Phenotypic Modulation of Corpus Cavernosum Smooth Muscle Cells in a Rat Model of Cavernous Neurectomy

Background

Patients undergoing radical prostatectomy (RP) are at high risk for erectile dysfunction (ED) due to potential cavernous nerve (CN) damage during surgery. Penile hypoxia after RP is thought to significantly contribute to ED pathogenesis.

Aim

We previously showed that corpora cavernosum smooth muscle cells (CCSMCs) undergo phenotypic modulation under hypoxic conditions in vitro. Here, we studied such changes in an in vivo post-RP ED model by investigating CCSMCs in bilateral cavernous neurectomy (BCN) rats.

Methods

Sprague-Dawley rats underwent sham (n = 12) or BCN (n = 12) surgery. After 12 weeks, they were injected with apomorphine to determine erectile function. The penile tissues were harvested and assessed for fibrosis using Masson trichrome staining and for molecular markers of phenotypic modulation using immunohistochemistry and western blotting. CCSMC morphological structure was evaluated by hematoxylin-eosin (H&E) staining and transmission electron microscopy (TEM).

Results

Erectile function was significantly lower in BCN rats than in sham rats. BCN increased hypoxia-inducible factor-1α and collagen protein expression in corpora cavernous tissue. H&E staining and TEM showed that CCSMCs in BCN rats underwent hypertrophy and showed rough endoplasmic reticulum formation. The expression of CCSMC phenotypic markers, such as smooth muscle α-actin, smooth muscle myosin heavy chain, and desmin, was markedly lower, whereas vimentin protein expression was significantly higher in BCN rats than in control rats.

Conclusions

CCSMCs undergo phenotype modulation in rats with cavernous neurectomy. The results have unveiled physiological transformations that occur at the cellular and molecular levels and have helped characterize CN injury–induced ED.     

Effect of Stem Cell Therapy on Bone Mineral Density: A Meta-Analysis of Preclinical Studies in Animal Models of Osteoporosis

Background

Preclinical studies of the therapeutic role of stem cell based therapy in animal models of osteoporosis have largely yielded inconsistent results. We performed a meta-analysis to provide an overview of the currently available evidence.

Methods

Pubmed, Embase and Cochrane Library databases were systematically searched for relevant controlled studies. A random-effect model was used for pooled analysis of the effect of stem cell based therapy on bone mineral density (BMD). Stratified analyses were performed to explore the effect of study characteristics on the outcomes.

Results

Pooled results from 12 preclinical studies (110 animals in stem cell treatment groups, and 106 animals in control groups) indicated that stem cell based treatment was associated with significantly improved BMD (standardized mean difference [SMD] = 1.29, 95% Confidence Interval [CI]: 0.84–1.74, P < 0.001) with moderate heterogeneity (Cochrane’s Q test: P = 0.02, I² = 45%) among the constituent studies. Implantation of bone marrow cells, bone marrow mesenchymal stem cells, adipose-derived stem cells, and human umbilical cord blood-derived CD34+ cells, were all associated with improved BMD as compared to that in the controls (P < 0.05 for all); the only exception being the use of embryonic stem cell transplantation (P > 0.05). Egger’s test detected potential publication bias (P = 0.055); however, ‘trim and fill’ analysis yielded similar results after statistically incorporating the hypothetical studies in the analysis (SMD = 1.24, 95% CI: 0.32–2.16, P < 0.001).

Conclusions

Stem cell transplantation may improve BMD in animal models of osteoporosis. Our meta-analysis indicates a potential therapeutic role of stem cell based therapy for osteoporosis, and serves to augment the rationale for clinical studies.     

Lichen Simplex Chronicus Associated With Erectile Dysfunction: A Population-Based Retrospective Cohort Study

Background

An association between lichen simplex chronicus (LSC) and sexual dysfunction was explored. However, no data are available from investigations into the relationship between erectile dysfunction (ED) and LSC.

