Abstract: The most severe premalignant lesion of glandular epithelium of the cervix is ade-nocarcinoma in situ (AIS). In most cases it is associated with persistent Human papillo-mavirus (HPV) infection and most often occurs in women in the fourth decade of life. In most high-income countries, primary screening has shifted to HPV testing, while cytology is used for patient triage. Even with current robust screening protocols, their sensitivity for glandular lesions remains limited. Diagnosis of AIS obtained by biopsy, brushing or curettage is confirmed by excisional methods and pathohistological verification. Therapy depends on the patient’s lifestyle and reproductive age. In our case, we present nulliparous patient with persistent ASC-US, HPV infection with alpha-7 types (without HPV 16 and 18 types), and AIS which was diagnosed after conization, follow up and two biopsies with curettage of cervical canal. Our case report highlights limitations in detection of glandular lesions and need for caution in patients with persistent and seemingly low-grade cytological abnormalities, notably in young patients with high-risk HPV types.

Abstract: Background: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disorder globally. Mazdutide has shown clinical benefits in weight management and metabolic regulation, indicating its potential as a therapeutic agent for NAFLD. This study aimed to investigate the efficacy and mechanism of action of Mazdutide against early-stage NAFLD. Methods: A NAFLD mouse model was induced by a 12-week high-fat diet, followed by a 4-week treatment with subcutaneous Mazdutide (100, 200, or 400 μg/kg). In vitro, a cellular NAFLD model was established by treating hepatocytes with 1 mM free fatty acids for 24 h, followed by co-treatment with Mazdutide (10, 20, or 50 nM) or the endoplasmic reticulum (ER) stress inhibitor 4-phenylbutyric acid (4-PBA). Serum and hepatic lipid profiles, liver injury markers, and pro-inflammatory cytokines were quantified. Liver histopathology was assessed by hematoxylin and eosin and Oil Red O staining. Protein expression related to ER stress, inflammation, and lipid metabolism was analyzed by immunohistochemistry and Western blot. Results: Mazdutide treatment significantly ameliorated systemic and hepatic lipid metabolism disorders, reduced liver injury markers and hepatic steatosis, and mitigated inflammation and oxidative stress in NAFLD mice and hepatocytes. Mechanistically, Mazdutide alleviated ER stress by modulating the PERK-eIF2α-ATF4-CHOP pathway, suppressed the NF-κB-mediated inflammatory response, and downregulated key lipogenic regulators, including SREBP-1, C/EBPβ, and PPARγ. Conclusion: Our findings demonstrate that Mazdutide alleviates hepatic ER stress in NAFLD, leading to suppressed inflammatory responses and improved lipid metabolism, which ultimately attenuates disease progression.

Abstract: Background. In actinic keratosis (AK), clinical clearance after field-directed therapies does not necessarily correspond to histological resolution, resulting in subclinical persistence and risk of recurrence. Objective. To provide a practical, up-to-date framework for non-invasive monitoring of treatment response in AK, integrating clinical assessment and dermoscopy with high-resolution imaging techniques, reflectance confocal microscopy (RCM), line-field confocal optical coherence tomography (LC-OCT), and high-frequency ultrasound (HFUS), and to discuss emerging optical biomarkers based on Raman spectroscopy. Results. For each modality, we summarize pre- and post-treatment imaging patterns, proposed response criteria, recommended follow-up timing, and correlations with clinical outcomes (including clearance and AKASI) and, when available, histological findings. The available evidence is derived from a limited number of observational studies, predominantly involving RCM and LC-OCT, whereas data on HFUS and Raman spectroscopy remain comparatively scarce. RCM and LC-OCT allow in vivo assessment of epidermal architectural normalization and reduction of intraepidermal keratinocyte atypia. HFUS captures quantitative trajectories of superficial dermal remodeling, including changes in the subepidermal low-echogenic band (SLEB) and dermal echogenicity after photodynamic therapy and other field treatments. Dermoscopy remains the first-line tool for routine follow-up but may fail to detect minimal subclinical persistence. Finally, we discuss the potential role of in vivo Raman spectroscopy for dynamic molecular endpoints and its possible integration with artificial intelligence–based analytical approaches. Conclusions. A standardized multimodal follow-up strategy improves the accuracy of treatment-response assessment compared with clinical evaluation alone. We propose a technique-specific checklist of minimal response criteria and a pragmatic temporal assessment scheme, and outline a research roadmap to support validation and clinical implementation of non-invasive imaging–guided monitoring in actinic keratosis.

