Search

Background With the increase in life expectancy and the subsequent increase in the older population, the clinical importance of late-onset psychosis also increases. Neuropathological findings play an important role in the differential diagnosis of dementing disorders in older adults. Herein, we report a case of late-onset schizophrenia that required differentiation from a dementing disorder. Case presentation: The patient was an 83-year-old woman who had experienced auditory hallucinations since she was 67 years old. She was hospitalized for treatment of her psychosis. Initially, various examinations were performed to consider the possibility that she had a dementing disorder such as dementia with Lewy bodies. 123I-meta-iodobenzylguanidine myocardial scintigraphy revealed no decrease in iodine accumulation in the myocardium, and 123I-ioflupane dopamine transporter imaging revealed no decrease in dopamine transporter accumulation in the striatum. The patient had an elevated concentration of total tau (488 pg/mL), a cerebrospinal fluid biomarker. After comprehensive testing, the patient was diagnosed with late-onset schizophrenia. Her psychiatric symptoms such as auditory hallucinations diminished after the administration of the recommended first-line drug risperidone (3 mg/day), and she was discharged on day 90. Conclusions This case was identified as late-onset schizophrenia. However, an elevated total tau concentration was observed, indicating that neurofibrillary tangles and neuronal death, which are characteristic of Alzheimer 's disease, may also have been present. Late-onset schizophrenia should be treated based on an appropriate differential diagnosis, including neuropathological consideration of dementing disorders.

Methylmercury (MeHg), an environmental toxicant, induces neuronal cell death and injures specific areas of the brain. MeHg is known to induce oxidative and endoplasmic reticulum (ER) stress. The unfolded protein response (UPR) pathway has a dual nature in that it regulates and protects cells from an overload of improperly folded proteins in the ER, whereas excessively stressed cells are eliminated by apoptosis. Oxidative stress/ER stress induced by methylmercury exposure may tilt the UPR toward apoptosis, but there is little in vivo evidence of a direct link to actual neuronal cell death. Here, by using the ER stress-activated indicator (ERAI) system, we investigated the time course signaling alterations of UPR in vivo in the most affected areas, the somatosensory cortex and striatum. In the ERAI-Venus transgenic mice exposed to MeHg (30 or 50 ppm in drinking water), the ERAI signal, which indicates the activation of the cytoprotective pathway of the UPR, was only transiently enhanced, whereas the apoptotic pathway of the UPR was persistently enhanced. Furthermore, detailed analysis following the time course showed that MeHg-induced apoptosis is strongly associated with alterations in UPR signaling. Our results suggest that UPR modulation could be a therapeutic target for treating neuropathy.

The epidermal growth factor receptor (EGFR) is the most extensively examined receptor tyrosine kinase. Several EGFR mutations and modifications have been shown to induce self-activation, which plays a central role in carcinogenesis. Recently, environmental chemicals such as PM2.5 can also activate EGFR and become risk factors for cancer. Although, the detailed mechanism remains unknown. In this study, we focused on 1,2-naphthoquinone (1,2-NQ) which is a secondary metabolite of naphthalene. Humans are exposed to 1,2-NQ through the combustion of fossil and diesel fuel and from tobacco smoke and PM2.5. Here, we demonstrate that 1,2-NQ is a novel EGFR-specific activator. We found that 1,2-NQ forms a covalent bond called N-arylation with EGFR Lys80 which is in the extracellular domain by LC-MS/MS. This modification activates the EGFR-Akt signaling pathway, which inhibits serum deprivation-induced apoptosis in A549 cells. Our study reveals an original mode of EGFR activation via covalent binding. We propose the correlation between EGFR activation without ligands and environmental pollutant-associated diseases such as cancer.

