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A 41-year-old woman was admitted to our hospital for epigastralgia. She had been admitted to another hospital for fundic gland polyposis (FGP) without any symptoms, and no malignancy had been noted in her previous endoscopy. However, a biopsy performed at our hospital revealed adenocarcinoma, and computed tomography (CT) revealed multiple liver and peritoneal metastases. We clinically suspected gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) and indicated genetic testing. The point mutation in exon 1B of APC was revealed. She was diagnosed with GAPPS with multiple liver metastases and underwent systemic chemotherapy. She has two older brothers who also have FGP. The same genomic mutation was observed in both brothers and their mother, and they were also diagnosed with GAPPS. The brothers underwent prophylactic laparoscopic total gastrectomy with D1 lymph-node dissection.

Stage IV Gastric/Esophagogastric junction cancer (G/EGJ) has an unfavorable prognosis and poor curability. In this study, we report the case of long-term survival after multidisciplinary treatments for advanced esophagogastric junction cancer. A 53-year-old male patient was diagnosed with HER2 positive advanced esophagogastric junction cancer and mediastinal and paraaortic lymph node metastasis. After systemic chemotherapy for 1 year, minimally invasive esophagectomy was conducted as conversion surgery. However, peritoneal and liver metastasis was observed on 3 months after curative surgery. 2 years after operation, solitary brain metastasis was detected and stereotactic radiosurgery (SRS) using a gamma knife was underwent. After 1 year, despite the continuous administration of Nivolumab, the paraaortic lymph node increased in size again and radiation therapy was conducted. Currently, he is alive and undergoing chemotherapy.

Background/aim Cervical oesophageal adenocarcinoma (COA) is extremely rare. We present a case of human epidermal growth factor receptor 2 (HER2)-positive COA that showed repeated recurrences despite multidisciplinary treatments. Case report A 49-year-old male was diagnosed with clinical stage IVA COA that originated from ectopic gastric mucosa. He initially underwent definitive chemoradiotherapy (CRT) (60.0 Gy/30 fractions, 5-fluorouracil, and cisplatin). Two months after CRT, the right supraclavicular lymph node (LN) reenlarged and salvage lymphadenectomy was performed. Immunohistochemical staining revealed a HER2-positive adenocarcinoma. Four months after lymphadenectomy, multiple metastases in the mediastinal LNs and lungs were detected, and S-1, oxaliplatin and trastuzumab were administered. Four months after chemotherapy, the patient presented with new liver metastasis. Further metastasis was prevented by Nivolumab treatment for four months. Conclusion HER2-positive COA may be more aggressive and may require further intensive treatments. This literature review may be helpful in determining treatment strategies for COA.

BACKGROUND: We report results of an internet-based field study evaluating the diagnostic guidelines for the newly introduced ICD-11 grouping of obsessive-compulsive and related disorders (OCRD). We examined accuracy of clinicians' diagnostic judgments applying draft ICD-11 as compared to the ICD-10 diagnostic guidelines to standardized case vignettes.METHODS: 1,717 mental health professionals who are members of the World Health Organization's Global Clinical Practice Network completed the study in Chinese, English, French, Japanese, Russian or Spanish. Participants were randomly assigned to apply ICD-11 or ICD-10 guidelines to one of nine pairs of case vignettes.RESULTS: Participants using ICD-11 outperformed those using ICD-10 in correctly identifying newly introduced OCRD, although results were mixed for differentiating OCRD from disorders in other groupings largely due to clinicians having difficulty differentiating challenging presentations of OCD. Clinicians had difficulty applying a three-level insight qualifier, although the 'poor to absent' level assisted with differentiating OCRD from psychotic disorders. Brief training on the rationale for an OCRD grouping did not improve diagnostic accuracy suggesting sufficient detail of the proposed guidelines.LIMITATIONS: Standardized case vignettes were manipulated to include specific characteristics; the degree of accuracy of clinicians' diagnostic judgments about these vignettes may not generalize to application in routine clinical practice.CONCLUSIONS: Overall, use of the ICD-11 guidelines resulted in more accurate diagnosis of case vignettes compared to the ICD-10 guidelines, particularly in differentiating OCRD presentations from one another. Specific areas in which the ICD-11 guidelines did not perform as intended provided the basis for further revisions to the guidelines.

Background This article reports the results of one of a series of global field studies implemented by the World Health Organization (WHO) to evaluate the accuracy, clinical utility, and global applicability of the new diagnostic guidelines for Mental, Behavioural and Neurological Disorders included in the next version of WHO's International Classification of Diseases (ICD-11). Aims of the study The purpose of this study was to compare the diagnostic accuracy and clinical utility ratings of global clinicians implementing the ICD-11 diagnostic guidelines for Anxiety and Fear-Related Disorders, relative to those applying ICD-10 guidelines. The study also aimed to identify elements of the guidelines that required further refinement or clarification. Methods 1840 global mental health professionals registered with WHO's Global Clinical Practice Network completed the study in one of six study languages. Participants were randomly assigned to apply either the ICD-11 or ICD-10 guidelines to diagnose standardized case vignettes, and to rate the clinical utility of their assigned guidelines. Results ICD-11's diagnostic accuracy and clinical utility were equivalent or superior to that of ICD-10. Global clinicians were significantly more accurate in diagnosing Generalized Anxiety Disorder, Specific Phobia and adult cases of Separation Anxiety Disorder when using ICD-11 and provided high clinical utility ratings for these disorders. Clinicians also found the ICD-11 guidelines easy to use, clear, and a good fit to patients they see in their clinical practice. However, clinicians had difficulty with distinguishing the boundary between disorder and normality for subthreshold cases of anxiety, and also with applying the new ICD-11 guidelines on panic attacks. Conclusions The new diagnostic guidelines for Anxiety Disorders in ICD-11 can be applied in an acceptably consistent manner by global clinicians and perform as well or better than the previous guidelines for ICD-10. Study findings also helped identify aspects of the ICD-11 guidelines that required refinement prior to their publication and areas that should be emphasized in training programs.

