Interaction of the NRF2 and p63 transcription factors promotes keratinocyte proliferation in the epidermis

Epigenetic regulation of cell and tissue function requires the coordinated action of transcription factors. However, their combinatorial activities during regeneration remain largely unexplored. Here, we discover an unexpected interaction between the cytoprotective transcription factor NRF2 and p63-a key player in epithelial morphogenesis. Chromatin immunoprecipitation combined with sequencing and reporter assays identifies enhancers and promoters that are simultaneously activated by NRF2 and p63 in human keratinocytes. Modeling of p63 and NRF2 binding to nucleosomal DNA suggests their chromatin-assisted interaction. Pharmacological and genetic activation of NRF2 increases NRF2-p63 binding to enhancers and promotes keratinocyte proliferation, which involves the common NRF2-p63 target cyclin-dependent kinase 12. These results unravel a collaborative function of NRF2 and p63 in the control of epidermal renewal and suggest their combined activation as a strategy to promote repair of human skin and other stratified epithelia

Produção de embriões em novilhas Nelore superovuladas submetidas à baixa ou alta ingestão alimentar.

Edição dos resumos do XXI Annual Meeting of the Brazilian Embryo Technology Society (SBTE), Salvador, BA, ago. 2007

Chemoecological studies on marine natural products: terpene chemistry from marine mollusks

Some species of nudibranchs (Mollusca) protect themselves from predatory attacks by storing defensive terpene chemicals acquired from dietary sponges (Porifera) in specialized body parts called MDFs (mantle dermal formations), often advertising their unpalatability to potential predators by means of bright coloration patterns. Consequently, the survival of these trophic specialist species is closely related to the possibility of obtaining the defensive tools from sponges that live in their immediate vicinity; therefore, it is important to determine as precisely as possible the chemical composition of nudibranch extracts prior to any ecological studies addressing issues that involve their alimentary behavior and their defensive strategies, including the significance of their color patterns. Some of our recent studies on the chemical composition of terpene extracts from nudibranchs belonging to the genera Chromodoris and Hypselodoris are summarized. We also report the development of a method to assay extracts and purified metabolites for their feeding deterrent activity against co-occurring generalist predators. In a recent chemoecological study, showing that repugnant terpene chemicals are accumulated at extremely high concentrations in exposed parts of the nudibranchs' bodies, the feeding deterrence assays were carried out on the generalist marine shrimp Palaemon elegans, very common in the Mediterranean. We have modified this assay for use with the Australian shrimp species P. serenus, and confirmed the ecological validity of the assay by analysis of extracts from species of sponges and mollusks that live in the same habitat as P. serenus. The deterrent properties of haliclonacyclamine alkaloids isolated from the sponge Haliclona sp. were demonstrated, with the alkaloid mixture demonstrating palatability deterrence at concentrations as low as 0.05 mg/mL, and complete deterrence at 0.75 mg/mL. In contrast, the diterpene thuridillin metabolites from the sacoglossan mollusk Thuridilla splendens did not deter feeding by P. serenus

Sonographic Assessment of Uterine Biometry for the Diagnosis of Diffuse Adenomyosis in a Tertiary Outpatient Clinic

Background: to compare several uterine biometric parameters at transvaginal ultrasound (TVUS) between adenomyosis and non-adenomyosis uteri and evaluate their role for the diagnosis of diffuse adenomyosis. Methods: prospective observational study conducted between the 1 February 2022 and the 30 April 2022. In this case, 56 patients with TVUS diagnosis of adenomyosis were included. A 1:1 ratio age and parity-matched group of non-adenomyosis patients was selected. We compared sonographic uterine biometric parameters (longitudinal (LD), anteroposterior (APD) and transverse (TD) diameters, volume, simple and complex diameter ratios) and investigated their diagnostic performance. Results: all sonographic parameters were significantly different between the study groups, except for TD/(LD+APD). Optimal cut-off values of APD and LD/APD showed the best sensitivity and specificity. APD diameter equal or superior to 39.5 mm (95% CI, 36.2–42.8) had sensitivity of 0.70 (95% CI, 0.57–0.80), specificity of 0.71 (95% CI, 0.59–0.82) and accuracy of 0.75 (95% CI, 0.66–0.84). LD/APD equal or inferior to 2.05 (95% CI, 1.96–2.13) showed sensitivity and specificity of 0.70 (95% CI, 0.57–0.80) each and accuracy of 0.72 (95% CI, 0.62–0.81). Conclusions: several biometric uterine parameters at TVUS in fertile-aged women were statistically different between adenomyosis and non-adenomyosis uteri, though their optimal cut-off values showed low accuracy in diagnosing adenomyosis

