Strongyloides stercoralis is a soil-transmitted helminth that is increasingly reported in dogs across Europe. While most infections are subclinical, hyperinfection syndrome, marked by excessive larval proliferation and systemic spread, can occur in immunocompromised hosts. An 11-year-old male Boston Terrier dog, originating from southern France with a history of chronic diarrhoea and recent splenectomy was presented with severe regenerative anaemia, thrombocytopenia, and a degenerative left shift. Haemotropic Mycoplasma haemocanis infection was diagnosed, and doxycycline therapy was initiated. During hospitalisation, the dog developed dyspnoea, pneumonia, and progressive pleural effusion containing motile nematode larvae. Strongyloides stercoralis infection was diagnosed by morphological identification of larvae in pleural effusion (third-stage larvae) and faeces (first- and third-stage larvae) and confirmed by PCR targeting mitochondrial cox1 and nuclear 18S rDNA hypervariable regions (HVR) I and IV), followed by sequencing, which revealed the haplotypes HP16 (cox1), VI (HVR-I) and A (HVR-IV). The HVR-IV haplotype A is found in both dogs and humans, characterizing the zoonotic population of S. stercoralis. Respiratory signs worsened despite combined fenbendazole and escalating ivermectin treatment, requiring euthanasia. Post-mortem examination revealed chronic granulomatous pneumonia, a pulmonary carcinomatous nodule, lymphoplasmacytic enterocolitis, and glomerulonephritis. This case represents the first report of S. stercoralis hyperinfection in an adult splenectomised dog. It highlights the importance of including strongyloidiasis in differential diagnoses of dogs with respiratory and gastrointestinal signs, particularly in animals with compromised immunity or relevant travel history.

A 1-year-old female-intact arctic fox (Vulpes lagopus) presented for diarrhea, lethargy, severe thrombocytopenia, and hyperbilirubinemia. Blood film evaluation revealed intracytoplasmic coccoid bacteria within moderate numbers of leukocytes consistent with infection by a rickettsial organism. Similar organisms were observed within many leukocytes from fine-needle aspirates of an enlarged peripheral lymph node. The lymph node also contained moderate necrosis and an expansion of granular lymphocytes. Parasitic ovum consistent with the trematode Nanophyetus salmincola was found on fecal floatation. The patient responded to treatment with doxycycline, enrofloxacin, ampicillin/sulbactam, and other supportive therapies. Polymerase chain reaction testing confirmed the presence of Neorickettsia sp., and DNA sequencing identified the organism as Stellantchasmus falcatus agent. To the authors' knowledge, this is the first report describing this organism microscopically in peripheral blood, the first reported case of infection in this species of canid, and describes the various clinicopathologic changes with this infection.

Leptospirosis is a globally prevalent zoonotic infection caused by pathogenic spirochaetes of the genus Leptospira Although typically associated with mild flu-like symptoms or Weil's disease (characterised by jaundice, renal failure and haemorrhagic manifestations), atypical and severe presentations can mimic other systemic disorders. A man in his 40s presented with fever, myalgia along with rapidly progressive jaundice, thrombocytopenia, microangiopathic haemolytic anaemia and acute kidney injury, preceded by a short episode of diarrhoea. The initial working diagnosis was haemolytic uraemic syndrome (HUS) secondary to Shiga toxin-producing Escherichia coli and he was treated with plasma exchange, transfusions and renal replacement therapy. However, stool examinations were negative for Shiga toxin and bacterial pathogens. Subsequent investigations confirmed leptospirosis. He improved significantly after treatment with doxycycline alongside supportive therapy. This case highlights the importance of considering leptospirosis as a differential diagnosis in patients with HUS, particularly in endemic regions, to avoid delays in targeted treatment.

