The role of digital rectal examination for diagnosis of acute appendicitis: A systematic review and meta-analysis

Background: Digital rectal examination (DRE) has been traditionally recommendedto evaluate acute appendicitis, although several reports indicate its lack of utility for this diagnosis. No metaanalysis has examined DRE for diagnosis of acute appendicitis. Objectives: To assess the role of DRE for diagnosis of acute appendicitis. Data Sources: Cochrane Library, PubMed, and SCOPUS from the earliest available date of indexing through November 23, 2014, with no language restrictions. Study Selection: Clinical studies assessing DRE as an index test for diagnosis of acute appendicitis. Data Extraction and Synthesis: Two independent reviewers extracted study data and assessed the quality, using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Bivariate random-effects models were used for the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio (DOR) as point estimates with 95% confidence intervals (CI). Main Outcomes and Measures: The main outcome measure was the diagnostic performance of DRE for diagnosis of acute appendicitis. Results: We identified 19 studies with a total of 7511 patients. The pooled sensitivity and specificity were 0.49 (95% CI 0.42-0.56) and 0.61 (95% CI 0.53-0.67), respectively. The positive and negative likelihood ratios were 1.24 (95% CI 0.97-1.58) and 0.85 (95% CI 0.70-1.02), respectively. The DOR was 1.46 (0.95-2.26). Conclusion and Relevance: Acute appendicitis cannot be ruled in or out through the result of DRE. Reconsideration is needed for the traditional teaching that rectal examination should be performed routinely in all patients with suspected appendicitis

The Japan Monkey Centre Primates Brain Imaging Repository of high-resolution postmortem magnetic resonance imaging: the second phase of the archive of digital records

超高磁場MRIで見る霊長類「全脳」神経回路の多様性 --分野横断型の霊長類脳標本画像リポジトリ：ヒト脳と精神・神経疾患の理解を加速する国際研究基盤--. 京都大学プレスリリース. 2023-05-22.A comparison of neuroanatomical features of the brain between humans and our evolutionary relatives, nonhuman primates, is key to understanding the human brain system and the neural basis of mental and neurological disorders. Although most comparative MRI studies of human and nonhuman primate brains have been based on brains of primates that had been used as subjects in experiments, it is essential to investigate various species of nonhuman primates in order to elucidate and interpret the diversity of neuroanatomy features among humans and nonhuman primates. To develop a research platform for this purpose, it is necessary to harmonize the scientific contributions of studies with the standards of animal ethics, animal welfare, and the conservation of brain information for long-term continuation of the field. In previous research, we first developed a gated data-repository of anatomical images obtained using 9.4-T ex vivo MRI of postmortem brain samples from 12 nonhuman primate species, and which are stored at the Japan Monkey Centre. In the present study, as a second phase, we released a collection of T2-weighted images and diffusion tensor images obtained in nine species: white-throated capuchin, Bolivian squirrel monkey, stump-tailed macaque, Tibet monkey, Sykes’ monkey, Assamese macaque, pig-tailed macaque, crested macaque, and chimpanzee. Our image repository should facilitate scientific discoveries in the field of comparative neuroscience. This repository can also promote animal ethics and animal welfare in experiments with nonhuman primate models by optimizing methods for in vivo and ex vivo MRI scanning of brains and supporting veterinary neuroradiological education. In addition, the repository is expected to contribute to conservation, preserving information about the brains of various primates, including endangered species, in a permanent digital form

ASSERT trial – How to assess the safety and efficacy of a high frequency rTMS in postpartum depression ? A multicenter, double blinded, randomized, placebo-controlled clinical trial

Background: Postpartum Depression affects a considerable number of women worldwide. This condition inflicts severe consequences to mother and child health. Thus far, available treatments have low response and high relapse rates. We designed this trial to evaluate a safe and more efficacious innovative therapy. Aims To report a feasible and ethical study design to assess the safety and efficacy of a high frequency repetitive Transcranial Magnetic Stimulation 10 Hz (rTMS) compared to sham rTMS in women with moderate to severe Post-Partum Depression using standard treatment (sertraline). To conduct an ancillary, exploratory, randomized, active controlled, double blind study with a hypothesis to assess the safety and efficacy of 10 Hz rTMS compared to sertraline. Methods: A multicenter, parallel arm, randomized, placebo-controlled, double-blind design to assess safety and efficacy of 10 Hz rTMS compared to sham. An ancillary study will be conducted with parallel arm, randomized, active controlled and double dummy design to assess safety and efficacy of 10 Hz rTMS compared to sertraline