Abstract:

Intraoperative assessment of pancreatic quality, followed by sampling for the potential isolation of Langerhans islets for subsequent autotransplantation, is currently a key component of post-total pancreatectomy diabetes mellitus treatment. The aim of this study was to quantitatively evaluate pancreatic parenchymal stiffness using optical coherence elastography (OCE) imaging, and to investigate the utility of the OCE method as a potential indicator of islet yield after pancreatectomy. A total of 41 freshly excised human pancreatic specimens, containing pancreatic ductal adenocarcinoma (PDAC) and surrounding non-tumorous tissues post-pancreatectomy, were studied. In this research, the stiffness (Young’s modulus, kPa) and its color-coded 2D distribution were calculated for various pancreatic samples using compression OCE. Stiffness values were compared between intact pancreatic parenchyma (islet-poor and islet-rich) and pancreatic lesion groups (parenchymal fibrosis and/or PDAC invasion). The data were confirmed by histological analysis. In addition, the measured stiffness values for various morphological groups of the pancreatic samples were compared with the number of isolated islets obtained from pancreatic samples after collagenase treatment. The study demonstrated that OCE can effectively distinguish areas of pancreatic lesions and identify intact pancreatic parenchyma containing Langerhans islets. A highly significant increase in mean stiffness (p<0.0001) was observed in postoperative pancreatic samples exhibiting signs of parenchymal fibrosis or PDAC invasion compared to unaffected, intact pancreatic parenchyma. For the first time, a relationship between stiffness values and the number of isolated pancreatic islets was demonstrated, in particular, the number of isolated islets significantly decreased (≤110 pcs/g) in samples exhibiting stiffness values above 150 kPa and below 75 kPa. The optimal stiffness range for the efficient isolation of islets (≥120 pcs/g) from pancreatic tissue was identified as 75–150 kPa. The study introduces a novel approach for rapid and objective intraoperative assessment of pancreatic tissue quality using real-time OCE data. This technique facilitates the identification of regions affected by pancreatic lesions and supports the selection of intact pancreatic parenchyma, potentially enhancing the accuracy of Langerhans islet yield predictions during surgical resection.

Abstract: Background: Chronic obstructive pulmonary disease (COPD) is increasingly recognized as a disorder linked to increased cardiovascular risk, often coexisting with coronary artery disease (CAD), yet angiographic data on coronary involvement in COPD remain limited. This study aimed to evaluate whether COPD is associated with a distinct angiographic pattern of CAD, focusing on vessel distribution. Methods: We retrospectively enrolled 94 patients who underwent coronary angiography between 2023 and 2024 for suspected or known CAD. Clinical data, comorbidities, laboratory testing, pulmonary function, electrocardiography, echocardiography, and angiography were collected. Participants were stratified into two groups: COPD (n = 47) and non-COPD (n = 47). Coronary vessels were classified by number, location, and diameter. The primary endpoint was the association between COPD and CAD severity. Results: Baseline characteristics, including age, sex, BMI, and smoking history, were comparable between groups. The overall extent of CAD, expressed as the number of diseased vessels, did not differ significantly (p = 0.1436). However, vessel-based analysis revealed a distinct pattern: COPD patients showed a significantly higher prevalence of left main coronary artery (LMCA) disease compared to non-COPD patients (14% vs. 4.7%, p &lt; 0.001). Intermediate-caliber vessels were most frequently affected in both groups, while small-caliber branches were less commonly involved in COPD patients. Conclusions: COPD is associated with a disproportionate burden of LMCA disease despite a similar overall angiographic extent of CAD. These findings suggest a distinct, high-risk coronary phenotype in COPD and highlight the need for enhanced cardiovascular vigilance and integrated cardiopulmonary management in this population.

