PD-L1 expression in sebaceous carcinomas.

BACKGROUND: Traditional systemic treatments for unresectable, recurrent, and/or advanced sebaceous carcinoma (SC) are ineffective. Tumoral immune microenvironment characterization is essential for considering immune checkpoint inhibitors as a treatment option. METHODS: A total of 173 resected SCs were reviewed. Clinical information, lesion size, and location were collected. Microscopic examination documented histopathologic features and expression of immunohistochemical markers PD-L1 and CD8. PD-L1 percentage was assessed amongst tumor (PD-L1 + Tu) and immune infiltrating cells (PD-L1 + Inf). Each case was attributed a combined positive score (CPS) following Head and Neck squamous cell carcinoma recommendations. PD-L1 expression was evaluated according to clinicopathologic parameters. Human Papilloma Virus presence (HPV) was analyzed using PCR microarray scanning. RESULTS: A therapeutically relevant CPS was seen in 51.4% of cases. Higher PD-L1 + Tu, PD-L1 + Inf, and CPSs were positively associated with greater lesion size and an extraocular location. No association was seen with patient age or gender. 9.2% of SCs showed PD-L1 + Tu ≥ 1, while 52.0% showed PD-L1 + Inf ≥ 1. A higher CD8 + T-lymphocyte density was significantly associated with a higher CPS, PD-L1 + Tu, and PD-L1 + Inf. Tumor-associated T-cell infiltrate's density was higher along tumor periphery. HPV-16, HPV-43, HPV-52, and HPV-66 were detected in 8.4% of SCs. There was no significant association between HPV status, PD-L1 expression, and CPS. A significant number of SCs express PD-L1 at therapeutic levels. Nevertheless, PD-L1 expression shows a higher intertumoral heterogeneity, in extraocular than in biologically distinct periocular cases. CONCLUSION: Our data support the need for large-scale prospective studies evaluating anti-PD-L1 immunotherapy mainly in extraocular SC treatment.

Investigating the antimicrobial activity of essential oils against pathogens isolated from sewage sludge of southern Lebanese villages.

Introduction: Due to the high load of pathogens in sewage, seeking for effective treatments became a priority. In this regard, testing the sensitivity of microorganisms isolated from sewage against essential oils (EOs) is suggested. In Lebanon, little evidence supports bacteria isolated from sewage reveals a sensitivity to EOs. Due to this fact, the present investigation aims at determining the sensitivity of microbes isolated from sewage sludge to three EOs: lettuce, coconut, and almond. Methods: Bacterial isolates were identified by VITEK screening. Yeast was identified by germ tube assay. The chemical components of the oils were identified by gas chromatography - mass spectrometry (GC-MS). Susceptibility of the microbial isolates was assessed by the agar well diffusion assay. Bacteriostatic and bactericidal effects of EOs were detected by minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) broth microdilution assay. The activity of EOs on biofilms was detected by antibiofilm screening. Results: The identified microorganisms include Gram-negative isolates (Escherichia coli, Citrobacter freundii, Citrobacter braakii, Leclercia adecarboxylata, and Stenotrophomonas maltophilia), Gram-positive isolates (Enterococcus faecium, Streptococcus intermedius, Staphylococcus aureus, Staphylococcus capitis, and Staphylococcus haemolyticus), and Candida albicans. Thirty oils' chemical components were identified. Among the antibiotics, doxycycline exhibited the best inhibitory effect. The three EOs were effective against bacterial isolates and yeast at concentrations ranging between 3.125% and 50%. They exhibited a bacteriostatic activity. Lettuce and coconut oils were effective against biofilm formation and the three oils were effective on pre-formed biofilms. Conclusions: The results reflected the significant antimicrobial and antibiofilm activities of the oils, thus suggesting their potential antimicrobial applications.

Toxoplasmosis: Current and Emerging Parasite Druggable Targets.

Toxoplasmosis is a prevalent disease affecting a wide range of hosts including approximately one-third of the human population. It is caused by the sporozoan parasite Toxoplasma gondii (T. gondii), which instigates a range of symptoms, manifesting as acute and chronic forms and varying from ocular to deleterious congenital or neuro-toxoplasmosis. Toxoplasmosis may cause serious health problems in fetuses, newborns, and immunocompromised patients. Recently, associations between toxoplasmosis and various neuropathies and different types of cancer were documented. In the veterinary sector, toxoplasmosis results in recurring abortions, leading to significant economic losses. Treatment of toxoplasmosis remains intricate and encompasses general antiparasitic and antibacterial drugs. The efficacy of these drugs is hindered by intolerance, side effects, and emergence of parasite resistance. Furthermore, all currently used drugs in the clinic target acute toxoplasmosis, with no or little effect on the chronic form. In this review, we will provide a comprehensive overview on the currently used and emergent drugs and their respective parasitic targets to combat toxoplasmosis. We will also abridge the repurposing of certain drugs, their targets, and highlight future druggable targets to enhance the therapeutic efficacy against toxoplasmosis, hence lessening its burden and potentially alleviating the complications of its associated diseases.