Blockade of Rho-associated kinase prevents inhibition of axon regeneration of peripheral nerves induced by anti-ganglioside antibodies

Anti-ganglioside antibodies are associated with delayed/poor clinical recovery in Guillain-Barrèsyndrome,mostly related to halted axon regeneration.Cross-linking of cell surface gangliosides by anti-ganglioside antibodies triggers inhibition of nerve repair in in vitro and in vivo paradigms of axon regeneration.These effects involve the activation of the small GTPase Rho A/ROCK signaling pathways,which negatively modulate growth cone cytoskeleton,similarly to well stablished inhibitors of axon regeneration described so far.The aim of this work was to perform a proof of concept study to demonstrate the effectiveness of Y-27632,a selective pharmacological inhibitor of ROCK,in a mouse model of axon regeneration of peripheral nerves,where the passive immunization with a monoclonal antibody targeting gangliosides GD1a and GT1b was previously reported to exert a potent inhibitory effect on regeneration of both myelinated and unmyelinated fibers.Our results demonstrate a differential sensitivity of myelinated and unmyelinated axons to the pro-regenerative effect of Y-27632.Treatment with a total dosage of 9 mg/kg of Y-27632 resulted in a complete prevention of anti-GD1a/GT1b monoclonal antibody-mediated inhibition of axon regeneration of unmyelinated fibers to skin and the functional recovery of mechanical cutaneous sensitivity.In contrast,the same dose showed toxic effects on the regeneration of myelinated fibers.Interestingly,scale down of the dosage of Y-27632 to 5 mg/kg resulted in a significant although not complete recovery of regenerated myelinated axons exposed to anti-GD1a/GT1b monoclonal antibody in the absence of toxicity in animals exposed to only Y-27632.Overall,these findings confirm the in vivo participation of Rho A/ROCK signaling pathways in the molecular mechanisms associated with the inhibition of axon regeneration induced by anti-GD1a/GT1b monoclonal antibody.Our findings open the possibility of therapeutic pharmacological intervention targeting Rho A/Rock pathway in immune neuropathies associated with the presence of anti-ganglioside antibodies and delayed or incomplete clinical recovery after injury in the peripheral nervous system.

A Survey among Texas Pain Society Physicians Regarding the Types and Dosages of Steroids Utilized Clinically in Epidural Steroid Injectates

Objective: Epidural steroid injections (ESI) are used extensively to treat radicular back pain. This study is designed to evaluate the types and dosages of steroids commonly used and understand prescribing habits of the Texas Pain Society pain management physicians. Method: From April to May 2014, we sent all 270 Texas Pain Society members a questionnaire to complete online. We collected 45 responses. Result: Type of steroid commonly used in injectate: Eighteen (41.9%) phy-sicians reported using methylprednisolone most. Fifteen (34.9%) physicians use triamcinolone, 9 (20.9%) physicians use dexamethasone, 1 (2.3%) uses betamethasone, and 2 skipped this question. Important factors influencing the type of steroid use in injectate: Half of the physicians reported that the location of the ESI was most important (19 responses, 48.7%). Ten (25.6%) reported that the approach of the ESI was most important. Another ten (25.6%) agreed that the potency of the steroid was most important. Dosage of steroid used in injectate: About half of the physicians use a fixed dose of steroid (22, 51.2%) while 21 (48.8%) use a variable dose of steroid. Of those who use a fixed dose of steroid, many use methylprednisolone 80 mg (9, 39.1%). Of those who use a variable dosage of steroid, the most important factor in their determination of the dosage is the patient’s comorbidities (20 responses, 58.8%). The use of depo-steroid in injectate: Thirty-two out of 43 (74.4%) use depo-steroid while 11 out of 43 (25.6%) wouldn’t use depo-steroid. Of those who use depo-steroid, the duration and availability in the epidural space is the most common reason for its use (23, 76.7%). Conclusion: By using a simple questionnaire detailing what types and dosages of steroids are used, compiling a list of best practices can help Texas Pain Society physicians tremendously in the treatment of radicular back pain.

