CREB Inhibits AP-2α Expression to Regulate the Malignant Phenotype of Melanoma

The loss of AP-2alpha and increased activity of cAMP-responsive element binding (CREB) protein are two hallmarks of malignant progression of cutaneous melanoma. However, the molecular mechanism responsible for the loss of AP-2alpha during melanoma progression remains unknown.Herein, we demonstrate that both inhibition of PKA-dependent CREB phosphorylation, as well as silencing of CREB expression by shRNA, restored AP-2alpha protein expression in two metastatic melanoma cell lines. Moreover, rescue of CREB expression in CREB-silenced cell lines downregulates expression of AP-2alpha. Loss of AP-2alpha expression in metastatic melanoma occurs via a dual mechanism involving binding of CREB to the AP-2alpha promoter and CREB-induced overexpression of another oncogenic transcription factor, E2F-1. Upregulation of AP-2alpha expression following CREB silencing increases endogenous p21(Waf1) and decreases MCAM/MUC18, both known to be downstream target genes of AP-2alpha involved in melanoma progression.Since AP-2alpha regulates several genes associated with the metastatic potential of melanoma including c-KIT, VEGF, PAR-1, MCAM/MUC18, and p21(Waf1), our data identified CREB as a major regulator of the malignant melanoma phenotype

Physical properties of the trans-Neptunian binary 2000 YW₁₃₄

The study of trans-Neptunian binaries (TNBs) remains one of the most active areas of progress in understanding the solar system beyond Neptune. TNBs have been found in every dynamical population of the trans-Neptunian region (Noll et al. 2020), with proportions ranging from 29 % in the cold classical population to 5.5 % for the remaining classes combined (Brunini 2020). The formation of the contact TNB Arrokoth is one of the challenges that formation models face nowadays. The current angular momentum of Arrokoth is too low and the current binary formation scenarios, by either rotational fission or streaming instability (Nesvorný et al. 2019), require also loss of angular momentum (McKinnon et al. 2020). Additionally, formation mechanisms of close binaries may be distinct from those for the wider pairs. As the angular momentum of a system approaches that of an object spinning near its critical rotation period, rotational fission is the most likely explanation for their formation (Descamps et al. 2008), which is thought to be the case for the proposed satellites of Varuna and 2002 TC302 systems (Fernández-Valenzuela et al. 2019; Ortiz et al. 2020). If close TNBs turn out to be common for objects rotating close to the breakup limit, that could reveal important clues about angular momentum evolution during accretion for TNOs (Petit et al. 2011). However, characterizing binary systems at such distances is challenging. From the ~120 known TNBs, only around 40 have their mutual orbit fully determined, let alone physical characterization. 2000 YW134 is a TNB in a 3:8 resonance with an orbital semi-major axis of 57.4 au (a rare occurrence). On February 23rd, 2022, it occulted the Gaia EDR3 star 627356458358636544 (V = 17.1 mag). The stellar occultation was initially predicted using the JPL orbit solution #24, and updated using data from the 1.5-m and 1.23-m telescopes at Sierra Nevada and Calar Alto Observatories, using the same methodology as explained in Ortiz et al (2020). From the 17 observatories involved, seven reported positive chords, with five of them corresponding to the main body and the other two chords corresponding to its satellite. We are currently working on the analysis of these data in order to obtain the physical properties that characterize the system. Preliminary results show that the lower limit for the equivalent projected diameter of the satellite is twice the previously estimated size from HST observations (Stephens et al. 2006). We will also compare our results with the area-equivalent diameter and albedo obtained using thermal data from Herschel and Spitzer observations (Farkas-Takács et al. 2020)

Intraperitoneal drain placement and outcomes after elective colorectal surgery: international matched, prospective, cohort study

Despite current guidelines, intraperitoneal drain placement after elective colorectal surgery remains widespread. Drains were not associated with earlier detection of intraperitoneal collections, but were associated with prolonged hospital stay and increased risk of surgical-site infections.Background Many surgeons routinely place intraperitoneal drains after elective colorectal surgery. However, enhanced recovery after surgery guidelines recommend against their routine use owing to a lack of clear clinical benefit. This study aimed to describe international variation in intraperitoneal drain placement and the safety of this practice. Methods COMPASS (COMPlicAted intra-abdominal collectionS after colorectal Surgery) was a prospective, international, cohort study which enrolled consecutive adults undergoing elective colorectal surgery (February to March 2020). The primary outcome was the rate of intraperitoneal drain placement. Secondary outcomes included: rate and time to diagnosis of postoperative intraperitoneal collections; rate of surgical site infections (SSIs); time to discharge; and 30-day major postoperative complications (Clavien-Dindo grade at least III). After propensity score matching, multivariable logistic regression and Cox proportional hazards regression were used to estimate the independent association of the secondary outcomes with drain placement. Results Overall, 1805 patients from 22 countries were included (798 women, 44.2 per cent; median age 67.0 years). The drain insertion rate was 51.9 per cent (937 patients). After matching, drains were not associated with reduced rates (odds ratio (OR) 1.33, 95 per cent c.i. 0.79 to 2.23; P = 0.287) or earlier detection (hazard ratio (HR) 0.87, 0.33 to 2.31; P = 0.780) of collections. Although not associated with worse major postoperative complications (OR 1.09, 0.68 to 1.75; P = 0.709), drains were associated with delayed hospital discharge (HR 0.58, 0.52 to 0.66; P < 0.001) and an increased risk of SSIs (OR 2.47, 1.50 to 4.05; P < 0.001). Conclusion Intraperitoneal drain placement after elective colorectal surgery is not associated with earlier detection of postoperative collections, but prolongs hospital stay and increases SSI risk

