Epidural Spinal Cord Stimulation for Spinal Cord Injury in Humans: A Systematic Review.

(1) Background: Spinal cord injury (SCI) represents a major health challenge, often leading to significant and permanent sensorimotor and autonomic dysfunctions. This study reviews the evolving role of epidural spinal cord stimulation (eSCS) in treating chronic SCI, focusing on its efficacy and safety. The objective was to analyze how eSCS contributes to the recovery of neurological functions in SCI patients. (2) Methods: We utilized the PRISMA guidelines and performed a comprehensive search across MEDLINE/PubMed, Embase, Web of Science, and IEEE Xplore databases up until September 2023. We identified studies relevant to eSCS in SCI and extracted assessments of locomotor, cardiovascular, pulmonary, and genitourinary functions. (3) Results: A total of 64 studies encompassing 306 patients were identified. Studies investigated various stimulation devices, parameters, and rehabilitation methods. Results indicated significant improvements in motor function: 44% of patients achieved assisted or independent stepping or standing; 87% showed enhanced muscle activity; 65% experienced faster walking speeds; and 80% improved in overground walking. Additionally, eSCS led to better autonomic function, evidenced by improvements in bladder and sexual functions, airway pressures, and bowel movements. Notable adverse effects included device migration, infections, and post-implant autonomic dysreflexia, although these were infrequent. (4) Conclusion: Epidural spinal cord stimulation is emerging as an effective and generally safe treatment for chronic SCI, particularly when combined with intensive physical rehabilitation. Future research on standardized stimulation parameters and well-defined therapy regimens will optimize benefits for specific patient populations.

Imaging in Retinopathy of Prematurity.

Retinopathy of prematurity (ROP) is a leading cause of preventable childhood blindness worldwide. Barriers to ROP screening and difficulties with subsequent evaluation and management include poor access to care, lack of physicians trained in ROP, and issues with objective documentation. Digital retinal imaging can help address these barriers and improve our knowledge of the pathophysiology of the disease. Advancements in technology have led to new, non-mydriatic and mydriatic cameras with wider fields of view as well as devices that can simultaneously incorporate fluorescein angiography, optical coherence tomography (OCT), and OCT angiography. Image analysis in ROP is also being employed through smartphones and computer-based software. Telemedicine programs in the United States and worldwide have utilized imaging to extend ROP screening to infants in remote areas and have shown that digital retinal imaging can be reliable, accurate, and cost-effective. In addition, tele-education programs are also using digital retinal images to increase the number of healthcare providers trained in ROP. Although indirect ophthalmoscopy is still an important skill for screening, digital retinal imaging holds promise for more widespread screening and management of ROP.

Does the addition of hyperbaric oxygen therapy to conventional treatment modalities influence the outcome of soldiers with idiopathic sudden sensorineural hearing loss?

BACKGROUND: Idiopathic sudden sensorineural hearing loss (ISSNHL) is defined as a 30-decibel (dB) loss in hearing over three contiguous frequencies within 3 days. The cause remains unknown, and there is currently no consensus in the literature as to how it is best treated. Conventional treatment in our unit comprises steroids, pentoxyphiline and dextran, with the potential addition of hyperbaric oxygen therapy (HBOT). METHODS: A prospective randomised trial was performed on all soldiers diagnosed with ISSNHL in our institution from 1 January 2007 to 31 December 2016. Participants were randomly allocated to one of two groups. Group A was treated with conventional treatment plus HBOT. Group B was treated with conventional treatment only. Data collection included age, gender, clinical symptoms, pure-tone audiometry results and treatment outcome. RESULTS: 60 participants were enrolled (53 male, 7 female) with ages ranging from 18 to 65 years (mean age of 30.3). No significant differences were observed in the baseline characteristics between the two groups, including gender, age, site, associated symptoms, duration of symptoms and severity of hearing loss. Hearing recovery using Siegel's criteria on days 8 and 13 showed no significant differences between treatment groups. However, the hearing recovery on day 180 was significantly better in those who received the conventional treatment plus HBOT (P<0.05). Additionally, no significant side effects were observed in either group. CONCLUSIONS: HBOT plus existing conventional treatment was associated with a better outcome than conventional treatment alone. We would recommend the addition of HBOT is recommended as a first-line treatment modality for all soldiers presenting with ISSNHL.

