POLD3 deficiency is associated with severe combined immunodeficiency, neurodevelopmental delay, and hearing impairment.

Combined immunodeficiency diseases (CID) represent the most severe forms of inborn errors of immunity. Defective T cell development and/or function, leading to an impairment in adaptive immunity are responsible for these diseases. The DNA polymerase δ complex is important for genome duplication and maintenance and consists of the catalytic subunit POLD1, and the accessory subunits POLD2 and POLD3 which stabilizes the complex. Mutations in POLD1 and POLD2 have been recently shown to be associated with a syndromic CID characterized by T cell lymphopenia with or without intellectual deficiency and sensorineural hearing loss. Here we report a homozygous POLD3 variant (NM_006591.3; p.Ile10Thr) in a Lebanese patient, the product of a consanguineous family, presenting with a syndromic severe combined immunodeficiency (SCID) with neurodevelopmental delay and hearing loss. The homozygous POLD3Ile10Thr variant abolishes POLD3 as well as POLD1 and POLD2 expression. Our findings implicate POLD3 deficiency as a novel cause of syndromic SCID.

Lebanese cannabis oil as a potential treatment for acute myeloid leukemia: In vitro and in vivo evaluations.

ETHNOPHARMACOLOGICAL RELEVANCE: The Cannabis sativa L. ssp. indica (Lam.) plant has been historically utilized as a natural herbal remedy for the treatment of several ailments. In Lebanon, cannabis extracts have long been traditionally used to treat arthritis, diabetes, and cancer. AIM OF THE STUDY: The current study aims to investigate the anti-cancer properties of Lebanese cannabis oil extract (COE) on acute myeloid leukemia using WEHI-3 cells, and a WEHI-3-induced leukemia mouse model. MATERIALS AND METHODS: WEHI-3 cells were treated with increasing concentrations of COE to determine the IC50 after 24, 48 and 72-h post treatment. Flow cytometry was utilized to identify the mode of cell death. Western blot assay was performed to assess apoptotic marker proteins. In vivo model was established by inoculating WEHI-3 cells in BALB/c mice, and treatment commencing 10 days post-inoculation and continued for a duration of 3 weeks. RESULTS: COE exhibited significant cytotoxicity with IC50 of 7.76, 3.82, and 3.34 µg/mL at 24, 48, and 72 h respectively post-treatment. COE treatment caused an induction of apoptosis through an inhibition of the MAPK/ERK pathway and triggering a caspase-dependent apoptosis via the extrinsic and intrinsic modes independent of ROS production. Animals treated with COE exhibited a significantly higher survival rate, reduction in spleen weight as well as white blood cells count. CONCLUSION: COE exhibited a potent anti-cancer activity against AML cells, both in vitro and in vivo. These findings emphasize the potential application of COE as a chemotherapeutic adjuvant in treatment of acute myeloid leukemia.

Infective endocarditis caused by Streptococcus acidominimus.

PURPOSE: A case of infective endocarditis caused by Streptococcus acidominimus is reported. SUMMARY: An 81-year-old Caucasian man underwent an elective transcatheter aortic valve implantation due to his severe aortic valve stenosis. He presented to the hospital 3 weeks later with a 1-week history of fever (39ºC) that did not resolve following a 3-day course of azithromycin and a 5-day course of ciprofloxacin. Three sets of blood sample cultures were taken. Empirical antimicrobial treatment was initiated to target gram-positive and gram-negative microorganisms and consisted of vancomycin 1 g intravenous (i.v.) every 12 hours and imipenem-cilastatin 500 mg i.v. every 6 hours. After 48 hours, the blood culture was positive for S. acidominimus. The strain was sensitive to ampicillin, cephalosporins, tetracycline, and vancomycin. It was resistant to penicillin, macrolides, trimethoprim-sulfamethoxazole, and fosfomycin. Transesophageal echocardiography showed a small mobile vegetation attached to the anterior mitral valve leaflet, along with mild mitral regurgitation. The patient was diagnosed with native mitral valve infective endocarditis, and imipenem-cilastatin was discontinued. The patient showed clinical and laboratory improvement during his 2-week hospitalization. A peripherally inserted central catheter was put in place, and the patient was discharged on i.v. vancomycin to complete a total of 6 weeks treatment, after which the infection resolved. CONCLUSION: An 81-year-old man diagnosed with mitral valve endocarditis caused by S. acidominimus was successfully treated with vancomycin.