Objective The prognosis of and optimal treatment for grade 3 endometrioid endometrial carcinoma (G3EEC) currently remain unclear. This study aimed to clarify the baseline recurrence risk in patients with early-stage (stage I–II) G3EEC without adjuvant therapy and the prognosis of patients with advanced-stage (stage III–IV) G3EEC. Materials and methods A total of 101 patients with pathologically confirmed G3EEC from 1997 to 2018 were identified. Their clinicopathological characteristics and survival outcomes were reviewed retrospectively. Disease-free survival and overall survival values were estimated according to the Kaplan–Meier method and compared using a log-rank test. Results Recurrence was observed in eight (13%) of 63 patients with early-stage G3EEC, none of whom had received adjuvant therapy. The 5-year disease-free survival and 5-year overall survival rates for these patients were 86.7% and 96.4%, respectively. Recurrence was also observed in 12 (41%) of 29 patients with stage III G3EEC. The 5-year overall survival rates for stage III patients who underwent adjuvant chemotherapy and adjuvant radiotherapy were 85.6% and 42.9%, respectively. The 3-year overall survival rate among stage IVB patients was only 12.7% despite multidisciplinary treatment provision. Conclusion Our study newly demonstrates that patients with early-stage G3EEC have a favorable prognosis and a low recurrence rate in the absence of adjuvant therapy. In patients with stage III G3EEC, adjuvant chemotherapy was more beneficial than adjuvant radiotherapy. The poor prognosis of patients with stage IV G3EEC indicates the need for more effective treatments. Unique therapeutic approaches based on staging are recommended for treatment of G3EEC.

No transporte de água quente ocorre um decaimento de temperatura entre o montante e a jusante de um trecho de tubulação, ocasionando perda de energia em forma de calor para o ambiente. Assim sendo, o tubo de Polipropileno Copolímero Random (PPR) é uma das soluções existentes para sistemas prediais de água quente, uma vez que, por possuir baixa condutividade térmica, o decaimento de temperatura do fluido transportado por este tubo também é baixo. No entanto, há poucas informações sobre a perda de temperatura nesse tubo disponíveis nos manuais de fabricantes. Dessa forma, o objetivo do presente trabalho é determinar o decaimento de temperatura no transporte de água quente nos tubos de PPR da classe de pressão PN 25 para diferentes valores de vazão e para todos os diâmetros normativos. Para tanto, foram realizados estudos com um modelo teórico e simulações computacionais, com o intuito de comparar os resultados dos dois métodos. Os cálculos com o modelo teórico foram feitos no software Microsoft Excel, enquanto as simulações foram feitas na versão estudantil do software Ansys Fluent, que utiliza o método dos volumes finitos. Os resultados de ambos os métodos mostraram que o decaimento de temperatura foi menor para os tubos de diâmetros pequenos e para vazões mais altas. Os dois métodos apresentaram diferenças menores que 0,1%, dessa forma, considerou-se que a simulação valida o modelo teórico. Portanto, este modelo pode ser utilizado no dimensionamento de sistemas de água quente, podendo ser alterados diversos parâmetros dos cálculos, de acordo com as condições de operação do sistema.

Background Patients with schizophrenia (SCZ) display impaired executive functions compared with healthy controls (HCs). Furthermore, unaffected first-degree relatives (FRs) of patients with SCZ independently perform worse executive functions than do HCs. However, few studies have investigated the differences in executive functions assessed among patients with SCZ, FRs, and HCs, and the findings are inconsistent. Methods We investigated diagnostic differences in executive functions, namely (1) numbers of categories achieved (CA), (2) total errors (TE), and (3) percentage of perseverative errors of Nelson types (%PEN), using the Wisconsin card sorting test among patients with SCZ (n = 116), unaffected FRs (n = 62), and HCs (n = 146) at a single institute. Correlations between these executive functions and clinical variables were investigated. Results Significant differences existed in all executive functions among diagnostic groups (CA, F2,319 = 15.5, P = 3.71 × 10–7; TE, F2,319 = 16.2, P = 2.06 × 10–7; and %PEN, F2,319 = 21.3, P = 2.15 × 10–9). Patients with SCZ had fewer CA and more TE and %PEN than those of HCs (CA, Cohen’s d = −0.70, P = 5.49 × 10–8; TE, d = 0.70, P = 5.62 × 10–8; and %PEN, d = 0.82, P = 2.85 × 10−10) and FRs (TE, d = 0.46, P = 3.73 × 10–3 and %PEN, d = 0.38, P = .017). Of the 3 executive functions, CA and %PEN of FRs were intermediately impaired between patients with SCZ and HCs (CA, d = −0.41, P = .011 and %PEN, d = 0.41, P = .012). In contrast, no significant difference in TE existed between FRs and HCs (d = 0.22, P = .18). Although CA and TE were affected by the duration of illness (P .017). Conclusions Executive function, particularly %PEN, could be a useful intermediate phenotype for understanding the genetic mechanisms implicated in SCZ pathophysiology.