Abstract: Background/Objectives: Dynamic movement orthoses (DMO) are elasto-compressive bodysuits used in the rehabilitation of children with motor disabilities and mainly in children with cerebral palsy. Among the DMO, the FLEXA® represents one of the most frequently used orthoses in clinical practice due to its adaptability and flexibility. The purpose of the present case study is to describe the application of FLEXA® in a female child of 18 months of correct age with a choreic form of cerebral palsy. Methods: To evaluate the effect of the dynamic movement orthosis's (FLEXA®), the Move-ment Disorder-Childhood Rating Scale (MD-CRS) 0-3 was administered. The child was eval-uated before the use of the FLEXA® bodysuit and with the bodysuit donned at approxi-mately 30 minutes after its application. Results: The results showed an important change in the severity of the movements ac-cording to the MD-CRS; mainly the child’s movement disorder severity changed from a a grade 5 severity (profoundly affected) performed without the bodysuit to grade 3 (moder-ately affected) with the use of the bodysuit. The evaluation also shows better trunk posture with use of FLEXA®. Conclusions: This case report highlights the potential benefits of dynamic movement orthosis like the FLEXA® in managing movement disorders in chil-dren with choreic form of cerebral palsy. A follow up evaluation is necessary to confirm the beneficial effects of continuous use of the DMO in a short and a long period of time.

Abstract: Background/Objectives: The rising prevalence of extended-spectrum beta-lactamase (ESBL)–producing pathogens has emerged as a significant challenge in the treatment of pyelonephritis. This study aimed to determine the frequency of ESBL-producing agents in hospitalized patients with pyelonephritis, identify associated risk factors, and assess the appropriateness of empirical antimicrobial therapy. Methods: This prospective study included patients hospitalized with pyelonephritis in the Infectious Diseases Clinic of Ankara Training and Research Hospital between October 1, 2022, and February 29, 2024. Demographic features, comorbidities, urinary system pathologies, history of urinary tract interventions, recent hospitalization, antibiotic use within the previous three months, and prior urinary tract infections were compared between patients infected with ESBL-producing and non-ESBL-producing organisms. Antimicrobial susceptibility pro-files and the appropriateness of empirical treatments were evaluated. Statistical analyses were performed using SPSS version 25.0, with p< 0.05 considered statistically significant. Results: Escherichia coli (n=142) and Klebsiella spp. (n=43) were isolated in 180 of 204 patients. ESBL positivity was detected in 95 patients (52.7%). Male sex (p=0.007), history of urinary intervention (p=0.019), hospitalization within the previous month (p< 0.001), and antibiotic use in the last three months (p=0.002) were identified as significant risk factors for ESBL positivity. ESBL production was not associated with prolonged hospitalization; however, bacteremia significantly increased length of stay (p< 0.001). Antimicrobial susceptibility rates were markedly lower in the ESBL-positive group. The appropriateness of empirical therapy was also significantly reduced, with piperacillin–tazobactam being the most frequently inappropriate agent due to high resistance rates and unnecessary broad-spectrum use. Conclusions: ESBL-producing pathogens were highly prevalent among hospitalized patients with pyelonephritis. The low appropriateness of empirical therapy in ESBL-positive cases underscores the need for careful evaluation of ESBL risk factors prior to treatment initiation, as ESBL rates may approach 50%.

Abstract: Background: Use of ART as the only effective way to control HIV infection results in HIV drug resistance. NGS became the common method for identifying drug-resistant variants and reducing analysis costs. The aim of the study was to develop the NGS based protocol for identifying resistance mutations and cell tropism of HIV-1 in adult patients with and without treatment experience in Russia in 2024–2025. Methods: Plasma samples from adult HIV-infected patients from Russia were analyzed. Consensus nucleotide sequences of pol and env genes were obtained using Illumina NextSeq NGS. HIV-1 drug resistance analysis was conducted using Stanford University HIVdb database. CXCR4 cell tropism was predicted using empirical rule classifier. Results: The protocol for NGS of HIV-1 pol and env genes was developed. The most common HIV-1 surveillance mutations were in the reverse transcriptase. In treatment-experienced patients, high levels of resistance were observed to NNRTIs and NRTIs, and in treatment-naive— to NNRTIs. Low levels of resistance were observed to protease and integrase inhibitors. CXCR4 cell tropism was extremely rare. Conclusion: NGS allows for the simultaneous processing of large data sets during epidemiological studies. The introduction of NGS based protocols allows performing ART efficiency and tropism monitoring at scale.