The impact of minimally invasive surgeries for the treatment of symptomatic benign prostatic hyperplasia on male sexual function： a systematic review

A systematic review of randomized controlled trials and cohort studies was conducted to evaluate data for the effects of minimally invasive procedures for treatment of symptomatic benign prostatic hyperplasia （BPH） on male sexual function. The studies searched were trials that enrolled men with symptomatic BPH who were treated with laser surgeries, transurethral microwave therapy （TUMT）, transurethral needle ablation of the prostate （TUNA）, transurethral ethanol ablation of the prostate （TEAP） and high-intensity frequency ultrasound （HIFU）, in comparison with traditional transurethral resection of the prostate （TURP） or sham operations. A total of 72 studies were identified, of which 33 met the inclusion criteria. Of the 33 studies, 21 were concerned with laser surgeries, six with TUMT, four with TUNA and two with TEAP containing information regarding male sexual function. No study is available regarding the effect of HIFU for BPH on male sexual function. Our analysis shows that minimally invasive surgeries for BPH have comparable effects to those of TURP on male erectile function. Collectively, less than 15.4% or 15.2% of patients will have either decrease or increase, respectively, of erectile function after laser procedures, TUMT and TUNA. As observed with TURP, a high incidence of ejaculatory dysfunction （EjD） is common after treatment of BPH with holmium, potassium-titanyl-phosphate and thulium laser therapies （〉 33.6%）. TUMT, TUNA and neodymium：yttrium aluminum garnet visual laser ablation or interstitial laser coagulation for BPH has less incidence of EjD, but these procedures are considered less effective for BPH treatment when compared with TURP.

Mobilisation of endothelial progenitor cells： one of the possible mechanisms involved in the chronic administration of melatonin preventing erectile dysfunction in diabetic rats

Diabetes-induced oxidative stress plays a critical role in the mobilisation of endothelial progenitor cells （EPCs） from the bone marrow to the circulation. This study was designed to explore the effects of chronic melatonin administration on the promotion of the mobilisation of EPCs and on the preservation of erectile function in type I diabetic rats. Melatonin was administered to streptozotocin-induced type I diabetic rats. EPCs levels were determined using flow cytometry. Oxidative stress in the bone marrow was indicated by the levels of superoxide dismutase and malondialdehyde. Erectile function was evaluated by measuring the intracavernous pressure during an electrostimulation of the cavernous nerve. The density of the endothelium and the proportions of smooth muscle and collagen in the corpus cavernosum were determined by immunohistochemistry. The administration of melatonin increased the superoxide dismutase level and decreased the malondialdehyde level in the bone marrow. This effect was accompanied by an increased level of circulating EPCs in the diabetic rats. The intracavernous pressure to mean arterial pressure ratio of the rats in the treatment group was significantly greater, compared with diabetic control rats. The histological analysis demonstrated an increase in the endothelial density of the corpus cavernosum after the administration of melatonin. However, melatonin treatment did not change the proportions of smooth muscle and collagen in the corpus cavernosum of diabetic rats. Chronic administration of melatonin has a beneficial effect on preventing erectile dysfunction （ED） in type I diabetic rats. Promoting the mobilisation of EPCs is one of the possible mechanisms involved in the improvement of ED.

Prospective and long-term evaluation of erect penile length obtained with inflatable penile prosthesis to that induced by intracavernosal injection

