Herpes simplex virus type 2 (HSV-2) is the principal cause of genital herpes, establishes lifelong latency with recurrent mucosal lesions, and facilitates acquisition of human immunodeficiency virus type 1 (HIV-1). Because current therapy still relies largely on nucleoside analogues and resistant isolates continue to emerge, alternative antiviral strategies are needed. In this study, halofuginone (HF), a halogenated analogue of the febrifugine scaffold, inhibited both wild-type and acyclovir-resistant HSV-2 in cultured cells at nanomolar concentrations. In a murine genital challenge model, topical administration before viral exposure reduced viral burden and alleviated local inflammatory responses. Pre-exposure experiments further showed that HF decreased the infectivity of extracellular HSV-2 particles and was associated with virion structural damage, whereas docking analysis suggested a possible interaction with glycoprotein D (gD). In parallel, partial reversal by L-proline supported a host-cell component linked to inhibition of the prolyl-tRNA synthetase (ProRS) domain of glutamyl-prolyl-tRNA synthetase (EPRS). HF also suppressed HSV-2-induced activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) axis and the nuclear factor kappa B (NF-κB) pathway. Beyond HSV-2, HF remained active against herpes simplex virus type 1 (HSV-1) and C-C chemokine receptor type 5 (CCR5)-tropic HIV-1 and retained antiviral activity in an HSV-2/HIV-1 co-infection model. Overall, the data support a two-component antiviral effect of HF, involving extracellular impairment of viral particles together with intracellular host-directed restriction, and warrant further evaluation of HF as a topical prevention-oriented candidate against HSV-2.

Mild encephalopathy with a reversible splenial lesion (MERS) is a clinico-radiological syndrome characterized by acute encephalopathy and a transient lesion in the splenium of the corpus callosum on magnetic resonance imaging (MRI). We report a case of a six-year-old girl who presented with behavioral disturbance and altered mental status after one week of a viral prodrome in the setting of household SARS-CoV-2 exposure. Cerebrospinal fluid analysis was unremarkable, and SARS-CoV-2 serology showed positive immunoglobulin G (IgG) and negative immunoglobulin M (IgM). Brain MRI demonstrated a focal splenial lesion with bilateral cerebellar involvement of the dentate nuclei, consistent with MERS type II. The patient initially received ceftriaxone and acyclovir for suspected encephalitis. Neurological deterioration with dysphagia led to treatment with intravenous methylprednisolone followed by intravenous immunoglobulin. Follow-up MRI at one month showed complete lesion resolution, and complete neurological recovery was achieved by three months. This case highlights the importance of recognizing this reversible clinico-radiological pattern in children with acute encephalopathy to facilitate diagnosis, guide management, and avoid unnecessary investigations.

For the determination of bioequivalence (BE) of generic topical dermatological drug products, In Vitro assessment of dermal pharmacokinetics is a critical aspect. The In Vitro Permeation Test (IVPT) is frequently used to evaluate the skin's drug absorption, using Ex Vivo human skin in conjunction with diffusion cells. The establishment of statistical methodology for BE assessment of IVPT data began in 2016 with the release of the FDA guidance for Acyclovir Cream 5%. Since then, there have been significant research activities that led to several advances and extensions of the original methodology. Such research includes extending the method to the case of unbalanced data, an adaptive design, and adopting a model-based approach for assessing BE in IVPT study data. While IVPT is recognized as a highly sensitive and discriminating method, there is a scarcity of the literature addressing the statistical methodology associated with it. This effort seeks to showcase the activities undertaken over the past decade, culminating in an efficient and rigorous process for the regulatory approval of topical generic products. The aim is to chronicle these activities as a journey from the inception of a statistical approach for assessing BE in IVPT data to the various advances promoted by regulatory challenges.