We examined the antiobesity effect of a limonoid 7-deacetoxy-7-oxogedunin, named CG-1, purified from the seeds of Carapa guianensis, Meliaceae, known as andiroba in high-fat-diet (HFD)-fed mice. C57BL/6 mice were fed a low-fat diet or an HFD and orally administered CG-1 (20 mg/kg) for 7 weeks. CG-1 lowered the body weight gain and improved the serum triglyceride level and insulin sensitivity in HFD-fed mice. The expression level of the adipogenesis-related genes was lowered by CG-1 in the visceral white adipose tissue (vWAT). The mRNA expression level of the macrophage-related genes decreased in vWAT following the administration of CG-1 to HFD-fed mice. It is noteworthy that CG-1 activated the brown adipose tissue (BAT) with enhanced expression of uncoupling protein 1 and increased the rectal temperature in HFD-fed mice. These results indicate that the limonoid CG-1 decreased body weight gain and ameliorated hypertriglyceridemia and insulin resistance with the activation of BAT in HFD-fed mice.

Polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) analysis was used to identify meat from biwa trout (Oncorhynchus masou rhodurus), amago trout (Oncorhynchus masou ishikawae), yamame trout (Oncorhynchus masou masou), and rainbow trout (Oncorhynchus mykiss). PCR amplification was conducted using primers flanking conserved regions of NADH dehydrogenase subunits 4 and 5 (ND4–ND5) (2848 bp) and ND1 (1091 bp) genes of mitochondrial DNA following restriction digestion with the enzyme HaeIII. Although the segments of ND4–ND5 and ND1 genes showed intraspecies variation, the generation of DNA fragments larger than 300 bp and 160 bp following cleavage by HaeIII of ND4–ND5 and ND1, respectively, was efficient to differentiate the four species. Furthermore, this method was successful in species identification even when using PCR-amplified products obtained from thermally processed biwa trout samples. This sensitive technique can be utilized to reveal commercial fraud, where biwa trout is adulterated with meat from cheaper counterparts.

Background We report results of an internet-based field study evaluating the diagnostic guidelines for ICD-11 mood disorders. Accuracy of clinicians' diagnostic judgments applying draft ICD-11 as compared to the ICD-10 guidelines to standardized case vignettes was assessed as well as perceived clinical utility. Methods 1357 clinician members of the World Health Organization's Global Clinical Practice Network completed the study in English, Spanish, Japanese or Russian. Participants were randomly assigned to apply ICD-11 or ICD-10 guidelines to one of eleven pairs of case vignettes. Results Clinicians using the ICD-11 and ICD-10 guidelines achieved similar levels of accuracy in diagnosing mood disorders depicted in vignettes. Those using the ICD-11 were more accurate in identifying depressive episode in recurrent depressive disorder. There were no statistically significant differences detected across classifications in the accuracy of identifying dysthymic or cyclothymic disorder. Circumscribed problems with the proposed ICD-11 guidelines were identified including difficulties differentiating bipolar type I from bipolar type II disorder and applying revised severity ratings to depressive episodes. Clinical utility of ICD-11 bipolar disorders was found to be significantly lower than for ICD-10 equivalent categories. Limitations Standardized case vignettes were manipulated to evaluate specific changes. The degree of accuracy of clinicians' diagnostic judgments may not reflect clinical decision-making with patients. Conclusions Alignment of the ICD-11 with current research appears to have been achieved without sacrificing diagnostic accuracy or clinical utility though specific training may be necessary as ICD-11 is implemented worldwide. Areas in which the ICD-11 guidelines did not perform as intended resulted in further revisions.

Intimate partner violence (IPV) is a serious public health problem associated with increased risk of developing mental health conditions. Assessment of IPV in mental health settings is important for appropriate treatment planning and referral; however, lack of training in how to identify and respond to IPV presents a significant barrier to assessment. To address this issue, the World Health Organization (WHO) advanced a series of evidence-based recommendations for IPV-related training programs. This study examines the relationship between mental health professionals’ experiences of IPV-related training, including the degree to which their training resembles WHO training recommendations, and their accuracy in correctly identifying relationship problems. Participants were psychologists and psychiatrists ( N = 321) from 24 countries who agreed to participate in an online survey in French, Japanese, or Spanish. They responded to questions regarding their IPV-related training (i.e., components and hours of training) and rated the presence or absence of clinically significant relationship problems and maltreatment (RPM) and mental disorders across four case vignettes. Participants who received IPV-related training, and whose training was more recent and more closely resembled WHO training recommendations, were more likely than those without training to accurately identify RPM when it was present. Clinicians regardless of IPV-related training were equally likely to misclassify normative couple issues as clinically significant RPM. Findings suggest that IPV-related training assists clinicians in making more accurate assessments of patients presenting with clinically significant relationship problems, including IPV. These data inform recommendations for IPV-related training programs and suggest that training should be repeated, multicomponent, and include experiential training exercises, and guidelines for distinguishing normative relationship problems from clinically significant RPM.

