Effects of different treatment frequencies of electromagnetic stimulation for urinary incontinence in women:study protocol for a randomized controlled trial

Background: Urinary incontinence is highly prevalent in women while pelvic floor muscle training is recommended as the first-line therapy. However, the exact treatment regimen is poorly understood. Also, patients with pelvic floor muscle damage may have decreased muscle proprioception and cannot contract their muscles properly. Other conservative treatments including electromagnetic stimulation are suggested by several guidelines. Thus, the present study aims to compare the effectiveness of electromagnetic stimulation combined with pelvic floor muscle training as a conjunct treatment for urinary incontinence and different treatment frequencies will be investigated.Methods/design: This is a randomized, controlled clinical trial. We will include 165 patients with urinary incontinence from the outpatient center. Participants who meet the inclusion criteria will be randomly allocated to three groups: the pelvic floor muscle training group (active control group), the low-frequency electromagnetic stimulation group (group 1), and the high-frequency electromagnetic stimulation group (group 2). Both group 1 and group 2 will receive ten sessions of electromagnetic stimulation. Group 1 will be treated twice per week for 5 weeks while group 2 will receive 10 days of continuous treatment. The primary outcome is the change in International Consultation on Incontinence Questionnaire–Short Form cores after the ten sessions of the treatment, while the secondary outcomes include a 3-day bladder diary, pelvic floor muscle function, pelvic organ prolapse quantification, and quality of life assessed by SF-12. All the measurements will be assessed at baseline, after the intervention, and after 3 months of follow-up.Discussion: The present trial is designed to investigate the effects of a conjunct physiotherapy program for urinary incontinence in women. We hypothesize that this strategy is more effective than pelvic floor muscle training alone, and high-frequency electromagnetic stimulation will be superior to the low-frequency magnetic stimulation group

Burden of disease resulting from chronic mountain sickness among young Chinese male immigrants in Tibet

BACKGROUND: In young Chinese men of the highland immigrant population, chronic mountain sickness (CMS) is a major public health problem. The aim of this study was to measure the disease burden of CMS in this population. METHODS: We used disability-adjusted life years (DALYs) to estimate the disease burden of CMS. Disability weights were derived using the person trade-off methodology. CMS diagnoses, symptom severity, and individual characteristics were obtained from surveys collected in Tibet in 2009 and 2010. The DALYs of individual patients and the DALYs/1,000 were calculated. RESULTS: Disability weights were obtained for 21 CMS health stages. The results of the analyses of the two surveys were consistent with each other. At different altitudes, the CMS rates ranged from 2.1-37.4%; the individual DALYs of patients ranged from 0.13-0.33, and the DALYs/1,000 ranged from 3.60-52.78. The age, highland service years, blood pressure, heart rate, smoking rate, and proportion of the sample working in engineering or construction were significantly higher in the CMS group than in the non-CMS group (p < 0.05). These variables were also positively associated with the individual DALYs (p < 0.05). Among the symptoms, headaches caused the largest proportion of DALYs. CONCLUSION: The results show that CMS imposes a considerable burden on Chinese immigrants to Tibet. Immigrants with characteristics such as a higher residential altitude, more advanced age, longer highland service years, being a smoker, and working in engineering or construction were more likely to develop CMS and to increase the disease burden. Higher blood pressure and heart rate as a result of CMS were also positively associated with the disease burden. The authorities should pay attention to the highland disease burden and support the development and application of DALYs studies of CMS and other highland diseases

Novel Function of Ceramide for Regulation of Mitochondrial ATP Release in Astrocytes

We reported that amyloid β peptide (Aβ42) activated neutral SMase 2 (nSMase2), thereby increasing the concentration of the sphingolipid ceramide in astrocytes. Here, we show that Aβ42 induced mitochondrial fragmentation in wild-type astrocytes, but not in nSMase2-deficient cells or astrocytes treated with fumonisin B1 (FB1), an inhibitor of ceramide synthases. Unexpectedly, ceramide depletion was concurrent with rapid movements of mitochondria, indicating an unknown function of ceramide for mitochondria. Using immunocytochemistry and super-resolution microscopy, we detected ceramide-enriched and mitochondria-associated membranes (CEMAMs) that were codistributed with microtubules. Interaction of ceramide with tubulin was confirmed by cross-linking to N-[9-(3-pent-4-ynyl-3-H-diazirine-3-yl)-nonanoyl]-D-erythro-sphingosine (pacFACer), a bifunctional ceramide analog, and binding of tubulin to ceramide-linked agarose beads. Ceramide-associated tubulin (CAT) translocated from the perinuclear region to peripheral CEMAMs and mitochondria, which was prevented in nSMase2-deficient or FB1-treated astrocytes. Proximity ligation and coimmunoprecipitation assays showed that ceramide depletion reduced association of tubulin with voltage-dependent anion channel 1 (VDAC1), an interaction known to block mitochondrial ADP/ATP transport. Ceramide-depleted astrocytes contained higher levels of ATP, suggesting that ceramide-induced CAT formation leads to VDAC1 closure, thereby reducing mitochondrial ATP release, and potentially motility and resistance to Aβ42. Our data also indicate that inhibiting ceramide generation may protect mitochondria in Alzheimer’s disease

Increased Liver Tumor Formation in Neutral Sphingomyelinase-2-Deficient Mice

Sphingolipids are key signaling lipids in cancer. Genome-wide studies have identified neutral SMase-2 (nSMase2), an enzyme generating ceramide from SM, as a potential repressor for hepatocellular carcinoma. However, little is known about the sphingolipids regulated by nSMase2 and their roles in liver tumor development. We discovered growth of spontaneous liver tumors in 27.3% (9 of 33) of aged male nSMase2-deficient (fro/fro) mice. Lipidomics analysis showed a marked increase of SM in the tumor. Unexpectedly, tumor tissues presented with more than a 7-fold increase of C16-ceramide, concurrent with upregulation of ceramide synthase 5. The fro/fro liver tumor, but not adjacent tissue, exhibited substantial accumulation of lipid droplets, suggesting that nSMase2 deficiency is associated with tumor growth and increased neutral lipid generation in the tumor. Tumor tissue expressed significantly increased levels of CD133 and EpCAM mRNA, two markers of liver cancer stem-like cells (CSCs) and higher levels of phosphorylated signal transducer and activator of transcription 3, an essential regulator of stemness. CD133(+) cells showed strong labeling for SM and ceramide. In conclusion, these results suggest that SMase-2 deficiency plays a role in the survival or proliferation of CSCs, leading to spontaneous tumors, which is associated with tumor-specific effects on lipid homeostasis

PSR J1926-0652: A Pulsar with Interesting Emission Properties Discovered at FAST

We describe PSR J1926-0652, a pulsar recently discovered with the Five-hundred-meter Aperture Spherical radio Telescope (FAST). Using sensitive single-pulse detections from FAST and long-term timing observations from the Parkes 64-m radio telescope, we probed phenomena on both long and short time scales. The FAST observations covered a wide frequency range from 270 to 800 MHz, enabling individual pulses to be studied in detail. The pulsar exhibits at least four profile components, short-term nulling lasting from 4 to 450 pulses, complex subpulse drifting behaviours and intermittency on scales of tens of minutes. While the average band spacing P3 is relatively constant across different bursts and components, significant variations in the separation of adjacent bands are seen, especially near the beginning and end of a burst. Band shapes and slopes are quite variable, especially for the trailing components and for the shorter bursts. We show that for each burst the last detectable pulse prior to emission ceasing has different properties compared to other pulses. These complexities pose challenges for the classic carousel-type models.Comment: 13pages with 12 figure