SGLT-2 inhibitors enhance the effect of metformin to ameliorate hormonal changes and inflammatory markers in a rat PCOS model.

Polycystic ovary syndrome (PCOS) is a common endocrine, reproductive, and metabolic disorder affecting females. The management of PCOS is challenging and current interventions are not enough to deal with all consequences of this syndrome. We explored the beneficial effect of combined sodium glucose co transporter-2 inhibitor (SGLT-2i); (empagliflozin) and metformin on hormonal and metabolic parameters in an animal model of PCOS and insulin resistance (IR). Forty adult female Wistar rats divided into five groups: control, PCOS-IR, PCOS-IR treated with metformin, PCOS-IR treated with empagliflozin, and PCOS-IR treated with combined metformin and empagliflozin. Single modality treatment with metformin or empagliflozin yielded significant improvement in body mass index, insulin resistance, lipid profile, sex hormones, inflammatory markers, and ovarian cystic follicles. Combined metformin with empagliflozin expressed further significant improvement in sex hormones, inflammatory markers with disappearance of ovarian cystic follicles. The superior significant improvement with combined treatment over the single modality was in line with significant improvement in the ovarian AMPKα-SIRT1 expression.

Strengths and challenges of the artificial intelligence in the assessment of dense breasts.

Objectives: High breast density is a risk factor for breast cancer and overlapping of glandular tissue can mask lesions thus lowering mammographic sensitivity. Also, dense breasts are more vulnerable to increase recall rate and false-positive results. New generations of artificial intelligence (AI) have been introduced to the realm of mammography. We aimed to assess the strengths and challenges of adopting artificial intelligence in reading mammograms of dense breasts. Methods: This study included 6600 mammograms of dense patterns "c" and "d" and presented 4061 breast abnormalities. All the patients were subjected to full-field digital mammography, breast ultrasound, and their mammographic images were scanned by AI software (Lunit INSIGHT MMG). Results: Diagnostic indices of the sono-mammography: a sensitivity of 98.71%, a specificity of 88.04%, a positive-predictive value of 80.16%, a negative-predictive value of 99.29%, and a diagnostic accuracy of 91.5%. AI-aided mammograms presented sensitivity of 88.29%, a specificity of 96.34%, a positive-predictive value of 92.2%, a negative-predictive value of 94.4%, and a diagnostic accuracy of 94.5% in its ability to read dense mammograms. Conclusion: Dense breasts scanned with AI showed a notable reduction of mammographic misdiagnosis. Knowledge of such software challenges would enhance its application as a decision support tool to mammography in the diagnosis of cancer. Advances in knowledge: Dense breast is challenging for radiologists and renders low sensitivity mammogram. Mammogram scanned by AI could be used to overcome such limitation, enhance the discrimination between benign and malignant breast abnormalities and the early detection of breast cancer.

Immunohistochemical Expression of CD200 in Renal Cell Carcinoma.

BACKGROUND AND OBJECTIVES: Renal cell carcinoma (RCC) is the most common malignant renal neoplasm in adults. CD200 is a transmembrane protein and is a promising target for cancer immunotherapy. The aim of this study is to assess the CD200 expression in RCC. MATERIALS AND METHODS: Eighty paraffin-embedded radical nephrectomy specimens, diagnosed with RCC were evaluated immunohistochemically for CD200 expression. RESULTS: Out of eighty cases studied, CD200 was expressed in n = 73 cases (91.25%) with high intensity in 27 cases (33.75%), moderate intensity in 22 cases (27.5%), and mild intensity in 24 cases (30%). No staining was observed in the adjacent apparently normal renal tissue in all examined sections. No significant relationship was found between CD200 expression and the gender, tumor size, tumor side, histologic type, nuclear grade, T stage, and tumor necrosis. CONCLUSION: CD200 expression in most of the studied cases of RCC may refer to the potential therapeutic of anti-CD200 antibody for this cancer.

Development of liver microtissues with functional biliary ductular network.

Liver tissue engineering aims to create transplantable liver grafts that can serve as substitutes for donor's livers. One major challenge in creating a fully functional liver tissue has been to recreate the biliary drainage in an engineered liver construct through integration of bile canaliculi (BC) with the biliary ductular network that would enable the clearance of bile from the hepatocytes to the host duodenum. In this study, we show the formation of such a hepatic microtissue by coculturing rat primary hepatocytes with cholangiocytes and stromal cells. Our results indicate that within the spheroids, hepatocytes maintained viability and function for up to 7 days. Viable hepatocytes became polarized by forming BC with the presence of tight junctions. Morphologically, hepatocytes formed the core of the spheroids, while cholangiocytes resided at the periphery forming a monolayer microcysts and tubular structures extending outward. The spheroids were subsequently cultured in clusters to create a higher order ductular network resembling hepatic lobule. The cholangiocytes formed functional biliary ductular channels in between hepatic spheroids that were able to collect, transport, and secrete bile. Our results constitute the first step to recreate hepatic building blocks with biliary drainage for repopulating the whole liver scaffolds to be used as transplantable liver grafts.