Acetylation is essential for nuclear heme oxygenase-1-enhanced tumor growth and invasiveness.

Overexpression of heme oxygenase-1 (HO-1), an endoplasmic reticulum-anchored enzyme, is observed in many cancers. HO-1 nuclear translocation has been shown to correlate with progression of several cancers. We recently reported that HO-1 is susceptible to intramembrane proteolysis and translocates to the nucleus to promote cancer growth and invasiveness without depending on its enzymatic activity. In the present study, we show that the HO-1 lacking C-terminal transmembrane segment (t-HO-1) was susceptible to acetylation by p300 and CREB-binding protein (CBP) histone acetyltransferase in the nucleus. Mass spectrometry analysis of HO-1 isolated from human embryonic kidney cells 293T (HEK293T) cells overexpressing CBP and t-HO-1 revealed two acetylation sites located at K243 and K256. Mutation of both lysine residues to arginine (R) abolished t-HO-1-enhanced tumor cell growth, migration and invasion. However, mutation of the lysine residues to glutamine (Q), a mimic of acetylated lysine, had no significant effect on t-HO-1-mediated tumorigenicity. Mechanistic studies demonstrated that transcriptional factor JunD interacted with wild-type (WT) t-HO-1 and mutant carrying K243/256Q but not K243/256 R mutation. Moreover, JunD-induced AP-1 transcriptional activity was significantly enhanced by coexpression with WT and acetylation-mimic but not acetylation-defective t-HO-1. Consistent with the in vitro observations, the implication of K243/256 acetylation in t-HO-1-enhanced tumorigenicity was also demonstrated in xenograft models. Immunohistochemistry performed with a specific antibody against acetyl-HO-1 showed the positive acetyl-HO-1 nuclear staining in human lung cancer tissues but not in the corresponding non-tumor tissues, supporting its clinical significance. Collectively, our findings highlight the importance of nuclear HO-1 post-translational modification in the induction of cancer progression.

Gonorrhea infection increases the risk of prostate cancer in Asian population: a nationwide population-based cohort study.

This nationwide population-based retrospective cohort study evaluated the risk of developing prostate cancer among patients with gonorrhea. We identified cases of newly diagnosed gonorrhea in men between 2000 and 2010 from the Taiwan National Health Insurance Research Database. Each patient with gonorrhea was matched to four controls, based on age and index year. All subjects were followed up from the index date to December 31, 2010. The Cox proportional hazards regression model was used to assess the risk of prostate cancer. A total of 355 men were included in the study group, and 1,420 age-matched subjects without gonorrhea were included in the control group. After adjusting for age, comorbidities, urbanization level, hospital level, and monthly income, gonorrhea was significantly associated with an increased risk of prostate cancer (adjusted hazard ratio = 5.66, 95% confidence interval = 1.36-23.52). Men aged 45-70 years and those with lower monthly income were more strongly associated with prostate cancer in the study group than the control group. The higher risk for developing prostate cancer were also found in those without syphilis, without genital warts, without diabetes mellitus, without chronic obstructive pulmonary disease, without benign prostatic hypertrophy, without chronic prostatitis, and without alcoholism. The Kaplan-Meier analysis showed the risk of prostate cancer was significantly higher in the study group than in the control group. Gonorrhea may be involved in the development of prostate cancer. More intensive screening and prevention interventions for prostate cancer should be recommended in men with gonorrhea.

Alternatives to colonoscopy for population-wide colorectal cancer screening.

Colorectal cancer is one of the top three cancers in the world in terms of incidence. Colonoscopy, which many regard as the gold standard in diagnosis of colonic polyps and neoplasm, is costly, invasive and labour-intensive, and deemed an unsuitable population-wide index screening tool. Alternative modalities, including guaiac and immunohistochemical faecal occult blood tests, computed tomographic colonography, colon capsule endoscopy, flexible sigmoidoscopy, and double-contrast barium enema are available. The procedures, test characteristics, and their implications are reviewed. Immunohistochemical faecal occult blood testing appears to be the most suitable population-wide screening test for an average-risk population, with flexible sigmoidoscopy as an alternative. More evidence is needed to determine the role of computed tomographic colonography and colon capsule endoscopy in colorectal cancer screening.

γ-Synuclein Expression Is a Malignant Index in Oral Squamous Cell Carcinoma.