Abstract: In this narrative review, we address the prevention and therapy of iron deficiency anemia (IDA) with oral iron products in pediatric patients. Fortification of complementary foods with iron-containing micronutrient powders is the preferred method for the prevention of IDA in resource-limited settings. In developed countries, the prevention of sideropenia is through the consumption of iron-rich foods of animal origin. Regarding oral iron therapy, ferrous sulfate is the most widely used and cheapest product, but it is less well tolerated due to gas-trointestinal side effects compared to complexes of ferric iron with polysaccharides, and complexes of iron with amino acids in casein, such as iron protein succinylate and iron acetyl aspartylate. These latter products are expensive and available only as single-dose vials with a fixed amount of elemental iron. Intermittent admin-istration of ferrous sulfate, once or twice a week, is equally effective to daily therapy, with fewer side effects, and should be advocated. Oral carbonyl iron has excellent bioavailability and the additional advantage of a high safety margin in cases of accidental overdose compared to iron salts, an important consideration given the po-tentially lethal consequences of iron overdose. Newer liposomal and sucrosomial iron products appear to have better intestinal tolerance and similar efficacy in the treatment of IDA, but limited pediatric data exist. In con-clusion, all oral medicinal iron products are effective when prescribed for the treatment of IDA, if well-absorbed and taken consistently for 3 to 6 months. Physicians should be prepared to use alternative oral agents with better tolerance in case of gastrointestinal side effects.

Abstract: Background: The limited aqueous solubility of basic drugs poses significant challenges for oral bioavailability, necessitating a different formulation approach. This study utilizes acidic or non-ionic polymers (its aqueous solution close to acidic-neutral pH) to stabilize a basic drug via drug-polymer interaction. Due to acid-base super solubilization effects, amorphous solid dispersions (ASDs) have good recrystallization inhibition, and improved dissolution and stability. Methods: To prepare nimodipine, a model drug, solid dispersion, spray–drying and melt–quenching techniques were used with carriers like HPC, HPMCAS, HPMCP, and PVP K25 polymers. Drug-polymer miscibility or interaction was carefully evaluated with different modeling to reduce processing temperature and inhibit recrystallization. Results: Based on preparation methods, there were two ASD types: one with a small particle size and low bulk density (spray–drying) and the other with big particle size and high bulk density, prepared at a low temperature to minimize degradation (melt–quenching). The solid–state analysis revealed a low glass transition temperature (Tg), suggesting amorphous forms. The surface morphology of nimodipine and its solid dispersions demonstrated a uniform and consistent system. Nimodipine with HPMCP via spray–drying (NIM.CP.SM) exhibited the highest drug release (89.51%) in phosphate buffer (pH 6.0) after 2 h without recrystallization. The in vivo pharmacokinetic profiles demonstrated a 33–fold increase in Cmax and a 15–fold increase in AUC0–∞ with NIM.CP.SM. Conclusions: These findings suggest that an HPMCP–based polymer combined with spray–drying technique produces a thermodynamically and physico-chemically stable ASD with enhanced in vitro and in vivo drug release.