S-Nitrosylation of protein cysteine thiol is a post-translational modification mediated by nitric oxide (NO). The overproduction of NO causes nitrosative stress, which is known to induce endoplasmic reticulum (ER) stress. We previously reported that S-nitrosylation of protein disulfide isomerase (PDI) and the ER stress sensor inositol-requiring enzyme 1 (IRE1) decreases their enzymatic activities. However, it remains unclear whether nitrosative stress affects ER-associated degradation (ERAD), a separate ER stress regulatory system responsible for the degradation of substrates via the ubiquitin-proteasomal pathway. In the present study, we found that the ubiquitination of a known ERAD substrate, serine/threonine-protein kinase 1 (SGK1), is attenuated by nitrosative stress. C-terminus of Hsc70-interacting protein (CHIP) together with ubiquitin-conjugating enzyme E2 D1 (UBE2D1) are involved in this modification. We detected that UBE2D1 is S-nitrosylated at its active site, Cys85 by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Furthermore, in vitro and cell-based experiments revealed that S-nitrosylated UBE2D1 has decreased ubiquitin-conjugating activity. Our results suggested that nitrosative stress interferes with ERAD, leading to prolongation of ER stress by co-disruption of various pathways, including the molecular chaperone and ER stress sensor pathways. Given that nitrosative stress and ER stress are upregulated in the brains of patient with Parkinson’s disease (PD) and of those with Alzheimer’s disease (AD), our findings may provide further insights into the pathogenesis of these neurodegenerative disorders.

Accumulating evidence implicates oxidative stress as a potential pathophysiological mechanism of schizophrenia. Accordingly, we synthesized new chemicals using apocynin and tandospirone as lead compounds (A-2, A-3 and A-4). These novel compounds decreased reactive oxygen species (ROS) concentrations in vitro and reversed decreases in glutathione levels in the medial prefrontal cortex of rats transiently exposed to MK-801, an N-methyl-d-aspartate receptor antagonist, in the neonatal period. To determine whether A-2, A-3 and A-4 show behavioral effects associated with antipsychotic properties, the effects of these compounds on methamphetamine (MAP)-induced locomotor and vertical activity were examined in the model rats. A-2 and A-3, administered for 14 days around the puberty period, ameliorated MAP-induced hyperlocomotion in MK-801-treated rats in the post-puberty period, while A-4 suppressed MAP-induced vertical activity. These findings indicate that apocynin-tandospirone derivatives present anti-dopaminergic effects and may alleviate psychotic symptoms of schizophrenia.

RESUMO: O Polietileno Reticulado (PEX) é um material flexível utilizado no mercado da construção civil em sistemas prediais de água quente e fria, e assim como outros materiais, ao conduzir água quente, perde temperatura entre o ponto inicial e o ponto final de um trecho analisado, ocasionando perda de energia em forma de calor para o ambiente. Este artigo tem como objetivo verificar o comportamento do decaimento de temperatura em tubulações PEX de água quente de diversos diâmetros e fornecer essas informações para as fichas técnicas e os projetistas, para isto, serão adotados métodos iterativos e de simulação. Utilizando o software de simulação como parâmetro, obteve-se que o DN16 perdeu 0,32°C, DN20 0,17°C, DN25 0,11°C e DN32 0,07°C de temperatura em um trecho de 1 m de comprimento. Assim, é possível conhecer o decaimento de temperatura em determinadas distâncias, fator que auxilia o projetista na escolha do tamanho da tubulação a ser projetada de acordo com o diâmetro, para uma vazão fixada.