Intimate partner violence (IPV) is a global public health problem that has been shown to lead to serious mental health consequences. Due to its frequent co-occurrence with psychiatric disorders, it is important to assess for IPV in mental health settings to improve treatment planning and referral. However, lack of training in how to identify and respond to IPV has been identified as a barrier for the assessment of IPV. The present study seeks to better understand this IPV-related training gap by assessing global mental health professionals’ experiences of IPV-related training and factors that contribute to their likelihood of receiving training. Participants were French-, Spanish-, and Japanese-speaking psychologists and psychiatrists ( N = 321) from 24 nations differing on variables related to IPV, including IPV prevalence, IPV-related norms, and IPV-related laws. Participants responded to an online survey asking them to describe their experiences of IPV-related training (i.e., components and hours of training) and were asked to rate the frequency with which they encountered IPV in clinical practice and their level of knowledge and experience related to relationship problems; 53.1% of participants indicated that they had received IPV-related training. Clinicians from countries with relatively better implemented laws addressing IPV and those who encountered IPV more often in their regular practice were more likely to have received training. Participants who had received IPV-related training, relative to those without training, were more likely to report greater knowledge and experience related to relationship problems. Findings suggest that clinicians’ awareness of IPV and the institutional context in which they practice are related to training. Training, in turn, is associated with subjective appraisals of knowledge and experience related to relationship problems. Increasing institutional efforts to address IPV (e.g., implementing IPV legislation) may contribute to improved practices with regard to IPV in mental health settings.

Metastases to the kidney are extremely rare and intrahepatic cholangiocarcinoma (ICC) is difficult to treat. In this study, we report a case of renal metastasis from ICC. A 72-year-old man who had been followed-up for chronic hepatitis C was diagnosed with ICC in the segment 8 and underwent S8 segmentectomy in 2014. During follow-up, the serum levels of carcinoembryonic antigen and carbohydrate antigen 19-9 were slightly elevated, and abdominal contrast-enhanced computed tomography revealed a low-density mass preceded by rim enhancement in the arterial phase measuring 1.5 × 1.5 cm in the segment 6, and a hypovascular mass measuring 2.2 × 2.0 cm in the upper pole of the left kidney in 2017. He underwent partial hepatectomy and partial nephrectomy. Based on postoperative histological findings combined with immunohistochemical analysis, the tumors both in the liver and kidney were diagnosed as recurrent ICC.

Background The gastrointestinal tract can occasionally be perforated or penetrated by an ingested foreign body, such as a fish bone. However, there are very few reported cases in which an ingested fish bone penetrated the gastrointestinal tract and was embedded in the pancreas. Case presentation An 80-year-old male presented with epigastric pain. Computed tomography of the abdomen showed a linear, hyperdense, foreign body that penetrated through the posterior wall of the gastric antrum. There was no evidence of free air, abscess formation, migration of the foreign body into the pancreas, or pancreatitis. As the patient had a history of fish bone ingestion, we made a diagnosis of localized peritonitis caused by fish bone penetration of the posterior wall of the gastric antrum. We first attempted to remove the foreign body endoscopically, but failed because it was not detected. Hence, an emergency laparoscopic surgery was performed. A linear, hard, foreign body penetrated through the posterior wall of the gastric antrum and was embedded in the pancreas. The foreign body was safely removed laparoscopically and was identified as a 2.5-cm-long fish bone. Intraperitoneal lavage was performed, and a drain was placed in the lesser sac. The patient recovered without complications and was discharged on the 7th postoperative day. Conclusion Laparoscopic surgery could be performed safely for the removal of an ingested fish bone embedded in the pancreas.

Reliable, clinically useful, and globally applicable diagnostic classification of mental disorders is an essential foundation for global mental health. The World Health Organization (WHO) is nearing completion of the 11th revision of the International Classification of Diseases and Related Health Problems (ICD‐11). The present study assessed inter‐diagnostician reliability of mental disorders accounting for the greatest proportion of global disease burden and the highest levels of service utilization – schizophrenia and other primary psychotic disorders, mood disorders, anxiety and fear‐related disorders, and disorders specifically associated with stress – among adult patients presenting for treatment at 28 participating centers in 13 countries. A concurrent joint‐rater design was used, focusing specifically on whether two clinicians, relying on the same clinical information, agreed on the diagnosis when separately applying the ICD‐11 diagnostic guidelines. A total of 1,806 patients were assessed by 339 clinicians in the local language. Intraclass kappa coefficients for diagnoses weighted by site and study prevalence ranged from 0.45 (dysthymic disorder) to 0.88 (social anxiety disorder) and would be considered moderate to almost perfect for all diagnoses. Overall, the reliability of the ICD‐11 diagnostic guidelines was superior to that previously reported for equivalent ICD‐10 guidelines. These data provide support for the suitability of the ICD‐11 diagnostic guidelines for implementation at a global level. The findings will inform further revision of the ICD‐11 diagnostic guidelines prior to their publication and the development of programs to support professional training and implementation of the ICD‐11 by WHO member states.