Abstract: Ultrasound is the primary imaging modality for evaluation of the scrotum and male reproductive tract. While high-frequency linear probes allow detailed assessment of testicular parenchyma, comprehensive visualization of epididymal anatomy and its spatial relationship to the testis may be limited using conventional two-dimensional imaging alone . This limitation is clinically relevant in the evaluation of male infertility, where epididymal abnormalities may contribute to obstructive processes We present a clinical image demonstrating a novel external scrotal application of a conventional three-dimensional (3D) transvaginal ultrasound probe. The images were obtained in an adult male undergoing infertility evaluation. With generous coupling gel and minimal probe pressure, the transvaginal probe was applied externally over the scrotum. High-resolution 2D images were first obtained, followed by volumetric 3D acquisition. The acquired dataset was analyzed using multiplanar reconstruction and volume-rendering techniques. This approach enabled clear visualization of the epididymal head, body, and tail, along with their anatomical continuity and relationship to the adjacent testis. The volume-rendered images provided an intuitive 3D depiction of epididymal curvature and spatial orientation, features that can be challenging to appreciate using standard linear scrotal ultrasound alone. Importantly, no patient discomfort, adverse effects, or technical complications were observed during the examination. This clinical image highlights the feasibility of repurposing a 3D transvaginal probe for external scrotal imaging to improve anatomical depiction of epididymal structures. While the technique is not intended to replace conventional scrotal ultra-sound, it may offer additional anatomical insight in selected infertility cases. This re-port serves as a hypothesis-generating illustration and supports further evaluation of its diagnostic utility in larger studies.

Abstract: Background/Objectives: Pediatric palliative care seeks to relieve suffering and im-33 prove the quality of life of children with severe conditions and their families. This pro-34 spective cohort study assessed changes in quality of life following enrollment in a pediat-35 ric palliative care program at a tertiary care center in Mexico and explored factors associ-36 ated with these changes. 37 Methods: Children with life-limiting or severe disabling conditions were followed 38 at baseline, 3 months, and 6 months. Quality of life was measured using the Pediatric 39 Quality of Life Inventory (PedsQL™) Cancer Module for oncologic patients and the Ped-40 sQL™ Family Impact Module for all families. Results: A total of 166 families completed the Family Impact Module questionnaires, 42 and 116 oncologic patients completed the Cancer Module. Mean children’s PedsQL Can-43 cer Module scores improved from 58.9 to 77.9, and family scores improved from 60.1 to 44 78.8 over six months (both p < 0.001). Families of oncologic patients and those residing 45 outside the Mexico City metropolitan area had lower baseline scores (adjusted differences 46 −9.84, 95% CI: −15.9 to −3.77; and −6.9, 95% CI: −12.38 to −1.44, respectively); however, the 47 latter group showed greater improvement over time. Survival varied by diagnosis, with 48 longer survival observed in children with neurologic or intracranial conditions. 49 Conclusions: The quality of life of families and of oncologic pediatric patients im-50 proved after enrollment in a specialist pediatric palliative care program in a middle-in-51 come setting. Equitable access should be ensured for families affected by chronic condi-52 tions, particularly those living beyond major urban areas.

Abstract: Background/Objectives: Obesity and type 2 diabetes are increasingly common among patients undergoing hip and knee arthroplasty and are associated with higher risks of prosthetic joint infection, impaired wound healing, and prolonged hospitalization. Dietary carbohydrate restriction has demonstrated benefits in glycemic control and weight reduction, but its feasibility and safety in the perioperative arthroplasty population remain underexplored. This pilot study evaluated the safety, feasibility, and short-term metabolic effects of a low-carbohydrate diet supported by WhatsApp-based meal photo-logging in patients undergoing total hip or knee arthroplasty. Methods: A retrospective cohort analysis was performed on 43 patients enrolled in a carbohydrate-restricted dietary programme between 2021 and 2024. Patients submitted photographs of all meals via WhatsApp with a minimum contact frequency of four times daily, enabling real-time feedback and medication adjustment. Anthropometric and metabolic parameters, including weight, BMI, HbA1c, renal function, and lipid profile, were assessed before and after the intervention. Results: Participants (mean age 69.12 ± 7.51 years) demonstrated significant improvement across several metabolic markers. Mean weight decreased by 5.74 kg (p &lt; 0.001), BMI by 2.26 kg/m² (p &lt; 0.001), and HbA1c by 0.72% (p &lt; 0.001). No episodes of severe hypoglycemia or perioperative discharge delays related to glycemic instability were observed. Renal function remained stable, with no significant change in eGFR (p = 0.442). Among patients with available lipid data, LDL-cholesterol and total cholesterol increased, while triglycerides showed a non-significant downward trend. Conclusions: A low-carbohydrate diet combined with high-frequency digital monitoring appears feasible and safe in an elderly arthroplasty population, achieving meaningful short-term improvements in weight and glycemic control without adverse renal or hypoglycemic events. The lipid changes observed warrant cautious interpretation. Larger prospective studies are needed to confirm the clinical impact of this approach and its relevance to perioperative optimization.