Uterine carcinosarcoma vs endometrial serous and clear cell carcinoma: a systematic review and meta-analysis of survival

Background: It is unclear whether uterine carcinosarcoma (UCS) is more aggressive than endometrial serous carcinoma (SC) and clear cell carcinoma (CCC). Objectives: To compare the prognosis of UCS to that of endometrial SC and CCC, through a systematic review and meta-analysis. Methods: Four electronic databases were searched from January 2000 to October 2020. All studies assessing hazard ratio (HR) for death in UCS vs SC and/or CCC. HRs for death with 95% confidence interval were extracted and pooled by using a random-effect model. A significant P-value <0.05 was adopted. Results: Six studies with 11 029 patients (4995 with UCS, 4634 with SC, 1346 with CCC and 54 with either SC or CCC) were included. UCS showed a significantly worse prognosis than SC/CCC both overall (HR = 1.51; P = 0.008) and at early stage (HR = 1.58; P < 0.001). Similar results were found for UCS vs SC (HR = 1.53; P < 0.001) and UCS vs CCC (HR = 1.60; P < 0.001). Conclusions: Compared to SC and CCC, UCS has a significantly worse prognosis, with a 1.5–1.6-fold increased risk of death. This might justify a more aggressive treatment for UCS compared to SC and CCC. Further studies are necessary to define the prognostic impact of different molecular subgroups

The VSiPMT project

Photon detection is a key factor to study many physical processes in several areas of fundamental physics research. Focusing the attention on photodetectors for particle astrophysics, the future experiments aimed at the study of very high-energy or extremely rare phenomena (e.g. dark matter, proton decay, neutrinos from astrophysical sources) will require additional improvements in linearity, gain, quantum efficiency and single photon counting capability. To meet the requirements of this class of experiments, we propose a new design for a modern hybrid photodetector: the VSiPMT (Vacuum Silicon PhotoMultiplier Tube). The idea is to replace the classical dynode chain of a PMT with a SiPM, which therefore acts as an electron detector and amplifier. The aim is to match the large sensitive area of a photocathode with the performances of the SiPM technology. We now present the preliminary study we are performing to realize a 3-inches VSiPMT prototype

Função ovariana em novilhas Nelore submetidas a baixa ou alta ingestão alimentar.

Edição dos resumos do XXI Annual Meeting of the Brazilian Embryo Technology Society (SBTE), Salvador, BA, ago. 2007

3D Patient-Specific Virtual Models for Presurgical Planning in Patients with Recto-Sigmoid Endometriosis Nodules: A Pilot Study

Background and Objective: In recent years, 3D printing has been used to support surgical planning or to guide intraoperative procedures in various surgical specialties. An improvement in surgical planning for recto-sigmoid endometriosis (RSE) excision might reduce the high complication rate related to this challenging surgery. The aim of this study was to build novel presurgical 3D models of RSE nodules from magnetic resonance imaging (MRI) and compare them with intraoperative findings. Materials and Methods: A single-center, observational, prospective, cohort, pilot study was performed by enrolling consecutive symptomatic women scheduled for minimally invasive surgery for RSE between November 2019 and June 2020 at our institution. Preoperative MRI were used for building 3D models of RSE nodules and surrounding pelvic organs. 3D models were examined during multi-disciplinary preoperative planning, focusing especially on three domains: degree of bowel stenosis, nodule's circumferential extension, and bowel angulation induced by the RSE nodule. After surgery, the surgeon was asked to subjectively evaluate the correlation of the 3D model with the intra-operative findings and to express his evaluation as "no correlation", "low correlation", or "high correlation" referring to the three described domains. Results: seven women were enrolled and 3D anatomical virtual models of RSE nodules and surrounding pelvic organs were generated. In all cases, surgeons reported a subjective "high correlation" with the surgical findings. Conclusion: Presurgical 3D models could be a feasible and useful tool to support surgical planning in women with recto-sigmoidal endometriotic involvement, appearing closely related to intraoperative findings

