No abstract

Purpose: Mutations in the BRCA1/2 genes are associated with breast and ovarian cancer susceptibility. Recent studies have suggested that the BRCA mutation might be associated with occult primary ovarian insufficiency. To evaluate fertility, several studies have validated anti-Mullerian hormone (AMH) as a direct biomarker for ovarian aging and it is considered a quantitative marker of ovarian reserve. We hypothesize that BRCA1 gene mutations will be negatively associated with AMH levels. Methods: We evaluated 124 women aged 18-45 years participating in the Northwestern Ovarian Cancer Early Detection and Prevention Program. Patients with a history of cancer, ovarian surgery, or exposure to chemotherapy were excluded. Linear and logistic regression modeling were performed to evaluate the association between AMH levels, age, and BRCA1 mutation. In logistic models, the outcome 'low AMH' was defined as AMH <0.05 ng/mL. Logistic regression models were used to adjust for other factors, including body mass index (BMI), duration of birth control (BC), smoking, gravidity, and parity. Results: Women with the BRCA1 mutation had a significant decline in AMH with age ( p = 0.0011). BRCA1-positive women >35 years had 10 times the odds of a low AMH (<0.5 ng/mL) compared with women p35 years. With adjustment for BMI, duration of BC, smoking, gravidity, parity, and age >35, BRCA1 was still strongly associated with a low AMH ( p = 0.037). Conclusion: Women >35 with the BRCA1 mutation have a lower AMH, and hence ovarian reserve, than women without a BRCA mutation. Therefore, young adults with the BRCA1 mutation should be counseled regarding this potential decrease in ovarian reserve.

Highlights Ozone therapy seems to have an immunological role within SARS-CoV-2 regimens, because of the modulation of cytokines and interferons, including the induction of gamma interferon. Ozone exerts antiviral activity through the inhibition of viral replication and direct inactivation of viruses. Ozone is an antiviral drug enhancer and is not an alternative to antiviral drugs. The routes of ozone administration are direct intravenous, major autohaemotherapy and extravascular blood oxygenation-ozonation. Combined treatment with involving ozone and antivirals demonstrated a reduction in inflammation and lung damage.

Glioblastoma, the most common primary brain tumor in adults, has an inauspicious prognosis, given that overcoming the blood-brain barrier is the major obstacle to the pharmacological treatment of brain tumors. As neoangiogenesis plays a key role in glioblastoma growth, the US Food and Drug Administration approved bevacizumab (BVZ), an antivascular endothelial growth factor antibody for the treatment of recurrent glioblastoma in patients whose the initial therapy has failed. In this experimental work, BVZ was entrapped in solid lipid nanoparticles (SLNs) prepared by the fatty-acid coacervation technique, thanks to the formation of a hydrophobic ion pair. BVZ activity, which was evaluated by means of four different in vitro tests on HUVEC cells, increased by 100- to 200-fold when delivered in SLNs. Moreover, SLNs can enhance the permeation of fluorescently labelled BVZ through an hCMEC/D3 cell monolayer-an in vitro model of the blood brain barrier. These results are promising, even if further in vivo studies are required to evaluate the effective potential of BVZ-loaded SLNs in glioblastoma treatment.