Abstract: The current consensus model of sepsis is that it is a dysregulated host response to infection associated with severe organ dysfunction and failure. In 2023 the author proposed a new model of sepsis in that it was a physiological response and defence to infection that failed or became “dysregulated” particularly if the infection was overwhelming or there was a deficiency of thiamine and/or intracellular glucose to provide ongoing fuel for the immune response and/or mitochondrial production of adenosine triphosphate (ATP).This new model proposed that during sepsis, the immune system received priority access to available glucose, prompting insulin resistance that minimised glucose utilisation by less essential tissues. Concurrently, mitochondrial ATP production via oxidative phosphorylation (OXPHOS) was deprioritised, with the immune system relying on anaerobic glycolysis for ATP generation. This suppression of OXPHOS was only a temporary measure; mitochondrial ATP production had to be resumed for complete recovery. Its persistent suppression could culminate in critical ATP deficits and cell death.This paper reviews the consensus model of sepsis and evidence for the new model.It also reviews glucose, thiamine and insulin metabolism in sepsis and concludes that administering high-dose insulin alongside mild hyperglycaemia and intravenous thiamine—a pyruvate dehydrogenase kinase (PDK) inhibitor—may help restore physiological mitochondrial ATP production when administered during a crucial window in the sepsis process, potentially improving survival outcomes.The thrust of this new model may have been validated by a recent experiment on sepsis in mice that found superior survival following treatment with combined glucose and thiamine compared to antibiotics.

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus are dangerous respiratory pathogens with high pandemic potential. Since 2021, these two viruses have been co-circulating, which implies additional risks of co-infection with both pathogens. According to clinical data, influenza and SARS-CoV-2 cause sim-ilar symptoms, and co-infection can increase disease severity and significantly enhance the risks of pneumonia and acute respiratory distress syndrome progressing with a poor outcome. Therefore, management of such patients requires special consideration. Prophylactic vaccination is widely recognized as the most effective way to prevent COVID-19 and influenza and to reduce the severity of these diseases. A range of influ-enza and COVID-19 vaccines built on different technological platforms is currently available on the market, with proven effectiveness, immunogenicity, and safety. Im-portantly, multiple countries have approved recommendations for simultaneous vac-cination against both viral pathogens. This approach is more convenient for patients and is associated with better response to treatment, while also improving vaccine cov-erage and compliance and offering significant resource savings for healthcare systems. This review analyzes recent data on the simultaneous circulation of influenza and SARS-CoV-2 viruses worldwide. We review epidemiological data and the pathogenetic mechanisms of co-infection with these two viruses. Next, we focus on current ap-proaches to simultaneous and combined vaccination against influenza and COVID-19. We outline the types of vaccines and summarize the available findings on the effec-tiveness and safety of co-vaccination.