Application of deep learning model in the sonographic diagnosis of uterine adenomyosis

Background: This study aims to evaluate the diagnostic performance of Deep Learning (DL) machine for the detection of adenomyosis on uterine ultrasonographic images and compare it to intermediate ultrasound skilled trainees. Methods: Prospective observational study were conducted between 1 and 30 April 2022. Transvaginal ultrasound (TVUS) diagnosis of adenomyosis was investigated by an experienced sonographer on 100 fertile-age patients. Videoclips of the uterine corpus were recorded and sequential ultrasound images were extracted. Intermediate ultrasound-skilled trainees and DL machine were asked to make a diagnosis reviewing uterine images. We evaluated and compared the accuracy, sensitivity, positive predictive value, F1-score, specificity and negative predictive value of the DL model and the trainees for adenomyosis diagnosis. Results: Accuracy of DL and intermediate ultrasound-skilled trainees for the diagnosis of adenomyosis were 0.51 (95% CI, 0.48–0.54) and 0.70 (95% CI, 0.60–0.79), respectively. Sensitivity, specificity and F1-score of DL were 0.43 (95% CI, 0.38–0.48), 0.82 (95% CI, 0.79–0.85) and 0.46 (0.42–0.50), respectively, whereas intermediate ultrasound-skilled trainees had sensitivity of 0.72 (95% CI, 0.52–0.86), specificity of 0.69 (95% CI, 0.58–0.79) and F1-score of 0.55 (95% CI, 0.43–0.66). Conclusions: In this preliminary study DL model showed a lower accuracy but a higher specificity in diagnosing adenomyosis on ultrasonographic images compared to intermediate-skilled trainees

The risk stratification of adverse neonatal outcomes in women with gestational diabetes (STRONG) study

Aims: To assess the risk of adverse neonatal outcomes in women with gestational diabetes (GDM) by identifying subgroups of women at higher risk to recognize the characteristics most associated with an excess of risk. Methods: Observational, retrospective, multicenter study involving consecutive women with GDM. To identify distinct and homogeneous subgroups of women at a higher risk, the RECursive Partitioning and AMalgamation (RECPAM) method was used. Overall, 2736 pregnancies complicated by GDM were analyzed. The main outcome measure was the occurrence of adverse neonatal outcomes in pregnancies complicated by GDM. Results: Among study participants (median age 36.8 years, pre-gestational BMI 24.8 kg/m2), six miscarriages, one neonatal death, but no maternal death was recorded. The occurrence of the cumulative adverse outcome (OR 2.48, 95% CI 1.59–3.87), large for gestational age (OR 3.99, 95% CI 2.40–6.63), fetal malformation (OR 2.66, 95% CI 1.00–7.18), and respiratory distress (OR 4.33, 95% CI 1.33–14.12) was associated with previous macrosomia. Large for gestational age was also associated with obesity (OR 1.46, 95% CI 1.00–2.15). Small for gestational age was associated with first trimester glucose levels (OR 1.96, 95% CI 1.04–3.69). Neonatal hypoglycemia was associated with overweight (OR 1.52, 95% CI 1.02–2.27) and obesity (OR 1.62, 95% CI 1.04–2.51). The RECPAM analysis identified high-risk subgroups mainly characterized by high pre-pregnancy BMI (OR 1.68, 95% CI 1.21–2.33 for obese; OR 1.38 95% CI 1.03–1.87 for overweight). Conclusions: A deep investigation on the factors associated with adverse neonatal outcomes requires a risk stratification. In particular, great attention must be paid to the prevention and treatment of obesity