Dysregulation of γ-synuclein (SNCG) has been reported in many cancers; however, its role in cancer development is still controversial. Here, we examined the potential involvement of DNA methylation in regulating SNCG and its role in oral squamous cell carcinoma (OSCC). We used 8 OSCC cell lines to investigate SNCG methylation and expression. SNCG methylation was examination by methylation-specific polymerase chain reaction and bisulfate sequencing. Cells showing a high degree of SNCG methylation were treated with 5-aza (methylation inhibitor), and changes in their methylation and expression profiles were analyzed. Functional effects of SNCG in OSCC were examined by its overexpression and knockdown. Additionally, methylation and expression of SNCG in OSCC tissues were investigated and correlated with clinicopathologic features. All OSCC cells showed detectable SNCG expression at the mRNA and protein levels. Methylation-specific polymerase chain reaction and bisulfate sequencing revealed high SNCG expression in SCC25 cells with the unmethylated allele, and their 15 CpG islands were unmethylated. The methylated allele was detected only in OEC-M1 cells exhibiting low SNCG expression, and their CpG islands were partially methylated. 5-aza treatment in OEC-M1 cells attenuated methylation and restored SNCG expression. SNCG overexpression increased colony forming, migration, and invasion abilities in OEC-M1 cells. Silencing SNCG in SCC25 cells suppressed these behaviors. All 25 tumor-adjacent normal tissues were negative for SNCG immunostaining. SNCG upregulation was frequently observed in dysplastic and OSCC tissues. Positive SNCG expression was found in 45% (37 of 82) OSCC tissues. Positive SNCG expression in OSCC significantly correlated with cancer staging and lymph node metastasis. However, SNCG methylation did not correlate with its expression and clinicopathologic variables in OSCC tissues. DNA methylation may participate in regulating SNCG expression in some OSCC cells. SNCG upregulation could be involved in OSCC progression.

Clinical and molecular characteristics of bloodstream infections caused by Candida albicans in children from 2003 to 2011.

We investigated the clinical and molecular characteristics of Candida albicans bloodstream infection (BSI) in children from a tertiary-level medical centre in Taiwan over a 9-year period from January 2003 to December 2011. We performed multilocus sequence typing (MLST) to investigate the genetic relatedness of these C. albicans BSI isolates. A total of 79 episodes of C. albicans BSI in 76 paediatric patients were identified, including 41 (51.9%) from the paediatric intensive care unit, 24 (30.4%) from the neonatal intensive care unit and 14 (17.7%) from general wards. More than half (59.5%) of these patients had underlying chronic co-morbidities, and the majority (94.9%) had a catheter or some other artificial device. All the isolates were susceptible to the antifungal agents tested. Only 32.9% (26/79) received effective antifungal agents within 24 h of onset of candidaemia. Twenty-five (31.6%) patients had persistent candidaemia (>3 days after the start of antifungal treatment) and candidaemia-attributable mortality rate was 22.8% (18/79). The 72 isolates available for MLST yielded 53 unique diploid sequence types (DSTs). Forty-five DSTs were singletons and eight DSTs were shared by 27 (37.5%) isolates. Seventy-one (98.6%) isolates were clustered within previously known clades. Based on the definition of two or more strains with shared DST occurring within a period of 90 days, 10.1% of the infections were categorized as nosocomial clusters, most commonly identified in the intensive care units. Although cluster-associated candidaemia was not associated with a higher mortality rate, none of the clusters were identified by the hospital infection control team.

Dealing with inter-expert variability in retinopathy of prematurity: A machine learning approach.

BACKGROUND AND OBJECTIVE: Understanding the causes of disagreement among experts in clinical decision making has been a challenge for decades. In particular, a high amount of variability exists in diagnosis of retinopathy of prematurity (ROP), which is a disease affecting low birth weight infants and a major cause of childhood blindness. A possible cause of variability, that has been mostly neglected in the literature, is related to discrepancies in the sets of important features considered by different experts. In this paper we propose a methodology which makes use of machine learning techniques to understand the underlying causes of inter-expert variability. METHODS: The experiments are carried out on a dataset consisting of 34 retinal images, each with diagnoses provided by 22 independent experts. Feature selection techniques are applied to discover the most important features considered by a given expert. Those features selected by each expert are then compared to the features selected by other experts by applying similarity measures. Finally, an automated diagnosis system is built in order to check if this approach can be helpful in solving the problem of understanding high inter-rater variability. RESULTS: The experimental results reveal that some features are mostly selected by the feature selection methods regardless the considered expert. Moreover, for pairs of experts with high percentage agreement among them, the feature selection algorithms also select similar features. By using the relevant selected features, the classification performance of the automatic system was improved or maintained. CONCLUSIONS: The proposed methodology provides a handy framework to identify important features for experts and check whether the selected features reflect the pairwise agreements/disagreements. These findings may lead to improved diagnostic accuracy and standardization among clinicians, and pave the way for the application of this methodology to other problems which present inter-expert variability.