We compared erect penile length after inflatable penile prosthesis （IPP） implantation with that induced by intracavemosal injection （ICI） before surgery. A total of 11 patients with full erections induced by ICI of 0.25 mL of Trimix （papaverine, phentolamine and prostaglandin E 1） at the time of penile color duplex Doppler ultrasonograpby were enrolled in this study. The patients subsequently underwent IPP implantation as the ultimate treatment for their erectile dysfunction （ED）. Erect penile length consequent to IPP implantation was measured at 6 weeks, 6 months and at I year after surgery. The Sexual Health Inventory for Men （SHIM） was administered before, and at 6 months and 1 year after IPP implantation. Erect penile length （mean ± s.c.） as induced by ICI was 13.2 ± 0.4 cm, whereas the lengths attained with IPP were 12.4 ± 0.3, 12.5 ± 0.3 and 12.5 ± 0.4 cm at the sixth week, sixth month and 1-year follow-ups, respectively. There were 0.83 ± 0.25, 0.75 ± 0.20 and 0.74 ± 0.15 cm decreases in erect penile length at 6 weeks, 6 months and 1 year, respectively, after IPP implantation when compared with that after ICI （P 〈 0.05）. The SHIM scores for patients reporting shorter penises were the same as those for patients without complaints at the 6-month and 1-year follow-ups （P 〉 0.05）. To our knowledge, this is the first study to objectively show a significant decrease in erect penile length after IPP implantation when compared with that after ICI. However, this decrease did not affect the effectiveness of IPP in treating ED.

Epigenetics of epithelial Na^+ channel-dependent sodium uptake and blood pressure regulation

The epithelial Na^＋ channel （ENaC） consists of α, β, γ subunits. Its expression and function are regulated by aldosterone at multiple levels including transcription. ENaC plays a key role in Na^＋ homeostasis and blood pressure. Mutations in ENaC subunit genes result in hypertension or hypotension, depending on the nature of the mutations. Transcription of αENaC is considered as the rate-limiting step in the formation of functional ENaC. As an aldosterone target gene, αENaC is activated upon aldosterone- mineralocorticoid receptor binding to the cis-elements in the αENaC promoter, which is packed into chromatin. However, how aldosterone alters chromatin structure to induce changes in transcription is poorly understood. Studies by others and us suggest that Dot1a-Af9 complex represses αENaC by directly binding and regulating targeted histone H3 K79 hypermethylation at the specific subregions of αENaC promoter. Aldosterone decreases Dot1a-Af9 formation by impairing expression of Dot1a and Af9 and by inducing Sgk1, which, in turn, phosphorylates Af9 at S435 to weaken Dot1a-Af9 interaction. MR attenuates Dot1a-Af9 effect by competing with Dot1a for binding Af9. Af17 relieves repression by interfering with Dot1a-Af9 interaction and promoting Dot1a nuclear export. Af17^-/- mice exhibit defects in ENaC expression, renal Na^＋ retention, and blood pressure control. This review gives a brief summary of these novel fndings.

Perifollicular granulomas with Ig G4 plasmacytosis:A case report and review of literature

Perifollicular granuloma is a unique histologic feature and whether it is associated with immunoglobulin G4(IgG 4)-related disease is controversial. We report a case of a 38-year-old man who presented with worsening left eye pain, proptosis, tearing, gritty sensation, blurred vision and multiple lymphadenopathy. An axillary lymph node resection showed reactive follicular and interfollicular lymph node hyperplasia, and increased eosinophils and plasma cells(at least 80% of Ig G+ plasma cells were positive for IgG 4). A distinct feature was the presence of multifocal, perifollicular histiocytic granulomas, which formed a wreath around the entire follicles. The human herpes virus 8 was not detected by immunohistochemistry. In addition, an extensive panel of special stains, immunohistochemistry, and flow cytometry was negative for lymphoma, fungal, or mycobacterial infection. The findings were suggestive of IgG 4-related sclerosing disease-associated lymphadenopathy. Further laboratory testing showed a significant increase of serum immunoglobulin E(> 23000 IU/mL) and slight increase of total Ig G, but normal serum Ig G4. Even though perifollicular granuloma is a nonspecific histopathologic feature and can be seen in other diseases, such as nodular lymphocyte predominant Hodgkin lymphoma, Ig G4-related lymphadenopathy should be listed in the differential diagnoses of benign reactive lymph nodes, especially when perifollicular granuloma and plasmacytosis coexist.

Review on hepatic explant pathology of pediatric intestinal transplant recipients:Is it time for an oil change?

