Gene therapy for neuropathic pain by silencing of TNF-α expression with lentiviral vectors targeting the dorsal root ganglion in mice.

Neuropathic pain can be a debilitating condition. Many types of drugs that have been used to treat neuropathic pain have only limited efficacy. Recent studies indicate that pro-inflammatory mediators including tumor necrosis factor α (TNF-α) are involved in the pathogenesis of neuropathic pain. In the present study, we engineered a gene therapy strategy to relieve neuropathic pain by silencing TNF-α expression in the dorsal root ganglion (DRG) using lentiviral vectors expressing TNF short hairpin RNA1-4 (LV-TNF-shRNA1-4) in mice. First, based on its efficacy in silencing TNF-α in vitro, we selected shRNA3 to construct LV-TNF-shRNA3 for in vivo study. We used L5 spinal nerve transection (SNT) mice as a neuropathic pain model. These animals were found to display up-regulated mRNA expression of activating transcription factor 3 (ATF3) and neuropeptide Y (NPY), injury markers, and interleukin (IL)-6, an inflammatory cytokine in the ipsilateral L5 DRG. Injection of LV-TNF-shRNA3 onto the proximal transected site suppressed significantly the mRNA levels of ATF3, NPY and IL-6, reduced mechanical allodynia and neuronal cell death of DRG neurons. These results suggest that lentiviral-mediated silencing of TNF-α in DRG relieves neuropathic pain and reduces neuronal cell death, and may constitute a novel therapeutic option for neuropathic pain.滋賀医科大学平成26年

Idiopathic pneumoperitoneum after trauma

Intra-abdominal free gas is a finding of extra-intestinal gas in the abdominal cavity on radiography or CT, mainly suggesting gastrointestinal perforation and necessitating emergency surgery. Idiopathic pneumoperitoneum is diagnosed when there is no obvious gastrointestinal perforation, but there is presence of free gas in the abdominal cavity with an unidentifiable cause. Herein, we report a case of idiopathic pneumoperitoneum secondary to high-energy trauma following a car rollover accident. A 95-year-old man was transferred to our clinic after a car-to-car rollover accident. He had abrasions on his right upper arm and left abdomen that appeared to be the result of the accident ; however, no other apparent traumatic injuries were noted. There was no pain in the abdomen, and peritoneal irritation symptoms were also not noted. A CT scan showed fine free air. Although idiopathic pneumoperitoneum could not be ruled out, considering the patient’s background and the possibility of traumatic small bowel perforation, emergency surgery was performed. A thorough search of the abdominal cavity was performed ; however, the surgery was completed without an obvious perforation site. Idiopathic pneumoperitoneum should be considered as a differential disease in cases who have free air on abdominal CT but clinically lack obvious inflammatory reaction findings

Transcriptional Regulation of ATP2C1 Gene by Sp1 and YY1 and Reduced Function of its Promoter in Hailey–Hailey Disease Keratinocytes

Hailey–Hailey disease (HHD) is a blistering skin disease caused by malfunction of the Ca2+-dependent ATPase, ATP2C1. In this study, key regulatory regions necessary for the expression of the gene encoding human ATP2C1 were investigated. The transient reporter assay demonstrated that region +21/+57 was necessary for activation of the ATP2C1 promoter, and the electrophoretic mobility shift assay demonstrated that the region was recognized by the transcription factors, Sp1 and YY1. In accordance with this result, when Sp1 or YY1 was overexpressed in keratinocytes, an obvious increase in ATP2C1 promoter activity was observed, which was in contrast with the case where a mutant promoter lacking the binding sites for Sp1 and YY1 was used as the reporter. Ca2+-stimulation signal increased nuclear Sp1 proteins and ATP2C1 mRNA levels in normal keratinocytes. In contrast, both these increases were suppressed in keratinocytes from HHD patients. These results indicate that Sp1 and YY1 transactivate the human ATP2C1 promoter via cis-enhancing elements and that incomplete upregulation of ATP2C1 transcription contributes to the keratinocyte-specific pathogenesis of HHD. This is a report describing the regulation of the expression of ATP2C1