Abstract: Background: Engagement of the NF-κB signaling pathway is crucial for controlling im-mune and inflammatory gene expression within the central nervous system (CNS). Naringenin, a flavonoid derived from citrus fruits, is known for its anti-inflammatory and antioxidant effects; however, its impact on LPS-induced neuroinflammation in HMC3 (human microglial) and SH-SY5Y (neuronal) cell lines has not been thoroughly studied. Objectives: To ascertain the neuroprotective role of Naringenin on LPS-induced neuroin-flammation in microglia and neuronal cell lines with focus on modulation of NF-κB sig-naling pathway. Methods: LPS treatment was given to HMC3 cells to induce an inflam-matory response and secretome of HMC3 cells to SH-SY5Y cells with the administration of Naringenin. The cell viability assay, ROS levels, Western blotting, immunocytochemis-try were employed to quantify and localize NF-κB and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β). Nuclear and cytosolic fractions of NF-κB were analyzed to screen its activation and translocation. Results: Naringenin treatment led to a dose-dependent de-crease in LPS-induced reactive oxygen species (ROS) production. It significantly reduced the expression of pro-inflammatory cytokines and inhibited NF-κB activation in HMC3 cells. The nuclear translocation of NF-κB was notably diminished after treatment, as demonstrated by both western blot and immunocytochemistry. These results suggest that Naringenin exerts an anti-inflammatory effect by suppressing the NF-κB signaling path-way. Conclusion: The findings suggest the potential therapeutic role of Naringenin using in vitro models in mitigating neuroinflammation through modulation of NF-κB signaling pathway

Abstract:

Background: Atrial fibrillation (AF) is independently associated with cognitive impairment and dementia through mechanisms extending far beyond traditional cardioembolic stroke risk. However, the relative contribution of distinct pathophysiological pathways and the efficacy of emerging therapeutic interventions for cognitive protection remain incompletely characterized. Objectives: This comprehensive review synthesizes current evidence on the epidemiology, pathophysiological mechanisms, therapeutic interventions (pharmacological, rhythm-control, and digital health), and research priorities addressing the AF–dementia relationship. Methods: A narrative review integrating evidence from observational studies, mechanistic research, randomized controlled trials, systematic reviews, and meta-analyses published through January 2026. Literature sources included MEDLINE/PubMed, major cardiology and neurology journals, and expert consensus statements. Searches used combinations of keywords: "atrial fibrillation," "cognitive decline," "dementia," "silent cerebral infarction," "cerebral hypoperfusion," "direct oral anticoagulants," "catheter ablation," and "digital health." Inclusion criteria encompassed studies examining the AF–cognition association, mechanistic pathways, therapeutic interventions with cognitive outcomes, and digital health technologies in AF management. Heterogeneous study designs prevented quantitative meta-analysis; qualitative synthesis focused on effect sizes, strength of evidence, and clinical implications. Results: Strong epidemiological evidence demonstrates that AF increases relative risk of dementia by 1.4–2.2 fold independently of clinical stroke, with silent cerebral infarction present in 25–40% of AF patients. Multiple interacting pathophysiological mechanisms account for AF-associated cognitive decline: cerebral microembolism (meta-analysis: OR 2.30 for silent infarction on MRI), chronic cerebral hypoperfusion (15–20% reduction in total cerebral blood flow in persistent AF), neuroinflammation, cerebral small vessel disease, and structural brain atrophy. Emerging therapeutic strategies offer complementary neuroprotective mechanisms: direct oral anticoagulants (DOACs)—particularly apixaban and rivaroxaban—reduce dementia risk by approximately 30% compared to warfarin (RR 0.69); rhythm control strategies and catheter ablation demonstrate dementia risk reduction (HR 0.52–0.69); and comprehensive digital health platforms implementing the ABC pathway reduce adverse cardiovascular events by 61% while optimizing adherence and enabling early AF detection. However, evidence-specific to cognitive endpoints remains limited, with the landmark BRAIN-AF trial showing no benefit of low-dose rivaroxaban in low-stroke-risk AF patients—suggesting that non-embolic mechanisms predominate in this population. Conclusions: AF represents a multifaceted threat to brain health requiring a paradigm shift from isolated stroke prevention toward comprehensive heart–brain health optimization. Integration of pharmacological neuroprotection (preferring DOACs), hemodynamic optimization (rhythm control in selected patients), cardiovascular risk factor management, and digital health technologies provides unprecedented opportunity for cognitive preservation. However, critical knowledge gaps persist regarding AF burden thresholds, the relative contribution of competing pathophysiological mechanisms, optimal anticoagulation strategies in low-risk populations, and the long-term cognitive benefits of emerging digital technologies. Prospective randomized clinical trials with cognitive impairment as a primary endpoint, serial neuroimaging, and diverse population representation are urgently needed to validate preventive strategies and refine therapeutic decision-making.