A recent study attempts to add to the body of evidence that is emerging regarding the fish oil parenteral lipid product OmegavenTM.The authors have shown from explant livers of children on chronic parenteral nutrition with OmegavenTM that biochemical improvement in cholestasis does not always reflect improvement in liver histology.These findings support 2 small case series that were previously published.Despite improvement and resolution of hyperbilirubinemia in all six infants,five of six infants had persistent or progressive hepatic fibrosis,while only one infant had regression of fibrosis.The study raises questions of whether there is a window of opportunity for efficacy of this preparation;also,an important question is if this omega-3 fatty acid-rich preparation is superior to newer "blended lipids" containing olive,coconut,soy,and fish oil.

Progenitor cells as remote "bioreactors": Neuroprotection via modulation of the systemic inflammatory response

Acute central nervous system(CNS)injuries such as spinal cord injury,traumatic brain injury,autoimmune encephalomyelitis,and ischemic stroke are associ- ated with significant morbidity,mortality,and health care costs worldwide.Preliminary research has shown potential neuroprotection associated with adult tissue derived stem/progenitor cell based therapies.While initial research indicated that engraftment and transdif- ferentiation into neural cells could explain the observed benefit,the exact mechanism remains controversial.A second hypothesis details localized stem/progenitor cell engraftment with alteration of the loco-regional milieu;however,the limited rate of cell engraftment makes this theory less likely.There is a growing amount of pre-clinical data supporting the idea that,after intravenous injection,stem/progenitor cells interact with immuno- logic cells located in organ systems distant to the CNS,thereby altering the systemic immunologic/inflammatory response.Such distant cell"bioreactors"could modulate the observed post-injury pro-inflammatory environment and lead to neuroprotection.In this review,we discuss the current literature detailing the above mechanisms of action for adult stem/progenitor cell based therapies in the CNS.

Consumption of energy beverage is associated with attenuation of arterial endothelial flow-mediated dilatation

AIMTo investigate whether consumption of an energy drink will acutely impair endothelial function in young healthy adults.METHODSEnergy drinks are being consumed more and more worldwide, and have been associated with some deaths in adolescents and young adults, especially when consumed while exercising. After fasting and not smoking for at least 8 h prior, eleven medical students (9 males) received an electrocardiogram, blood pressure and pulse check, and underwent baseline testing (BL) of endothelial function using the technique of endothelium-dependent flow mediated dilatation (FMD) with high-resolution ultrasound (according to recommended guidelines of the University of Wisconsin Atherosclerosis Imaging Research Program Core Laboratory). The subjects then drank an energy beverage (EB), a 24-oz can of Monster Energy, and the above was repeated at 90 min after consumption. The relative FMD (%) was calculated as the ratio between the average post-cuff release and the baseline diameter. Each image was checked for quality control, and each artery diameter was measured from the media to media points by two experts, 3 measurements at the QRS complex, repeated on 3 separate beats, and then all were averaged.RESULTSSubjects characteristics averages (given with standard deviations) include: Age 24.5 ± 1.5 years, sex 9 male and 2 female, weight 71.0 ± 9.1 kg, height 176.4 ± 6.0 cm, BMI 22.8 ± 2.7 kg/m2. The hemodynamics were as follows, BL vs EB group respectively (mean ± SD): Heart rate 65.2 ± 11.3 vs 68.2 ± 11.8 beats per minute, systolic blood pressure 114.0 ± 10.4 mmHg vs 114.1 ± 10.4 mmHg, diastolic blood pressure 68.8 ± 9.3 mmHg vs 70.6 ± 7.1 mmHg; all were not significantly different. However after drinking the EB, a significantly attenuated peak FMD response was measured (mean ± SD): BL group 5.9% ± 4.6% vs EB group 1.9% ± 2.1%; P = 0.03). Given the increased consumption of energy beverages associated with exercise in young adults, more research is needed.CONCLUSIONEnergy beverage consumption has a negative impact on arterial endothelial function in young healthy adults.