RESUMO: O Polipropileno Copolímero Random (PPR) é um material muito usado em instalações prediais e industriais de água fria e quente. No transporte de água quente, a água perde temperatura entre o início e o fim de um trecho de tubulação analisado, o que ocasiona perda de energia em forma de calor para o ambiente. Este trabalho analisa o decaimento de temperatura em tubulações de PPR PN 25 nos diversos diâmetros existentes, com métodos iterativos e simulações computacionais. Os resultados obtidos no Excel e no Ansys Fluent apresentaram diferenças menores que 0,2%, sendo que as maiores diferenças (0,154%) ocorreram na análise com regime turbulento no Ansys Fluent. Este artigo apresenta resultados preliminares da pesquisa que necessitará de mais estudos para alcançar resultados mais precisos.

Endometriosis-related cervical neoplasms are rare, and their clinicopathological features and association with human papilloma virus infection are unclear. A postmenopausal woman with recently diagnosed cervical adenocarcinoma was referred to our hospital. After further investigation, we suspected a stage IIB neoplasm that originated from endometriosis of the cervix or left parametrium. A radical hysterectomy was performed, and pathological examination confirmed a stage IIB cervical endometrioid carcinoma arising from the endometriosis in the cervix to the left parametrium that invaded the cervix; human papilloma virus infection of tumor cells was not detected. Endometriosis-related neoplasms can occur in the cervix or parametrium and present as cervical cancer. The neoplasm described here was not associated with human papilloma virus infection.

Uterine leiomyosarcoma (ULMS) is the major subtype of uterine sarcoma (US) and contributes to uterine cancer deaths. Although preoperative diagnosis of US remains challenging, frequent application of laparoscopic surgery for benign uterine leiomyomas (ULM) requires precise exclusion of US. MicroRNAs are stably present in the bloodstream, and the application of circulating miRNAs as disease biomarkers has been recognized. In the present study, we aimed to identify diagnostic biomarkers for distinguishing US from ULM by focusing on circulating miRNAs. All serum samples were collected preoperatively between 2009 and 2017, and all cases were histopathologically diagnosed. Whole miRNA profiles were obtained using a miRNA microarray. By analyzing expression levels of the miRNAs, candidate miRNAs were selected based on diagnostic performance in discriminating US from ULM, and a diagnostic model was then constructed. A total of 90 serum samples were analyzed, and clustering analyses revealed that the profiles of ULMS were distinct from those of controls. Based on leave‐one‐out cross‐validation, seven miRNAs were selected as biomarker candidates. Based on model construction, the optimal model consisted of two miRNAs (miR‐1246 and miR‐191‐5p), with an area under the receiver operating characteristic curve (AUC) for identifying ULMS of 0.97 (95% confidence interval [CI], 0.91‐1.00). In contrast, serum lactate dehydrogenase had an AUC of only 0.64 (95% CI, 0.34‐0.94). Seven serum miRNAs with high diagnostic performance for preoperative US screening were detected, and a promising diagnostic model for ULMS was generated., Whole circulating miRNA profiles in uterine sarcoma patient serum are analyzed. The result demonstrates feasibility for application as a novel preoperative biomarker.

Primary vulvar clear cell carcinoma (CCC) is extremely rare. In this article, we report a primary vulvar CCC along with immunohistochemical and gene mutation analyses results and literature review to discuss the clinicopathological features and tumorigenesis of this rare tumor. A 70-year-old (gravida 2 para 2) Japanese woman complained of bleeding from a vulvar mass at a past episiotomy site. A 1.8 × 1.8 × 0.5 cm exophytic sessile mass was present on the vestibular area inside the left labium minora. Radical local excision of the tumor and resection of the inguinal lymph nodes on both sides were performed. Histopathology revealed a vulvar CCC with immunohistochemical positivity for PAX8, HNF-1β, ER, and CA125, and negativity for p16, CD10, GATA3, PTEN, and PAX2, suggesting its Müllerian origin. No lymph node metastasis was observed. The tumor was a 5-mm exophytic growth without deep stromal invasion; thus, it was difficult to measure the invasion depth assuming a squamous cell carcinoma. To investigate pathogenic/oncogenic mutations in 50 cancer-related genes, we used the AmpliSeq Cancer Hotspot Panel. However, no pathogenic/oncogenic mutations were detected. Literature review revealed that most cases of vulvar CCC are associated with vulvar endometriosis. In particular, cases with clinically evident endometriosis at the episiotomy scar should be carefully observed. Evidence-based pathological stages of vulvar adenocarcinoma including CCC remain to be established owing to its rarity, with nationwide or global accumulation of cases required in future.