This case describes a 29-year-old man with Morbihan disease, characterized by a 5-year history of recurrent facial erythema, papules, and pustules, followed by persistent right face edema. Initially misdiagnosed as lupus erythematosus, he received multiple treatments with only transient relief. Clinical manifestations combined with pathological findings confirmed a diagnosis of Morbihan disease associated with rosacea. Notably, the patient developed erythema and papules on the inner thighs, along with small papules on the trunk and upper limbs for 3 months. A biopsy revealed nonspecific inflammation. Since the morphology of these lesions differed from any known skin disease and no other cause could be identified, we believe this may be a manifestation of the disease. Extra-facial manifestation not previously reported. Various therapies were attempted: doxycycline and azelaic acid improved erythema; baricitinib was ineffective; while omalizumab and intense pulsed light (IPL) achieved partial improvement in erythema and edema. Long-term isotretinoin therapy provided sustained remission without relapse during tapering, confirming its efficacy and safety. This case expands the clinical spectrum of Morbihan disease by documenting extra-facial involvement and reported isotretinoin as an effective long-term therapy, with omalizumab and IPL as promising adjuncts. Furthermore, the literature review (2004-2025) summarizes the clinical features, pathology, and treatment responses of reported cases, showing a male-to-female ratio of 2.81:1. Lymphatic or vascular dilation was significantly correlated with a favorable outcome. Conversely, dermal edema and granuloma were inversely associated with treatment efficacy, indicating poorer prognosis. However, based on uncontrolled data, these findings are strictly hypothesis-generating and do not establish a definitive treatment hierarchy.

Kaposi's Sarcoma Herpesvirus (KSHV), an enveloped double-stranded DNA virus, is the etiological agent of Kaposi's sarcoma (KS), an endothelial cell-based tumor. KSHV is a leading cause of infection-related cancers in sub-Saharan Africa and immunocompromised individuals worldwide. Therefore, it is vital to identify the underlying mechanisms of viral infection and transmission to effectively identify specific therapeutic strategies and combat the disease. Here, we demonstrate that KSHV rewires the host cell lipidome during lytic infection. Bulk lipidomic analysis shows significant changes in the abundance of neutral lipids and phospholipids during lytic infection. We further investigated fatty acid-binding proteins (FABPs) to understand the underlying mechanisms that support KSHV pathogenesis. Using the doxycyclin-inducible iSLK.BAC16 cell line, we find that FABP genes are differentially regulated by lytic KSHV infection compared to latent infection. We report that FABP4 is significantly upregulated during lytic infection. Loss of FABP4 during lytic infection does not impact viral gene transcription however, lytic protein translation is reduced. Moreover, our intracellular and extracellular viral titers indicate that FABP4 affects maximal infectious virion production. This study highlights the role of FABP4 and its therapeutic potential as a target that facilitates KSHV infection and pathogenesis.

This prospective, randomized clinical trial compared the therapeutic efficacy and rate of platelet recovery of doxycycline 10 mg/kg once daily (SID) (Group A, n=17) versus 5 mg/kg twice daily (BID) (Group B, n=12) in 29 dogs naturally infected with Ehrlichia canis. Using a "treat-to-target" protocol that mandated both molecular clearance and platelet normalization prior to cessation, results showed that while both regimens achieved 100% molecular clearance, the BID regimen demonstrated significantly more rapid hematological recovery (P < 0.05 at Days 7 and 14) and required a significantly shorter median treatment duration (28.5 days vs. 39.0 days; P = 0.015). Notably, delayed molecular clearance (>28 days) was observed exclusively in the SID group, and post-treatment recrudescence was detected in two dogs at Day 98. We conclude that the 5 mg/kg BID protocol offers superior pharmacodynamic performance, and a "treat-to-target" strategy involving long-term monitoring is recommended over a fixed 28-day course to ensure complete clinical and parasitological resolution.

