Inhibition of SARS-CoV-2 infection by Porphyromonas gingivalis and the oral microbiome.

The COVID-19 pandemic persists despite the availability of vaccines, and it is, therefore, crucial to develop new therapeutic and preventive approaches. In this study, we investigated the potential role of oral microbiome in SARS-CoV-2 infection. Using an in vitro SARS-CoV-2 pseudovirus infection assay, we found a potent inhibitory effect exerted by Porphyromonas gingivalis on SARS-CoV-2 infection mediated by known P. gingivalis compounds such as phosphoglycerol dihydroceramide (PGDHC) and gingipains as well as by unknown bacterial factors. We found that the gingipain-mediated inhibition of infection is likely due to cytotoxicity, whereas PGDHC inhibited virus infection by an unknown mechanism. Unidentified factors present in P. gingivalis supernatant inhibited SARS-CoV-2 likely via the fusion step of the virus life cycle. We addressed the role of other oral bacteria and found certain periodontal pathogens capable of inhibiting SARS-CoV-2 pseudovirus infection by inducing cytotoxicity on target cells. In the human oral cavity, we observed that the modulatory activity of oral microbial communities varied among individuals, in that some saliva-based cultures were capable of inhibiting while others were enhancing infection. These findings contribute to our understanding of the complex relationship between the oral microbiome and viral infections, offering potential avenues for innovative therapeutic strategies in combating COVID-19. IMPORTANCE: The oral microbiome is important in health and disease, and in this study, we addressed the potential role of the oral microbiome in COVID-19 infection. Our in vitro studies suggest that certain bacteria of the oral microbiome such as P. gingivalis produce compounds that could potentially inhibit SARS-CoV-2 infection. These findings elucidating the interactions between the oral microbiome and SARS-CoV-2 infection will be important in our understanding of COVID-19 pathogenesis and the development of innovative therapeutic and preventive strategies against COVID-19 infection.

Inhibition of SARS-CoV-2 infection by Porphyromonas gingivalis and the oral microbiome.

The COVID-19 pandemic persists despite the availability of vaccines, and it is therefore crucial to develop new therapeutic and preventive approaches. In this study, we investigated the potential role of the oral microbiome in SARS-CoV-2 infection. Using an in vitro SARS-CoV-2 pseudovirus infection assay, we found a potent inhibitory effect exerted by Porphyromonas gingivalis on SARS-CoV-2 infection mediated by known P. gingivalis compounds such as phosphoglycerol dihydroceramide (PGDHC) and gingipains as well as by unknown bacterial factors. We found that the gingipain-mediated inhibition of infection is likely due to cytotoxicity, while PGDHC inhibited virus infection by an unknown mechanism. Unidentified factors present in P. gingivalis supernatant inhibited SARS-CoV-2 likely via the fusion step of the virus life cycle. We addressed the role of other oral bacteria and found certain periodontal pathogens capable of inhibiting SARS-CoV-2 pseudovirus infection by inducing cytotoxicity on target cells. In the human oral cavity, we observed the modulatory activity of oral microbial communities varied among individuals in that some saliva-based cultures were capable of inhibiting while others were enhancing infection. These findings contribute to our understanding of the complex relationship between the oral microbiome and viral infections, offering potential avenues for innovative therapeutic strategies in combating COVID-19.

Comparative study of weekly and three-weekly neoadjuvant carboplatin in triple-negative breast cancer: retrospective analysis in real-world settings.

PURPOSE: Tri-weekly carboplatin is an established neoadjuvant treatment for triple-negative breast cancer, enhancing pathological complete response (pCR) and overall survival. This study explores if weekly carboplatin provides lower toxicity and comparable pCR rates. METHODS/PATIENTS: A retrospective multicenter study (January 2021 to March 2023) compares outcomes of weekly and tri-weekly carboplatin. RESULTS: Among 104 participants, 60% received weekly and 40% tri-weekly treatments. Weekly administration had fewer discontinuations (56.5 vs. 70.7%, p = 0.154). Both schedules exhibited similar overall toxicity (p = 0.087), with slightly higher grade 3-4 toxicity in the tri-weekly group (56.1 vs. 48.4%, p = 0.126). Hematological toxicity was comparable, but the weekly group experienced more diarrhea (p = 0.432) and asthenia (p = 0.012). Weekly treatment correlated with more frequent breast-conserving surgeries (p = 0.004). pCR rates were 50% with weekly and 61% with tri-weekly regimens (p = 0.186). CONCLUSIONS: Weekly carboplatin exhibited comparable toxicity, a trend toward fewer interruptions, and similar pCR rates. Prospective studies are essential for validating these findings.

Enfermedad de Moya-Moya / Moya-Moya disease

Enfermedad esteno-oclusiva de la porción terminal de las arterias carótidas internas y de sus ramas principales (arteria carótida media y arteria carótida anterior), progresiva, prevalente en el este Asiático (Japón, Corea), muy rara en nuestro país como en el resto del mundo, de causa desconocida. Se manifiesta mas frecuentemente como un accidente cerebrovascular isquémico transitorio o permanente en los niños menores de 10 años y como accidente cerebrovascular hemorrágico en el adulto. El diagnóstico se realiza con la Angiografía Digital Cerebral y el tratamiento consiste en la revascularización cerebral, que mejora el cuadro neurológico y la calidad de vida.`Se presenta el caso de una niña de 3 años de edad con convulsiones, afasia de expresión, lúcida y hemiparesia izquierda, que luego de una franca mejoría vuelve a presentar una semana después, otra crisis más severa con compromiso de conciencia y hemiplejía derecha, cuyo estudio neurorradiológico reveló la imagen típica de volutas de humo de cigarrillo en la base del cerebro, característico de la enfermedad de Moya-Moya e intervenida quirúrgicamente con la revascularización cerebral por medio de la técnica: EncefaloDuroArterioSinangiosis (EDAS), con buen resultado.

Moya-Moya is a progressive steno-occlusive disease of the internal carotid arteries and its major branches (middle cerebral artery, and anterior cerebral artery) whose cause is unknown, and which is reported primarily in east Asia (Japan and Korea) but rare in Paraguay and the rest of the world. In children under age 10, it presents most commonly as a transient or permanent ischemic attack and in adults as a hemorrhagic stroke. Diagnosis is done by digital subtraction cerebral angiography, and treatment consists of cerebral revascularization to improve the neurological profile and quality of life. We present the case of a 3-year old female child with seizures and motor aphasia who was lucid, with left hemiparesis, and who after complete recovery presented again a week later with a more severe attack, with impaired consciousness and right hemiplegia. Radiological study revealed a typical image of swirls of 'cigarette smoke' at the base of the brain that are characteristic of Moya-Moya disease, and who was operated on using encephaloduroarteriosynangiosis (EDAS), with good results.