Schizophrenia patients (SCZ) display widespread cognitive deficits that are strongly associated with functional outcomes. Cognitive impairments occur along a genetic continuum among SCZ, their unaffected first-degree relatives (FRs) and healthy controls (HCs). Although SCZ impairs the premorbid intelligence quotient (IQ) and causes a subsequent intelligence decline (ID), a decrease in present IQ from the premorbid level, it remains unclear when during the illness course these impairments develop. Differences in premorbid and present IQ and ID were investigated among 125 SCZ, 61 FRs and 107 HCs, using analysis of covariance and a paired t-test. Furthermore, these subjects were classified into preserved and deteriorated IQ groups based on the degree of ID, and we investigated which factors contribute to this classification. We found significant differences in premorbid and present IQ among the diagnostic groups. Compared with HCs, SCZ and FRs displayed lower premorbid and present IQ. There was no significant difference in premorbid IQ between SCZ and FRs, but SCZ had a significantly lower present IQ than FRs. Only SCZ showed a significant ID. As most FRs and HCs did not display an ID, there were fewer subjects with deteriorated IQ among FRs and HCs than among SCZ. Subjects with preserved IQ showed higher educational attainment than those with deteriorated IQ among SCZ and FRs. These findings suggest that the impairment of premorbid IQ and the ID in SCZ become evident before and around the time of onset, respectively, and different pathophysiological mechanisms might be related to these impairments.

β-amyloid precursor protein (APP) and their metabolites are deeply involved in the development of Alzheimer’s disease (AD). Upon the upregulation of β-site APP cleaving enzyme 1 (BACE1), its product, the β-carboxyl-terminal fragment of APP (βCTF), is accumulated in the early stage of sporadic AD brains. βCTF accumulation is currently considered the trigger for endosomal anomalies to form enlarged endosomes, one of the earliest pathologies in AD. However, the details of the underlying mechanism remain largely unclear. In this study, using BACE1 stably-overexpressing cells, we describe that lipid flippase subcomponent TMEM30A interacts with accumulated βCTF. Among the lipid flippases in endosomes, those composed of TMEM30A and active subcomponent ATP8A1 transports phospholipid, phosphatidylserine (PS), to the cytosolic side of the endosomes. The lipid flippase activity and cytosolic PS distribution are critical for membrane fission and vesicle transport. Intriguingly, accumulated βCTF in model cells impaired lipid flippase physiological formation and activity, along with endosome enlargement. Moreover, in the brains of AD model mice before the amyloid-β (Aβ) deposition, the TMEM30A/βCTF complex formation occurred, followed by lipid flippase dysfunction. Importantly, our novel Aβ/βCTF interacting TMEM30A-derived peptide “T-RAP” improved endosome enlargement and reduced βCTF levels. These T-RAP effects could result from the recovery of lipid flippase activity. Therefore, we propose lipid flippase dysfunction as a key pathogenic event and a novel therapeutic target for AD.

Methylmercury (MeHg), an environmental toxicant, induces neuronal cell death and injures a specific area of the brain. MeHg-mediated neurotoxicity is believed to be caused by oxidative stress and endoplasmic reticulum (ER) stress but the mechanism by which those stresses lead to neuronal loss is unclear. Here, by utilizing the ER stress-activated indicator (ERAI) system, we investigated the signaling alterations in the unfolded protein response (UPR) prior to neuronal apoptosis in the mouse brain. In ERAI transgenic mice exposed to MeHg (25 mg/kg, S.C.), the ERAI signal, which indicates activation of the cytoprotective pathway of the UPR, was detected in the brain. Interestingly, detailed ex vivo analysis showed that the ERAI signal was localized predominantly in neurons. Time course analysis of MeHg exposure (30 ppm in drinking water) showed that whereas the ERAI signal was gradually attenuated at the late phase after increasing at the early phase, activation of the apoptotic pathway of the UPR was enhanced in proportion to the exposure time. These results suggest that MeHg induces not only ER stress but also neuronal cell death via a UPR shift. UPR modulation could be a therapeutic target for treating neuropathy caused by electrophiles similar to MeHg.