Herpes Simplex Virus-2 (HSV-2) is the leading cause of genital herpes. Currently, no vaccines are available to prevent HSV-2 infection. Moreover, resistance to acyclovir, a commonly used drug to treat HSV-2 infection, is a growing concern. Herein, we show that the stapled peptide SPep7B, originally developed as a potential antiviral against HSV-1 for treating human herpes ocular keratitis, has the extended ability to target HSV-2 replication in vitro and block HSV-2 infection in three-dimensional (3D) human vaginal cells. We also demonstrate that SPep7B exhibits low cytotoxicity, non-mutagenicity, remarkable metabolic stability in plasma, and the ability to penetrate epithelial tissue. Together, these findings support the potential of SPep7B as a topical treatment for HSV-2 genital herpes.

Neonatal varicella is uncommon but may lead to severe complications, including central nervous system involvement. Cerebrospinal fluid findings may be misleading in neonates, and polymerase chain reaction-confirmed viral central nervous system infection may occur without pleocytosis, particularly when lumbar puncture is performed early in the course of illness. We report a 17-day-old term male neonate admitted with generalized vesicular rash and fever associated with irritability and poor feeding. Lumbar puncture performed on admission showed normal cerebrospinal fluid parameters without pleocytosis; however, a multiplex cerebrospinal fluid polymerase chain reaction panel was positive for varicella-zoster virus, and vesicular lesion polymerase chain reaction confirmed varicella-zoster virus infection. The neonate received intravenous acyclovir for 21 days with complete clinical recovery and normal follow-up. This case highlights that a normal cerebrospinal fluid cell count does not exclude neonatal viral central nervous system infection and supports early cerebrospinal fluid polymerase chain reaction testing to confirm varicella-zoster virus central nervous system involvement while rapidly excluding major differentials such as neonatal herpes simplex virus infection.

3D-printed porous TiO2/BiFeO3 nanocomposite monoliths with surface areas of up to 65 m[2] g[-1] were fabricated via two ways employing 3D printing. In method A, BiFeO3 nanoparticles were directly embedded into a TiO2-based hybrid ink for the direct ink writing (DIW) technique, while in method B, BiFeO3 nanoparticles were deposited as a surface coating onto a 3D-printed TiO2 scaffold. The obtained materials were comprehensively characterized by X-ray diffraction (XRD), electron microscopy (SEM, TEM), nitrogen adsorption-desorption, UV-vis spectroscopy, photoluminescence spectroscopy, and X-ray photoelectron spectroscopy (XPS). The photocatalytic performance of the materials was evaluated for the degradation of acyclovir under three different irradiation conditions: a medium-pressure Hg lamp (emission mostly in the UV region, 150 W) and blue LED sources at 420 nm (6 W) and 440 nm (40 W). The sample prepared by method A, including 1 wt % BiFeO3 inside a TiO2 matrix, showed the best performance under all irradiation conditions, which could be attributed to the combination of high surface area and the improved charge separation across the heterojunction interface. Additionally, Density Functional Theory (DFT) calculations were performed to confirm the formation of type-II heterojunctions between BiFeO3 embedded in TiO2 materials, consistent with the experimentally observed enhancement. These 3D-printed materials represent a significant advancement toward the development of photocatalytic water treatment under visible light conditions.

Retinal necrosis (RN) is typically caused by herpesviridae, most commonly varicella-zoster virus (VZV), followed by HSV and occasionally cytomegalovirus (CMV). While RN is generally unilateral, bilateral cases are more common in immunocompromised individuals. We report a rare case of bilateral retinal necrosis caused by CMV in an immunocompetent 31-year old male. He initially presented with defective vision in both eyes and was diagnosed after PCR confirmed the CMV as the causative agent. Despite initial treatment with intravenous acyclovir, he showed persistent vitreous inflammation with membranes, leading to intravitreal ganciclovir injections. While the patient experienced significant improvement, complications such as a macular hole and epiretinal membrane developed. This case highlights the need for clinicians to consider CMV as a possible cause of RN in immunocompetent adults, especially in non-responding cases, and underlines the importance of early etiological diagnosis and targeted treatment.

