Nerve growth factor combined with vascular endothelial growth factor enhances regeneration of bladder acellular matrix graft in spinal cord injury-induced neurogenic rat bladder

OBJECTIVE

To determine the combined effects of nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) on regeneration of the bladder acellular matrix graft (BAMG) in spinal cord injury (SCI)‐mediated neurogenic bladder in rats.

MATERIALS AND METHODS

In all, 40 female Sprague‐Dawley rats were used. At 8 weeks after spinalization surgery (neurogenic bladder), they were divided into five groups consisting of untreated controls and those whose bladders were injected with either no growth factor, NGF (2 µg/rat), VEGF (2 µg/rat) or both at partial BAMG replacement surgery. After 8 weeks, bladder function was assessed by urodynamic studies and the bladders were harvested for histological examination. Smooth muscle induction, collagen and nerve fibre regeneration were assessed immunohistochemically using antibodies to smooth muscle actin (α‐actin), Masson’s trichrome and protein gene product 9.5, respectively.

RESULTS

Bladder capacity and compliance were significantly increased in all BAMG groups 8 weeks after surgery compared with that before bladder replacement surgery. Bladder capacity and compliance were much higher in the VEGF and NGF combined group than in the control, or NGF and VEGF alone groups. There was no significant difference in the residual volume ratio among all groups.

CONCLUSIONS

This is the first report showing that NGF has a significant synergistic effect on the development, differentiation and functional restoration of the BAMG when administered with VEGF in neurogenic bladder. Our results indicate that NGF may be a useful cytokine for enhancing the regeneration of a functional bladder following acellular matrix grafting in a neurogenic rat model.     

Employment and occupation effects on depressive symptoms in older Americans: does working past age 65 protect against depression?

OBJECTIVES: This article examines the effects of work status, occupational sector, and occupation type on depressive symptoms in older Americans. We partially controlled for the healthy worker selection effect by including disability as a predictor of both work status and depressive symptoms. METHODS: We analyzed a nationally representative sample of 23,247 respondents aged 65 to 88 from the National Health Interview Survey pooled over 1997 to 2000. We used structural equation models with latent variables to assess relationships between work/occupation and depressive symptoms. RESULTS: Older Americans who work had lower levels of depressive symptoms as compared to older nonworkers. Membership in several worker groups, generally higher status occupations, protected against depressive symptoms. After controlling for disability, the difference in level of depressive symptoms for workers versus nonworkers did not persist. However, workers in specific occupational sectors and types reported different levels of depressive symptoms even when we controlled for disability. DISCUSSION: The mental health benefit of working, among persons aged 65 and older, may be due to the healthy worker effect. However, the particular job sector in which older workers are employed matters. Socioeconomic status and financial versus personal motivations for working are potentially important explanations for differences.     

Short, discontinuous exposure to butyrate effectively sensitizes latently EBV-infected lymphoma cells to nucleoside analogue antiviral agents

Antiviral drugs alone have been unsuccessful in the treatment of Epstein-Barr virus (EBV)-associated malignancies because the virus maintains a latent state of replication in these tumors. In recent years, novel therapeutic approaches are being investigated wherein lytic replication of the virus is induced prior to the use of cytotoxic antiviral drugs. The choice of suitable agents to induce lytic replication has been a critical step in this novel approach. We have previously demonstrated that butyrate derivatives induce a lytic pattern of EBV gene expression in patient-derived EBV-positive lymphoblastoid cell lines and, together with nucleoside analogue ganciclovir, effectively reduce or eliminate tumor growth in humans. Butyrate has drawbacks as a therapeutic agent, however, as constant intravenous infusion is required to achieve detectable plasma levels of this drug. In this study, we investigated whether discontinuous exposure to butyrate is capable of initiating lytic phase gene expression and thymidine kinase induction, and sensitizing EBV-positive lymphoma cells to ganciclovir-mediated cell growth arrest and apoptosis. We demonstrate that multiple daily 6-h exposures of the EBV-positive Burkitt's lymphoma cell line P3HR1 to butyrate induced sustained expression of the EBV lytic phase protein BMRF. Viral thymidine kinase was also induced by intermittent exposure, although to a lower level than with continuous exposure treatment. However, discontinuous exposure to butyrate in combination with ganciclovir induced a similar level of tumor cell growth inhibition as did continuous treatment, as measured by serial enumeration of viable cells, MTT cell proliferation assays and measurement of cellular DNA content. We further demonstrated that those cells which survived initial exposure to butyrate plus ganciclovir remained susceptible to further cycles of combination treatment. These findings suggests that continuous infusion of butyrate may not be necessary for maintaining viral thymidine kinase gene expression and sensitization to antiviral agents in EBV-associated tumors, and that therapeutic regimens which employ more convenient, discontinuous exposure to butyrate may also be effective clinically.     

What Can We Learn From Pilot Studies?