A solitary pelvic tumor after treating a primary endometriosis-related neoplasm is usually considered a recurrence but may actually be a primary endometriosis-related peritoneal neoplasm. A Japanese woman in her late 60s was referred to our hospital for a solitary pelvic tumor. The tumor was suspected as a recurrence of a previously treated stage IA ovarian clear-cell carcinoma, and resected. Pathological analysis revealed that the tumor was a peritoneal seromucinous carcinoma associated with pelvic endometriosis. Both tumors displayed distinct histopathologies, although both neoplasms were endometriosis related. An apparent recurrent tumor after treating of an endometriosis-related neoplasm might not be a true recurrent tumor but a second primary endometriosis-related neoplasm. Histological confirmation is indicated in such cases., Highlights • Different histologic subtypes of endometriosis-related neoplasms can metachronically occur in a patient. • An apparent recurrent tumor after treating endometriosis-related ovarian neoplasms (ERONs) may be a primary tumor. • Histological confirmation of an apparent recurrent tumor after treating ERONs is indicated. • Peritoneal endometriosis resection may prevent the occurrence of endometriosis-related peritoneal neoplasms.

Ayu fish are actively released by many fishery cooperatives in Japan. These fish exhibit the density-dependent population dynamics within territorial competition. At low density, all fish can hold feeding territories. Once all territory sites are occupied, surplus fish become floaters. As the density further increases, all fish give up their own territories and then form a school. Territory holders are more valuable than floaters as a food source and a target of recreational fishing. Thus, the main purpose of the release of ayu is to increase the amount of territory holders. For these reasons, the release policy for ayu should take into account the influence of a change in density on the population dynamics. We develop a rate equation to describe the density-dependent population dynamics of ayu accompanied by the release of fingerlings. Our results indicate that the release of ayu demands unique policy different from other fish species. The release of ayu should be carried out so as not to break down territories due to the increase in density caused by released fingerlings. Specifically, the release policy that reduces the amount of fingerlings that are released at one time, and lengthens the time interval between each release, increases the catch of territory holders.

A major obstacle to improving prognoses in ovarian cancer is the lack of effective screening methods for early detection. Circulating microRNAs (miRNAs) have been recognized as promising biomarkers that could lead to clinical applications. Here, to develop an optimal detection method, we use microarrays to obtain comprehensive miRNA profiles from 4046 serum samples, including 428 patients with ovarian tumors. A diagnostic model based on expression levels of ten miRNAs is constructed in the discovery set. Validation in an independent cohort reveals that the model is very accurate (sensitivity, 0.99; specificity, 1.00), and the diagnostic accuracy is maintained even in early-stage ovarian cancers. Furthermore, we construct two additional models, each using 9–10 serum miRNAs, aimed at discriminating ovarian cancers from the other types of solid tumors or benign ovarian tumors. Our findings provide robust evidence that the serum miRNA profile represents a promising diagnostic biomarker for ovarian cancer., Screening methods for early detection of ovarian cancer is technically difficult. Here, the authors investigated circulating microRNA in human blood serum and developed a model using 10 microRNAs to discern between ovarian cancer and being ovarian tumors, solid tumors, and non-cancer patients.

