Lymphoepithelioma-like carcinoma of the bladder: three cases with clinicopathological and p53 protein expression study

Lymphoepithelioma-like carcinoma of the bladder is an uncommon neoplasm, of which 49 cases have been described in the English literature, none of which has been studied for p53 protein expression. We studied three muscle-infiltrating cases of this tumor using immunohistochemical, in situ hybridization and polymerase chain reaction (PCR) methods. The three cases were positive for epithelial markers and negative for lymphoid antigens in the tumoral syncytial areas. The intensive infiltrate of small cells was negative for epithelial and positive for lymphoid markers. This population was mainly made up of cytotoxic T-lymphocytes, positive for TIA-1. p53 protein was intensely positive in more than 90% of the epithelial component nuclei, being negative in the lymphoid cells. PCR study did not show mutations on p53. Both lymphocytes and epithelium were negative for Epstein–Barr virus markers, such as the latent membrane protein and EBER (Epstein–Barr-encoded RNA). The prognosis was very good after radiotherapy and chemotherapy treatment, preserving the bladder despite the muscle infiltration. The presence of an intense cytotoxic T-lymphocyte population may be related to this good prognosis. Both aspects, p53 protein status and T-lymphoid population, had never been studied before in bladder lymphoepithelioma-like carcinoma.     

Increased interleukin 4 (IL-4) receptor expression and IL-4-induced decrease in IL-12 production by Langerhans cells infected with Leishmania major

Langerhans cells (LC) take up Leishmania major and are critical for the induction of the parasite-specific T-cell response. Their functional activities are regulated by cytokines. We analyzed whether infection of LC with L. major modulates the expression of their cytokine receptors. The expression of the interleukin 4 (IL-4) receptor was increased on infected LC from susceptible mice but not on those from resistant mice. Moreover, IL-4 treatment strongly decreased the lipopolysaccharide-induced IL-12 response of infected LC from susceptible mice. This modulation of IL-4 receptor expression and IL-12 production by infection of LC with Leishmania may contribute to the development of Th2 cells and to susceptibility to infection.     

Geminin regulates neuronal differentiation by antagonizing Brg1 activity

Precise control of cell proliferation and differentiation is critical for organogenesis. Geminin (Gem) has been proposed to link cell cycle exit and differentiation as a prodifferentiation factor and plays a role in neural cell fate acquisition. Here, we identified the SWI/SNF chromatin-remodeling protein Brg1 as an interacting partner of Gem. Brg1 has been implicated in cell cycle withdrawal and cellular differentiation. Surprisingly, we discovered that Gem antagonizes Brg1 activity during neurogenesis to maintain the undifferentiated cell state. Down-regulation of Gem expression normally precedes neuronal differentiation, and gain- and loss-of-function experiments in Xenopus embryos and mouse P19 cells demonstrated that Gem was essential to prevent premature neurogenesis. Misexpression of Gem also suppressed ectopic neurogenesis driven by Ngn and NeuroD. Gem's activity to block differentiation depended upon its ability to bind Brg1 and could be mediated by Gem's inhibition of proneural basic helix-loop-helix (bHLH)-Brg1 interactions required for bHLH target gene activation. Our data demonstrate a novel mechanism of Gem activity, through regulation of SWI/SNF chromatin-remodeling proteins, and indicate that Gem is an essential regulator of neurogenesis that can control the timing of neural progenitor differentiation and maintain the undifferentiated cell state.     

Randomized trial of cognitive behavior therapy versus supportive psychotherapy for HIV-related peripheral neuropathic pain

The feasibility and acceptability of cognitive behavior therapy for HIV-related peripheral neuropathic pain was examined and the potential efficacy of the intervention was compared with that of supportive psychotherapy in reducing pain, pain-related interference with functioning, and distress. Sixty-one patients were randomly assigned to receive six weekly sessions of cognitive behavior therapy or supportive psychotherapy. Thirty-three subjects completed the protocol. Both groups showed significant reductions in pain. The cognitive behavior group improved in most domains of pain-related functional interference and distress; the supportive psychotherapy group showed fewer gains. The high dropout rate suggests that psychotherapeutic treatments for HIV-related pain may have limited feasibility and acceptability.     

When people matter: The ethics of qualitative research in the health and social sciences

When research involves people, ethics are fundamental. In the health and social sciences, when qualitative methodologies are used, in addition to ensuring an ethical process approved by the ethics review board, it is also necessary to guarantee an ethical practice capable of responding adequately to the complex questions and dilemmas which arise as the study progresses. This theoretical article analyses some of the most sensitive issues involved in qualitative research and discusses the following questions: (a) How should ethics be approached when working with vulnerable groups? (b) Is informed consent enough? (c) Should we rethink anonymity? (d) What is the difference between confidentiality and anonymity? (e) What exactly do we mean by relational ethics? (f) How can we avoid hurting people, yet remain honest? In the conclusions, we discuss some basic aspects for ensuring ethical studies. This paper, therefore, may be of interest to all health and social researchers concerned about ensuring that their studies comply with ethical principles which recognise, protect and respect participants’ rights.     