Cytomegalovirus (CMV) infection of the anterior segment is increasingly recognized as an important cause of corneal endotheliitis and secondary glaucoma, even in immunocompetent individuals. CMV corneal endotheliitis typically presents with coin-shaped or linear keratic precipitates (KPs), corneal edema, mild anterior chamber inflammation, and recurrent intraocular pressure (IOP) elevation; persistent or episodic ocular hypertension may progress to glaucomatous optic neuropathy if inadequately treated. Definitive diagnosis relies on aqueous humor polymerase chain reaction (PCR) testing for CMV DNA, supported by adjunctive imaging including specular microscopy, anterior segment optical coherence tomography (AS-OCT), and in vivo confocal microscopy (IVCM). Management requires a comprehensive strategy integrating antiviral therapy, anti-inflammatory treatment, and appropriate IOP control. Topical or systemic ganciclovir remains the cornerstone, while refractory disease may necessitate surgical intervention. Older age and male sex, host immune status, prolonged or recurrent CMV infection, and pre-existing ocular conditions are major risk factors for progression and poor outcomes. The pathogenesis of secondary glaucoma is thought to involve both direct viral cytopathic effects and inflammation-mediated damage to the trabecular meshwork (TM), resulting in impaired aqueous outflow. Therefore, early recognition, accurate diagnosis, and effective treatment are essential to prevent corneal decompensation and permanent vision loss.

Background and Objectives: Appropriate antimicrobial dosing according to kidney function is essential to ensure therapeutic efficacy while minimizing toxicity and antimicrobial resistance. Despite established dosing guidelines and electronic prescribing systems, errors in renal dose adjustment of antimicrobials, particularly in the setting of acute kidney injury, remain common among hospitalized patients. Materials and Methods: A point-prevalence study was conducted on 31 October 2024 at a tertiary-care hospital in Greece to evaluate the appropriateness of antimicrobial dosing in relation to renal function. Patient characteristics, renal parameters, and antimicrobial prescriptions were extracted from electronic medical records. Glomerular filtration rate (GFR) was estimated using the MDRD formula. Comparative analyses were performed between correctly and incorrectly dosed cases, and between overdosing and underdosing episodes. Results: A total of 235 hospitalized patients were evaluated (mean age 64.8 ± 18.6 years; 43.4% female). Overall, 15.7% (37/235) received at least one antimicrobial dose inappropriate for their renal function. Among 37 patients where dosing errors were identified, overdosing was noted in 23 (62.2%), underdosing in 16 (43.2%), adding up to 39 prescriptions, while in 2 patients (5.4%), both mistakes were noted in different prescribed antimicrobials. Drug-specific error rates varied considerably: ceftazidime and cefuroxime showed the highest rates of inappropriate dosing (40% each), followed by colistin (33.3%) and acyclovir (33.3%). Piperacillin/tazobactam, the most frequently prescribed agent (n = 50), had a 14% error rate, mainly due to underdosing (10%). Patients with dosing errors were significantly older (71.5 vs. 64.1 years, p = 0.0220) and had worse renal function, including higher serum creatinine (1.68 vs. 1.19 mg/dL, p = 0.0174), lower GFR (58.5 vs. 75.9 mL/min/1.73 m[2], p = 0.0009), and more frequent dialysis (13.5% vs. 4.3%, p = 0.0422). They also received a higher median number of antimicrobials (2 vs. 1, p = 0.0185). Conclusions: Inappropriate antimicrobial dosing based on kidney function remains common in hospitalized patients, particularly among older individuals and those with impaired renal function or polypharmacy. Targeted antimicrobial stewardship strategies focusing on renal dose adjustment and agents that are more frequently dosed inappropriately, such as colistin, acyclovir, cefuroxime, and ceftazidime, as well as agents that are frequently prescribed despite a relatively lower rate of inappropriate dose, such as piperacillin/tazobactam, are needed to enhance prescribing safety and optimize therapeutic outcomes.