We report on a global survey of diagnosing mental health professionals, primarily psychiatrists, conducted as a part of the development of the ICD-11 mental and behavioural disorders classification. The survey assessed these professionals' use of various components of the ICD-10 and the DSM, their attitudes concerning the utility of these systems, and usage of "residual" (i.e., "other" or "unspecified") categories. In previous surveys, most mental health professionals reported they often use a formal classification system in everyday clinical work, but very little is known about precisely how they are using those systems. For example, it has been suggested that most clinicians employ only the diagnostic labels or codes from the ICD-10 in order to meet administrative requirements. The present survey was conducted with clinicians who were members of the Global Clinical Practice Network (GCPN), established by the World Health Organization as a tool for global participation in ICD-11 field studies. A total of 1,764 GCPN members from 92 countries completed the survey, with 1,335 answering the questions with reference to the ICD-10 and 429 to the DSM (DSM-IV, DSM-IV-TR or DSM-5). The most frequent reported use of the classification systems was for administrative or billing purposes, with 68.1% reporting often or routinely using them for that purpose. A bit more than half (57.4%) of respondents reported often or routinely going through diagnostic guidelines or criteria systematically to determine whether they apply to individual patients. Although ICD-10 users were more likely than DSM-5 users to utilize the classification for administrative purposes, other differences were either slight or not significant. Both classifications were rated to be most useful for assigning a diagnosis, communicating with other health care professionals and teaching, and least useful for treatment selection and determining prognosis. ICD-10 was rated more useful than DSM-5 for administrative purposes. A majority of clinicians reported using "residual" categories at least sometimes, with around 12% of ICD-10 users and 19% of DSM users employing them often or routinely, most commonly for clinical presentations that do not conform to a specific diagnostic category or when there is insufficient information to make a more specific diagnosis. These results provide the most comprehensive available information about the use of diagnostic classifications of mental disorders in ordinary clinical practice.

Limonoids are phytochemicals with a variety of biological properties. In the present study, we elucidated the molecular mechanism of suppression of adipogenesis in adipocytes by a limonoid, 7-deacetoxy-7-oxogedunin (CG-1) from Carapa guianensis (Meliaceae), known as andiroba. CG-1 reduced the accumulation of intracellular triglycerides in a concentration-dependent manner. The expression levels of the adipogenic, lipogenic, and lipolytic genes were decreased by CG-1 treatment, whereas the glycerol release level was not affected. When CG-1 was added into the medium during days 0-2 of 6-days-adipogenesis, the accumulation of intracellular lipids and the mRNA levels of the adipogenesis-related genes were decreased. In addition, the phosphorylation level of insulin receptor substrate-1 (IRS-1) and Akt in the early phase of adipocyte differentiation (within 1 day after initiating adipocyte differentiation) was reduced by CG-1. Furthermore, insulin-activated translocation of glucose transporter 4 to the plasma membranes in adipocytes was suppressed by CG-1, followed by decreased glucose uptake into the cells. These results indicate that an andiroba limonoid CG-1 suppressed the accumulation of intracellular lipids in the early phase of adipocyte differentiation through repression of IRS-1/Akt-mediated glucose uptake in adipocytes.

Background The World Health Organization (WHO) International Classification of Diseases and Related Health Problems (ICD) is used globally by 194 WHO member nations. It is used for assigning clinical diagnoses, providing the framework for reporting public health data, and to inform the organization and reimbursement of health services. Guided by overarching principles of increasing clinical utility and global applicability, the 11th revision of the ICD proposes major changes that incorporate empirical advances since the previous revision in 1992. To test recommended changes in the Mental, Behavioral, and Neurodevelopmental Disorders chapter, multiple vignette-based case-controlled field studies have been conducted which examine clinicians’ ability to accurately and consistently use the new guidelines and assess their overall clinical utility. This manuscript reports on the results from the study of the proposed ICD-11 guidelines for feeding and eating disorders (FEDs). Method Participants were 2288 mental health professionals registered with WHO’s Global Clinical Practice Network. The study was conducted in Chinese, English, French, Japanese, and Spanish. Clinicians were randomly assigned to apply either the ICD-11 or ICD-10 diagnostic guidelines for FEDs to a pair of case vignettes designed to test specific clinical questions. Clinicians selected the diagnosis they thought was correct for each vignette, evaluated the presence of each essential feature of the selected diagnosis, and the clinical utility of the diagnostic guidelines. Results The proposed ICD-11 diagnostic guidelines significantly improved accuracy for all FEDs tested relative to ICD-10 and attained higher clinical utility ratings; similar results were obtained across all five languages. The inclusion of binge eating disorder and avoidant-restrictive food intake disorder reduced the use of residual diagnoses. Areas needing further refinement were identified. Conclusions The proposed ICD-11 diagnostic guidelines consistently outperformed ICD-10 in distinguishing cases of eating disorders and showed global applicability and appropriate clinical utility. These results suggest that the proposed ICD-11 guidelines for FEDs will help increase accuracy of public health data, improve clinical diagnosis, and enhance health service organization and provision. This is the first time in the revision of the ICD that data from large-scale, empirical research examining proposed guidelines is completed in time to inform the final diagnostic guidelines.