Clinical practice guideline for drug-induced kidney injury in Japan 2016: digest version

Approximately one in eight adults has chronic kidney disease (CKD) in Japan, and the prevalence rate is expected to rise steeply due to the aging of the population in this country. In patients with CKD, quite a few medications require the dosage reduction or discontinuation because of their reduced urinary excretion and the increased risk of further renal impairment. Therefore, CKD patients are often treated by insufficient amounts of the medications, even though they may suffer from various complications. Moreover, it is empirically known that drug-induced kidney injury (DKI) accelerates the progression of renal failure, while it is not superficially ranked as a primary cause of kidney disease.In this context, the early detection, prevention, and treatment of DKI are very important issue in preventing the progression of CKD and the development of renal failure. However, there are no comprehensive and practical guideline on the diagnosis and treatment of DKI for CKD patients and on dosage adjustments for these patients.In response to this need, a clinical practice guideline for DKI was developed with the support of a Health and Labour Science Research Grant from the Ministry of Health, Labour, and Welfare (MHLW) and the Japan Agency for Medical Research and Development (AMED) for Practical Research Project for Renal Diseases, “Early detection and treatment of drug-induced kidney injury that aggravate chronic kidney disease.” This guideline was established by doing a clinical survey on DKIs, evaluating clinicopathological factors, investigating the methods of the early detection of the disease, and analyzing animal models. The present article represents a Committee of Clinical Practice Guideline for DKI. We collected supportive evidence and analyzed data, focusing on several clinical questions that have practical importance

The association of the difference in hemoglobin levels before and after hemodialysis with the risk of 1-year mortality in patients undergoing hemodialysis. Results from a nationwide cohort study of the Japanese Renal Data Registry.

BackgroundFew clinical studies have directly examined the associations of hemoglobin (Hb) levels after hemodialysis (HD) and of the difference in Hb levels before and after HD (ΔHb) with patient outcomes. The present study aimed to determine ΔHb and post-HD Hb levels with nationwide data and to examine their associations with all-cause mortality in patients undergoing HD.MethodsThis study is based on data from 2008 and 2009 recorded in the Japanese Renal Data Registry. Study endpoints were all-cause mortality within 1-year. The ΔHb and post-HD Hb level as categorical variables using Cox regression for 1-year mortality, adjusting for potential confounders.ResultsThe median ΔHb was 1.0 g/dl, and the post-HD Hb level was 11.3 g/d. The median pre-HD Hb level was 10.4 g/dl. The risk of mortality was lower with a ΔHb of 0 to 1.0 g/dl (adjusted hazard ratio [aHR], 0.90; 95% confidence interval [CI], 0.70-1.01) or > 1.0 g/dl (aHR, 0.73; 95% CI, 0.64-0.84) than with a ΔHb 12 g/dl (aHR, 0.77; 95% CI, 0.68-0.87) than with a post-HD Hb ConclusionsBoth a low ΔHb and a low post-HD Hb level were associated with a higher risk of 1-year mortality

Mechanisms of tumor necrosis factor-α-induced interleukin-6 synthesis in glioma cells