Latent transforming growth factor-ß binding proteins (LTBP-1 and LTBP-2) and gingiva keratinization.

OBJECTIVE: Transforming growth factor-beta (TGF-ß) proteins are involved in epithelial keratinization. The major function of latent TGF-ß binding proteins (LTBPs) is modulating TGF-ß activity. However, whether LTBP-1 and LTBP-2 play roles in gingiva keratinization remains unclear. MATERIALS AND METHODS: Human keratinized gingiva and non-keratinized alveolar mucosa were processed for LTBP-1, LTBP-2, cytokeratin-1 (K1), cytokeratin-4 (K4), and TGF-ß immunohistochemical (IHC) staining. Porcine heterotopically transplanted connective tissues and newly grown epithelia were harvested for IHC staining. The expression levels of LTBP-1 and LTBP-2 were compared between differentiated and undifferentiated human normal oral keratinocytes (hNOK). The expression of LTBP-1 and LTBP-2 was knocked down in a cell line (OEC-M1) to evaluate the effects on the expression of K1, K4, and involucrin (INV). RESULTS: In human and porcine specimens, LTBP-2 expression patterns distinguished keratinized and non-keratinized oral epithelia. Western blotting results showed that K1, LTBP-1, and INV proteins were upregulated in differentiated hNOK. In OEC-M1 cells, LTBP-2 knockdown resulted in upregulated the expression of K1 and INV and downregulated the expression of K4. LTBP-1 knockdown resulted in opposite effects. CONCLUSION: The expression patterns of LTBP-2 differ in keratinized gingiva and non-keratinized mucosa. LTBP-1 and LTBP-2 are involved in the keratinization of oral epithelium; however, the underlying mechanism remains to be elucidated.

Predictors of clinical and microbiological treatment failure in neonatal bloodstream infections.

This study aimed to identify independent predictors of clinical and microbiological treatment failure and develop a predictive model for neonates with bloodstream infection (BSI). This study included 1087 episodes of BSIs in 793 neonates in a tertiary-level neonatal intensive care unit of northern Taiwan between 2004 and 2012. Patient demographics, underlying chronic comorbidities, clinical features, antimicrobial treatment and microbiological characteristics were evaluated. The presence of underlying congenital anomalies (odds ratio [OR] 2.12, 95% confidence interval [CI] 1.09 to 4.10) and pulmonary hypertension (OR 3.63, 95% CI 1.70 to 7.74), infections caused by multidrug-resistant gram-negative bacteria (OR 2.89, 95% CI 1.23 to 6.79), group B Streptococcus (OR 3.15, 95% CI 1.33 to 7.46), and fungi (OR 4.13, 95% CI 2.02 to 8.46), a Neonatal Therapeutic Intervention Scoring System score of ≥ 23 (OR 6.96, 95% CI 2.55 to 28.58), inappropriate antibiotics (OR 2.13, 95% CI 1.41 to 3.23), and concomitant meningitis (OR 4.25, 95% CI 2.08 to 8.69) and ventilator-associated pneumonia (OR 2.73, 95% CI 1.22 to 6.13) were identified as independent risk factors for 28-day treatment failure in neonatal BSI. A risk score model was created by adding the points for each independent risk factor, and had a c-statistic of 0.83. Patients with risk scores of 0, 4, 8, 12 and 15 had estimated 28-day treatment failure rates of approximately 3.5%, 17.0%, 53.5%, 86.6% and 95.9%, respectively. This predictive model, calculated after documentation of a BSI, reflects a spectrum of BSI severity and was associated with subsequent treatment failure through illness severity score and case mix variables. This simple score could prove useful in clinical and research settings, and practical in estimating the prognosis.