Objectives

This retrospective population-based cohort study aimed to clarify the risk of ED associated with LSC.

Methods

By using the Taiwan National Health Insurance Research dataset, we identified 5611 male patients who had been newly diagnosed with LSC from 2000 to 2004. The date of diagnosis was identified as the index date. LSC patients with incomplete demographic information or with a history of ED before the index date were excluded. In total, 22444 age-matched patients without LSC were randomly selected as the non-LSC group based on a 1:4 ratio. Subsequence occurrence of ED was measured until 2011. The association between LSC and the risk of developing ED was estimated using Cox proportional hazard regression model.

Results

After adjusting for age and comorbidities, patients with LSC had a 1.74-fold greater risk of developing ED compared with those without LSC (95% confidence interval=1.44–2.10). LSC patients with comorbidities including diabetes, hyperlipidemia, hypertension, cardiovascular disease, peripheral arterial disease, chronic obstructive pulmonary disease, chronic kidney disease, depression, and anxiety were at a higher risk of ED compared with the non-LSC patients without comorbidities.

Conclusions

LSC confers a greater risk in the development of ED. Physicians should be aware of the potential of ED occurrence in LSC patients.     

The Effect of Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) on Erectile Function: A Systematic Review and Meta-Analysis

Background

High prevalence of erectile dysfunction (ED) has been observed in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). However, whether or not CP/CPPS is a risk factor of ED remains unknown and controversial. Therefore, we conducted this systematic review and meta-analysis to evaluate the relationship between CP/CPPS and ED.

Methods

PubMed, Embase, Web of Science, and The Cochrane Library were searched up to November 11, 2014 to identify studies reporting the association between CP/CPPS and ED. Case–control, cohort and cross-sectional studies were included. Quality of the included studies was assessed. The odds ratio of ED and the mean difference of five-item International Index of Erectile Function (IIEF-5) score were pooled using a random effects model. Subgroup analysis and sensitivity analyses were performed.

Results

Three cross-sectional studies, two case–control studies, and four retrospective studies with 31,956 participants were included to calculate the pooled odds ratio of ED, and two studies with 1499 participants were included to calculate the pooled mean difference of IIEF-5 scores. A strong correlation was found between CP/CPPS and ED (pooled odds ratio: 3.02, 95% CI: 2.18–4.17, P < 0.01), with heterogeneity across studies (I ² = 65%; P < 0.01). A significant decrease in the IIFE-5 score was observed in the CP/CPPS group (pooled mean difference: −4.54, 95% CI: −5.11–−3.98; P < 0.01).

Conclusion

Our study indicates that patients with CP/CPPS have an increased risk of suffering from ED. Assessment of erectile function is necessary for the therapy of patients with CP/CPPS. Further evidence is necessary to confirm the relationship between CP/CPPS and ED.     

Bone Marrow Mononuclear Cell Transplantation Restores Inflammatory Balance of Cytokines after ST Segment Elevation Myocardial Infarction

Background

Acute myocardial infarction (AMI) launches an inflammatory response and a repair process to compensate cardiac function. During this process, the balance between proinflammatory and anti-inflammatory cytokines is important for optimal cardiac repair. Stem cell transplantation after AMI improves tissue repair and increases the ventricular ejection fraction. Here, we studied in detail the acute effect of bone marrow mononuclear cell (BMMNC) transplantation on proinflammatory and anti-inflammatory cytokines in patients with ST segment elevation myocardial infarction (STEMI).

Methods

Patients with STEMI treated with thrombolysis followed by percutaneous coronary intervention (PCI) were randomly assigned to receive either BMMNC or saline as an intracoronary injection. Cardiac function was evaluated by left ventricle angiogram during the PCI and again after 6 months. The concentrations of 27 cytokines were measured from plasma samples up to 4 days after the PCI and the intracoronary injection.

