Expression of bcl-6 and CD10 protein is associated with longer overall survival and time to treatment failure in follicular lymphoma

Follicular lymphomas (FLs) are a heterogeneous group of tumors, but prognostic factors are evaluated insufficiently in this common hematologic neoplasm. While bcl-6 and CD10 are expressed characteristically in FLs, their significance for biologic behavior of FL has not been studied previously. Samples from 73 patients with FL and clinical follow-up from 7 to 231 months were evaluated by immunohistochemical analysis. Patients with high levels of bcl-6 expression had favorable overall survival (OS) (P = .003), disease-specific survival (DSS) (P = .033), and time to treatment failure (P = .003) compared with patients with low levels of bcl-6 expression. Multivariate analysis showed that the results for OS, DSS, and time to treatment failure were independent of the international prognostic index. Patients with CD10+ FLs also had longer OS (P = .001), DSS (P = .007), and time to treatment failure (P = .004), and grade 1 FL was associated with better OS (P = .01) and a statistical trend for longer DSS (P = .05) and time to treatment failure (P = .05), but these results were not independent of bcl-6 expression or the international prognostic index in multivariate analysis.     

Metabotropic glutamate receptors modulate feedback inhibition in a developmentally regulated manner in rat dentate gyrus

We investigated group II metabotropic glutamate receptor (mGluR) modulation of glutamatergic input onto hilar-border interneurones and its regulation of feedback inhibition in the dentate gyrus. Selective activation of group II mGluRs with (2 S ,2' R ,3' R )-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV) depressed mossy fibre (MF)-evoked excitatory drive to these interneurones with significantly greater depression in juvenile than adult rats. During 20 Hz MF stimulus trains, EPSCs became depressed. Depression during the early, but not later part of the train was significantly greater in juvenile than adult rats and was blocked by the mGluR antagonist (2 S )-2-amino-2-[(1 S ,2 S )-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid (LY341495). In dentate granule cells from juvenile rats polysynaptic feedback IPSCs, but not monosynaptic IPSCs, were strongly suppressed by DCG-IV. DCG-IV also suppressed feedback inhibition of perforant path-evoked population spikes. In contrast, in adult animals DCG-IV did not significantly depress feedback inhibition. During 20 Hz stimulus trains in juvenile animals the summation of polysynaptic, but not monosynaptic IPSCs was suppressed by synaptically activated group II mGluRs. Blockade of these mGluRs with LY341495 significantly increased the area and duration of the summated IPSC, causing greater feedback inhibition of granule cell firing. In contrast, in adult animals LY341495 did not alter feedback inhibition following the stimulus train. These findings indicate that group II mGluRs modulate excitatory drive to interneurones in a developmentally regulated manner and thereby modulate feedback inhibition in the dentate gyrus.     

Do the socioeconomic context and the European geographical area modify parental influences on smoking experimentation among adolescents?

Adolescent smoking is a major public health problem. While the socioeconomic status (SES) of the neighbourhood and that of the family are known to play a role in smoking onset and progression, it is not clear whether it modifies the association between parental influences and adolescent behaviour. The purpose of this study is to investigate family correlates of adolescent smoking experimentation and to explore the modifying role of socioeconomic context and European geographical area in a sample of European adolescents. This is a secondary analysis of the baseline survey of the European Drug Addiction Prevention (EU-Dap) trial which took place in seven European countries and involved 7079 students. School SES was used as indicator of socioeconomic context. European countries were aggregated in two geographical areas: North-Central and South. The associations between parental, family factors, and adolescents smoking experimentation were analysed through multilevel mixed-effect logistic regression models, stratified by school SES and European geographical area. Parental smoking, permissiveness towards tobacco, family conflicts, problematic relationships, low connectedness, and low parental control were significantly associated with adolescent smoking experimentation. Paternal smoking was a stronger correlate of adolescent smoking in low SES schools, while maternal smoking in high SES schools. Parental permissiveness was a stronger correlate in low SES schools. Family conflicts and low parental control were correlates only in low SES schools. The associations did not substantially differ between European geographical areas, with the exception of parental smoking that was a stronger correlate in the North, and parental control that was a correlate only in the South of Europe. To reduce inequalities in tobacco-related outcomes, prevention efforts in low socioeconomic contexts appear to be a public health priority. Parental smoking, permissiveness, family relationships, and connectedness should be addressed in preventive programs.

     

Influence of Body Position on Defecation in Humans

Objectives: To compare three positions for defecation by measuring abdominal pressure and the anorectal angle simultaneously. Methods: We recruited six healthy volunteers. The videomanometric measures included simultaneous fluoroscopic images, abdominal pressures, subtracted rectal pressures and anal sphincter pressures. Three positions were used: sitting, sitting with the hip flexing at 60 ° with respect to the rest of the body, and squatting with the hip flexing at 22.5 ° with respect to the rest of the body. Results: Basal abdominal pressure before defecation on hip‐flex sitting was lower than that with normal sitting, although the difference did not reach statistical significance. Basal abdominal pressure before defecation on squatting (26 cmH₂O) was lower than that with normal sitting (P < 0.01). Abdominal pressure increase (strain) on hip‐flex sitting was lower than that with normal sitting, although this difference did not reach statistical significance. Similarly, the abdominal pressure increase on squatting was smaller than that with normal sitting, and yet the difference did not reach statistical significance. The rectoanal angle on defecation on hip‐flex sitting did not differ from that with normal sitting. The rectoanal angle on defecation on squatting (126 °) was larger than that with normal sitting (100 °) (P < 0.05), and was also larger than that with hip‐flex sitting (99 °) (P < 0.01). Conclusion: The results of the present study suggest that the greater the hip flexion achieved by squatting, the straighter the rectoanal canal will be, and accordingly, less strain will be required for defecation.     

