A computer model for describing the effect of urethral afferents on simulated lower urinary tract function

A computer model of mechanical properties of the bladder, the urethra and the rhabdosphincter, as well as their neural control is presented in this paper. The model has a rather simple design and processes sensory information from both the bladder wall tension and urethral stretch. It is assumed that afferent signals from the urethra are involved in a sacral excitatory reflex and a supraspinal inhibitory reflex. Pressure and flow signals that resemble experimentally measured normal human behaviour could be simulated with this model. From these simulations the relation between the neural control mechanisms used in the model and the neural control mechanism in vivo cannot be judged entirely because similar behaviour could be simulated with models that are bas ed on different neural control mechanisms. Also behaviour that resembles detrusor overactivity was simulated with our model after an externally induced rise in detrusor pressure was added. Detrusor overactivity, sometimes in combination with urethral relaxation, can occur during a urodynamic investigation. A possible explanation for this detrusor overactivity might be that the micturition reflex is triggered by unknown disturbances and is inhibited immediately after by the same mechanism that normally ceases voiding. The described model provides such a mechanism. Based on these simulations, therefore, it is concluded that urethral afferent signals might be important in lower urinary tract control.     

Total intermittent Pringle maneuver during liver resection can induce intestinal epithelial cell damage and endotoxemia

Objectives

The intermittent Pringle maneuver (IPM) is frequently applied to minimize blood loss during liver transection. Clamping the hepatoduodenal ligament blocks the hepatic inflow, which leads to a non circulating (hepato)splanchnic outflow. Also, IPM blocks the mesenteric venous drainage (as well as the splenic drainage) with raising pressure in the microvascular network of the intestinal structures. It is unknown whether the IPM is harmful to the gut. The aim was to investigate intestinal epithelial cell damage reflected by circulating intestinal fatty acid binding protein levels (I-FABP) in patients undergoing liver resection with IPM.

Methods

Patients who underwent liver surgery received total IPM (total-IPM) or selective IPM (sel-IPM). A selective IPM was performed by selectively clamping the right portal pedicle. Patients without IPM served as controls (no-IPM). Arterial blood samples were taken immediately after incision, ischemia and reperfusion of the liver, transection, 8 hours after start of surgery and on the first post-operative day.

Results

24 patients (13 males) were included. 7 patients received cycles of 15 minutes and 5 patients received cycles of 30 minutes of hepatic inflow occlusion. 6 patients received cycles of 15 minutes selective hepatic occlusion and 6 patients underwent surgery without inflow occlusion. Application of total-IPM resulted in a significant increase in I-FABP 8 hours after start of surgery compared to baseline (p<0.005). In the no-IPM group and sel-IPM group no significant increase in I-FABP at any time point compared to baseline was observed.

Conclusion

Total-IPM in patients undergoing liver resection is associated with a substantial increase in arterial I-FABP, pointing to intestinal epithelial injury during liver surgery.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01099475","term_id":"NCT01099475"}}NCT01099475     

A Single Intravenous AAV9 Injection Mediates Bilateral Gene Transfer to the Adult Mouse Retina

Widespread gene delivery to the retina is an important challenge for the treatment of retinal diseases, such as retinal dystrophies. We and others have recently shown that the intravenous injection of a self-complementary (sc) AAV9 vector can direct efficient cell transduction in the central nervous system, in both neonatal and adult animals. We show here that the intravenous injection of scAAV9 encoding green fluorescent protein (GFP) resulted in gene transfer to all layers of the retina in adult mice, despite the presence of a mature blood-eye barrier. Cell morphology studies and double-labeling with retinal cell-specific markers showed that GFP was expressed in retinal pigment epithelium cells, photoreceptors, bipolar cells, Müller cells and retinal ganglion cells. The cells on the inner side of the retina, including retinal ganglion cells in particular, were transduced with the highest efficiency. Quantification of the cell population co-expressing GFP and Brn-3a showed that 45% of the retinal ganglion cells were efficiently transduced after intravenous scAAV9-GFP injection in adult mice. This study provides the first demonstration that a single intravenous scAAV9 injection can deliver transgenes to the retinas of both eyes in adult mice, suggesting that this vector serotype is able to cross mature blood-eye barriers. This intravascular gene transfer approach, by eliminating the potential invasiveness of ocular surgery, could constitute an alternative when fragility of the retina precludes subretinal or intravitreal injections of viral vectors, opening up new possibilities for gene therapy for retinal diseases.     

Weight Status,Psychological Health,Suicidal Thoughts,and Suicide Attempts in Dutch Adolescents: Results From the 2003 E‐MOVO Project

This study describes the association between weight status and psychological health, suicidal thoughts and suicide attempts in adolescents from a population‐based study of 21,730 adolescents who responded to a classroom‐based internet questionnaire. It demonstrated clear associations between weight status in adolescents and poor psychological health, suicidal thoughts and suicide attempts, especially in obese individuals. Obese boys and girls were more likely to be classified as “psychologically unhealthy” than were normal weight subjects. They also reported more suicidal thoughts and suicide attempts.     