Results

Twenty-six patients (control group, n = 12; BMMNC group, n = 14) from the previously reported FINCELL study (n = 80) were included to this study. At day 2, the change in the proinflammatory cytokines correlated with the change in the anti-inflammatory cytokines in both groups (Kendall’s tau, control 0.6; BMMNC 0.7). At day 4, the correlation had completely disappeared in the control group but was preserved in the BMMNC group (Kendall’s tau, control 0.3; BMMNC 0.7).

Conclusions

BMMNC transplantation is associated with preserved balance between pro- and anti-inflammatory cytokines after STEMI in PCI-treated patients. This may partly explain the favorable effect of stem cell transplantation after AMI.     

Neuronal Survival,Morphology and Outgrowth of Spiral Ganglion Neurons Using a Defined Growth Factor Combination

Objectives

The functionality of cochlear implants (CI) depends, among others, on the number and excitability of surviving spiral ganglion neurons (SGN). The spatial separation between the SGN, located in the bony axis of the inner ear, and the CI, which is inserted in the scala tympani, results in suboptimal performance of CI patients and may be decreased by attracting the SGN neurites towards the electrode contacts. Neurotrophic factors (NTFs) can support neuronal survival and neurite outgrowth.

Methods

Since brain-derived neurotrophic factor (BDNF) is well known for its neuroprotective effect and ciliary neurotrophic factor (CNTF) increases neurite outgrowth, we evaluated if the combination of BDNF and CNTF leads to an enhanced neuronal survival with extended neurite outgrowth. Both NTFs were added in effective high concentrations (BDNF 50ng/ml, CNTF 100ng/ml), alone and in combination, to cultured dissociated SGN of neonatal rats for 48 hours.

Results

The neuronal survival and neurite outgrowth were significantly higher in SGN treated with the combination of the two NTFs compared to treatment with each factor alone. Additionally, with respect to the morphology, the combination of BDNF and CNTF leads to a significantly higher number of bipolar neurons and a decreased number of neurons without neurites in culture.

Conclusion

The combination of BDNF and CNTF shows a great potential to increase the neuronal survival and the number of bipolar neurons in vitro and to regenerate retracted nerve fibers.     

Intravitreal Transplantation of Human Umbilical Cord Blood Stem Cells Protects Rats from Traumatic Optic Neuropathy

Objectives

To treat traumatic optic neuropathy (TON) with transplantation of human umbilical cord blood stem cells (hUCBSC) and explore how transplanted stem cells participate in the neuron repairing process.

Methods

A total of 195 Sprague-Dawley rats were randomly assigned to three groups: sham-surgery, optic nerve injury, and stem cell transplant group. Optic nerve injury was established in rats by directly clamping the optic nerve for 30 seconds. hUCBSC was microinjected into the vitreous cavity of injured rats. Optic nerve function was evaluated by flash visual evoked potentials (F-VEP). Apoptosis in retina tissues was detected by TUNEL staining. GRP78 and CHOP gene expression was measured by RT-PCR.

Results

After injury, transplantation of hUCBSC significantly blunted a reduction in optic nerve function indicated by smaller decreases in amplitude and smaller increases in peak latency of F-VEP waveform compared to the injury alone group. Also, significant more in retinal ganglion cell (RGC) count and less in RGC apoptosis were detected after transplantation compared to injured rats. The protective effect correlated with upregulated GRP78 and downregulated CHOP mRNA expression.

Conclusion

Intravitreal transplantation of hUCBSCs significantly blunted a reduction in optic nerve function through increasing RGC survival and decreasing retinal cell apoptosis. The protective role of transplantation was associated with upregulation of GRP78 expression and downregulation of CHOP expression in retinal cells.     

Explore the Features of Brain-Derived Neurotrophic Factor in Mood Disorders

Objectives

Brain-derived neurotrophic factor (BDNF) plays important roles in neuronal survival and differentiation; however, the effects of BDNF on mood disorders remain unclear. We investigated BDNF from the perspective of various aspects of systems biology, including its molecular evolution, genomic studies, protein functions, and pathway analysis.