Cigarette smokers with schizophrenia consume more cigarettes than smokers in the general population. Schizophrenia and smoking quantity may have shared genetic liability. Genome-wide association studies (GWASs) of schizophrenia and smoking quantity have highlighted a biological pleiotropy in which a robust 15q25 locus affects both traits. To identify the genetic variants shared between these traits on 15q25, we used summary statistics from large-scale GWAS meta-analyses of schizophrenia in the Psychiatric Genomics Consortium 2 and smoking quantity assessed by cigarettes smoked per day in the Tobacco and Genetics Consortium. To evaluate the regulatory potential of the shared genetic variants, expression quantitative trait loci analysis in 10 postmortem brain regions was performed using the BRAINEAC dataset in 134 neuropathologically normal individuals. Twenty-two genetic variants on 15q25 were associated with both smoking quantity and schizophrenia at the genome-wide significance level (P < 5.00 × 10(−8)). Major alleles of all variants were associated with higher smoking quantity and risk of schizophrenia. These genetic variants were associated with PSMA4, CHRNA3, and CHRNB4 expression in specific brain regions (lowest P = 4.81 × 10(−4)) and with CHRNA5 expression in multiple brain regions (lowest P = 8.70 × 10(−6)). Risk-associated major alleles of these variants were commonly associated with higher expression in several brain regions, excluding the medulla, at the transcript level. In addition, the risk-associated major allele at rs637137 was associated with higher CHRNA5 expression at the specific exon level in multiple brain regions (lowest P = 2.37 × 10(−5)). Our findings suggest that genome-wide variants shared between smoking quantity and schizophrenia contribute to a common pathophysiology underlying these traits involving altered CHRNA5 expression in the brain.

Background Cigarette smoking is consistently more common among schizophrenia patients than the general population worldwide; however, the findings of studies in Japan are inconsistent. Recently, the smoking rate has gradually decreased among the general population. Methods We performed a meta-analysis of smoking status in a large Japanese cohort of (1) 1845 schizophrenia patients and 196845 general population and (2) 842 schizophrenia patients and 766 psychiatrically healthy controls from 12 studies over a 25-year period, including 301 patients and 131 controls from our study. Results In our case-control sample, schizophrenia patients had a significantly higher smoking rate than healthy controls (P=.031). The proportion of heavy smokers (P=.027) and the number of cigarettes smoked per day (P=8.20×10–3) were significantly higher among schizophrenia patients than healthy controls. For the smokers in the schizophrenia group, atypical antipsychotics dosage was positively correlated with cigarettes per day (P=1.00×10–3). A meta-analysis found that schizophrenia patients had a higher smoking rate than the general population for both men (OR=1.53, P=.035; schizophrenia patients, 52.9%; general population, 40.1%) and women (OR=2.40, P=1.08×10–5; schizophrenia patients, 24.4%; general population, 11.8%). In addition, male schizophrenia patients had a higher smoking rate than male healthy controls (OR=2.84, P=9.48×10–3; schizophrenia patients, 53.6%; healthy controls, 32.9%), but the difference was not significant for women (OR=1.36, P=.53; schizophrenia patients, 17.0%; healthy controls,14.1%). Among both males and females, schizophrenia patients had a higher smoking rate than both the general population (OR=1.88, P=2.60×10–5) and healthy controls (OR=2.05, P=.018). These rates were not affected by the patients’ recruitment year (P>.05). The cigarettes per day values of schizophrenia patients and the general population were 22.0 and 18.8, respectively. Conclusions Schizophrenia patients are approximately 2 times more likely to smoke than the general population and healthy controls based on data collected over a decade in Japan.

Cogan's syndrome (CS) is defined by the combination of hearing loss, vertigo, and ocular inflammation of uncertain cause, and can be associated with variable vessel vasculitis. Vasculitic manifestations may include arteritis (affecting large, medium or small arteries), aortitis, and aortic and mitral valvulitis. Cutaneous manifestations including erythema, papules, subcutaneous nodules, and purpura sometimes occur; however, to date, only six cases have been histologically confirmed to have genuine vasculitis. Here, we report two cases of CS, one of which involved a patient who developed the typical symptoms of Takayasu arteritis and purpuric lesions in the legs, with histologic findings consistent with small vessel vaculitis in the dermis. The second case involved a patient who developed subcutaneous nodules in the legs and the axilla, and histologic findings revealed a necrotizing vasculitis of the small arteries in the interlobular area. Both cases were successfully treated with systemic steroid therapy. Based on the clinical features and the examination data, there is a possibility that a Chlamydia trachomatis infection played a pivotal role in the pathogenesis of those vasculitides.