDNF, and acceleration of axonal sprouting through calcium-dependent intracellular signaling. Notably, the Brown et al. trial of high-intensity mPNS reported a 53% reduction in numbness—a finding that cannot be explained by analgesia alone and raises the possibility that clinical-grade devices may drive structural regeneration. Whether the regenerative mechanisms identified with lower-power devices translate to, or are amplified by, high-intensity mPNS remains an open and important question.

Abstract: Plague remains a significant natural focal zoonotic infection, maintaining epidemiological relevance in the Republic of Kazakhstan. This study provides a comprehensive assessment of epizootological dynamics in natural plague foci during 2020–2025, integrating historical epidemiological data, phenotypic and molecular characterization of Yersinia pestis, and GIS-based spatial analysis. The study utilized long-term surveillance data (1920–2025), epidemiological records of human cases (1926–2003), analysis of 1,526 strains, and whole-genome sequencing of 75 isolates. Epizootological monitoring demonstrated high coverage and stable surveillance capacity, alongside a marked increase in molecular diagnostics. By 2025, expansion of epizootically active areas, a threefold increase in isolated strains, and a substantial rise in PCR-positive detections were observed, indicating intensified pathogen circulation. Despite this, Y. pestis populations remained highly stable, with 94.9% phenotypically typical and 97.5% genotypically typical strains, and no evidence of antimicrobial resistance. Spatial analysis revealed significant clustering (Moran’s I = 1.627; p < 0.001), persistent directional spread, and stable high-risk zones in the North Aral, Betpakdala, Moyynkum, and Kyzylkum foci. No human cases have been recorded since 2003, reflecting effective surveillance. These findings support the integration of spatial modeling and molecular surveillance into risk-oriented plague control strategies.

Abstract: Bioelectrical impedance analysis (BIA) is a widely used technique in clinical and research settings because it provides non-invasive estimates of body composition. However, the quality of a measurement depends on more than the perceived accuracy and precision of numbers produced by a BIA device. This review considers BIA through the lens of metrology, defined as the science of measurement. It highlights several key factors that affect measurement quality. These include accuracy, precision, calibration, standardisation, and uncertainty quantification, all of which are essential for meaningful, clinically feasible BIA measurements. Applying prediction equations generated by the device outside their intended context, poor electrode placement, or uncalibrated devices can introduce bias, whereas biological variability can complicate the interpretation of bioimpedance results. The traditional emphasis on using a reference method for validation is considered along with clinical relevance, which is argued to be an equally important benchmark for evaluating measurement utility. We also present best practices and practical guidelines for improving measurement quality, interpretation, and integration into clinical workflows. By adopting a metrological mindset in clinical practice and treating BIA with the same rigour as other diagnostic tools, its utility in areas such as fluid management, nutrition, and preventive health can be further enhanced. Trustworthy decisions depend not only on the data itself but also on how it is measured, interpreted, and used.

Abstract: Background: Adipose tissue expansion in obesity is accompanied by extracellular matrix (ECM) remodelling, regulated by matrix metalloproteinases (MMPs). Visceral adipose tissue (VAT) is metabolically more active than subcutaneous adipose tissue (SAT). However, depot-specific differences in proteolytic activity and protein glycooxi-dation remain incompletely characterized. Methods: In this case-control study, we assessed the activity of six matrix metallo-proteinases (MMP-1, -2, -7, -9, -11, -13) using a fluorescence resonance energy transfer (FRET) assay and quantified advanced glycation and glycooxidation-related markers in paired VAT, SAT and plasma samples obtained from 40 patients with obesity and 21 non-obese controls. Results: The activities of all assessed MMPs were greater in patients with obesity than in the control group (p < 0.01 for all MMPs). Direct tissue-compartment comparisons showed that MMP activity and glycooxidation-related markers were most pronounced in VAT, with markedly higher values in obese individuals compared with controls. In VAT of obese individuals, median MMP activity was approximately 50–60% higher compared with controls. Amyloid cross-β-structure, vesperlysine and pentosidine were significantly elevated in VAT in obesity, whereas plasma levels were markedly lower and showed limited group differences. No significant differences were observed between obese par-ticipants with and without metabolic syndrome. Conclusions: Obesity is associated with a depot-specific molecular profile charac-terized by enhanced proteolytic and glycooxidative activity predominantly within vis-ceral adipose tissue. These findings highlight the importance of tissue-compartment–specific assessment in obesity.