Cocaine Alters the Daily Activity Patterns of Adult SD Female Rats

The effects of chronic cocaine administration on the locomotor rhythmic patterns of adult female Sprague-Dawley (SD) rats were recorded using an open-field testing assay. The animals were divided into four groups, control (saline), 3.0 mg/kg, 7.5 mg/kg, and 15.0 mg/kg i.p. cocaine group respectively. On experimental day (ED 1), all animals were treated with saline. On ED 2 to ED 7, either saline or cocaine (3.0, 7.5, or 15.0 mg/kg i.p.) was given followed by three days of no treatment (ED 8 to ED 10). On ED 11, rats were treated as they were on ED 2 to ED 7, i.e. either saline, 3.0, 7.5, or 15.0 mg/kg i.p. cocaine. The locomotor activities of rats were recorded for 23 hours daily, allowing one hour for the animal handling and injections, using open field cages with 16 infrared beams of motion detectors. Any breakages of these beams due to the movement of the animals were recorded and compiled by a computer and analyzed. It was observed that all three doses of repeated cocaine administration (3.0 mg/kg, 7.5 mg/kg, and 15.0 mg/kg i.p. cocaine) significantly alter the locomotor rhythmic activity patterns of the adult female SD rats, which suggest that repeated cocaine exposure modulates body homeostasis.

Role of self-expanding metal stents in patients with malignant colorectal obstruction: A systematic review and meta-analysis

AIM: To assess the safety and efficacy of self-expandable metal stents(SEMSs) for malignant colorectal obstruction. METHODS: Data regarding technical success, clinical success, and procedure related complications were collected from included studies. Der Simonian-Laird random effects model was used to generate the overall outcome. Thirty international studies with a total of 2058 patients with malignant colorectal obstruction were included. RESULTS: The technical and clinical success rates for SEMS placement were 94%(95%CI: 92-96) and 91%(95%CI: 88-93), respectively. Overall complication rate for SEMS was 23%(95%CI: 18-29). Stent migration8%(95%CI: 6-10) and stent obstruction 8%(95%CI: 6-11) were the most common complications, followed by perforation 5%(95%CI: 4%-7%). Surgical or endoscopic re-interventions were needed in 14%(95%CI: 10-18) of patients. Endoscopic repeat stent placement was required in 8%(95%CI: 6-10), while surgical intervention was needed in 6%(95%CI: 4-8).CONCLUSION: SEMS are effective when used as palliation or bridge to surgery for malignant colorectal obstruction with high technical and clinical success. About 14% of patients require repeat endoscopic or surgical intervention for stent failure or to manage stent related complications.

Granisetron Transdermal Patch for Treatment of Nausea in Patients Undergoing Cisplatin Based Chemotherapy for Cervical Cancer

Objective: The purpose of this study was to define the incidence of chemotherapy-induced nausea and vomiting (CINV) in newly diagnosed cervical cancer patients receiving cisplatin and radiation treatment;and to determine if the granisetron transdermal patch (Sancuso?) would be appropriate to recommend as part of standard antiemetic regimen for the cisplatin radiation chemotherapy order set. Methods: This is a retrospective case-controlled study of cervical cancer patients receiving cisplatin chemotherapy with radiation (cisXRT);comparing patients receiving the granisetron transdermal patch to matched patients receiving oral 5HT3 blockers. All patients prescribed cisXRT between September 15th 2008 and November 30, 2011 were identified using pharmacy dispensing records. Patients were included if they received at least a partial dose of cisXRT and Sancuso? patch as standard antiemetic prophylaxis prior to cisXRT for cervical cancer treatment. Exclusion criteria included concomitant investigational agents, biotherapy and/or chemotherapy agents;prior chemotherapy;or incomplete or restricted medical records. Patients will be matched based on age. Patients were matched 3:1 (oral:patch). A total of 404 patients that received and completed cisXRT were identified utilizing an existing de-identified database from previous study were reviewed to evaluate parameters of interest. Results: A total of 285 patients’ medication records were reviewed for Sancuso? use, and 47 were identified. Of these 47 charts only five patient cases met eligibility criteria to be included in the study. All five patients that received the granisetron patch had at least three known risk factors for nausea. The nausea/vomiting in these patients did not worsen after receiving the Sancuso? patch, and four out of five had subjective improvement. CINV was unrelated to changes in laboratory values or incidence of other toxicity and was not dose-related. Conclusions: While no definitive conclusions could be drawn from this retrospective analysis, the limited data suggests that patients’ nausea and vomiting did not worsen after receiving the Sancuso? patch, and four out of five patients had subjective improvement. The challenges met and limitations identified justify the need for a prospective study that is now underway to control other contributing variables and evaluate overall efficacy of the granisetron patch for controlling CINV in patients receiving cisplatin plus radiation.