Methods

We conducted analyses examining sequences, multiple alignments, phylogenetic trees and positive selection across 12 species and several human populations. We summarized the results of previous genomic and functional studies of pro-BDNF and mature-BDNF (m-BDNF) found in a literature review. We identified proteins that interact with BDNF and performed pathway-based analysis using large genome-wide association (GWA) datasets obtained for mood disorders.

Results

BDNF is encoded by a highly conserved gene. The chordate BDNF genes exhibit an average of 75% identity with the human gene, while vertebrate orthologues are 85.9%-100% identical to human BDNF. No signs of recent positive selection were found. Associations between BDNF and mood disorders were not significant in most of the genomic studies (e.g., linkage, association, gene expression, GWA), while relationships between serum/plasma BDNF level and mood disorders were consistently reported. Pro-BDNF is important in the response to stress; the literature review suggests the necessity of studying both pro- and m-BDNF with regard to mood disorders. In addition to conventional pathway analysis, we further considered proteins that interact with BDNF (I-Genes) and identified several biological pathways involved with BDNF or I-Genes to be significantly associated with mood disorders.

Conclusions

Systematically examining the features and biological pathways of BDNF may provide opportunities to deepen our understanding of the mechanisms underlying mood disorders.     

Role of Caffeine Intake on Erectile Dysfunction in US Men: Results from NHANES 2001-2004

Objectives

Caffeine is consumed by more than 85% of adults and little is known about its role on erectile dysfunction (ED) in population-based studies. We investigated the association of caffeine intake and caffeinated beverages with ED, and whether these associations vary among comorbidities for ED.

Material and Method

Data were analyzed for 3724 men (≥20 years old) who participated in the National Health and Nutrition Examination Survey (NHANES). ED was assessed by a single question during a self-paced, computer-assisted self-interview. We analyzed 24-h dietary recall data to estimate caffeine intake (mg/day). Multivariable logistic regression analyses using appropriate sampling weights were conducted.

Results

We found that men in the 3^rd (85-170 mg/day) and 4^th (171-303 mg/day) quintiles of caffeine intake were less likely to report ED compared to men in the lowest 1^st quintile (0-7 mg/day) [OR: 0.58; 95% CI, 0.37–0.89; and OR: 0.61; 95% CI, 0.38–0.97, respectively], but no evidence for a trend. Similarly, among overweight/obese and hypertensive men, there was an inverse association between higher quintiles of caffeine intake and ED compared to men in the lowest 1^st quintile, P≤0.05 for each quintile. However, only among men without diabetes we found a similar inverse association (P_trend = 0.01).

Conclusion

Caffeine intake reduced the odds of prevalent ED, especially an intake equivalent to approximately 2-3 daily cups of coffee (170-375 mg/day). This reduction was also observed among overweight/obese and hypertensive, but not among diabetic men. Yet, these associations are warranted to be investigated in prospective studies.     

Role of Brain-Derived Neurotrophic Factor in Beneficial Effects of Repetitive Transcranial Magnetic Stimulation for Upper Limb Hemiparesis after Stroke

Background

Repetitive transcranial magnetic stimulation (rTMS) can improve upper limb hemiparesis after stroke but the mechanism underlying its efficacy remains elusive. rTMS seems to alter brain-derived neurotrophic factor (BDNF) and such effect is influenced by BDNF gene polymorphism.

Objectives

To investigate the molecular effects of rTMS on serum levels of BDNF, its precursor proBDNF and matrix metalloproteinase-9 (MMP-9) in poststroke patients with upper limb hemiparesis.

Methods

Poststroke patients with upper limb hemiparesis were studied. Sixty-two patients underwent rehabilitation plus rTMS combination therapy and 33 patients underwent rehabilitation monotherapy without rTMS for 14 days at our hospital. One Hz rTMS was applied over the motor representation of the first dorsal interosseous muscle on the non-lesional hemisphere. Fugl-Meyer Assessment and Wolf Motor Function (WMFT) were used to evaluate motor function on the affected upper limb before and after intervention. Blood samples were collected for analysis of BDNF polymorphism and measurement of BDNF, proBDNF and MMP-9 levels.