Occlusal and Esthetic Enhancement: A Noninvasive Approach to an Old Dilemma

SUMMARY This article describes an indirect composite restoration technique for diastema closure and tooth lengthening with a noninvasive approach using regularly available materials such as silicone, composite resin, and an adhesive system. The procedure resulted in occlusal and functional improvement, with diastema closure, protrusive guide adjustment, and an increase in central incisor length. The procedure provided an adequate proportion of the central incisors with an esthetically natural appearance. It also resulted in simple, fast, and accurate manufacturing with a noninvasive esthetic indirect rehabilitation compared with more invasive preparation of ceramic veneers.</jats:p

Angiotensin II contributes to glomerular hyperfiltration in diabetic rats independently of adenosine type I receptors

Increased angiotensin II (ANG II) or adenosine can potentiate each other in the regulation of renal hemodynamics and tubular function. Diabetes is characterized by hyperfiltration, yet the roles of ANG II and adenosine receptors for controlling baseline renal blood flow (RBF) or tubular Na(+) handling in diabetes is presently unknown. Accordingly, the changes in their functions were investigated in control and 2-wk streptozotocin-diabetic rats after intrarenal infusion of the ANG II AT(1) receptor antagonist candesartan, the adenosine A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), or their combination. Compared with controls, the baseline blood pressure, RBF, and renal vascular resistance (RVR) were similar in diabetics, whereas the glomerular filtration rate (GFR) and filtration fraction (FF) were increased. Candesartan, DPCPX, or the combination increased RBF and decreased RVR similarly in all groups. In controls, the GFR was increased by DPCPX, but in diabetics, it was decreased by candesartan. The FF was decreased by candesartan and DPCPX, independently. DPCPX caused the most pronounced increase in fractional Na(+) excretion in both controls and diabetics, whereas candesartan or the combination only affected fractional Li(+) excretion in diabetics. These results suggest that RBF, via a unifying mechanism, and tubular function are under strict tonic control of both ANG II and adenosine in both control and diabetic kidneys. Furthermore, increased vascular AT(1) receptor activity is a contribution to diabetes-induced hyperfiltration independent of any effect of adenosine A(1) receptors

Churg-Strauss Syndrome, Femoral Venous Aneurysms and Pulmonary Thromboembolism

OBJECTIVE: Venous aneurysms of the lower limbs are rare. When they involve the deep venous system, they can be associated with deep venous thrombosis and pulmonary embolism. The authors report the case of a 63-year-old women evaluated by duplex imaging and venography, in the context of a pulmonary embolism, and detected bilateral large aneurysms of the femoral veins (5 cm in the right femoral vein and 4 cm in the left femoral vein). The aneurysms were located at the bifurcation of the common femoral vein with the superficial and profound veins. METHOD: The right aneurysm was partially thrombosed. The patient was asymptomatic in the lower-limb extremities. After a period of anticoagulation, the authors proceeded to surgically excise the right aneurysm and replaced the venous system using a polytetrafluoroethylene (PTFE) graft with the construction of an a-v fistula. RESULT: The patient had no complications in the postoperative period and her 8-month follow-up examination revealed no symptoms, not even leg edema. The duplex scan showed patency of the graft. She continued with oral anticoagulation. The histologic examination revealed an eosinophilic inflammatory reaction of the vein wall, compatible with the diagnosis of Churg-Strauss syndrome. CONCLUSION: The authors conclude that they have probably described the first case in the international literature of a venous aneurysm with a Churg-Strauss syndrome and pulmonary embolism

Churg-Strauss Syndrome, Femoral Venous Aneurysms and Pulmonary Thromboembolism

OBJECTIVE: Venous aneurysms of the lower limbs are rare. When they involve the deep venous system, they can be associated with deep venous thrombosis and pulmonary embolism. The authors report the case of a 63-year-old women evaluated by duplex imaging and venography, in the context of a pulmonary embolism, and detected bilateral large aneurysms of the femoral veins (5 cm in the right femoral vein and 4 cm in the left femoral vein). The aneurysms were located at the bifurcation of the common femoral vein with the superficial and profound veins. METHOD: The right aneurysm was partially thrombosed. The patient was asymptomatic in the lower-limb extremities. After a period of anticoagulation, the authors proceeded to surgically excise the right aneurysm and replaced the venous system using a polytetrafluoroethylene (PTFE) graft with the construction of an a-v fistula. RESULT: The patient had no complications in the postoperative period and her 8-month follow-up examination revealed no symptoms, not even leg edema. The duplex scan showed patency of the graft. She continued with oral anticoagulation. The histologic examination revealed an eosinophilic inflammatory reaction of the vein wall, compatible with the diagnosis of Churg-Strauss syndrome. CONCLUSION: The authors conclude that they have probably described the first case in the international literature of a venous aneurysm with a Churg-Strauss syndrome and pulmonary embolism