The marine toxin dinophysistoxin-2 induces differential apoptotic death of rat cerebellar neurons and astrocytes.

Diarrhetic shellfish poisoning (DSP) toxins of algal origin are frequent contaminants of coastal waters and seafood. The potential risk for human health due to the continuous presence of these toxins in food has not been clearly established. We have used cerebellar primary cultures to investigate the effects of the DSP toxin dinophysistoxin-2 (DTX-2) on central nervous system neurons and glial cells. Exposure to DTX-2 produced neurotoxicity at concentrations starting at 2.5 nM, characterized first by disintegration of neurites and later by cell death. DTX-2-induced neurodegeneration required long exposures (at least 20 h), involved DNA fragmentation and condensation and fragmentation of chromatin, typical hallmarks of apoptosis, and required the synthesis of new proteins. The concentration that reduced by 50% the maximum neuronal survival after 24 h exposure to DTX-2 (EC50(24)) was approximately 8 nM. Morphology and viability of glial cells remained unaffected up to at least 15 nM DTX-2. Higher concentrations of the toxin caused strong shrinkage of glial cell bodies and retraction of processes, and a significant reduction of glial cell viability. Glial toxicity by DTX-2 involved typical apoptotic condensation and fragmentation of chromatin. Compared to neurons, the effect on glial cells was a much shorter process, and extensive glial degeneration and death occurred after 7 h exposure to DTX-2 (EC50(7) approximately 50 nM; EC50(24) approximately 30 nM). Although further experiments are needed to confirm these toxic actions in vivo, our in vitro data suggest that chronic exposure to amounts of DSP toxins below the current safety regulatory limits may represent a risk for human health that should be taken into consideration.     

High Mortality in Late Octogenarians Undergoing Isolated Aortic Valve Replacement for Aortic Valve Stenosis: EuroSCORE Underestimates Mortality in this Cohort

Objectives Considering the expanding technology of catheter-based aortic valve implantation, high-risk patients who would not be suitable for conventional aortic valve replacement (AVR) should be identified.Methods From 1997 to April 2007, 190 patients aged from 80 and 89 years old received isolated AVR. Patients between 80 and 84 years old were categorized as the early octogenarians (n = 148) and patients between 85 and 89 years old were categorized as the late octogenarians (n = 42).Results Thirty days mortality in the early and late octogenarians were 6 and 21%, respectively (p = 0.003). The additive and logistic EuroSCORE were 8.0 ± 2.4 and 8.8 ± 1.8 in the early octogenarians and 13.2 ± 11.8 and 14.6 ± 8.7 in the late octogenarians. Multivariate analysis revealed the late octogenarians (OR 6.7, 95%CL 1.8-24.4, p = 0.004) and poor left ventricular function (OR 8.0, 95%CL 1.2-53.5, p = 0.032) as significant risk factors for 30 days mortality. Early octogenarians showed 1-year, 3-year, 5-year, and 8-year survival of 82.4, 67.6, 54.7, and 33%, respectively. Late octogenarians showed 1-year, 3-year, 5-year, and 8-year survivals of 69.0, 66.2, 41.6, 22.3%, respectively.Conclusions Mortality after AVR in the late octogenarians was very high, and was underestimated by EuroSCORE in this patients group. In late octogenarians, catheter-based aortic valve implantation despite relative low EuroSCORE level could be considered as a reasonable alternative.     

Predatory behavior of Synthesiomyia nudiseta larvae (Diptera: Muscidae) on several necrophagous blowfly species (Diptera: Calliphoridae)

Intraguild interactions play a prominent role in sarcosaprophagous communities, so intraspecific and interspecific competition phenomena between fly larvae take place. Synthesiomyia nudiseta is a species that has recently been recorded on human corpses in Europe, and it has been cited in forensic cases in Spain and Italy. The mature larvae are known to be facultative predators on necrophagous fly larvae, but their role as predators is unknown. The aim of this paper is to investigate the predatory behavior of S. nudiseta on the most abundant blowfly larvae in sarcosaprophagous communities in southwestern Europe (i.e., Chrysomya albiceps, Lucilia sericata, and Calliphora vicina). Intraspecific and interspecific competition experiments were carried out to study the effect of this species in the necrophagous diptera community. First-instar larvae were placed in plastic cups with the same amount of pig liver (15 g) at different densities (50, 100, 150, and 300 individuals/cup). Mortality in blowflies increased when S. nudiseta larvae were present: up to 98.40% in Ch. albiceps, 89.60% in L. sericata, and 84.93% in C. vicina. Pre-imaginal developmental time and adult wing size were analyzed and compared under each of the intraspecific and interspecific conditions; both variables were affected by competition in all cases. The implications of the presence of S. nudiseta for sarcosaprophagous community dynamics and its effect on the estimation of postmortem interval (PMI) are discussed.