Mucinous tubular and spindle cell carcinoma of kidney is probably a variant of papillary renal cell carcinoma with spindle cell features

Mucinous tubular and spindle cell carcinoma is a rare and newly described type of renal cell carcinoma (RCC) with a relatively indolent behavior. However, its histogenetic origin or line of differentiation remains unclear. Twelve cases of mucinous tubular and spindle cell carcinoma were identified and retrieved from the files of 3 institutions. Detailed morphological features, as well as their immunohistochemical profile established with markers of proximal renal tubules (RCC marker antigen, CD15, and alpha-methylacyl-CoA racemase) and of distal renal tubules (kidney-specific cadherin and cytokeratin 7), were studied. The age range of the patients was 35 to 73 years with a median of 56 years. The male to female ratio was 1:3. All of the patients were alive with follow-up between 4 and 38 months. All the tumors were confined to the kidney with a mean tumor size of 6.9 cm (range, 1.8-17 cm). The tumors were composed of variable proportions of tubular and spindle cell areas with focal to prominent mucinous or myxoid stroma. Foamy macrophages were seen in 10 cases and were prominent in 4 cases. A focal compressed tubulopapillary growth pattern was seen in 10 cases. The tumor cells were uniformly cuboidal with ovoid to round nuclei and inconspicuous nucleoli (Furhman nuclear grade 3 in 6 cases). Focal necrosis was seen in 3 cases. Immunostains showed that tumors were positive for RCC marker antigen (11/12), alpha-methylacyl-CoA racemase (11/12), CD15 (8/12), CD10 (2/12), kidney-specific cadherin (1/12), and cytokeratin 7 (11/12). Its morphological features as well as a strong preferential expression of proximal tubule markers suggest that this tumor is a type of RCC with proximal tubular differentiation, which appears closely related to or represents a morphological variant of papillary RCC.     

Ligand-induced conformational changes allosterically activate Toll-like receptor 9

Microbial and synthetic DNA rich in CpG dinucleotides stimulates Toll-like receptor 9 (TLR9), whereas DNA lacking CpG either is inert or can inhibit TLR9 activation. The molecular mechanisms by which TLR9 becomes activated or is inhibited are not well understood. Here we show that TLR9 bound to stimulatory and inhibitory DNA; however, only stimulatory DNA led to substantial conformational changes in the TLR9 ectodomain. In the steady state, 'inactive' TLR9 homodimers formed in an inactivated conformation. Binding of DNA containing CpG, but not of DNA lacking CpG, to TLR9 dimers resulted in allosteric changes in the TLR9 cytoplasmic signaling domains. In endosomes, conformational changes induced by DNA containing CpG resulted in close apposition of the cytoplasmic signaling domains, a change that is probably required for the recruitment of signaling adaptor molecules. Our results indicate that the formation of TLR9 dimers is not sufficient for its activation but instead that TLR9 activation is regulated by conformational changes induced by DNA containing CpG.     

Impact of syphilis infection on HIV viral load and CD4 cell counts in HIV-infected patients

OBJECTIVES: To assess the effect of early syphilis on HIV viral load (VL) and CD4 cell count in patients with HIV and to analyze factors associated with changes in HIV VL and CD4 cell count. DESIGN: Multicenter study of a series of patients with HIV who were diagnosed with early syphilis infection during 2004 through 2005. Patients who started or changed their highly active antiretroviral therapy (HAART) regimen during the analysis period were excluded. RESULTS: One hundred eighteen patients were analyzed: 95.8% were men, mean patient age was 38.2 years, 83.9% were homosexual men, 50.8% were on antiretroviral therapy at the time syphilis was diagnosed, and HIV and syphilis diagnoses were coincident in 38 (32.2%) cases. CD4 cell counts were lower during syphilis than before (590 vs. 496 cells/microL; P = 0.0001) and after syphilis treatment (509 vs. 597 cells/microL; P = 0.0001). The HIV VL increased in 27.6% of patients during syphilis. The only factor associated with an HIV VL increase was not being on HAART, and the only factor associated with a CD4 count decrease >100 cells/microL during syphilis was the prior CD4 cell count. CONCLUSIONS: Syphilis infection was associated with a decrease in the CD4 cell count and an increase in the HIV VL in almost one third of the patients. In this series, more than two thirds of the syphilis cases were diagnosed in patients who were previously known to be infected with HIV.     

Post silanization improves bond strength of translucent posts to flowable composite resins

The aim of the study is to evaluate the effect of post silanization on the microtensile bond strength (MTBS) of translucent fiber posts to seven flowable composite resins used as core material. Seventy fiber posts were employed. In half of the posts, silanization was performed with Monobond-S. A cylindrical plastic matrix was placed around the post and filled with different resins: UniFil Flow Experimental, UniFil Low Flow Plus Experimental, Venus Flow, Revolution Formula 2, Point 4 Flowable, X-Flow, and Wave mv. Five posts were bonded per group. After polymerization, two longitudinal cuts were made on two opposite sides of the post at its outermost periphery. Then, each specimen was serially sectioned, obtaining 30-35 beams with 1-mm(2) cross-sectional area. Each beam was tested in tension in an Instron machine at 0.5 mm/min. ANOVA and Student Newman Keuls tests were performed. The different resin composite materials and the post silanization procedure had a significant effect on MTBS. The application of a silane coupling agent increased MTBS of flowable composite resins to translucent posts. X-flow and Point 4 attained the highest MTBS regardless of the silane treatment.     