Health-related quality of life outcomes in Scandinavian patients after radical prostatectomy or watchful waiting： a critical appraisal

The Scandinavian Prostate Cancer Group- 4 recently reported the long-term survival benefit in men who were randomized to radical prostatectomy versus men watchful waiting for localized prostate cancer.1 The authors have now presented the companion article that updates the long-term quality of life evaluation in these men.2 Given the excellent prognosis of patients with early stage prostate cancer, the impact of therapy on patient＇s quality of life is a significant factor in the optimal management of this disease.

Review of 500 single incision laparoscopic colorectalsurgery cases-Lessons learned

Single incision laparoscopic surgery(SILS) is a minimally invasive platform with specific benefits over traditional multiport laparoscopic surgery. The safety and feasibility of SILS has been proven, and the applications continue to grow with experience. After 500 cases at a high-volume, single-institution, we were able to standardize instrumentation and operative steps, as well as develop adaptations in technique to help overcome technical and ergonomic challenges. These technical adaptations have allowed the successful application of SILS to technically difficult patient populations, such as pelvic cases, inflammatory bowel disease cases, and high body mass index patients. This review is a frame of reference for the application and wider integration of the single incision laparoscopic platform in colorectal surgery.

Review of single incision laparoscopic surgery in colorectal surgery

As surgical techniques continue to move towards less invasive techniques,single incision laparoscopic surgery(SILS),a hybrid between traditional multiport laparoscopy and natural orifice transluminal endoscopic surgery,was introduced to further the enhanced outcomes of multiport laparoscopy. The safety and feasibility of SILS for both benign and malignant colorectal disease has been proven. SILS provides the potential for improved cosmesis,postoperative pain,recovery time,and quality of life at the drawback of higher technical skill required. In this article,we review the history,describe the available technology and techniques,and evaluate the benefits and limitations of SILS for colorectal surgery in the published literature.

Combination therapy for erectile dysfunction： an update review

The introduction of oral phosphodiesterase-5 inhibitors （PDE51s） in the late 1990s and early 2000s revolutionized the field of sexual medicine and PDE51s are currently first-line monotherapy for erectile dysfunction （ED）. However, a significant proportion of patients with complex ED will be therapeutic non-responders to PDE51 monotherapy. Combination therapy has recently been adopted for more refractory cases of ED, but a critical evaluation of current combination therapies is lacking. A thorough PubMed and Cochrane Library search was conducted focusing on the effectiveness of combination therapies for ED in therapeutic non-responders to PDE51 therapy. Journal articles spanning the time period between January 1990 and December 2010 were reviewed. Criteria included all pertinent review articles, randomized controlled trials, cohort studies and retrospective analyses. References from retrieved articles were also manually scanned for additional relevant publications. Published combination therapies include PDE51 plus vacuum erectile device （VED）, intraurethral medication, intracavernosal injection （ICI）, androgen supplement, a-blocker or miscellaneous combinations. Based on this review, some of these combination treatments appeared to be quite effective in preliminary testing. Caution must be advised, however, as the majority of combination therapy articles in the last decade have numerous limitations including study biases and small subject size. Regardless of limitations, present combination therapy research provides a solid foundation for future studies in complex ED management.