Clinical significance of PMI with GC patients

Aim : We investigated whether preoperative or postoperative inflammatory markers and psoas muscle index (PMI), and their change after surgery, could predict postoperative recurrence in gastric cancer (GC). Methods : Thirty-five patients who underwent curative gastrectomy for pStage II and III GC were retrospectively reviewed. The relationship between neutrophil–lymphocyte ratio (NLR), prognostic nutritional index (PNI), Glasgow Prognostic Score (GPS), and PMI, as well as postoperative recurrence, was analyzed presurgery and at 6 months after surgery. Results : In the preoperative data, there was a significant association between postoperative recurrence and high NLR, low total protein, low albumin, low PNI, and high GPS. In the data from 6 months after surgery, there was a significant association between postoperative recurrence and high NLR, high C-reactive protein, and high GPS. The reduction in PMI at 6 months after surgery relative to preoperative data was significantly greater in the cases with recurrence than in those without recurrence. No patients whose PMI increased compared with presurgery had recurrence. Conclusions : The postoperative reduction in PMI at 6 months after surgery relative to presurgery could be a predictive marker of recurrence after curative gastrectomy for patients with pStage II and III GC

HASC2011corpus: Towards the Common Ground of Human Activity Recognition

UbiComp '11 Proceedings of the 13th international conference on Ubiquitous computing, September 17-21, 2011, Beijing, ChinaHuman activity recognition through the wearable sensor will enable a next-generation human-oriented biquitous computing. However, most of research on human activity recognition so far is based on small number of subjects, and non-public data. To overcome the situation, we have gathered 4897 accelerometer data with 116 subjects and compose them as HASC2011corpus. In the field of pattern recognition, it is very important to evaluate and to improve the recognition methods by using the same dataset as a common ground. We make the HASC2011corpus into public for the research community to use it as a common ground of the Human Activity Recognition. We also show several facts and results of obtained from the corpus

Treatment for recurrence after esophagectomy

Background : With regard to the recurrence of esophageal cancer after surgery, the prognosis has improved with the progress of multimodal perioperative treatment. In this study, the recurrence pattern, treatment method, and prognosis of recurrent cases following esophageal cancer surgery were retrospectively examined. Materials and Methods : Three hundred seven patients with histologically proven squamous cell carcinoma, adenocarcinoma, and others were enrolled in the study. With respect to clinicopathologic factors and recurrence patterns, recurrence risk factors, recurrence period, treatment for recurrence, and prognosis were investigated. Results : Ninety two percent of all recurrent cases were observed within two years after radical esophagectomy. Locoregional recurrence, distant recurrence, and mixed recurrence were observed in 38 (35%), 56 (51%), and 16 (14%) cases, respectively. Patients with lymph node metastasis showed a significantly longer survival in comparison to those with metastasis to other organs (p = 0.0032). When analyzed using the treatment method, patients who underwent surgery (only surgery or additional postoperative chemotherapy) exhibited better survival in comparison to those who underwent other treatments. Discussion : Detailed and strict follow-up within two years are necessary in cases with deeper than muscular invasion, cases with extensive lymph node metastasis, or cases with lymphatic or vascular invasion

Novel oestrogen receptor beta-selective ligand reduces obesity and depressive-like behaviour in ovariectomized mice

Hormonal changes due to menopause can cause various health problems including weight gain and depressive symptoms. Multiple lines of evidence indicate that oestrogen receptors (ERs) play a major role in postmenopausal obesity and depression. However, little is known regarding the ER subtype-specific effects on obesity and depressive symptoms. To delineate potential effects of ER beta activation in postmenopausal women, we investigated the effects of a novel oestrogen receptor beta-selective ligand (C-1) in ovariectomized mice. Uterine weight, depressive behaviour, and weight gain were examined in sham-operated control mice and ovariectomized mice administered placebo, C-1, or 17 beta-oestradiol (E2). Administration of C-1 or E2 reduced body weight gain and depressive-like behaviour in ovariectomized mice, as assessed by the forced swim test. In addition, administration of E2 to ovariectomized mice increased uterine weight, but administration of C-1 did not result in a significant increase in uterine weight. These results suggest that the selective activation of ERa in ovariectomized mice may have protective effects against obesity and depressive-like behaviour without causing an increase in uterine weight. The present findings raise the possibility of the application of ER beta-ligands such as C-1 as a novel treatment for obesity and depression in postmenopausal women.ArticleSCIENTIFIC REPORTS. 7:4663 (2017)journal articl

Do mothers pick up a phone? A cross-sectional study on delivery of MCH voice messages in Lagos, Nigeria