Results

Two-week combination therapy increased BDNF and MMP-9 serum levels, but not serum proBDNF. Serum BDNF and MMP-9 levels did not correlate with motor function improvement, though baseline serum proBDNF levels correlated negatively and significantly with improvement in WMFT (ρ = -0.422, p = 0.002). The outcome of rTMS therapy was not altered by BDNF gene polymorphism.

Conclusions

The combination therapy of rehabilitation plus low-frequency rTMS seems to improve motor function in the affected limb, by activating BDNF processing. BDNF and its precursor proBDNF could be potentially suitable biomarkers for poststroke motor recovery.     

Bladder Recovery by Stem Cell Based Cell Therapy in the Bladder Dysfunction Induced by Spinal Cord Injury: Systematic Review and Meta-Analysis

Background

Bladder dysfunction induced by spinal cord injury (SCI) can become problematic and severely impair the quality of life. Preclinical studies of spinal cord injury have largely focused on the recovery of limb function while neglecting to investigate bladder recovery.

Objective

The present study was performed to investigate and review the effect of stem cell-based cell therapy on bladder recovery in SCI.

Methods

We conducted a meta-analysis of urodynamic findings of experimental trials that included studies of stem cell-based cell therapy in SCI. Relevant studies were searched using MEDLINE, EMBASE and Cochrane Library (January 1990 - December 2012). Final inclusion was determined by a urodynamic study involving detailed numerical values. Urodynamic parameters for analysis included voiding pressure, residual urine, bladder capacity and non-voiding contraction (NVC). Meta-analysis of the data, including findings from urodynamic studies, was performed using the Mantel-Haenszel method.

Results

A total of eight studies were included with a sample size of 224 subjects. The studies were divided into different subgroups by different models of SCI. After a stem cell-based cell therapy, voiding pressure (-6.35, p <0.00001, I² = 77%), NVC (-3.58, p <0.00001, I² = 82%), residual urine (-024, p = 0.004, I² = 95%) showed overall significant improvement. Bladder capacity showed improvement after treatment only in the transection type (-0.23, p = 0.0002, I² = 0%).

Conclusion

After stem cell-based cell therapy in SCI, partial bladder recovery including improvement of voiding pressure, NVC, and residual urine was demonstrated. Additional studies are needed to confirm the detailed mechanism and to obtain an ideal treatment strategy for bladder recovery.     

Weight Loss and Decrease of Body Mass Index during Allogeneic Stem Cell Transplantation Are Common Events with Limited Clinical Impact

Purpose

Weight loss in cancer patients has been attributed with significant morbidity and mortality. During allogeneic stem cell transplantation (SCT), oral nutrition is often hampered and hence total parenteral nutrition (TPN) is necessary. We therefore investigated the course of weight during stem cell transplantation and the clinical consequences of weight change.

Methods

180 consecutive patients who received allogeneic SCT between January 2010 and December 2011 at our center were analyzed for weight loss, laboratory and clinical parameters.

Results

During SCT, a median decrease of 6.6% of body mass index (BMI) was observed for the whole population (from 25.3 at admission to 23.6 at discharge), and a 1.6fold increase of malnutrition despite use of TPN (28.3% to 45.0%). 55.6% of patients experienced a significant weight loss of ≥5% with a median decrease of 9.2% in BMI. Serum levels of albumin, total protein and cholesterol rapidly decreased during conditioning therapy. After a median of 2.4 years, the median BMI was still only 23.4 (not different from discharge). However, we did not observe a meaningful difference in side effects and survival between patients that did or did not lose weight.