Flash microwave-assisted solvothermal (FMS) synthesis of photoactive anatase sub-microspheres with hierarchical porosity

The synthesis of nanostructured sub-microspheres of TiO₂ anatase with hierarchical nano- and mesoporosity was successfully achieved by using an innovative approach that applies the principles of acidic digestion to microwave (MW) solvothermal synthesis. This process, termed flash microwave-assisted solvothermal (FMS) synthesis, facilitates the formation of spherical particles without surfactants or templating agents, exploiting the rapid reaction kinetics engendered by MW heating. Unlike many other MW-assisted solvothermal methods, the application of constant MW power leads to a rapid increase of the autogenous pressure, inducing burst-nucleation of small primary crystallites and subsequent rapid agglomeration into secondary particles, with reaction times reduced to minute-timescales. The use of non-aqueous polar solvents such as ethanol is key to the production of regular spheres with a narrow size distribution, composed of nanocrystallites. Morphology, porosity, specific surface area, phase composition, crystallite size and optical properties of the particles can be controlled via a judicious selection of physical and chemical synthesis parameters, especially precursor choice and acid concentration. The complex structure of the particles leads to surface areas of up to ca. 500 m² g⁻¹ with intergranular mesoporosity. The as-synthesised FMS particles show increased adsorption under dark conditions and selective de-ethylation of rhodamine B under visible light compared to a commercial photocatalyst (Degussa P25). The photodegradation mechanism hinges on the capacity of the spheres to accept electrons from the photoexcited state of molecules at the particle surface, with the large sphere surface area maximising adsorption capacity and improving the efficiency of the photocatalytic processes. The singular characteristics and properties of the particles could pave the way for further applications in water purification and optoelectronic devices.

Photoactive nanostructured TiO₂ sub-microspheres can be fabricated by “microwave flash synthesis” in minute timescales.     

Tissue-specific regulation of growth hormone (GH) receptor and insulin-like growth factor-I gene expression in the pituitary and liver of GH-deficient (lit/lit) mice and transgenic mice that overexpress bovine GH (bGH) or a bGH antagonist

GH has diverse biological actions that are mediated by binding to a specific, high-affinity cell surface receptor (GHR). Expression of GHR is tissue specific and a requirement for cellular responsiveness to GH. IGF-I is produced in multiple tissues and regulated in part by GH through GHR. In this study, we evaluated GHR and IGF-I mRNA expression in pituitary gland and compared the levels with those derived from liver of bovine GH transgenic, GH antagonist transgenic, lit/lit mice, and their respective controls using real-time RT-PCR. In liver, both GHR and IGF-I mRNA expressions were regulated in parallel with GH action in all three animal models, and there was a strong correlation between GHR and IGF-I mRNA levels. In the pituitary gland, increased expression of IGF-I mRNA in the pituitary of bovine GH transgenic mice was observed, whereas IGF-I expression in GH antagonist transgenic or lit/lit mice was similar to that observed in control animals. There were no differences of GHR mRNA levels in pituitary gland of any groups we examined. There was also no correlation between GHR and IGF-I mRNA levels in any group in the pituitary gland. In conclusion, we found that hepatic GHR and IGF-I mRNA levels were strongly correlated with each other in chronic GH excess or deficient state, and that regulation and correlation between local GHR and IGF-I mRNA levels induced by GH is different between liver and pituitary gland.     

The contribution of protease-activated receptor 1 to neuronal damage caused by transient focal cerebral ischemia

The serine proteases tissue plasminogen activator, plasmin, and thrombin and their receptors have previously been suggested to contribute to neuronal damage in certain pathological situations. Here we demonstrate that mice lacking protease-activated receptor 1 (PAR1) have a 3.1-fold reduction in infarct volume after transient focal cerebral ischemia. Intracerebroventricular injection of PAR1 antagonist BMS-200261 reduced infarct volume 2.7-fold. There are no detectable differences between PAR1-/- and WT mice in cerebrovascular anatomy, capillary density, or capillary diameter, demonstrating that the neuroprotective phenotype is not likely related to congenital abnormalities in vascular development. We also show that the exogenously applied serine proteases thrombin, plasmin, and tissue plasminogen activator can activate PAR1 signaling in brain tissue. These data together suggest that if blood-derived serine proteases that enter brain tissue in ischemic situations can activate PAR1, this sequence of events may contribute to the harmful effects observed. Furthermore, PAR1 immunoreactivity is present in human brain, suggesting that inhibition of PAR1 may provide a novel potential therapeutic strategy for decreasing neuronal damage associated with ischemia and blood-brain barrier breakdown.