Medicine and Pharmacology

Abstract: Background: Periodontitis and type 2 diabetes (T2D) maintain a bidirectional pathophysiological relationship that impairs conventional periodontal treatment outcomes. Chitosan, a biopolymer derived from chitin, possesses well-documented antimicrobial, hemostatic, wound-healing, and osteo-inductive properties. Objective: We aimed to evaluate whether 1% chitosan gel delivered nightly via a custom occlusal guard, as an adjunct to full-mouth scaling and root planning (SRP), would improve periodontal clinical and radiographic outcomes in patients with T2DM and Stage I-II periodontitis compared to placebo. Methods: A double-blind, randomized, placebo-controlled, parallel-group clinical trial was conducted (n = 16; 8 per group) in adults aged 40-65 years with T2D and periodontitis. Following SRP, participants received either 1% chitosan gel or placebo nightly via a custom occlusal guard for 30 days. Primary outcomes included periodontal pocket depth (PPD), clinical attachment level (CAL), and radiographic bone level (RBL). Secondary outcomes were probing depth (PD), bleeding on probing (BOP), and Miller mobility grade. Statistical analysis employed the Wilcoxon signed-rank test (within-group) and Mann-Whitney U test (between-group); p < 0.05 was considered significant. Results: Groups were comparable at baseline. Within-group analysis at 30 days revealed significant reductions in PPD (4.2 +/- 1.1 to 3.4 +/- 1.1 mm; p = 0.019) and RBL (5.6 +/- 2.2 to 5.1 +/- 1.9 mm; p = 0.030) in the chitosan group, and a clinically meaningful trend in CAL (5.1 +/- 2.8 to 3.8 +/- 1.7 mm; p = 0.069). The placebo group showed significant BOP reduction (78.3 +/- 23.4 to 51.5 +/- 26.0%; p = 0.017), consistent with the known effect of mechanical debridement. No between-group differences reached significance in delta values. Conclusions: Adjunctive use of 1% chitosan gel via a custom occlusal guard as a delivery system produces clinically relevant improvements in PPD and RBL in T2D patients with periodontitis. The occlusal guard represents a novel, patient-administered, sustained-contact delivery platform for periodontal local therapy. Larger, long-term randomized trials with microbiological and glycemic endpoints are warranted.

Abstract: Despite advances in neurosurgery and oncology, many gliomas—particularly highly aggressive variants such as glioblastoma multiforme—remain exceedingly difficult to treat. While surgical resection can eliminate a considerable proportion of tumor mass, clinical outcomes are frequently compromised by tumor recurrence, increased invasiveness, metastatic spread, and the development of glioma-associated epilepsy. These persistent challenges continue to drive intensive research efforts. Accumulating evidence suggests that glioma cell plasma membranes express several key classes of ion channels that contribute to tumor behavior. The four principal types identified to date include voltage-gated Na⁺ channels, large-conductance Ca²⁺-activated K⁺ (BKCa) channels, intermediate-conductance Ca²⁺-activated K⁺ (IKCa) channels, and inwardly rectifying K⁺ (Kir) channels. In this review article, eight representative drugs or phytoconstituents are discussed with particular emphasis on their modulatory actions on these ion channels. Perampanel and valproic acid can suppress the amplitude of voltage-gated Na+ current in glioma cells, an effect that may be particularly beneficial for managing glioma-associated epilepsy. Cilostazol is originally a vasodilatory drug; however, through drug repurposing approaches, it has been shown to stimulate BKCa channels in glioma cells, thereby potentially exerting anti-tumor effects. Berberine, an isoquinoline alkaloid, has been shown to suppress the activity of IKCa channels and this effect is associated with the suppression of tumors. Oxaliplatin, belonging to a family of platinum-based chemotherapeutic compounds, has been shown to diminish IKCa-channel activity in glioma cells, thereby affecting their malignant behaviors. Temozolomide, an oral alkylator of the imidazotetrazine family, was found to suppress IKCa-channel activity effectively in glioma cells. Arecoline, an alkaloid extracted from areca nut, is effective in suppressing the activity IKCa and Kir channels in neoplastic astrocytes. Triptolide, a diterpene triepoxide, has been shown to inhibit the activity of Kir channels in glioma cells. Some compounds have also been subjected to docking predictions on specific ion channels. Although these are hypothetical approaches, they provide useful insights into how such molecules might engage in distinctive molecular interactions with the channels. With appropriate and judicious use, these ion channel–specific modulators are expected to provide significant pharmacological and therapeutic benefits in glioma treatment.

Abstract: Psychiatric decision-making frequently occurs under conditions of substantial uncertainty in which both intervention and non-intervention may carry clinically significant consequences. Although therapeutic inertia has been extensively studied in chronic medical conditions such as diabetes and cardiovascular disease, its implications for psychiatry remain comparatively underexplored despite the distinctive epistemological, emotional, and institutional challenges characterizing mental healthcare. This narrative review examines how cognitive biases, asymmetrical risk perception, defensive clinical cultures, institutional pressures, and uncertainty intolerance may contribute to therapeutic inertia in psychiatric practice. Particular attention is given to the tendency to perceive harms associated with active intervention as more salient and professionally consequential than the often slower and less visible harms associated with undertreatment, persistent suicidality, chronic suffering, psychosocial deterioration, and functional disability. The review discusses how therapeutic inertia may manifest through delayed treatment intensification, prolonged continuation of partially ineffective therapies, normalization of chronic symptoms, and hesitation toward interventions perceived as high risk or institutionally burdensome. Clozapine underutilization in treatment-resistant schizophrenia is examined as a paradigmatic example of the tension between fear of iatrogenic harm and the substantial risks associated with persistent severe mental illness. Finally, the article explores future directions for more balanced psychiatric risk–benefit models capable of incorporating both the risks of intervention and the risks of non-intervention within reflective, patient-centered approaches to clinical decision-making under uncertainty.