The Costs and Cost-Effectiveness of a School-Based Comprehensive Intervention Study on Childhood Obesity in China

Background

The dramatic rise of overweight and obesity among Chinese children has greatly affected the social economic development. However, no information on the cost-effectiveness of interventions in China is available. The objective of this study is to evaluate the cost and the cost-effectiveness of a comprehensive intervention program for childhood obesity. We hypothesized the integrated intervention which combined nutrition education and physical activity (PA) is more cost-effective than the same intensity of single intervention.

Methods

And Findings: A multi-center randomized controlled trial conducted in six large cities during 2009-2010. A total of 8301 primary school students were categorized into five groups and followed one academic year. Nutrition intervention, PA intervention and their shared common control group were located in Beijing. The combined intervention and its’ control group were located in other 5 cities. In nutrition education group, ‘nutrition and health classes’ were given 6 times for the students, 2 times for the parents and 4 times for the teachers and health workers. "Happy 10" was carried out twice per day in PA group. The comprehensive intervention was a combination of nutrition and PA interventions. BMI and BAZ increment was 0.65 kg/m² (SE 0.09) and 0.01 (SE 0.11) in the combined intervention, respectively, significantly lower than that in its’ control group (0.82±0.09 for BMI, 0.10±0.11 for BAZ). No significant difference were found neither in BMI nor in BAZ change between the PA intervention and its’ control, which is the same case in the nutrition intervention. The single intervention has a relative lower intervention costs compared with the combined intervention. Labor costs in Guangzhou, Shanghai and Jinan was higher compared to other cities. The cost-effectiveness ratio was $120.3 for BMI and $249.3 for BAZ in combined intervention, respectively.

Conclusions

The school-based integrated obesity intervention program was cost-effectiveness for children in urban China.

Trial Registration

Chinese Clinical Trial Registry ChiCTR-PRC-09000402 URL:http://www.chictr.org/cn/     

Taurine Provides Neuroprotection against Retinal Ganglion Cell Degeneration

Retinal ganglion cell (RGC) degeneration occurs in numerous retinal diseases leading to blindness, either as a primary process like in glaucoma, or secondary to photoreceptor loss. However, no commercial drug is yet directly targeting RGCs for their neuroprotection. In the 70s, taurine, a small sulfonic acid provided by nutrition, was found to be essential for the survival of photoreceptors, but this dependence was not related to any retinal disease. More recently, taurine deprivation was incriminated in the retinal toxicity of an antiepileptic drug. We demonstrate here that taurine can improve RGC survival in culture or in different animal models of RGC degeneration. Taurine effect on RGC survival was assessed in vitro on primary pure RCG cultures under serum-deprivation conditions, and on NMDA-treated retinal explants from adult rats. In vivo, taurine was administered through the drinking water in two glaucomatous animal models (DBA/2J mice and rats with vein occlusion) and in a model of Retinitis pigmentosa with secondary RGC degeneration (P23H rats). After a 6-day incubation, 1 mM taurine significantly enhanced RGCs survival (+68%), whereas control RGCs were cultured in a taurine-free medium, containing all natural amino-acids. This effect was found to rely on taurine-uptake by RGCs. Furthermore taurine (1 mM) partly prevented NMDA-induced RGC excitotoxicity. Finally, taurine supplementation increased RGC densities both in DBA/2J mice, in rats with vein occlusion and in P23H rats by contrast to controls drinking taurine-free water. This study indicates that enriched taurine nutrition can directly promote RGC survival through RGC intracellular pathways. It provides evidence that taurine can positively interfere with retinal degenerative diseases.     

Influence of calendar period on the association between BMI and coronary heart disease: A meta‐analysis of 31 cohorts

Objective:

The association between obesity and coronary heart disease (CHD) may have changed over time, for example due to improved pharmacological treatment of CHD risk factors. This meta‐analysis of 31 prospective cohort studies explores the influence of calendar period on CHD risk associated with body mass index (BMI).

Design and Methods:

The relative risks (RRs) of CHD for a five‐BMI‐unit increment and BMI categories were pooled by means of random effects models. Meta‐regression analysis was used to examine the influence of calendar period (>1985 v ≤1985) in univariate and multivariate analyses (including mean population age as a covariate).

Results:

The age, sex, and smoking adjusted RR (95% confidence intervals) of CHD for a five‐BMI‐unit increment was 1.28(1.22:1.34). For underweight, overweight and obesity, the RRs (compared to normal weight) were 1.11(0.91:1.36), 1.31(1.22:1.41), and 1.78(1.55:2.04), respectively. The univariate analysis indicated 31% (95%CI: ?56:0) lower RR of CHD associated with a five‐BMI‐unit increment and a 51% (95%CI: ?78: ?14)) lower RR associated with obesity in studies starting after 1985 (n = 15 and 10, respectively) compared to studies starting in or before 1985 (n = 16 and 10). However, in the multivariate analysis, only mean population age was independently associated with the RRs for a five‐BMI‐unit increment and obesity (?29(95%CI: ?55: ?5)) and ?31(95%CI: ?66:3), respectively) per 10‐year increment in mean age).

Conclusion:

This study provides no consistent evidence for a difference in the association between BMI and CHD by calendar period. The mean population age seems to be the most important factor that modifies the association between the risk of CHD and BMI, in which the RR decreases with increasing age.