Abstract: Background/Objectives: The objective of the present study was to determine the association between blood cadmium (Cd) and lead (Pb) levels and survival of the patients with kidney cancer. In this prospective study, we analyzed 272 consecutive, unselected kidney cancer patients and assessed their 8-year survival in relation to Cd and Pb levels. Methods: Cd and Pb concentrations were measured using inductively coupled plasma mass spectrometry (ICP-MS). Patients were categorized into four groups according to the quartile distribution of Cd and Pb levels, ranked in ascending order. Multivariable models were adjusted for covariates including age at diagnosis, sex, smoking status, type of surgery, histopathological classification and blood levels of selenium, zinc, copper, iodine, cadmium and lead. Results: We observed no association between blood Cd and Pb levels and all-cause mortality in patients with kidney cancer. Conclusions: To our knowledge, this study is the first to investigate the relationship between blood levels of cadmium and lead and kidney cancer survival.

Abstract: Background Amyloidosis is an infiltrative cardiomyopathy caused by amyloid deposition into the myocardium. In recent years, recognition of this treatable cause of heart failure has increased. There are striking sex differences in diagnosis, clinical course, and outcome. Notably, women have a worse prognosis than men with similar amounts of cardiac involvement. Methods This review provides an overview of the current state of knowledge on the epidemiology, clinical features, diagnosis and treatment of amyloid heart disease. The differences observed between men and women are discussed and recent advances in the field are highlighted. Results Compared with men, women are generally older at diagnosis, appear to have less severe cardiac disease at time of impairment and are given a late diagnosis. The less apparent disease in women may be responsible for the delay in diagnosis. Women may be under-diagnosed using neutral sex diagnostic criteria. Conclusions Addressing diagnostic disparities may require the use of sex-specific diagnostic thresholds, as well as a more expansive use of multimodality imaging. Future studies trials should aim to enroll greater numbers of female participants to inform optimal therapeutic approaches and to define the sex-specific disease phenotype for this increasingly treatable disease.

Abstract: Camels are increasingly recognized as an important epizootological and epidemiological link in natural plague foci, facilitating the transmission of Yersinia pestis from wildlife to humans. In the Republic of Kazakhstan, where natural plague foci occupy up to 40% of the territory, the rapid growth of camel populations may significantly enhance epidemiological risks. The aim of this study was to perform a comprehensive assessment of the role of camels in the epizootology and epidemiology of plague based on retrospective data (1907–2003) and contemporary monitoring (2000–2025), including spatial analysis and risk zoning. A total of 64 cases of camel plague and 43 epizootic foci were identified during the historical period, associated with more than 400 human cases and deaths. Direct contact during slaughter and meat processing accounted for 94.7% of human infections. Modern data demonstrate that over 90% of the camel population is concentrated in plague-endemic regions. Spatial analysis and epidemiological zoning revealed a heterogeneous risk distribution, with western and southern regions representing the highest-risk areas. Serological investigation (n = 2726) showed 75.6% seropositivity, indicating a high level of population immunity, largely associated with vaccination. Despite increasing camel population size (from 227.7 to 304.0 thousand heads in 2020–2025), vaccination coverage varied between 32.0% and 51.0%, reflecting risk-based preventive strategies. The absence of recent camel plague cases confirms the effectiveness of integrated control measures, including vaccination, surveillance, and establishment of protective zones. These findings demonstrate that camels remain a critical component of plague transmission systems and should be systematically integrated into surveillance programs within a One Health framework.