Abstract Background Interleukin (IL)-6 plays a pivotal role in a variety of CNS functions such as the induction and modulation of reactive astrogliosis, pathological inflammatory responses and neuroprotection. Tumor necrosis factor (TNF)-α induces IL-6 release from rat C6 glioma cells through the inhibitory kappa B (IκB)-nuclear factor kappa B (NFκB) pathway, p38 mitogen-activated protein (MAP) kinase and stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK). The present study investigated the mechanism of TNF-α-induced IL-6 release in more detail than has previously been reported. Methods Cultured C6 cells were stimulated by TNF-α. IL-6 release from the cells was measured by an enzyme-linked immunosorbent assay, and the phosphorylation of IκB, NFκB, the MAP kinase superfamily, and signal transducer and activator of transcription (STAT)3 was analyzed by Western blotting. Levels of IL-6 mRNA in cells were evaluated by real-time reverse transcription-polymerase chain reaction. Results TNF-α significantly induced phosphorylation of NFκB at Ser 536 and Ser 468, but not at Ser 529 or Ser 276. Wedelolactone, an inhibitor of IκB kinase, suppressed both TNF-α-induced IκB phosphorylation and NFκB phosphorylation at Ser 536 and Ser 468. TNF-α-stimulated increases in IL-6 levels were suppressed by wedelolactone. TNF-α induced phosphorylation of STAT3. The Janus family of tyrosine kinase (JAK) inhibitor I, an inhibitor of JAK 1, 2 and 3, attenuated TNF-α-induced phosphorylation of STAT3 and significantly reduced TNF-α-stimulated IL-6 release. Apocynin, an inhibitor of NADPH oxidase that suppresses intracellular reactive oxygen species, significantly suppressed TNF-α-induced IL-6 release and mRNA expression. However, apocynin failed to affect the phosphorylation of IκB, NFκB, p38 MAP kinase, SAPK/JNK or STAT3. Conclusion These results strongly suggest that TNF-α induces IL-6 synthesis through the JAK/STAT3 pathway in addition to p38 MAP kinase and SAPK/JNK in C6 glioma cells, and that phosphorylation of NFκB at Ser 536 and Ser 468, and NADPH oxidase are involved in TNF-α-stimulated IL-6 synthesis.</p

Mechanisms of tumor necrosis factor-alpha-induced interleukin-6 synthesis in glioma cells

BACKGROUND: Interleukin (IL)-6 plays a pivotal role in a variety of CNS functions such as the induction and modulation of reactive astrogliosis, pathological inflammatory responses and neuroprotection. Tumor necrosis factor (TNF)-α induces IL-6 release from rat C6 glioma cells through the inhibitory kappa B (IκB)-nuclear factor kappa B (NFκB) pathway, p38 mitogen-activated protein (MAP) kinase and stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK). The present study investigated the mechanism of TNF-α-induced IL-6 release in more detail than has previously been reported. METHODS: Cultured C6 cells were stimulated by TNF-α. IL-6 release from the cells was measured by an enzyme-linked immunosorbent assay, and the phosphorylation of IκB, NFκB, the MAP kinase superfamily, and signal transducer and activator of transcription (STAT)3 was analyzed by Western blotting. Levels of IL-6 mRNA in cells were evaluated by real-time reverse transcription-polymerase chain reaction. RESULTS: TNF-α significantly induced phosphorylation of NFκB at Ser 536 and Ser 468, but not at Ser 529 or Ser 276. Wedelolactone, an inhibitor of IκB kinase, suppressed both TNF-α-induced IκB phosphorylation and NFκB phosphorylation at Ser 536 and Ser 468. TNF-α-stimulated increases in IL-6 levels were suppressed by wedelolactone. TNF-α induced phosphorylation of STAT3. The Janus family of tyrosine kinase (JAK) inhibitor I, an inhibitor of JAK 1, 2 and 3, attenuated TNF-α-induced phosphorylation of STAT3 and significantly reduced TNF-α-stimulated IL-6 release. Apocynin, an inhibitor of NADPH oxidase that suppresses intracellular reactive oxygen species, significantly suppressed TNF-α-induced IL-6 release and mRNA expression. However, apocynin failed to affect the phosphorylation of IκB, NFκB, p38 MAP kinase, SAPK/JNK or STAT3. CONCLUSION: These results strongly suggest that TNF-α induces IL-6 synthesis through the JAK/STAT3 pathway in addition to p38 MAP kinase and SAPK/JNK in C6 glioma cells, and that phosphorylation of NFκB at Ser 536 and Ser 468, and NADPH oxidase are involved in TNF-α-stimulated IL-6 synthesis