A major goal for the revision of the International Classification of Diseases and Related Health Problems, Tenth Edition (ICD-10) is to increase the clinical utility of the diagnostic system. Schizoaffective disorder has a history of poor diagnostic reliability due to the similarities and overlap in symptoms that it shares with other disorders, especially primary psychotic and mood disorders. The present study was part of the case-controlled field trials for ICD-11 and examines how the proposed changes for schizoaffective disorder may improve differential diagnosis and diagnostic accuracy. Clinicians from around the globe (n = 873) were provided with either ICD-10 or ICD-11 diagnostic guidelines and asked to apply them to case vignettes comparing schizoaffective disorder to schizophrenia and mood disorders with psychotic symptoms. Participants were asked to respond to follow-up diagnostic questions to determine which components of the diagnostic guidelines affected diagnostic accuracy. Overall, clinicians showed small improvements in accurately diagnosing vignettes using ICD-11 over ICD-10. Results suggest the discrepancy in diagnosing schizoaffective disorder is related primarily to the presence of mood symptoms and discrepancies about whether those symptoms are more consistent with schizoaffective disorder or a mood disorder diagnosis. Continuing to identify ways to more accurately capture this symptom picture will be important in the future as well as systematic efforts to educate clinicians about differential diagnosis.

Following approval of the ICD‐11 by the World Health Assembly in May 2019, World Health Organization (WHO) member states will transition from the ICD‐10 to the ICD‐11, with reporting of health statistics based on the new system to begin on January 1, 2022. The WHO Department of Mental Health and Substance Abuse will publish Clinical Descriptions and Diagnostic Guidelines (CDDG) for ICD‐11 Mental, Behavioural and Neurodevelopmental Disorders following ICD‐11’s approval. The development of the ICD‐11 CDDG over the past decade, based on the principles of clinical utility and global applicability, has been the most broadly international, multilingual, multidisciplinary and participative revision process ever implemented for a classification of mental disorders. Innovations in the ICD‐11 include the provision of consistent and systematically characterized information, the adoption of a lifespan approach, and culture‐related guidance for each disorder. Dimensional approaches have been incorporated into the classification, particularly for personality disorders and primary psychotic disorders, in ways that are consistent with current evidence, are more compatible with recovery‐based approaches, eliminate artificial comorbidity, and more effectively capture changes over time. Here we describe major changes to the structure of the ICD‐11 classification of mental disorders as compared to the ICD‐10, and the development of two new ICD‐11 chapters relevant to mental health practice. We illustrate a set of new categories that have been added to the ICD‐11 and present the rationale for their inclusion. Finally, we provide a description of the important changes that have been made in each ICD‐11 disorder grouping. This information is intended to be useful for both clinicians and researchers in orienting themselves to the ICD‐11 and in preparing for implementation in their own professional contexts.

ErbB4 is the protein implicated in familial amyotrophic lateral sclerosis (ALS), designated as ALS19. ErbB4 is a receptor tyrosine kinase activated by its ligands, neuregulins (NRG), and plays an essential role in the function and viability of motor neurons. Mutations in the ALS19 gene lead to the reduced autophosphorylation capacity of the ErbB4 protein upon stimulation with NRG-1, suggesting that the disruption of the NRG-ErbB4 pathway causes motor neuron degeneration. We used immunohistochemistry to study ErbB4 in the spinal cord of patients with sporadic ALS (SALS) to test the hypothesis that ErbB4 may be involved in the pathogenesis of SALS. ErbB4 was specifically immunoreactive in the cytoplasm of motor neurons in the anterior horns of the spinal cord. In patients with SALS, some of the motor neurons lost immunoreactivity with ErbB4, with the proportion of motor neurons with a loss of immunoreactivity correlated with the severity of motor neuron loss. The subcellular localization was altered, demonstrating nucleolar or nuclear localization, threads/dots and spheroids. The ectopic glial immunoreactivity was observed, mainly in the oligodendrocytes of the lateral columns and anterior horns. The reduction in the ErbB4 immunoreactivity was significantly correlated with the cytoplasmic mislocalization of transactivation response DNA-binding protein 43 kDa (TDP-43) in the motor neurons. No alteration in immunoreactivity was observed in the motor neurons of mice carrying atransgene for mutant form of the superoxide dismutase 1 gene (SOD1). This study provided compelling evidence that ErbB4 is also involved in the pathophysiology of SALS, and that the disruption of the NRG-ErbB4 pathway may underlie the TDP-43-dependent motor neuron degeneration in ALS.

Gastric cancer during pregnancy is extremely rare and difficult to diagnose at early stages because of its nature. Furthermore, it is often difficult to determine the appropriate treatment strategy considering both the patient's condition and the effect of the treatment on the fetus. We present a case of a 34-year-old woman with gastric cancer who was 22 weeks pregnant and had multiple liver and bone metastases at the time of diagnosis. The disease progressed to disseminated carcinomatosis of the bone marrow, in which cancer invades and spreads diffusely to the bone marrow and then presents disseminated intravascular coagulation. Fortunately, the selected systematic chemotherapy dramatically reduced the severity of the patient's cancer and she could deliver her baby successfully. There are few reports of disseminated carcinomatosis of the bone marrow from gastric cancer during pregnancy. Even in such an oncological emergency, prompt chemotherapy saved the mother's life and enabled safe delivery of the fetus.

