The extensive use of antiviral drugs has raised growing concerns in environmental and analytical studies due to their persistence in the environment and potential ecological impacts. In this work, a highly sensitive electrochemical sensing platform for valganciclovir (VAL) was constructed using an electrode incorporating NiFeSe₂@Ni-MOF composite. Structural characterization confirmed the successful formation of the nanocomposite and the synergistic integration of both components. FTIR and XRD analyses verified the coexistence of NiFeSe₂ and Ni-MOF with strong interfacial interactions, while XRD revealed a crystallite size of 31.05 nm for the NiFeSe₂@Ni-MOF nanocomposite. BET analysis demonstrated a mesoporous structure with a specific surface area of 15.17 m2 g⁻1 and preserved accessible pore channels favorable for mass transport. FESEM images showed the homogeneous dispersion of NiFeSe₂ nanoparticles over the flower-like Ni-MOF structure, and EDS analysis confirmed the presence and uniform distribution of C, O, Ni, Fe, and Se elements. The analytical performance of the sensor was evaluated using differential pulse voltammetry (DPV) under optimized experimental conditions. A linear relationship was achieved within the concentration range of 0.5-27 μM, with a coefficient of determination of R2 = 0.996. The limits of detection and quantification were found to be 0.0174 μM and 0.058 μM, respectively. The sensor exhibited excellent selectivity in the presence of various interfering substances, along with satisfactory repeatability (RSD = 1.1%) and reproducibility (RSD = 1.3%). In addition, the electrode showed good stability, retaining 95% of its initial response after two weeks. The proposed method was effectively validated in real matrices, including pharmaceutical products, biological fluids (human plasma and urine), and environmental water samples (lake and seawater), yielding satisfactory recoveries between 96.16% and 104.1%. Thus, the proposed sensor offers a dependable, sensitive, and practical method for the detection of VAL in complex sample environments.

The ongoing emergence of respiratory viral pathogens, including novel variants and established threats such as influenza, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and Respiratory Syncytial Virus (RSV), continues to challenge global health systems due to limited specific therapeutic options. Intranasal antiviral delivery represents a promising approach for targeting respiratory tract infections; however, drug development frequently fails due to inappropriate pharmacokinetic properties. This study employed computational ADMET Predictor tools to systematically evaluate the physicochemical and potential pharmacokinetic properties of ten reference compounds, including nine approved antiviral drugs and ivermectin, a repurposed antiparasitic agent with reported antiviral activity and prior intranasal investigation: Zanamivir, Ribavirin, Oseltamivir, Favipiravir, Remdesivir, Nitazoxanide, Acyclovir, Lopinavir, Molnupiravir, and Ivermectin. Computational predictions were validated against experimental literature data to establish evidence-based criteria ranges. Key parameters related to intranasal drug delivery, covering physicochemical, absorption, distribution, metabolism, elimination, and toxicity properties, were systematically analyzed. The analysis resulted in revised criteria including molecular weight (Mwt), pH, lipophilicity (Log P), water solubility (Sw and SpH), Volume of distribution (Vd), P-glycoproteins substrate (Pgp substrate), and skin sensitization (Sens_Skin) to demonstrate 80% concordance with approved drug properties. This framework provides the preliminary evidence-based screening criteria as a tool to identify promising drug candidates suitable for preclinical evaluation in intranasal formulation development.

Recombinant adjuvanted herpes zoster vaccine (Shingrix) effectively prevents varicella-zoster virus (VZV) reactivation and is recommended for older and immunocompromised adults.

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a severe form of autoimmune encephalitis. Symptoms include psychiatric manifestations, seizures, dyskinesias, autonomic instability, and altered consciousness. Recently, Herpes simplex virus (HSV) encephalitis has been recognised as a major cause of secondary autoimmune encephalitis. We report the case of a 23-year-old woman who developed behavioural changes and altered sensorium. She was initially suspected of having a primary psychiatric disorder. Subsequent tests showed the presence of anti-NMDAR antibodies in the cerebrospinal fluid (CSF), and positivity for HSV-1 was confirmed by real-time polymerase chain reaction (PCR). Despite receiving high-dose corticosteroids, IVIG, plasmapheresis, rituximab, acyclovir, and antiviral therapy, the patient was admitted to the ICU, where she stayed for a prolonged period due to respiratory failure, septic shock, and acute kidney injury. This case highlights the diagnostic challenge between viral and autoimmune encephalitis and underlines that patients with acute neuropsychiatric symptoms require early recognition, repeated CSF testing, and multidisciplinary management.