Abstract: Background: Killed Whole Cell Genome-Reduced Bacteria (KWC/GRB), a versatile vaccine platform, can produce very low cost, thermostable, easily manufactured vaccines expressing complex immunogens that include potent immunomodulators. This system supports iterative optimization through a Design–Build–Test–Learn (DBTL) workflow aimed at enhancing immunogenicity. We applied this approach to developing an HIV-1 gp41 Membrane-Proximal External Region (MPER) vaccine using the scaffolded MPER antigen, 3AGJ, a recombinant heterologous protein engineered to mimic MPER structures recognized by broadly neutralizing monoclonal antibodies (bNAbs). Methods: Five KWC/GRB vaccines expressing versions of 3AGJ were designed, including versions linked to immunomodulators and multimers of the immunogen. Display on the surface of the bacteria was evaluated by flow cytometry using the broadly neutralizing monoclonal antibody 2F5. Outbred HET3 mice were vaccinated intramuscularly, MPER-specific an-tibody responses were assessed by ELISA, and the ability of the vaccines to induce neutralizing antibodies determined. Neutralization was measured against tier 1 and tier 2 HIV-1 pseudoviruses. Results: All five vaccines were strongly expressed on the bacterial surface and induced clear MPER-specific antibody responses in every mouse. About 33% of the animals showed detectable HIV-1 neutralization. Conclusion: A KWC/GRB 3AGJ scaffold-MPER vaccine can induce HIV-1 neutralizing antibodies. While improvements in the responses would be needed for a clinically useful vaccine, the findings provide an initial validation of the concept. There are many strategies that can be used to enhance and extend immune responses induced by KWC/GRB vaccines that can be employed to yield improved anti-HIV immune responses.

Abstract: Autism spectrum disorder (ASD) is a prevalent and largely idiopathic developmental disorder with relatively widespread etiology. Currently there are no validated diagnostic or screening biomarkers for ASD, besides addressing the associated comorbidities. ASD is primarily diagnosed based on behavioral motor and cognitive characteristics. Until recently, the cerebellum had been particularly implicated in motor control, and under-researched for its potential role in the development of ASD. However, cerebellar circuitry is altered in ASD, impacting its brain interconnections, affecting brain development, and social and behavioral outcomes associated with ASD. We review the potential role of the cerebellum in ASD, how its dysfunction during development or its early postnatal injury may impact the maturation of other connected circuits, and play a role in the development of core ASD symptoms. We address cerebellar changes that may alter synaptic pruning, immune cells’ function, neurotransmitters, blood brain barrier permeability, and potential signaling pathways involved in ASD and how all these changes interplay may contribute to ASD pathophysiology. Understanding of these interactions, may provide novel therapeutic options specifically targeted to the cerebellum.

Abstract: Lithium remains endorsed as first-line treatment for bipolar disorders across major clinical guidelines, yet robust evidence demonstrates its progressive decline in use in psychiatric practice across numerous countries. To justify this decline, concerns regarding lithium's efficacy, safety profile, and monitoring requirements are frequently cited. Yet, these apprehensions largely stem from misunderstanding of lithium's clinical uses. In fact, when patients are selected for lithium stabilization according to a characteristic clinical profile and not just a bipolar verdict, lithium continues demonstrating excellent efficacy compared to all other psychiatric medications currently available. Moreover, after sufficient clinician and patient education regarding lithium stabilization principles, monitoring requirements stop being burdensome. Furthermore, among lithium-responsive patients, adverse effects are typically mild and clinically manageable, except for glomerular filtration rate decline, which tends to develop after decades of continuous administration. Thus, it may be possible to reverse this unfortunate decline in lithium's use by teaching clinicians to identify the patient profile responsive to lithium stabilization, by investigating intermittent lithium administration to mitigate renal complications, and by implementing educational programs regarding optimal lithium utilization for psychiatrists, patients, and their families.