Penile rehabilitation with a vacuum erectile device in an animal model is related to an antihypoxic mechanism： blood gas evidence

Our previous study showed that vacuum erectile device （VED） therapy has improved erectile function in rats with bilateral cavernous nerve crush （BCNC） injuries. This study was designed to explore the mechanism of VED in penile rehabilitation by analyzing cavernous oxygen saturation （SO2） and to examine the effect of VED therapy on preventing penile shrinkage after BCNC. Thirty adult Sprague- Dawley rats were randomly assigned into three groups： group 1, sham surgery; group 2, BCNC; and group 3, BCNC＋VED. Penile length and diameter were measured on a weekly basis. After 4 weeks of therapy, the penile blood was extracted by three methods for blood gas analysis （BGA）： method 1, cavernous blood was aspirated at the flaccid state; method 2, cavernous blood was aspirated at the traction state; and method 3, cavernous blood was aspirated immediately after applying VED. SO2 values were tested by the blood gas analyzer. The results showed that VED therapy is effective in preventing penile shrinkage induced by BCNC （Penile shortening： BCNC group 1.9±1.1 mm; VED group 0.3±1.0 mm; P〈0.01. Penile diameter reduction： BCNC group 0.28±0.14 mm; VED group 0.04±0.14 mm; P〈0.01）. The mean SO2±s.d. values were increased by VED application （88.25%±4.94%） compared to the flaccid （76.53%±4.16%） or traction groups （78.93%±2.56%） （P〈0.05）. The calculated blood constructs in the corpus cavernosum right after VED application were 62% arterial and 38% venous blood. These findings suggest that VED therapy can effectively preserve penile size in rats with BCNC injury. The beneficial effect of VED therapy is related to antihypoxia by increasing cavernous blood SO2.

Alternative splicing: An important mechanism in stem cell biology

Alternative splicing(AS) is an essential mechanism in post-transcriptional regulation and leads to protein diversity. It has been shown that AS is prevalent in metazoan genomes, and the splicing pattern is dynamically regulated in different tissues and cell types, including embryonic stem cells. These observations suggest that AS may play critical roles in stem cell biology. Since embryonic stem cells and induced pluripotent stem cells have the ability to give rise to alltypes of cells and tissues, they hold the promise of future cell-based therapy. Many efforts have been devoted to understanding the mechanisms underlying stem cell selfrenewal and differentiation. However, most of the studies focused on the expression of a core set of transcription factors and regulatory RNAs. The role of AS in stem cell differentiation was not clear. Recent advances in highthroughput technologies have all owed the profiling of dynamic splicing patterns and cis-motifs that are responsible for AS at a genome-wide scale, and provided novel insights in a number of studies. In this review, we discuss some recent findings involving AS and stem cells. An emerging picture from these findings is that AS is integrated in the transcriptional and post-transcriptional networks and together they control pluripotency maintenance and differentiation of stem cells.

Should patients with erectile dysfunction be evaluated for cardiovascular disease？

The landmark Massachusetts Male Ageing Study shed new light on the prevalence of erectile dysfunction （ED） and drew attention to ED as a disease of ageing. Over the years, ED has been linked to the development of cardiovascular disease （CVD） in some patients. There is clear evidence that ED and CVD share and have a similar risk factor profile. CVD is one of the most recognizable causes of mortality and early detection coupled with prevention of mortality from CVD has been the prime interest of many researchers. Consequently, there has been a multidisciplinary curiosity regarding the proposal to use ED as a marker for future CVD. I n fact, there have been several proposals to use ED as a screening tool for future CVD. We performed a comprehensive Search of two main databases--PubMed and Cochrane Library using a combination of keywords such as acute myocardial infarction, coronary artery disease （CAD） and ED. Journal articles from January 2000 to June 2011 were reviewed. We included all articles discussing the relationship between ED and CVD in the English language. All the relevant randomized controlled trials, cohort and retrospective studies, and review articles were included in our overall analysis in an attempt to answer the question whether all patients with ED should be clinically evaluated for CVD. The results showed a link between ED and the development of future CVD in some patients, but ED was not shown to be an independent risk predictor that is any better than the traditional Framingham risk factors. Screening for CVD may, however, be rewarding in younger patients with severe ED and in patients with concurrent CVD risk factors.