Conclusion

Weight loss is commonly observed during allogeneic SCT despite TPN, but the clinical consequences thereof seem limited: we observed no significant impact on patients with a decrease ≥ 5% in BMI on transplant outcome, side effects or survival.     

Vitamin D Supplementation for Childhood Asthma: A Systematic Review and Meta-Analysis

Importance

There is growing evidence that vitamin D plays a role in the pathogenesis of asthma but it is unclear whether supplementation during childhood may improve asthma outcomes.

Objectives

The objective of this systematic review and meta-analysis was to evaluate the efficacy and safety of vitamin D supplementation as a treatment or adjunct treatment for asthma.

Data Sources

We searched MEDLINE, Embase, CENTRAL, and CINAHL through July 2014.

Study Selection

We included RCTs that evaluated vitamin D supplementation in children versus active control or placebo for asthma.

Data Extraction and Synthesis

One reviewer extracted data and one reviewer verified data accuracy. We qualitatively summarized the main results of efficacy and safety and meta-analyzed data on comparable outcomes across studies. We used GRADE for strength of evidence.

Main Outcome Measures

Main planned outcomes measures were ED visits and hospitalizations. As secondary outcomes, we examined measures of asthma control, including frequency of asthma exacerbations, asthma symptom scores, measures of lung function, β₂-agonist use and daily steroid use, adverse events and 25-hydroxyvitamin D levels.

Results

Eight RCTs (one parallel, one crossover design) comprising 573 children aged 3 to 18 years were included. One study (moderate-quality, n = 100) reported significantly less ED visits for children treated with vitamin D. No other studies examined the primary outcome (ED visits and hospitalizations). There was a reduced risk of asthma exacerbations in children receiving vitamin D (low-quality; RR 0.41, 95% CI 0.27 to 0.63, 3 studies, n = 378). There was no significant effect for asthma symptom scores and lung function. The serum 25(OH)D level was higher in the vitamin D group at the end of the intervention (low-quality; MD 19.66 nmol/L, 95% CI 5.96 nmol/L to 33.37 nmol/L, 5 studies, n = 167).

Limitations

We identified a high degree of clinical diversity (interventions and outcomes) and methodological heterogeneity (sample size and risk of bias) in included trials.

Conclusions and Relevance

Randomized controlled trials provide some low-quality evidence to support vitamin D supplementation for the reduction of asthma exacerbations. Evidence on the benefits of vitamin D supplementation for other asthma-related outcomes in children is either limited or inconclusive. We recommend that future trials focus on patient-relevant outcomes that are comparable across studies, including standardized definitions of asthma exacerbations.     

Tracking the Fate of Stem Cell Implants with Fluorine-19 MRI

Background

In this study we used cellular magnetic resonance imaging (MRI) to detect mesenchymal stem cells (MSC) labeled with a Fluorine-19 (¹⁹F) agent. ¹⁹F-MRI offers unambiguous detection and in vivo quantification of labeled cells.

Methods

We investigated two common stem cell transplant mouse models: an immune competent, syngeneic transplant model and an immune compromised, xenograft transplant model. ¹⁹F labelled stem cells were implanted intramuscularly into the hindlimb of healthy mice. The transplant was then monitored for up to 17 days using ¹⁹F-MRI, after which the tissue was excised for fluorescence microscopy and immunohistochemisty.

Results

Immediately following transplantation, ¹⁹F-MRI quantification correlated very well with the expected cell number in both models. The 19F signal decreased over time in both models, with a more rapid decrease in the syngeneic model. By endpoint, only 2/7 syngeneic mice had any detectable ¹⁹F signal. In the xenograft model, all mice had detectable signal at endpoint. Fluorescence microscopy and immunohistochemistry were used to show that the ¹⁹F signal was related to the presence of bystander labeled macrophages, and not original MSC.

Conclusions

Our results show that ¹⁹F-MRI is an excellent tool for verifying the delivery of therapeutic cells early after transplantation. However, in certain circumstances the transfer of cellular label to other bystander cells may confuse interpretation of the long-term fate of the transplanted cells.     

