Aquaporin-4 (AQP4) is located mainly in the astrocytic end-feet around cerebral blood vessels and regulates ion and water homeostasis in the brain. While deletion of AQP4 is shown to reduce amyloid-β (Aβ) clearance and exacerbate Aβ peptide accumulation in plaques and vessels of Alzheimer’s disease mouse models, the mechanism and clearing pathways involved are debated. Here, we investigated how inhibiting the function of AQP4 in healthy male C57BL/6 J mice impacts clearance of Aβ40, the more soluble Aβ isoform. Using two-photon in vivo imaging and visualizing vessels with Sulfurodamine 101 (SR101), we first showed that Aβ40 injected as a ≤ 0.5-μl volume in the cerebral cortex diffused rapidly in parenchyma and accumulated around blood vessels. In animals treated with the AQP4 inhibitor TGN-020, the perivascular Aβ40 accumulation was significantly (P < 0.001) intensified by involving four times more vessels, thus suggesting a generalized clearance defect associated with vessels. Increasing the injecting volume to ≥ 0.5 ≤ 1 μl decreased the difference of Aβ40-positive vessels observed in non-treated and AQP4 inhibitor-treated animals, although the difference was still significant (P = 0.001), suggesting that larger injection volumes could overwhelm intramural vascular clearance mechanisms. While both small and large vessels accumulated Aβ40, for the ≤ 0.5-μl volume group, the average diameter of the Aβ40-positive vessels tended to be larger in control animals compared with TGN-020-treated animals, although the difference was non-significant (P = 0.066). Using histopathology and ultrastructural microscopy, no vascular structural change was observed after a single massive dose of TGN-020. These data suggest that AQP4 deficiency is directly involved in impaired Aβ brain clearance via the peri-/para-vascular routes, and AQP4-mediated vascular clearance might counteract blood-brain barrier abnormalities and age-related vascular amyloidopathy.

Clinical and pathological aspects of condyloma acuminatum -review of literature and case presentationDAMIAN DIŢESCU 1) , ANCA-MARIA ISTRATE-OFIŢERU 2-4) , GABRIELA-CAMELIA ROŞU 2,3) , LARISA IOVAN 2-5) , ILONA MIHAELA LILIAC 2,3,5) , GEORGE-LUCIAN ZORILĂ 4) , MARIA BĂLĂŞOIU 6) , LILIANA CERCELARU 7)

Ectopic endometrial epithelium associates a wide spectrum of symptomatology. Their evolution can be influenced by inflammatory and vascular changes, that affect not only the structure and cell proliferation rate, but also symptoms. This prospective study involved tissue samples from surgically treated patients, stained using classical histotechniques and immunohistochemistry. We assessed ectopic endometrial glands (CK7+, CK20−), adjacent blood vessels (CD34+), estrogen/progesterone hormone receptors (ER+, PR+), inflammatory cells (CD3+, CD20+, CD68+, Tryptase+), rate of inflammatory cells (Ki67+) and oncoproteins (BCL2+, PTEN+, p53+) involved in the development of endometriosis/adenomyosis. A CK7+/CK20− expression profile was present in the ectopic epithelium and differentiated it from digestive metastases. ER+/PR+ were present in all cases analyzed. We found an increased vascularity (CD34+) in the areas with abdominal endometriosis and CD3+−:T-lymphocytes, CD20+−:B-lymphocytes, CD68+:macrophages, and Tryptase+: mastocytes were abundant, especially in cases with adenomyosis as a marker of proinflammatory microenvironment. In addition, we found a significantly higher division index-(Ki67+) in the areas with adenomyosis, and inactivation of tumor suppressor genes-p53+ in areas with neoplastic changes. The inflammatory/vascular/hormonal mechanisms trigger endometriosis progression and neoplastic changes increasing local pain. Furthermore, they may represent future therapeutic targets. Simultaneous-multiple immunohistochemical labelling represents a valuable technique for rapidly detecting cellular features that facilitate comparative analysis of the studied predictors.

Background and objectives. The risk of developing invasive cancer increased during the COVID-19 pandemic, especially in Romania, where the incidence of this disease is high due to limited medical education and broad screening. This study’s objective is to analyze the number of patients admitted with different types of cervical dysplasia and the treatment applied for the lesions during the SARS-CoV-2 pandemic compared to the same period for the year before the pandemic. Materials and methods: This is a retrospective study that took place in the Obstetrics and Gynecology Clinics I/II (OG I/II) of the Emergency County Hospital of Craiova during the SARS-CoV-2 pandemic (SP) (15.03.2020–14.03.2021) and in the 12 months before (non-pandemic period) (NPP) (15.03.2019–14.03.2020). The study includes 396 patients with pathological PAP smear results. All the patients included in this study were clinically examined and with colposcopy. The patients with Low-Grade Dysplasia were managed in a conservatory manner and reevaluated after six months. The patients with High-Grade Dysplasia were admitted for an excisional biopsy of the lesion. The excised fragments were sent to the Pathological Anatomy Laboratory for a histopathological examination. Results: This study reveals a decrease of more than half in the number of patients admitted with cervical intraepithelial neoplasia (CIN) lesions during the pandemic compared to the same period of the year before. The number of biopsies and excisional procedures has been decreasing by more than a factor of three during the pandemic period compared to the year before. Conclusion: During the SARS-CoV-2 pandemic, we found that the patients’ admission rate, diagnosis, and treatment was almost four times lower. As hospital restrictions were not dictated for cancer/precancer management during SP, we may assume that the differences were due to the fear of becoming infected with SARS-CoV-2 due to hospitalization. In the context of poor screening performance and high cervical cancer incidence, the influence of the SP may result in a further increase of severe cases related to this condition.

Worldwide elderly traumatic brain injury (TBI) patients tend to become an increasing burden to the society. Thus, a faster and less expensive way of evaluating TBI victims is needed. In the present study we investigated if optical coherence tomography (OCT) could be used as such a method. By using an animal model, we established if OCT can detect cortical changes in the acute phase of a penetrating TBI, in young (5–7 months) and old (20–22 months) rats. Due to the long‐term evolution of TBI's, we wanted to investigate to what extent OCT could detect changes within the cortex in the chronic phase. Adult (7–12 months) male rats were used. Surprisingly, OCT imaging of the normal hemisphere was able to discriminate age‐related differences in the mean gray values (MGV) of recorded pixels (p = .032). Furthermore, in the acute phase of TBI, OCT images recorded at 24 hr after the injury showed differences between the apparent damaged area of young and aged animals. Changes of MGV and skewness were only recorded 48 hr after injury. Monitoring the chronical evolution of the TBI with OCT revealed changes over time exceeding the normal range recorded for MGV, skewness and kurtosis, 14 and 21 days after TBI. Although in the present study we still used an extremely invasive approach, as technology improves, less invasive and non‐harmful ways of recording OCT may allow for an objective way to detect changes within the brain structure after brain injuries.