Schizophrenia is a common disease with a prevalence rate of 1 %. Worldwide, roughly 24 million people suffer from it. The condition, initially coined “dementia praecox” by Kraepelin, was later termed “schizophrenie (schizophrenia)” by Bleuler, and the name has been used for over a century. In recent years, however, there has been a discussion whether schizophrenia, the disorder label, should be reconsidered.

Objective To explore the rationales of mental health professionals (mainly psychiatrists and psychologists) from 8 countries for removing specific diagnostic categories from mental disorders classification systems. Method As part of a larger study, 505 participants indicated which of 60 major disorders should be omitted from mental disorders classification systems and provided rationales. Rationale statements were analyzed using inductive content analysis. Results The majority of clinicians (60.4%) indicated that 1 or more disorders should be removed. The most common rationales were (a) problematic boundaries between normal and psychopathological conditions (45.9% of total removal recommendations), (b) problematic boundaries among mental disorders (25.4%), and (c) problematic boundaries between mental and physical disorders (24.0%). The categories most frequently recommended for deletion were gender identity disorder, sexual dysfunction, and paraphilias, usually because clinicians viewed these categories as being based on stigmatization of a way of being and behaving. A range of neurocognitive disorders were described as better conceptualized as nonpsychiatric medical conditions. Results were analyzed by country and country income level. Although gender identity disorder was the category most frequently recommended for removal overall, clinicians from Spain, India, and Mexico were most likely to do so and clinicians from Nigeria and Japan least likely, probably because of social and systemic factors that vary by country. Systematic differences in removal rationales by country income level may be related to the development, structure, and functioning of health systems. Conclusion Implications for development and dissemination of the classification of mental and behavioral disorders in WHO's ICD-11 are discussed.

The cricket (Gryllus bimaculatus) is a hemimetabolous insect that is emerging as a model organism for the study of neural and molecular mechanisms of behavioral traits. However, research strategies have been limited by a lack of genetic manipulation techniques that target the nervous system of the cricket. The development of a new method for efficient gene delivery into cricket brains, using in vivo electroporation, is described here. Plasmid DNA, which contained an enhanced green fluorescent protein (eGFP) gene, under the control of a G. bimaculatus actin (Gb'-act) promoter, was injected into adult cricket brains. Injection was followed by electroporation at a sufficient voltage. Expression of eGFP was observed within the brain tissue. Localized gene expression, targeted to specific regions of the brain, was also achieved using a combination of local DNA injection and fine arrangement of the electroporation electrodes. Further studies using this technique will lead to a better understanding of the neural and molecular mechanisms that underlie cricket behaviors.

Objective To examine the conceptualizations held by psychiatrists and psychologists around the world of the relationships among mental disorders in order to inform decisions about the structure of the classification of mental and behavioral disorders in World Health Organization's International Classification of Diseases and Related Health Problems 11th Revision (ICD-11). Method 517 mental health professionals in 8 countries sorted 60 cards containing the names of mental disorders into groups of similar disorders, and then formed a hierarchical structure by aggregating and disaggregating these groupings. Distance matrices were created from the sorting data and used in cluster and correlation analyses. Results Clinicians’ taxonomies were rational, interpretable, and extremely stable across countries, diagnostic system used, and profession. Clinicians’ consensus classification structure was different from ICD-10 and the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders 4th Edition (DSM-IV), but in many respects consistent with ICD-11 proposals. Conclusions The clinical utility of the ICD-11 may be improved by making its structure more compatible with the common conceptual organization of mental disorders observed across diverse global clinicians.

The 3q27 and 18q21 chromosomal translocations are major hallmarks in B-cell lymphoma. We aimed to determine the frequencies of these translocations in follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) and to evaluate their prognostic impact in the rituximab era. This study included 98 FL and 93 DLBCL patients whose abnormal karyotypes had been detected using G-banding. Patients uniformly underwent R-CHOP therapy : doxorubicin, cyclophosphamide, vincristine, prednisolone, and rituximab ; survivors were followed up for 29 months (median). The 3q27 and 18q21 translocations were detected in 14 and 77 FL patients and 14 and 22 DLBCL patients, respectively. Overall survival (OS) and progression-free survival (PFS) did not differ significantly between the groups with 3q27, 18q21, concurrent 3q27 and 18q21 translocations, and other chromosomal abnormalities for FL and DLBCL. There were no significant differences in OS and PFS between patients with 3q27 translocation-positive FL and those with 3q27 translocation-positive DLBCL or between the patients with 18q21 translocation-positive FL and those with 18q21 translocation-positive DLBCL. The presence of 3q27 and 18q21 translocations did not correlate with the clinical outcomes of FL or DLBCL patients following R-CHOP treatment. 〔J Clin Exp Hematop 53(2) : 107-114, 2013〕

Spinocerebellar degeneration (SCD) is a group of disorders characterized by progressive ataxia caused by dysfunction and atrophy of the cerebellum or its projections. Approximately one-third of SCD cases are familial SCD, the majority of which are attributed to CAG triplet repeat expansions including spinocerebellar ataxia (SCA)1, SCA2, Machado-Joseph disease (MJD)/SCA3, SCA6, SCA8, SCA12, SCA17, and dentate-rubro-pallido-luysian atrophy (DRPLA). The triplet repeat number of the alleles representing complete penetrance varies among diseases. Generally, there is a gap between the normal alleles and the complete penetrance alleles. Rarely, intermediate alleles with the repeat numbers between the abnormal and normal ranges are observed, although the implications of these intermediate alleles remain ambiguous.