Oral mucosa stem cells alleviates spinal cord injury-induced neurogenic bladder symptoms in rats

Background

Spinal cord injury (SCI) deteriorates various physical functions, in particular, bladder problems occur as a result of damage to the spinal cord. Stem cell therapy for SCI has been focused as the new strategy to treat the injuries and to restore the lost functions. The oral mucosa cells are considered as the stem cells-like progenitor cells. In the present study, we investigated the effects of oral mucosa stem cells on the SCI-induced neurogenic bladder in relation with apoptotic neuronal cell death and cell proliferation.

Results

The contraction pressure and the contraction time in the urinary bladder were increased after induction of SCI, in contrast, transplantation of the oral mucosa stem cells decreased the contraction pressure and the contraction time in the SCI-induced rats. Induction of SCI initiated apoptosis in the spinal cord tissues, whereas treatment with the oral mucosa stem cells suppressed the SCI-induced apoptosis. Disrupted spinal cord by SCI was improved by transplantation of the oral mucosa stem cells, and new tissues were increased around the damaged tissues. In addition, transplantation of the oral mucosa stem cells suppressed SCI-induced neuronal activation in the voiding centers.

Conclusions

Transplantation of oral mucosa stem cells ameliorates the SCI-induced neurogenic bladder symptoms by inhibiting apoptosis and by enhancing cell proliferation. As the results, SCI-induced neuronal activation in the neuronal voiding centers was suppressed, showing the normalization of voiding function.     

Magnetic Beads Enhance Adhesion of NIH 3T3 Fibroblasts: A Proof-of-Principle In Vitro Study for Implant-Mediated Long-Term Drug Delivery to the Inner Ear

Introduction

Long-term drug delivery to the inner ear may be achieved by functionalizing cochlear implant (CI) electrodes with cells providing neuroprotective factors. However, effective strategies in order to coat implant surfaces with cells need to be developed. Our vision is to make benefit of electromagnetic field attracting forces generated by CI electrodes to bind BDNF-secreting cells that are labelled with magnetic beads (MB) onto the electrode surfaces. Thus, the effect of MB-labelling on cell viability and BDNF production were investigated.

Materials and Methods

Murine NIH 3T3 fibroblasts—genetically modified to produce BDNF—were labelled with MB.

Results

Atomic force and bright field microscopy illustrated the internalization of MB by fibroblasts after 24 h of cultivation. Labelling cells with MB did not expose cytotoxic effects on fibroblasts and allowed adhesion on magnetic surfaces with sufficient BDNF release.

Discussion

Our data demonstrate a novel approach for mediating enhanced long-term adhesion of BDNF-secreting fibroblasts on model electrode surfaces for cell-based drug delivery applications in vitro and in vivo. This therapeutic strategy, once transferred to cells suitable for clinical application, may allow the biological modifications of CI surfaces with cells releasing neurotrophic or other factors of interest.     

Pre-Emergency-Department Care-Seeking Patterns Are Associated with the Severity of Presenting Condition for Emergency Department Visit and Subsequent Adverse Events: A Timeframe Episode Analysis

Background

Many patients treated in Emergency Department (ED) visits can be treated at primary or urgent care sectors, despite the fact that a number of ED visitors seek other forms of care prior to an ED visit. However, little is known regarding how the pre-ED activity episodes affect ED visits.

Objectives

We investigated whether care-seeking patterns involve the use of health care services of various types prior to ED visits and examined the associations of these patterns with the severity of the presenting condition for the ED visit (EDVS) and subsequent events.

Methods

This retrospective observational study used administrative data on beneficiaries of the universal health care insurance program in Taiwan. The service type, treatment capacity, and relative diagnosis were used to classify pre-ED visits into 8 care types. Frequent pattern analysis was used to identify sequential care-seeking patterns and to classify 667,183 eligible pre-ED episodes into patterns. Generalized linear models were developed using generalized estimating equations to examine the associations of these patterns with EDVS and subsequent events.