Scrub typhus is a common cause of acute febrile illness in endemic regions; however, musculoskeletal involvement is usually limited to myalgia, and true inflammatory arthritis is rarely reported. We describe a 19-year-old previously healthy male military recruit who presented with a two-month history of progressive bilateral knee swelling and left ankle pain, accompanied by fever, weight loss, and lymphadenopathy. Clinical evaluation revealed inflammatory oligoarthritis with culture-negative synovial fluid. Given the chronicity of symptoms and systemic features, tubercular and septic arthritis were initially considered. Imaging showed preserved joint architecture, and synovial fluid analysis demonstrated inflammatory features without microbial growth. Investigations for tuberculosis, autoimmune disorders, and other tropical infections were negative. Serological testing was positive for scrub typhus immunoglobulin M using a rapid immunochromatographic assay. Following the initiation of doxycycline therapy, the patient showed rapid clinical improvement with resolution of fever and marked reduction in joint symptoms. This case highlights an uncommon presentation of scrub typhus-associated inflammatory oligoarthritis mimicking tubercular arthritis in endemic regions. Clinicians should consider scrub typhus in patients presenting with febrile oligoarthritis and culture-negative joint effusion, as early recognition and appropriate treatment can result in excellent outcomes.

Background/Objectives: Drug repurposing offers a time- and cost-efficient strategy for accelerating the development of anticancer therapies by leveraging the established safety profiles of existing pharmaceuticals. This study aimed to investigate the anticancer potential of three tetracycline analogues chemically modified tetracycline-3 (COL-3), doxycycline (DOX), and minocycline (MIN) in leukemia models, with a particular focus on their cytotoxic effects and modulation of the JAK2/STAT3 signaling pathway. Methods: Cytotoxicity was evaluated in K562, KG-1a and Jurkat cell lines using luminescence-based viability assays, whereas the mechanisms of cell death were analyzed by Annexin-V/7-AAD staining and Western blotting. Results: COL-3 displayed the highest cytotoxic potency across all cell lines, with Jurkat cells showing the greatest overall sensitivity. Flow cytometry revealed that tetracycline analogues primarily induced apoptosis, although the molecular mechanisms differed between cell lines. In K562 and KG-1a cells, apoptosis occurred largely through JAK2/STAT3-independent mechanisms, involving differential regulation of BCL-2 family proteins: COL-3 reduced BCL-2 expression, whereas DOX and MIN increased BAX expression. In contrast, Jurkat cell apoptosis correlated with suppression of phosphorylated JAK2 and STAT3 and downregulation of BCL-2, implicating a JAK2/STAT3-dependent mechanism. Conclusions: Taken together, these findings demonstrate that tetracycline analogues exert cell line-specific anticancer activities through distinct molecular pathways. Among them, COL-3 emerges as the most potent analogue and acts through both JAK/STAT-dependent and -independent mechanisms. This work supports further investigation of COL-3 as a candidate for drug repurposing strategies in hematological malignancies.

Background/Objectives: Seasonal waves of respiratory viruses-including SARS-CoV-2, influenza A virus (IAV), and respiratory syncytial virus (RSV)-continue to pose a global health burden and highlight the need for antiviral agents that are effective, safe, broadly active, affordable, and widely accessible. Current interventions are limited by the need for their early administration, the risk of resistance, their costs, and the restricted availability in large parts of the world. For certain natural products, such as European black elderberry (Sambucus nigra L.) fruit extract (ElderCraft[®]; EC) and the seaweed-derived sulfated polymer iota-carrageenan (IC), antiviral activities against respiratory viruses, particularly IAV and SARS-CoV-2, have previously been shown. Here, we assessed the antiviral activity of IC and an anthocyanin-standardized EC extract against SARS-CoV-2, IAV, and RSV, either as monotherapy or in multiple-dose combinations. Methods: MDCKII cells were infected with IAVPR8, human Calu-3 lung epithelial cells with the SARS-CoV-2 Omicron variant, and HEp-2 cells with RSV (A2 strain). Inhibitors were administered either by pre-incubation of cell-free virions prior to infection or, in separate time-of-addition experiments, during or post-infection. Viral replication was quantified by qRT-PCR or intracellular immunostaining. Cytotoxicity was evaluated using a neutral red uptake assay. Results: Most intriguingly, both EC and IC are able to neutralize virions derived from SARS-CoV-2, IAV, or RSV extracellularly in a dose-dependent manner. Notably, EC and IC alone exhibited strong anti-RSV activity, which was not reported previously. Most importantly, combined treatment with IC and EC caused a pronounced synergistic antiviral effect against the tested viruses, as confirmed by the Bliss independence model, without any detectable impact on cell viability. Finally, solutions prepared from matrix-standardized mono- or combi-lozenges, containing IC and/or EC in high or low doses, reproduced the antiviral and synergistic combination effects observed with the pure compounds. Conclusions: In summary, these findings support further development of EC and IC as a topically accessible, virion-neutralizing combination (e.g., lozenges) to provide additional protection against major respiratory viruses and potentially strengthen pandemic preparedness.