Oncolytic virotherapy offers a promising avenue for solid tumor treatment, yet single-agent approaches are frequently limited by insufficient tumor lysis and inadequate immune activation. Here we report that combined therapy with two recombinant variants of the oncolytic vaccinia virus, armed with either herpes simplex virus thymidine kinase (VV-HSVtk) or the interleukin 15 receptor subunit alpha (VV-mIL15Rα), leads to enhanced cytotoxicity and immune stimulation in a murine mammary adenocarcinoma model (4T1). In vitro, VV-HSVtk exhibited dose-dependent cytotoxicity markedly potentiated by ganciclovir (GCV) through HSVtk-mediated phosphorylation into a cytotoxic nucleoside analog, and co-culture of VV-infected tumor cells with donor-derived NK cells further increased oncolytic efficiency. In vivo, combined treatment with VV-HSVtk, VV-mIL15Rα, and GCV resulted in significant tumor regression and extended survival relative to monotherapy controls in 4T1 syngeneic mice. Histological examination revealed increased lymphocytic infiltration at tumor sites and absence of hepatic or splenic toxicity. Together, these data indicate that integrating direct viral cytotoxicity, HSVtk/GCV-mediated suicide gene therapy, and IL-15-pathway-targeted immunomodulation within an oncolytic vaccinia platform can improve antitumor efficacy in a stringent breast cancer model.

Dermatitis herpetiformis (DH) is a chronic autoimmune blistering dermatosis associated with gluten-sensitive enteropathy and characterized by intensely pruritic papulovesicular eruptions, typically distributed symmetrically on extensor surfaces. Although DH classically presents with grouped vesicles and excoriated papules, atypical and exuberant manifestations may represent a substantial diagnostic challenge, frequently mimicking infectious, inflammatory, and autoimmune blistering disorders. We report the case of a 30-year-old woman presenting with a one-year history of progressive, intensely pruritic vesiculobullous and erosive lesions involving the trunk and extremities, accompanied by painful oral ulcerations, hemorrhagic crusts, extensive excoriations, secondary bacterial infection, and diffuse post-inflammatory hyperpigmentation. The patient was initially diagnosed with Behçet disease and subsequently hospitalized for suspected disseminated herpetic infection, receiving systemic corticosteroids and intravenous acyclovir without significant clinical improvement. Dermatological examination revealed widespread erosive and vesiculobullous lesions associated with severe inflammatory activity and oral aphthoid ulcerations. Histopathological examination of active lesions demonstrated intraepidermal blister formation associated with eosinophilic infiltrate and scattered acantholytic cells, findings that initially suggested alternative autoimmune blistering disorders. Direct immunofluorescence (DIF) demonstrated characteristic granular IgA deposition predominantly localized at the tips of dermal papillae, confirming the diagnosis of DH despite atypical histopathological findings. Serological evaluation further revealed positive anti-tissue transglutaminase and anti-endomysial antibodies, corroborating the diagnosis. Treatment with dapsone combined with a strict gluten-free diet resulted in marked clinical improvement. This case highlights the importance of clinicopathological and immunopathological correlation in atypical presentations of autoimmune blistering diseases and underscores the essential role of DIF in establishing the diagnosis of DH.

Immune checkpoint inhibitor colitis is a common immune-related adverse event associated with immunotherapy and may be refractory to corticosteroids and biologic therapy. Evidence guiding management beyond anti-tumour necrosis factor and anti-integrin therapy remains limited. We report a case of severe immune checkpoint inhibitor colitis in a man in his 60s with metastatic melanoma treated with combination ipilimumab and nivolumab. Colitis was refractory to corticosteroids, dose-escalated infliximab and vedolizumab. Upadacitinib was commenced with rapid improvement, with stool frequency decreasing from 40 bowel motions per day to 6 within 24 hours. This response was accompanied by a marked decrease in C-reactive protein and faecal calprotectin. His recovery was complicated by cytomegalovirus infection, successfully treated with valganciclovir. A repeat colonoscopy demonstrated complete mucosal healing and the patient achieved durable steroid-free remission following treatment cessation. This case illustrates the potential role of Janus kinase 1 inhibition as a salvage strategy in refractory immune checkpoint inhibitor colitis.

Topical dosage forms are widely used to treat various skin disorders, but increase healthcare costs because of the limited number of generic competitors. The development of a generic version of complex topical products is facing several scientific and regulatory challenges related to demonstrating bioequivalence, advanced physicochemical characterization, and the requirement of clinical endpoint equivalence. This narrative review explores the contemporary scientific and regulatory approaches used for BE assessment of topical generics, with a greater focus on in vitro alternatives and Q3 microstructural characterization. The integration of quality by design principles can support the development of robust Q3-based BE strategies. Key in vitro tools such as IVRT, IVPT, and dermal PBPK modeling are emerging approaches for identifying scientific parameters for regulatory acceptability and overcoming these methodological challenges. Case studies involving bifonazole, acyclovir, clotrimazole, and innovative vehicles such as Recura illustrate the practical challenges of existing regulatory frameworks and the increasing use of in vitro and Q3-based approaches. This review highlights the critical gaps in harmonizing global regulatory requirements and underscores the need to foster early regulatory engagement and standardize methodological protocols. Together, these initiatives pave the way for a more predictable, scientifically sound, and cost-effective regulatory environment. This transformation is essential for improving access, reducing development timelines, and advancing the future of topical generic medicines.