Results

The results revealed 17 care-seeking patterns. The EDVS and likelihood of subsequent events significantly differed among patterns. The ED severity index of patterns differ from patterns seeking directly ED care (coefficients ranged from -0.05 to 0.13), and the odds-ratios for the likelihood of subsequent ED visits and hospitalization ranged from 1.18 to 1.86 and 1.16 to 2.84, respectively.

Conclusions

The pre-ED care-seeking patterns differ in severity of presenting condition and subsequent events that may represent different causes of ED visit. Future health policy maker may adopt different intervention strategies for targeted population to reduce unnecessary ED visit effectively.     

Insulin Resistance Is an Independent Determinate of ED in Young Adult Men

Background

Insulin resistance (IR) triggers endothelial dysfunction, which contributes to erectile dysfunction (ED) and cardiovascular disease.

Aim

To evaluate whether IR was related to ED in young adult patients.

Methods

A total of 283 consecutive men complaining of ED at least six months were enrolled, with a full medical history, physical examination, and laboratory tests collected. Quantitative Insulin Sensitivity Check Index (QUICKI) was used to determine IR. The severity of ED was assessed by IIEF-5 questionnaire. Endothelial function was assessed by ultrasonographic examination of brachial artery flow mediated dilation (FMD).

Results

IR was detected in 52% patients. Subjects with IR had significant higher total cholesterol, triglycerides, low density lipoprotein-cholesterol (LDL-c), glycated haemoglobin (HBA1c), high sensitivity C-reactive protein (hs-CRP) and body mass index (BMI), but showed significant lower IIEF-5 score, FMD%, high density lipoprotein -cholesterol (HDL-c), testosterone, sex hormone binding globulin (SHBG) levels than patients without IR. Multiple regression analysis showed QUICKI and testosterone were independent predictors of IIEF-5 score. Furthermore, the incidence of IR was correlated with the severity of ED.

Conclusions

Compared with other CVFs, IR was found as the most prevalent in our subjects. Besides, IR was independently associated with ED and its severity, suggesting an adverse effect of insulin resistance on erectile function.     

Reducing Frequent Visits to the Emergency Department: A Systematic Review of Interventions

Objective

The objective of this study was to establish the effectiveness of interventions to reduce frequent emergency department (ED) use among a general adult high ED-use population.

Methods

Systematic review of the literature from 1950-January 2015. Studies were included if they: had a control group (controlled trials or comparative cohort studies), were set in an ED or acute care facility, and examined the impact of an intervention to reduce frequent ED use in a general adult population. Studies reporting non-original data or focused on a specific patient population were excluded. Study design, patient population, intervention, the frequency of ED visits, and costs of frequent ED use and/or interventions were extracted and narratively synthesized.

Results

Among 17 included articles, three intervention categories were identified: case management (n = 12), individualized care plans (n = 3), and information sharing (n = 2). Ten studies examining case management reported reductions in mean (-0.66 to -37) or median (-0.1 to -20) number of ED visits after 12-months; one study reported an increase in mean ED visits (+2.79); and one reported no change. Of these, 6 studies also reported reduced hospital costs. Only 1 study evaluating individualized care plans examined ED utilization and found no change in median ED visits post-intervention. Costs following individualized care plans were also only evaluated in 1 study, which reported savings in hospital costs of $742/patient. Evidence was mixed regarding information sharing: 1 study reported no change in mean ED visits and did not examine costs; whereas the other reported a decrease in mean ED visits (-16.9) and ED cost savings of $15,513/patient.

Conclusions

The impact of all three frequent-user interventions was modest. Case management had the most rigorous evidence base, yielded moderate cost savings, but with variable reductions in ED use. Future studies evaluating non-traditional interventions, tailoring to patient subgroups or socio-cultural contexts, are warranted.