Abstract: Background: Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of morbidity and mortality worldwide. Despite effective lipid-lowering therapies, substantial residual cardiovascular risk persists, suggesting that additional mechanisms beyond lipid accumulation contribute to disease progression.Objective: To examine vascular integrity as a central, yet under-addressed dimension of ASCVD, and to integrate current evidence with clinical observations from a series of 10 patients managed using a systems-based approach.Methods: This narrative review synthesizes literature on vascular biology, inflammation, and metabolic health, alongside a retrospective case series of 10 patients with ASCVD or vascular risk. Interventions included dietary modification, micronutrient support (including vitamin C and cofactors), and lifestyle optimization.Results: Clinical improvements were observed across the cohort in blood pressure stability, symptom burden, and vascular markers where available. Patterns suggest that addressing metabolic stress, inflammation, and nutrient status may contribute to improved vascular stability.Conclusion: Vascular integrity provides a unifying framework for understanding residual cardiovascular risk. A systems-based approach targeting structural and functional aspects of the vasculature may complement conventional lipid-focused strategies.

Abstract: Objective: First-degree relatives, especially siblings are at increased risk of developing celiac disease (CD). The aim of this study was to determine the prevalence of CD in siblings of children with CD, and to evaluate the applicability of the non-biopsy diagnostic criteria recommended in the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) 2020 guidelines. Material and Methods: This study was conducted between January 2024 and November 2025. Siblings of children with biopsy-confirmed CD who had not previously been diagnosed with CD were included in the study. According to the ESPGHAN 2020 guidelines, cases with elevated anti-tTG IgA levels (more than 10 times the upper limit of normal) were diagnosed without a biopsy. Results: 250 siblings of 81 children biopsy-confirmed CD were included in the study. The median age of the siblings was 9.00 years. Anti-tTG IgA positivity was detected in 31 siblings. A total of 26 siblings (10.4%) were diagnosed with CD. Of the diagnosed cases, and 21 (80.76%) were asymptomatic. In 12 cases with anti-tTG IgA levels more than 10xULN, the diagnosis was done without biopsy. Conclusion: The prevalence of CD in siblings of celiac patients was found to be 10.4%. This rate is approximately 22 times higher than in the general population in our country. Since half of the diagnosed patients are asymptomatic, screening all siblings for CD, regardless of the presence of symptoms, is crucial for early diagnosis. Additionally, diagnosis can be done without biopsy in eligible cases meeting the ESPGHAN 2020 no-biopsy criteria.

Abstract: Background: Gut dysbiosis may trigger inflammation and steatohepatitis (SH) in subjects with metabolic associated steatotic liver disease (MASLD). Both incidence and impact of ileocecal valve (ICV) dysfunction as cause of small intestine bacterial overgrowth in MASLD remain unknown because of the unmet need of non-radiology dependent diagnostic procedures. Methods: Exploiting water as contrast medium and a hydro colon machine (Clean Colon Srl, Monza, Italy) for automated retrograde gentle colonic irrigation, we developed a new abdominal ultrasound procedure for diagnosis of ICV incontinence and we present the results of a pilot feasibility study for the assessment of its relationship with triggering of inflammation in steatotic liver disease. Results: Consecutive patients (32) performing colonic irrigation in colonoscopy preparation underwent concomitant abdominal ultrasound examination. Patients were predominantly males (59%) with body mass index (BMI) 26,6±2,6 kg/m2 and liver steatosis was present in half of the patients. Liver stiffness was 26,6±2,6 kPa, while serum transaminases ALT and AST were 33,1±9,5 and 25,9±8,4 U.I., respectively. The procedure that lasted a mean of 27min (range 20-35 min) was well tolerated in all, but 2 males with large prostate hypertrophy. Three ICV continence patterns (A - Early reflux, already at small water volume without evident cecum distension; B - Late reflux, after evident cecum distension; C - No reflux, either early or late after overall water irrigation and significant cecum distension) were observed during water irrigation (4266 ml mean, range 2000-8000 ml). ICV continence was significantly associated with IBS, steatosis, and liver stiffness (all p ≤ 0.0001). Furthermore, IBS (OR 3.97), steatosis (OR 3.30), and liver stiffness (OR 2.43 per unit increase) were also independently associated with dichotomization of impaired ICV continence.A 35-year-old male with SIBO and LS = 8.7 kPa underwent a liver biopsy showing histologically-determined high level of steatosis (S3), hepatocyte ballooning, lobular inflammation (Grade 6/8) in absence of fibrosis (Stage 0/4 F0).Conclusion: This proof-of-concept study indicates that an easy and quick mini-invasive diagnosis of ICV incontinence is feasible using water as contrast medium during abdominal ultrasound examination. Preliminary results suggest that this new technique is worth of being validated in prospective studies investigating the impact ICV incontinence as possible co-factor of steatohepatitis in patients with MAFLD.