Schizophrenia is a common disease with a prevalence rate of 1 %. Worldwide, roughly 24 million people suffer from it. The condition, initially coined “dementia praecox” by Kraepelin, was later termed “schizophrenie (schizophrenia)” by Bleuler, and the name has been used for over a century. In recent years, however, there has been a discussion whether schizophrenia, the disorder label, should be reconsidered.

As part of the development of the Eleventh Revision of International Classification of Diseases and Related Health Problems (ICD-11), the World Health Organization Department of Mental Health and Substance Abuse is conducting a series of case-controlled field studies using a new and powerful method to test the application by clinicians of the proposed ICD-11 diagnostic guidelines for mental and behavioural disorders. This article describes the case-controlled field study for Disorders Specifically Associated with Stress. Using a vignette-based experimental methodology, 1,738 international mental health professionals diagnosed standardized cases designed to test key differences between the proposed diagnostic guidelines for ICD-11 and corresponding guidelines for ICD-10. Across eight comparisons, several proposed changes for ICD-11, including the addition of Complex PTSD and Prolonged Grief Disorder, produced significantly improved diagnostic decisions and clearer application of diagnostic guidelines compared to ICD-10. However, several key areas were also identified, such as the description of the diagnostic requirement of re-experiencing in PTSD, in which the guidelines were not consistently applied as intended. These results informed specific revisions to improve the clarity of the proposed ICD-11 diagnostic guidelines. The next step will be to further test these guidelines in clinic-based studies using real patients in relevant settings.Como parte del desarrollo de la onceava versión de la Clasificación Internacional de Enfermedades y Problemas de Salud Relacionados (CIE-11), la Organización Mundial de la Salud está conduciendo una serie de estudios de campo de casos controlados utilizando un novedoso y potente método para evaluar la aplicación por parte de clínicos de las guías diagnósticas para los trastornos mentales y del comportamiento. Este artículo describe el estudio de campo de casos controlados para los Trastornos específicamente relacionados con el estrés. Con base en una metodología experimental de viñetas, 1.738 profesionales de la salud mental diagnosticaron casos estandarizados específicamente diseñados para evaluar diferencias clave entre las guías propuestas para la CIE-11 y las que les corresponden en la CIE-10. Diversos cambios propuestos para la CIE-11, incluyendo la adición del TEPT complejo y del Trastorno por duelo prolongado, produjeron mejores decisiones diagnósticas en comparación con la versión previa del manual. Sin embargo, se identificaron también áreas en las que las guías no se aplicaron de manera consistente, como el requisito diagnóstico de re-experimentación para el TEPT, lo que informó revisiones específicas para mejorar las guías diagnósticas, que serán evaluadas en futuros estudios basados en la clínica con pacientes reales en escenarios relevantes.

In this paper, we discuss avoidant personality disorder and its complexities by presenting a case in which the differential diagnosis was extremely difficult. The presented case concerns a patient, who initially received the diagnosis of ‘Taijin kyofusho’, a diagnosis commonly made in the traditional psychiatry in Japan, and later, his diagnosis was changed to avoidant personality disorder as the DSM-III gained popularity. His chief complaint was his concern over his odour from his genitourinary organs, which led him to avoid interpersonal relationships. During the course of illness, his concern over his body odour and appearance grew to the extent that he sought surgical treatment, but he managed to succeed in his business. Currently, he is being treated with the medium dose of selective serotonin reuptake inhibitors in addition to psychotherapy, but his symptoms concerning interpersonal relationships still remain. Many symptoms other than typical ones of avoidant personality disorder were observed, and other psychiatric diagnoses, including delusional disorder, somatization disorder, and body dysmorphic disorder, were considered for differential diagnosis. Although they were ruled out in light of the criteria in the current diagnostic classification, this case illustrates the complex nature of the diagnosis of avoidant personality disorder, and furthermore, of psychiatric diagnoses. Copyright © 2012 John Wiley & Sons, Ltd.

We newly diagnosed 131 patients with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue lymphoma between 1998 and 2010. We retrospectively studied 124 patients for whom complete clinical data were available at presentation and who had minimally undergone tumour staging by physical examination, computed tomography (CT), bone marrow aspiration, and biopsy. A slight female predominance (men, 58; women, 66) was observed in the study population; the median age was 67 years. The primary locations at presentation were the stomach (38%), orbita (20%), lung (12%), intestinal tract (8%), thyroid gland (6%), others (14%), and unknown (2%). Seventy per cent of patients had localized disease. Of the 124 patients, 14 (11%) had lymph node involvement, and 5 (4%) had bone marrow involvement. Five (4%) patients had both lung and gastric involvement. The 5-year overall survival rate for the 124 patients was 96.1%. The overall vital prognosis was excellent. Moreover, gastro-intestinal fiberscopic examination is essential, especially in cases with lung involvement at presentation.