Background: Voice messages have been employed as an effective and efficient approach for increasing health service utilization and health promotion in low- and middleincome countries. However, unlike SMS, voice message services require their users to pick up a phone call at its delivery time. Furthermore, voice messages are difficult for the users to review their contents afterward. While recognizing that voice messages are more friendly to specific groups (eg, illiterate or less literate populations), there should be several challenges in successfully operationalizing its intervention program.Objective: This study is aimed to estimate the extent to which voice message service users pick up the phone calls of voice messages and complete listening up to or beyond the core part of voice messages.Methods: A voice message service program composed of 14 episodes on maternal, newborn, and child health was piloted in Lagos, Nigeria, from 2018 to 2019. A voice message call of each of 14 episodes was delivered to the mobile phones of the program participants per day for 14 consecutive days. A total of 513 participants in the voice message service chose one of five locally spoken languages as the language to be used for voice messages. Two multilevel logistic regression models were created to understand participants’ adherence to the voice message: (a) Model 1 for testing whether a voice message call is picked up; and (b) Model 2 for testing whether a voice message call having been picked up is listened to up to the core messaging part.Results: The greater the voice message episode number became, the smaller proportion of the participants picked up the phone calls of voice message (aOR: 0.98; 95% CI: 0.97–0.99; P =.01). Only 854 of 3765 voice message calls having been picked up by the participants (22.7%) were listened to up to their core message parts. It was found that picking up a phone call did not necessarily ensure listening up to the core message part. This indicates a discontinuity between these two actions. Conclusions: The participants were likely to stop picking up the phone as the episode number of voice messages progressed. In view of the discontinuity between picking up a phone call and listening up to the core message part, we should not assume that those picking up the phone would automatically complete listening to the entire or core voice message

Transient left ventricular apical ballooning without coronary artery stenosis: a novel heart syndrome mimicking acute myocardial infarction

AbstractOBJECTIVESTo determine the clinical features of a novel heart syndrome with transient left ventricular (LV) apical ballooning, but without coronary artery stenosis, that mimics acute myocardial infarction, we performed a multicenter retrospective enrollment study.BACKGROUNDOnly several case presentations have been reported with regard to this syndrome.METHODSWe analyzed 88 patients (12 men and 76 women), aged 67 ± 13 years, who fulfilled the following criteria: 1) transient LV apical ballooning, 2) no significant angiographic stenosis, and 3) no known cardiomyopathies.RESULTSThirty-eight (43%) patients had preceding aggravation of underlying disorders (cerebrovascular accident [n = 3], epilepsy [n = 3], exacerbated bronchial asthma [n = 3], acute abdomen [n = 7]) and noncardiac surgery or medical procedure (n = 11) at the onset. Twenty-four (27%) patients had emotional and physical problems (sudden accident [n = 2], death/funeral of a family member [n = 7], inexperience with exercise [n = 6], quarreling or excessive alcohol consumption [n = 5] and vigorous excitation [n = 4]). Chest symptoms (67%), electrocardiographic changes (ST elevation [90%], Q-wave formation [27%] and T-wave inversion [97%]) and elevated creatine kinase (56%) were found. After treatment of pulmonary edema (22%), cardiogenic shock (15%) and ventricular tachycardia/fibrillation (9%), 85 patients had class I New York Heart Association function on discharge. The LV ejection fraction improved from 41 ± 11% to 64 ± 10%. Transient intraventricular pressure gradient and provocative vasospasm were documented in 13/72 (18%) and 10/48 (21%) of the patients, respectively. During follow-up for 13 ± 14 months, two patients showed recurrence, and one died suddenly.CONCLUSIONSA novel cardiomyopathy with transient apical ballooning was reported. Emotional or physical stress might play a key role in this cardiomyopathy, but the precise etiologic basis still remains unclear

Optimal Indirect Tax Design for a Developing Country

Given that tariffs continue to serve as a primary source of government revenue in many developing countries, we analyze the optimal indirect tax problem, consisting of commodity taxes and tariffs, under a revenue constraint. This study derives the revenue-constrained optimal commodity taxes and tariffs in both a small and a large country and then examines their structure and properties. We show that the optimal commodity tax structure follows the Ramsey rule regardless of whether a country is small or large, which implies that the same optimal commodity tax rules are applied across a range of situations. We also show that the optimal tariffs are not zero, but negative, even in the small country case, which implies stronger support for the World Bank’s recommendation of tariff reductions for a country facing a revenue constraint. In addition, this study analyzes the optimal commodity taxation when tariffs cannot be fully adjusted. Numerical examples demonstrate some of our major findings and the welfare gain of the optimal taxation for a few developing countries.JEL Classification Codes: F11, F13, H21This study was partly financially supported by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science to Ogawa (26380385) and to Hosoe (16K03613).http://www.grips.ac.jp/list/jp/facultyinfo/hosoe_nobuhiro