Bone tissue engineering requires biomaterials capable of simultaneously supporting regeneration and preventing infection. Platelet-rich fibrin (PRF) has been widely used due to its autologous origin and growth factor release, but its rapid resorption limits its clinical applications. Albumin-PRF (Alb-PRF) membranes were developed to improve stability, and their combination with carbonated nanostructured hydroxyapatite (nCHA) may further reinforce osteoconductive properties. In this proof-of-concept study, we fabricated Alb-PRF, Alb-nCHA-PRF, and Alb-nCHA-PRF + doxycycline (DOX) membranes and characterized their physicochemical, antimicrobial, and biological performance in vitro. Membrane stability was monitored for up to 14 days; DOX incorporation and release were evaluated by autofluorescence and spectrophotometry; antimicrobial activity was assessed against E. faecalis and S. aureus; and MG-63 osteoblast-like cells were used to test cytocompatibility, proliferation, mineralization, and alkaline phosphatase (ALP) activity. The release of 27 cytokines and growth factors was quantified by multiplex immunoassay. Alb-PRF exhibited morphological integrity and an enhanced trophic secretome, and supported proliferation and late mineralization. nCHA incorporation reduced cell proliferation and secretome output, while DOX conferred sustained antibacterial activity and enhanced early ALP expression even with attenuated cytokine release, positively impacting mineralization, when compared to nCHA alone. These preliminary results provide preliminary feasibility evidence that Alb-PRF can be engineered as a multifunctional scaffold combining antimicrobial and regenerative functions, though some trade-offs indicate the need for dose optimization and validation with in vivo models.

Lamellar ichthyosis is a rare congenital disorder of keratinization frequently associated with ocular complications, most commonly cicatricial ectropion and exposure keratopathy. We present a case of severe mixed exposure-related and neurotrophic keratopathy with marked corneal thinning in a 61-year-old man with genetically confirmed lamellar ichthyosis. At presentation, the best-corrected visual acuity (BCVA) in the right eye was limited to hand motion (logMAR 2.3). Slit-lamp examination revealed a large central to inferocentral corneal ulcer measuring approximately 3 × 4 mm with severe stromal thinning in the setting of marked lower eyelid ectropion, incomplete eyelid closure, and chronic ocular surface exposure, while anterior segment optical coherence tomography (AS-OCT) demonstrated a minimal corneal thickness of approximately 165 µm. Microbiological swabs obtained from the conjunctival sac were negative, and no purulent discharge, hypopyon, or anterior chamber inflammatory reaction was present, making active infectious keratitis unlikely. Corneal sensitivity measured with Cochet-Bonnet esthesiometry at presentation, centrally and in all four peripheral quadrants of both eyes, was markedly reduced, more severely in the affected right eye, supporting the presence of a severe neurotrophic component contributing to impaired corneal healing. Intensive conservative therapy including preservative-free lubricants, dexpanthenol gel, autologous serum eye drops, topical insulin, prophylactic antibiotics, and systemic doxycycline was initiated. Serial AS-OCT imaging demonstrated progressive structural recovery, with corneal thickness increasing to 438 µm after one month of treatment and complete corneal epithelialization. The BCVA improved to 0.2 Snellen (0.7 logMAR). This case highlights the diagnostic value of multimodal anterior segment imaging in monitoring severe mixed keratopathy with advanced corneal thinning and demonstrates that intensive conservative therapy may stabilize the ocular surface and prevent corneal perforation in patients with lamellar ichthyosis.