We retrospectively analysed 16 cases of newly diagnosed pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma in the Japanese population. The disease was found on the basis of examination findings in 14 cases, and clinical manifestations in 2. According to the extensive staging procedure, four patients had concomitant gastric involvement. Primary treatment involved surgery alone in two patients; surgery followed by rituximab (R)-containing chemotherapy in two; R-containing chemotherapy alone in 11; and chemoradiotherapy without R in one. Over the median observation period of 28 months, disease progression was recorded in three patients, but all 16 patients were alive at the end of the observation period. One patient was treated with R alone and achieved partial remission; subsequent tentative surgery showed no evidence of residual lymphoma. It has been 72 months of progression-free survival after the diagnosis. Primary pulmonary MALT lymphoma exhibited an indolent clinical course. R has potential as a therapeutic agent in patients with pulmonary MALT lymphoma. Copyright © 2012 John Wiley & Sons, Ltd.

Primary hepatic lymphoma is a very rare condition, and the majority of the cases reported are of B-cell origin. We report a case of a 65-year-old man with primary hepatic peripheral T-cell lymphoma, not otherwise specified (PTCL-nos) who presented with 15% weight loss and general fatigue over the previous 9 months. Imaging studies and bone marrow examination could not confirm a diagnosis of lymphoma. Liver biopsy was performed because of an elevated soluble interleukin-2 receptor (sIL-2R) level (17,000 U/I) and hepatomegaly. After the diagnosis of primary hepatic PTCL-nos, treatment with low-dose corticosteroid was initiated, and the sIL-2R level decreased. Discontinuation of corticosteroid treatment resulted in the re-elevation of the sIL-2R level, and subsequently, treatment with low-dose corticosteroid was reinitiated. The sIL-2R level decreased rapidly, and the patient is alive with no evidence of lymphoma for 50 months after diagnosis. Thus, we found that a low-dose corticosteroid was effective in the long-term control of the disease, whereas many previous studies reported that primary hepatic PTCL-nos has a poor prognosis.

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It is controversial whether the STN or the GPi, the main targets of DBS therapy in patients with Parkinson's disease, is the appropriate target. We select GPi-DBS in patients judged by our cognitive function test battery to be at high-risk for cognitive decline after STN-DBS. While DBS surgery is usually performed under local anesthesia for the precise placement of DBS electrodes, general anesthesia might be useful in patients intolerant of long-lasting surgical stress. Our monkey experiments revealed that the most medial part of the STN receives direct input from the limbic cortex, suggesting that the spread of stimulation to these limbic territories may elicit adverse emotional effects. Other monkey experiments on the physiological mechanism of DBS suggest that high-frequency GPi stimulation disrupts information flow through the GPi.

In insects, cholinergic neurons are thought to transmit olfactory conditioned stimulus (CS) to the sites for associating the CS with unconditioned stimulus (US), but the types of acetylcholine (ACh) receptor used by neurons participating in the association have not been determined. In cockroaches, a type of nicotinic ACh receptor specifically antagonized by mecamylamine (MEC) has been characterized. Here we investigated the roles of neurons possessing MEC-sensitive ACh receptors (MEC-sensitive neurons) in olfactory conditioning of salivation, monitored by changes in activities of salivary neurons, in cockroaches. Local and bilateral microinjection of MEC into each of the three olfactory centers, antennal lobes, calyces of the mushroom bodies and lateral protocerebra, impaired olfactory responses of salivary neurons, indicating that MEC-sensitive neurons in all olfactory centers participate in pathways mediating olfactory responses of salivary neurons. Conditioning of olfactory CS with sucrose US was impaired by injection of MEC into the antennal lobes or calyces, i.e., conditioned responses were absent even after recovery from MEC injection, suggesting that the CS-US association occurs in MEC-sensitive neurons in calyces (most probably Kenyon cells) or in neurons in downstream pathways. In contrast, conditioned responses appeared after recovery from MEC injection into the lateral protocerebra, suggesting that MEC-sensitive neurons in the lateral protocerebra are downstream of the association sites. Since lateral protocerebra are major termination areas of mushroom body efferent neurons, we suggest that input synapses of MEC-sensitive Kenyon cells, or their output synapses upon mushroom body efferent neurons, are the sites for CS-US association for conditioning of salivation.

Introduction Some psychiatric diagnoses are stigmatizing. In August of 2002, the Japanese Society of Psychiatry and Neurology decided to change the name of schizophrenia in Japanese from seishinbunretsu-byo (‘split mind disease’) to togoshitcho-sho (‘loss of coordination disorder’). The objective of the present study was to investigate whether there was the same movement internationally or not, and how the experts in different countries thought about the term ‘schizophrenia’. Methods To attempt to gain insight into the thinking concerning this point among international psychiatric authorities, we conducted a survey in 2010. This questionnaire was sent to members of the Section on Schizophrenia of the World Psychiatric Association, the European Psychiatric Association and schizophrenia experts of the Asian Federation of Psychiatric Associations via email. The mean years of the respondents' experiences as psychiatrists was 18.6 years (SD; 10.1). Results 65% of respondents said that the term “schizophrenia” was not an appropriate term, and 89% replied that it denoted stigma. In addition, 67% replied that “schizophrenia” should be renamed to another term and 59% replied that the new name should convey acceptable scientific concept about the disorder. Conclusion The results of this survey were obtained from only 46 experts, although they were from throughout the world. However, we believe that now is the time to think whether the term “schizophrenia” should be changed or not, considering that the release dates of the ICD-11 and DSM-5 are approaching.