Abstract: Background/Objectives: Cancer vaccines represent the next frontier in immunotherapy, aiming to elicit long-lasting protective anti-tumor protective immune responses. Human epidermal growth factor receptor 2 (HER2) is a well-established therapeutic target in breast cancer. Active immunization with HER2-displaying M13 bacteriophages can induce a therapeutic immune response against HER2-positive breast cancer, offering a promising alternative to trastuzumab. However, the duration of anticancer immune protection triggered by anti-HER2 phage-based vaccines is limited by tumor-immune suppressive mechanisms. Methods: In this study, two vaccination cycles with ECTM phages displaying the extracellular (EC) and transmembrane (TM) domains of human HER2 were combined with palbociclib, a CDK4/6 inhibitor, to enhance antitumor im-munity in the clinically relevant Δ16HER2 transgenic preclinical model of breast cancer. Results: The proposed combination treatment resulted in a better and long-lasting control of tumor growth rate and multiplicity than either palbociclib or phage vaccination alone, correlating with a significantly stronger anti-HER2 humoral response (IgG2a isotype). Analysis of the tumor immune infiltrate revealed an increased presence of CD8⁺ T cells concomitant with a reduction in FoxP3⁺ regulatory T cells (Tregs) in tumors explanted from mice receiving the combination therapy. Conclusions: These preclinical results provide a rationale for the clinical translation of CDK4/6 inhibitors combined with anti-HER2 active immunotherapies in breast cancer, as they may yield sustained antitumor responses by reverting the immunosuppressive tumor environment.

Abstract: Background: Poor appetite, a major contributor to malnutrition, is highly prevalent among older adults and associated with adverse clinical outcomes. Nevertheless, no effective appetite targeted treatments are currently part of clinical practice alongside nutritional interventions. Medical cannabis has been proposed as a potential appetite stimulant in older adults with poor appetite through modulation of appetite regulating hormones such as glucagon like peptide 1 (GLP 1) and ghrelin, but the evidence remains limited. Aims: To investigate the associations between a fixed dose of Sativex® (8.1 mg Δ9-tetrahydrocannabinol (THC) and 7.5 mg cannabidiol (CBD)) versus placebo and postprandial GLP 1, total ghrelin concentrations as well as subjective appetite in older adults with poor appetite, and the associations between THC and its metabolites on these outcomes. Methods: This protocolized secondary analysis included 17 participants (≥65 years) with poor appetite from a double blinded, randomized, placebo controlled crossover trial. Participants received Sativex® or placebo on two separate study days. GLP 1 and total ghrelin were measured following a standardized breakfast, and subjective appetite was assessed repeatedly using visual analogue scales. Associations were analyzed using linear mixed effects models. Results: Sativex® administration compared with placebo was associated with an estimated 2.38 pmol/L (95% confidence intervals (CI) -0.71−5.46; p = 0.137) reduction in mean GLP 1 concentration, time dependent changes in mean total ghrelin (p = 0.054), and overall estimates of reduced subjective appetite. Increased THC and metabolite concentrations were associated with reduced estimates of mean GLP-1 concentrations and subjective appetite, and an increased mean total ghrelin. However, no clinically relevant or statistically significant associations were observed, and estimates had wide CIs, warranting cautious interpretation. Conclusions: In conclusion, the administration of medical cannabis, formulated as Sativex®, did not differ from placebo with respect to postprandial GLP-1, total ghrelin as well as subjective appetite over time in older adults with poor appetite. The same was found for associations between THC and its metabolites, and GLP-1, total-ghrelin, and subjective appetite.

Abstract: Vascular stents are crucial devices in the treatment of cardiovascular diseases, and their structural design and function critically affect therapeutic efficacy and patient prognosis. Conventional stents can effectively restore vascular patency by providing mechanical support to blood vessels. However, they still face significant challenges including restenosis, thrombosis, and limited adaptability to complex patient-specific lesion characteristics. To address these limitations, drug delivery offers an important strategy to modulate the pathological microenvironment, enhance long-term vascular healing, and reduce systemic side effects. Meanwhile, advances in computational simulations have provided powerful tools for optimizing stent design through structural mechanics, hemodynamics, and drug release modeling, computational approaches enable the rational design of stent architectures with improved mechanical stability, vascular compatibility, and therapeutic regulation. Consequently, the development of vascular stents is evolving toward the synergistic integration of drug delivery, structural optimization, and intelligent design. This review summarizes the latest advances in functional vascular stents, clinical applications and computational design. This work aims to provide valuable insights for the engineering of efficient, precise, and intelligent vascular stents for cardiovascular therapies.