Bone morphogenetic protein-2/4 signalling pathway components are expressed in the human thymus and inhibit early T-cell development

T-cell differentiation is driven by a complex network of signals mainly derived from the thymic epithelium. In this study we demonstrate in the human thymus that cortical epithelial cells produce bone morphogenetic protein 2 (BMP2) and BMP4 and that both thymocytes and thymic epithelium express all the molecular machinery required for a response to these proteins. BMP receptors, BMPRIA and BMPRII, are mainly expressed by cortical thymocytes while BMPRIB is expressed in the majority of the human thymocytes. Some thymic epithelial cells from cortical and medullary areas express BMP receptors, being also cell targets for in vivo BMP2/4 signalling. The treatment with BMP4 of chimeric human-mouse fetal thymic organ cultures seeded with CD34+ human thymic progenitors results in reduced cell recovery and inhibition of the differentiation of human thymocytes from CD4- CD8- to CD4+ CD8+ cell stages. These results support a role for BMP2/4 signalling in human T-cell differentiation.     

Dendritic spines in the posterodorsal medial amygdala after restraint stress and ageing in rats

Several evidences suggest that the posterodorsal medial amygdala (MePD) can be a relevant part of the rat neural circuitry for the regulation of hypothalamic neuroendocrine secretion and for ontogenetically different behavioral displays. The dendritic spine density of Golgi-impregnated neurons from the MePD was evaluated in young rats following acute or chronic restraint stress and in aged animals (24 months old). Compared to the control group, a single 1 h restraint stress session promoted a decreased spine density (p < 0.01) whereas a single 6 h restraint stress session or daily 6-h restraint sessions for 28 consecutive days did not lead to the same effect (p > 0.05). Aged rats showed no difference in this dendritic spine parameter when compared to young adults (p > 0.05). These results indicate that short-term stress (1 h) can affect MePD dendritic spines and that neural plasticity is involved with adaptive responses onwards in restrained rats. On the other hand, brain structural modifications related with ageing appear not to influence the number of certain postsynaptic sites in the MePD of rats.     

Evaluation of a 3D serious game for advanced life support retraining

ObjectiveAdvanced life support (ALS) knowledge and skills decrease in as little as three months, but only a few ALS providers actually attend retraining courses. We assess the effectiveness of a 3D serious game as a new tool for frequent ALS retraining.MethodsWe developed a 3D serious game for scenario-based ALS retraining. The serious game, called EMSAVE, was designed to promote self-correction while playing. We organized a retraining course in which 40 ALS providers played two cardiac arrest scenarios with EMSAVE and took a test with 38 multiple-choice questions before and after playing. We administered the same test again 3 months later to evaluate retention. Participants also rated EMSAVE and the overall retraining experience.ResultsAfter using EMSAVE, the number of correct answers per participant increased by 4.8 (95%CI +3.4, +6.2, p < 0.001) and all but one participant improved. After 3 months, despite an expected decrease in ALS knowledge and skills (?1.9 correct answers, 95%CI ?0.6, ?3.3, p < 0.01), there was a significant retention benefit (+2.9 correct answers per participant, 95%CI +1.5, +4.2, p < 0.001). Moreover, all but one participant regarded EMSAVE as a valuable tool to refresh ALS knowledge and skills, and 85% of participants were also willing to devote 1 h/month to retrain with the serious game.ConclusionsA 3D serious game for scenario-based retraining proved effective to retrain in ALS and supported retention of acquired knowledge and skills at 3 months. EMSAVE also positively engaged and motivated participants.     

Dedifferentiated endometrial cancer: an atypical case diagnosed from cerebellar and adrenal metastasis: case presentation and review of literature

Dedifferentiated endometrial cancer (DEC) is microscopically characterized by the presence of high-grade areas emerging from low-grade tumour. DEC is an aggressive tumour even when the dedifferentiated component represents only 20% of the entire neoplasm. A proper histological diagnosis is essential to define the most appropriate therapeutic approach for these tumors, since they are characterized by a particularly aggressive trend and by an extremely poor prognosis. We report a single case of DEC associated with dedifferentiated and adrenal metastasis, for which the patient underwent both abdominal-pelvic and cerebellar surgery. Dedifferentiated carcinoma of the endometrium is a poorly recognized neoplasm since they have not been clearly defined the histological features discriminating this neoplasm from high-grade endometrioid adenocarcinoma. Revising existing literature we found 79 described cases of central nervous system secondary involvement and 13 cases where the onset of the disease was characterized by neurological signs and symptoms. We could only find two reported cases of adrenal metastases originating from endometrial neoplasia but in no case of dedifferentiated endometrial carcinoma previously described has been reported the concomitant adrenal-cerebellar involvement.