Abstract: Adolescents with congenital heart disease (CHD) increasingly survive into reproductive age, making contraceptive counseling a routine component of pediatric cardiology, adolescent medicine, and transition care. For this population, contraceptive choice is not determined by efficacy alone. It is shaped by lesion-specific pregnancy risk, cyanosis, ventricular function, pulmonary vascular disease, thrombosis history, mechanical valves, anticoagulation, menstrual bleeding burden, adherence, confidentiality, and the risk of interruption during transfer to adult congenital heart disease care. This practical clinical review translates current contraceptive guidance and congenital heart disease literature into a same-day workflow for initiation and follow-up. The proposed sequence is to obtain a confidential reproductive and cardiac history; identify whether pregnancy and estrogen exposure would be poorly tolerated; determine whether pregnancy can be reasonably excluded; initiate the safest effective method without unnecessary delay; address emergency contraception when indicated; and structure follow-up around bleeding, adherence, medication changes, and evolving cardiovascular status. Long-acting reversible contraception, particularly levonorgestrel intrauterine devices and etonogestrel implants, should be prioritized when pregnancy would carry substantial maternal risk. Estrogen-containing methods require caution or avoidance in high-risk cardiovascular states, including Fontan circulation, cyanosis or right-to-left shunting, pulmonary arterial hypertension, Eisenmenger physiology, prior thrombosis, mechanical valves, major ventricular dysfunction, and selected aortopathies. The goal is not to replace cardiology or gynecology judgment, but to provide a lesion-aware, same-day clinical pathway that reduces avoidable delays, supports adolescent autonomy, and preserves contraceptive safety during transition to adult care.

Abstract: Objective: To compare biochemical characteristics of blood samples obtained from dif-ferent anatomical sites: mandibular bone marrow, iliac bone marrow, and peripheral blood. Methods: This study included 26 patients undergoing dental implant placement and maxillary reconstruction with iliac bone grafting. Blood samples were collected from mandibular bone marrow, iliac bone marrow, and peripheral venous blood. Gasometric analysis evaluated PCO₂, PO₂, TCO₂, oxygen saturation (SatO₂), ionized calcium, pH, lactate, and magnesium. Statistical analysis included the Shapiro-Wilk test, repeated measures ANOVA with Bonferroni post hoc, and the Friedman test with Wilcoxon comparisons (p < 0.05). Results: Mandibular bone marrow blood showed significantly higher pH, PO₂, and oxygen saturation, and lower PCO₂ and HCO₃⁻ compared to other sites. These findings indicate a more oxygenated and less acidic microenvironment. No significant differences were observed for lactate, magnesium, and ionized calcium. Conclusion: Mandibular bone marrow exhibits a more favorable biochemical profile for osteogenic metabolism, suggesting its potential advantage for bone graft integration and autologous blood derivatives.