TOPIC. This paper discusses some of the potential lessons to be learned from pilot studies, using a recently completed pilot study of exercise in outpatients with schizophrenia as a case example. CONCLUSIONS. Pilot studies are a source of important research and clinical information in the areas of recruitment barriers, attendance at study intervention sessions, monitoring procedures, physical sensations from study interventions, and additional outcomes. PRACTICE IMPLICATIONS. The author challenges psychiatric nurse clinicians to conduct and report the findings of pilot studies to enhance our knowledge and advance nursing science.     

Molecular evolution of adiponectin in Carnivora and its mRNA expression in relation to hepatic lipidosis

Adiponectin is a novel adipocyte-derived hormone with low circulating concentrations and/or mRNA expression in obesity and non-alcoholic fatty liver disease (NAFLD). The adiponectin mRNA of several Carnivora species was sequenced to enable further gene expression studies in this clade with potential experimental species to examine the connections of hypoadiponectinemia to hepatic lipidosis. In addition, adiponectin mRNA expression was studied in the retroperitoneal fat of the American mink (Neovison vison), as hepatic lipidosis with close similarities to NAFLD can be rapidly induced to the species by fasting. The mRNA expression was determined after overnight-7 d of food deprivation and 28 d of re-feeding and correlated to the liver fat %. The homologies between the determined carnivoran mRNA sequences and that of the domestic dog were 92.2-99.1%. As the mRNA expression was not affected by short-term fasting and did not correlate with the liver fat %, there seems to be no clear connection between adiponectin and the development of lipidosis in the American mink. In the future, the obtained sequences can be utilized in further studies of adiponectin expression in comparative endocrinology.     

From the Cover: Deep phenotyping to predict live birth outcomes in in vitro fertilization

Nearly 75% of in vitro fertilization (IVF) treatments do not result in live births and patients are largely guided by a generalized age-based prognostic stratification. We sought to provide personalized and validated prognosis by using available clinical and embryo data from prior, failed treatments to predict live birth probabilities in the subsequent treatment. We generated a boosted tree model, IVF_BT, by training it with IVF outcomes data from 1,676 first cycles (C1s) from 2003–2006, followed by external validation with 634 cycles from 2007–2008, respectively. We tested whether this model could predict the probability of having a live birth in the subsequent treatment (C2). By using nondeterministic methods to identify prognostic factors and their relative nonredundant contribution, we generated a prediction model, IVF_BT, that was superior to the age-based control by providing over 1,000-fold improvement to fit new data (p < 0.05), and increased discrimination by receiver–operative characteristic analysis (area-under-the-curve, 0.80 vs. 0.68 for C1, 0.68 vs. 0.58 for C2). IVF_BT provided predictions that were more accurate for ∼83% of C1 and ∼60% of C2 cycles that were out of the range predicted by age. Over half of those patients were reclassified to have higher live birth probabilities. We showed that data from a prior cycle could be used effectively to provide personalized and validated live birth probabilities in a subsequent cycle. Our approach may be replicated and further validated in other IVF clinics.     

Sensory Impairment Among Older US Workers

We used 1997–2004 National Health Interview Survey data to evaluate the prevalence of sensory impairment among US workers 65 years and older. Hearing impairment prevalence was 3 times that of visual impairment (33.4% vs 10.2%), and 38% of older workers reported experiencing either impairment. Farm operators, mechanics, and motor vehicle operators had the highest prevalence of sensory impairment. Workplace screening and accommodations, including sensory protection devices for older workers, are warranted given the greater risk for injuries among the sensory impaired.Americans are living longer and are delaying retirement. As a result, the number of older US workers is increasing rapidly, with more than 40 million American workers 65 years and older projected to be in the workforce by 2012.¹ Older age is associated with a higher prevalence of sensory impairment,^2,3 which in turn is associated with an increased risk of occupational injury.^4–6 One public health implication of an increasingly older workforce is a continued rise in workplace injuries. An estimated 3.9 million cases of workplace injuries were reported in 2006,⁷ a disproportionate amount of which were among older employed men.⁸ Research on the prevalence of sensory impairment by occupational and industrial worker groups is needed to identify older US workers in greatest need of workplace accommodations. We examined the prevalence of vision and hearing impairment among older workers with data from a nationally representative sample of US worker groups.     

A sea change ahead for recreational water quality criteria

The United States Environmental Protection Agency is committed to developing new recreational water quality criteria for coastal waters by 2012 to provide increased protection to swimmers. We review the uncertainties and shortcomings of the current recreational water quality criteria, describe critical research needs for the development of new criteria, as well as recommend a path forward for new criteria development. We believe that among the most needed research needs are the completion of epidemiology studies in tropical waters and in waters adversely impacted by urban runoff and animal feces, as well as studies aimed to validate the use of models for indicator and pathogen concentration and health risk predictions.