Analysis of underlying causes of inter-expert disagreement in retinopathy of prematurity diagnosis. Application of machine learning principles.

OBJECTIVE: Inter-expert variability in image-based clinical diagnosis has been demonstrated in many diseases including retinopathy of prematurity (ROP), which is a disease affecting low birth weight infants and is a major cause of childhood blindness. In order to better understand the underlying causes of variability among experts, we propose a method to quantify the variability of expert decisions and analyze the relationship between expert diagnoses and features computed from the images. Identification of these features is relevant for development of computer-based decision support systems and educational systems in ROP, and these methods may be applicable to other diseases where inter-expert variability is observed. METHODS: The experiments were carried out on a dataset of 34 retinal images, each with diagnoses provided independently by 22 experts. Analysis was performed using concepts of Mutual Information (MI) and Kernel Density Estimation. A large set of structural features (a total of 66) were extracted from retinal images. Feature selection was utilized to identify the most important features that correlated to actual clinical decisions by the 22 study experts. The best three features for each observer were selected by an exhaustive search on all possible feature subsets and considering joint MI as a relevance criterion. We also compared our results with the results of Cohen's Kappa [36] as an inter-rater reliability measure. RESULTS: The results demonstrate that a group of observers (17 among 22) decide consistently with each other. Mean and second central moment of arteriolar tortuosity is among the reasons of disagreement between this group and the rest of the observers, meaning that the group of experts consider amount of tortuosity as well as the variation of tortuosity in the image. CONCLUSION: Given a set of image-based features, the proposed analysis method can identify critical image-based features that lead to expert agreement and disagreement in diagnosis of ROP. Although tree-based features and various statistics such as central moment are not popular in the literature, our results suggest that they are important for diagnosis.

Signal peptide peptidase-mediated nuclear localization of heme oxygenase-1 promotes cancer cell proliferation and invasion independent of its enzymatic activity.

Heme oxygenase-1 (HO-1) is a heme-degrading enzyme anchored in the endoplasmic reticulum by a carboxyl-terminal transmembrane segment (TMS). HO-1 is highly expressed in various cancers and its nuclear localization is associated with the progression of some cancers. Nevertheless, the mechanism underlying HO-1 nuclear translocation and its pathological significance remain elusive. Here we show that the signal peptide peptidase (SPP) catalyzes the intramembrane cleavage of HO-1. Coexpression of HO-1 with wild-type SPP, but not a dominant-negative SPP, promoted the nuclear localization of HO-1 in cells. Mass spectrometry analysis of cytosolic HO-1 isolated from HeLa cells overexpressing HO-1 and SPP revealed two adjacent intramembrane cleavage sites located after S275 and F276 within the TMS. Mutations of S275F276 to A275L276 significantly hindered SPP-mediated HO-1 cleavage and nuclear localization. Nuclear HO-1 was detected in A549 and DU145 cancer cell lines expressing high levels of endogenous HO-1 and SPP. SPP knockdown or inhibition significantly reduced nuclear HO-1 localization in A549 and DU145 cells. The positive nuclear HO-1 stain was also evident in lung cancer tissues expressing high levels of HO-1 and SPP. Overexpression of a truncated HO-1 (t-HO-1) lacking the TMS in HeLa and H1299 cells promoted cell proliferation and migration/invasion. The effect of t-HO-1 was not affected by a mutation in the catalytic site. However, blockade of t-HO-1 nuclear localization abolished t-HO-1-mediated effect. The tumorigenic effect of t-HO-1 was also demonstrated in the mouse model. These findings disclose that SPP-mediated intramembrane cleavage of HO-1 promotes HO-1 nuclear localization and cancer progression independent of HO-1 enzymatic activity.

Recurrent late-onset sepsis in the neonatal intensive care unit: incidence, clinical characteristics and risk factors.

