Changes in the expression of extracellular regulated kinase (ERK 1/2) in the R6/2 mouse model of Huntington's disease after phosphodiesterase IV inhibition

The mitogen-activated protein kinases (MAPKs) superfamily comprises three major signaling pathways: the extracellular signal-regulated protein kinases (ERKs), the c-Jun N-terminal kinases or stress-activated protein kinases (JNKs/SAPKs) and the p38 family of kinases. ERK 1/2 signaling has been implicated in a number of neurodegenerative disorders, including Huntington's disease (HD). Phosphorylation patterns of ERK 1/2 and JNK are altered in cell models of HD. In this study, we aimed at studying the correlations between ERK 1/2 and the neuronal vulnerability to HD degeneration in the R6/2 transgenic mouse model of HD. Single and double-label immunofluorescence for phospho-ERK (pERK, the activated form of ERK) and for each of the striatal neuronal markers were employed on perfusion-fixed brain sections from R6/2 and wild-type mice. Moreover, Phosphodiesterase 4 inhibition through rolipram was used to study the effects on pERK expression in the different types of striatal neurons. We completed our study with western blot analysis. Our study shows that pERK levels increase with age in the medium spiny striatal neurons and in the parvalbumin interneurons, and that rolipram counteracts such increase in pERK. Conversely, cholinergic and somatostatinergic interneurons of the striatum contain higher levels of pERK in the R6/2 mice compared to the controls. Rolipram induces an increase in pERK expression in these interneurons. Thus, our study confirms and extends the concept that the expression of phosphorylated ERK 1/2 is related to neuronal vulnerability and is implicated in the pathophysiology of cell death in HD.     

A simple method to correct aortic tube graft kinking without cardiopulmonary by-pass and aortic clamping.

A method for correcting the tube kinking after ascending aortic replacement for acute dissection is described. Its main advantage is the no need for cardiopulmonary by-pass (CPB) and aortic clamping to solve the problem.     

Patent ductus arteriosus. Follow-up of 677 operated cases 40 years later

BACKGROUND: This review is about the patency of ductus arteriosus (PDA), with particular care concerning diagnosis, surgical techniques, survival and postoperative pregnancy in operated females. METHODS: a) Sperimental study: the research has been conducted retrospectively and the follow-up is 40 years. b) Environment: all the patients were operated on in the Division of Cardiac Surgery, University of Turin (public structure) and in the Italian Institution of Cardiac Surgery (private structure). c) Patients: from 1958 to 1987, 677 patients were operated on: mean age was 11.5 +/- 8.7 years. A complete follow-up was made on 487 patients (72%). d) Technique of operation: left lateral thoracotomy was often performed; in younger children, however, the tying of PDA was frequently made within the pericardium by left anterior thoracotomy in the third intercostal space. In uncomplicated situations, PDA was tied more frequently than divided, by two purse string stitches and one or two transfixed ligatures. e) Survey: overall early and late mortality, the clinical conditions of all patients, pregnancies and preor postoperative miscarriages of operated women were examined. RESULTS: From 1958 to 1967 overall early mortality was 5%; during the following years, there was no hospital mortality. The recurrence of PDA occurred only in 4 patients. 72% of the operated females became pregnant. CONCLUSION: Life expectancy is normal after surgical closure of an uncomplicated PDA in infancy or in childhood but premature death may not always be avoided operating on adults with long-standing chronic congestive heart failure. At least, postoperative pregnancy is not a risk factor for the mother and PDA seems not to be correlated to foetal transmission.     

Human longevity and variation in DNA damage response and repair: study of the contribution of sub-processes using competitive gene-set analysis

DNA-damage response and repair are crucial to maintain genetic stability, and are consequently considered central to aging and longevity. Here, we investigate whether this pathway overall associates to longevity, and whether specific sub-processes are more strongly associated with longevity than others. Data were applied on 592 SNPs from 77 genes involved in nine sub-processes: DNA-damage response, base excision repair (BER), nucleotide excision repair, mismatch repair, non-homologous end-joining, homologous recombinational repair (HRR), RecQ helicase activities (RECQ), telomere functioning and mitochondrial DNA processes. The study population was 1089 long-lived and 736 middle-aged Danes. A self-contained set-based test of all SNPs displayed association with longevity (P-value=9.9 × 10⁻⁵), supporting that the overall pathway could affect longevity. Investigation of the nine sub-processes using the competitive gene-set analysis by Wang et al indicated that BER, HRR and RECQ associated stronger with longevity than the respective remaining genes of the pathway (P-values=0.004–0.048). For HRR and RECQ, only one gene contributed to the significance, whereas for BER several genes contributed. These associations did, however, generally not pass correction for multiple testing. Still, these findings indicate that, of the entire pathway, variation in BER might influence longevity the most. These modest sized P-values were not replicated in a German sample. This might, though, be due to differences in genotyping procedures and investigated SNPs, potentially inducing differences in the coverage of gene regions. Specifically, five genes were not covered at all in the German data. Therefore, investigations in additional study populations are needed before final conclusion can be drawn.     

A capacity mapping approach to public health training resources

The capacity mapping approach can be used to identify existing community resources. As part of this approach, inventories are used to provide information for a capacity map. The authors describe the development of two inventories and a capacity map for public health workforce development. For the first inventory, the authors contacted 754 institutions to determine available public health training resources; 191 institutions reported resources, including 126 directly providing distance learning technologies and courses or modules addressing important competency domains. Distance learning technologies included video conferencing facilities (61%) and satellite download facilities (50%). For the second inventory, the authors obtained information on 129 distance-accessible public health training modules. The workforce development capacity map produced from these two inventories revealed substantial resources available for use by individuals or agencies wishing to improve training in public health competencies.     

Bjork-Shiley convexo-concave valve: is a prophylactic re-replacement justified?

BACKGROUND: The Bjork-Shiley convexo-concave (BS-CC) heart valves represent the improved model of the standard valve first introduced with a different design of the disc valve to ameliorate hemodynamic performances and reduce thromboembolic complications. About 86,000 BS-CC were implanted during 1979-1986 and of them a small number developed an intrinsic dysfunction resulting in sudden death. METHODS: From 1979 to 1986 we implanted in 117 patients (48 males, 69 females, mean age 46.35+/-12.47, range 8-65 years) 125 BS-CC. In 38.5% (45/117) of the cases heart valve replacement represented the second cardiac procedure after a previous closed heart digital commissurotomy. The mean size of the implanted prosthesis was 25.6+/-2.8 for aortic valve and 29.5+/-1.2 for mitral valve. RESULTS: Hospital mortality was 4.27% (5/117) and survival rate at 10 years is 71.4% and at 17 years 54.7% (Kaplan-Meier). At follow-up causes of death proved valve related in most of the patients but with no evidence of valve fracture. We had 1 case of sudden death in patients at high risk (largest size, aortic position) and 30 cases of death by unknown causes but they did not have an autopsy to confirm the cause of death. CONCLUSIONS: We conclude that in our population with BS-CC at the moment there is no indication for prophylactic replacement because of the higher risks of a reoperation (third or fourth in the 35.4% of our patients) than a strut fracture. Nevertheless we believe an autopsy mandatory in all these patients at risk, when sudden death occurs.