We aimed to characterize the incidence, clinical features, risk factors and outcomes of recurrent late-onset sepsis (LOS) in the neonatal intensive care unit (NICU). All neonates with LOS from the NICU of a tertiary-level teaching hospital in northern Taiwan between 2004 and 2011 were enrolled for analyses. A case-control study was performed to determine risk factors for recurrence. Of 713 neonates with LOS, 150 (21.0%) experienced recurrence and 48 (6.7%) had >1 recurrences; c. two-thirds of recurrent LOS occurred in infants with birth weight (BW)≦1500 g or gestational age (GA)≦30 weeks. The recurrent LOS episodes were significantly more severe and had a higher sepsis-attributable mortality rate than the first episodes. The overall in-hospital mortality rate was 30.7% for neonates with recurrent LOS and 7.8% for those with single LOS (odds ratio (OR), 5.22; 95% CI, 3.28-8.30). When both BW and GA were controlled, neonates with recurrent LOS had a significantly prolonged hospitalization compared with the controls (median 109 vs. 84 days, p<0.001). After multivariate logistic regression, longer duration of total parenteral nutrition (TPN; OR, 1.30; 95% CI, 1.10-1.52 for every 10-day increment), presence of congenital anomalies (OR, 2.64; 95% CI, 1.10-6.35) and neurological co-morbidities (OR, 4.14; 95% CI, 1.14-15.10) were identified as the independent risk factors for LOS recurrence. We concluded that c. one-fifth of neonates with LOS had recurrence, which significantly resulted in prolonged hospitalization and increased mortality. Longer TPN administration, presence of congenital anomalies and neurological co-morbidities are independently associated with recurrent LOS.

Left circumflex coronary-to-pulmonary artery fistula as the exclusive collateral to the occluded left anterior descending artery.

A 64 year-old male presented with a five month history of effort angina. Non-invasive studies demonstrated preserved left ventricular function and a modest stress-induced myocardial perfusion defect at the anterior wall. Coronary angiography revealed occlusion of the proximal left anterior descending coronary artery with its distal segment well supplied by collaterals branching from a left circumflex-to-main pulmonary artery fistula. The occluded left anterior descending coronary artery was recanalised by percutaneous interventions, the collaterals vanished immediately, and the patient lived free of symptoms for the following five months.

Tratamiento endoscópico de cálculos ureterales: experiencia en una serie de 102 casos / Endoscopic treatment of ureteral stones: experience in a series of 102 cases

INTRODUCCIÓN: La ureterolitectomía endoscópica (URS) es una técnica validada para el manejo de cálculos ureterales, ya que tiene alto poder resolutivo y es poco invasiva. El desarrollo de instrumentos flexibles ha facilitado el manejo endoscópico de los cálculos en uréter medio y proximal. El objetivo de este trabajo es describir la experiencia de nuestro centro en URS. Material y metodos: Análisis retrospectivo de las URS realizadas en nuestro centro entre Diciembre 2009 y Mayo 2012. Se consignaron las características del cálculo, el método de fragmentación, la efectividad del procedimiento y las complicaciones. Se utilizaron los ureteroscopios semirrígido Wolf (6,0-9,5 Fr) y flexible Karl Storz Flex X2. Resultados: Se revisaron 102 ureteroscopías, 85 con ureteroscopio semirrígido y 17 con flexible. Los cálculos tuvieron un promedio de 5,7 mm y 642 UH. El 89,4 por ciento de los cálculos resueltos mediante URS semirrígida se localizaban en uréter distal y 52,9 por ciento de los resueltos con URS flexible en uréter proximal. Se realizó litotripsia con láser Holmium en un 25,9 por ciento y 70,6 por ciento de los casos con URS semirrígida y flexible, respectivamente. Se utilizó litotripsia pneumática en un 4,7 por ciento de los casos de URS semirrígida. En URS semirrígida y flexible, la tasa de stone-free + fragmentos < 2 mm fue de 89,4 por ciento y 88,2 por ciento, respectivamente. Sólo hubo una complicación en nuestra serie (infección urinaria febril en 1 caso con URS flexible). La mediana de hospitalización fue de 1 día (rango 1-5 días). Conclusion: Nuestros resultados reafirman a la URS como una técnica eficaz, segura y poco invasiva para el tratamiento de los cálculos ureterales.

INTRODUCTION: The endoscopic ureterolithotomy (URS) is a validated technique for the management of ureteral calculi, which is highly resolutive and minimally invasive. The development of flexible instruments has facilitated the endoscopic management of stones in the mid and proximal segments of the ureter. The aim of this paper is to describe the experience of our center in endoscopic ureterolithotomy. Material and methods: Retrospective analysis of URS performed at our center between December 2009 and May 2012. We recorded the characteristics of the stones, the fragmentation method, the effectiveness of the procedure and complications. The Wolf semi-rigid (6.0 to 9.5 Fr) and the flexible Karl Storz Flex X2 ureteroscopes were used. RESULTS: We reviewed 102 URS, 85 with semi-rigid and 17 with flexible ureteroscope. The calculi were 5.7 mm and 642 HU in average. 89.4 percent of the stones treated with a semi-rigid URS were localized in the distal ureter and 52.9 percent of the calculi treated with a flexible URS were in the proximal ureter. Holmium laser lithotripsy was performed in 25.9 percent and 70.6 percent of the cases of semi-rigid and flexible URS, respectively. Pneumatic lithotripsy was used in 4.7 percent of the semi-rigid URS. In semi-rigid and flexible URS, the rate of stone-free + fragments < 2 mm was 89.4 percent and 88.2 percent, respectively. There was only one complication in our series (febrile urinary tract infection in 1 case of flexible URS). The median length of stay was 1 day (range 1-5 days). CONCLUSION: Our results confirm that URS is an effective, safe and minimally invasive treatment for ureteral calculi.

Long-term follow-up of arrhythmia characteristics and clinical outcomes in heart transplant patients.

INTRODUCTION: Arrhythmias occur frequently after heart transplantation (HT), but knowledge of their impact on long-term outcomes is limited. This study sought to investigate the characteristics of the arrhythmias among biatrial orthotopic HT patients during long-term follow-up. METHODS: This study included 217 patients who received biatrial orthotopic HT. Patients were classified into 5 groups according to the arrhythmia episodes that occurred >1 month after HT: no arrhythmias (group 1; n = 149); atrial tachyarrhythmias only (group 2; n = 34); ventricular tachyarrhythmias only (group 3; n = 9); bradyarrhythmias only (group 4; n = 7); or double/triple arrhythmias (group 5; n = 18). We analyzed their long-term outcomes respectively. RESULTS: During 83 ± 51 months of follow-up, all-cause mortality rates were higher in groups 3 (88.9%) and 5 (72.2%) compared with the other groups (groups 1, 2, and 4: 21.5%, 41.2%, and 57.1%, respectively; P < .001). Cardiovascular mortality rates were higher in groups 4 (42.9%) and 5 (61.1%) compared with the other groups (groups 1, 2, and 3: 8.1%, 20.6%, and 0% respectively; P < .001). Noncardiovascular mortality rate was greater in group 3 (88.9%) compared with the other groups (groups 1, 2, 4, and 5: 13.4%, 20.6%, 14.3%, and 11.1%, respectively; P < .001). Sudden death rates were higher in groups 4 (42.9%) and 5 (44.4%) compared with the other groups (groups 1, 2, and 3: 7.4%, 8.8%, and 0%, respectively; P < .001). CONCLUSION: Patients with posttransplantation arrhythmias experienced significantly worse clinical outcomes.

PPARγ regulates the mitochondrial dysfunction in human neural stem cells with tumor necrosis factor alpha.

Peroxisome proliferator-activated receptor gamma (PPARγ) belongs to a family of ligand-activated transcription factors, and its ligands are known to control many physiological and pathological conditions. The hypothesis of our study was that the PPARγ agonist (rosiglitazone) could mediate tumor necrosis factor alpha (TNFα) related to the regulation of human neural stem cells (hNSCs), by which TNFα possibly fulfills important roles in neuronal impairment. The results show that PPARγ mediates the cell viability of hNSCs via the downregulation of the activity of caspase 3, indicating that this rescue effect of PPARγ could improve the reduced levels of two mitochondrial regulators, adenosine monophosphate-activated protein kinase (AMPK) and Sirtuin 1 (SIRT1) in the hNSCs with TNFα. The stimulation of mitochondrial function by PPARγ was associated with activation of the PPAR coactivator1 alpha (PGC1α) pathway by up-regulation of oxidative defense and mitochondrial systems. The above protective effects appeared to be exerted by a direct activation of the rosiglitazone, because it protected hNSCs from TNFα-evoked oxidative stress and mitochondrial deficiency. Here we show that the rosiglitazone protects hNSCs against Aß-induced apoptosis and promotes cell survival. These findings extend our understanding of the central role of PPARγ in TNFα-related neuronal impairment, which probably increases risks of neurodegenerative diseases. The anti-inflammatory effects of PPARγ in the hNSCs with TNFα, and the involved mechanisms were also characterized.