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Objectives　This study aimed to develop scales for evaluating the level of implementation of community practices and explore the perception of public health nurses in municipalities regarding their community practices.Methods　Draft scales were developed based on a literature review and interviews with municipal public health nurses. Subsequently, a questionnaire survey was conducted with municipal public health nurses across Japan in response to these draft scales. Respondents were recruited based on the municipality population size. Questionnaires were distributed to 2,074 individuals from 52 municipalities ensuring representation from diverse municipalities. Exploratory factor analysis was performed to determine the number of factors, while confirmatory factor analysis was performed to determine the factor structure. The reliability of the scales was assessed by calculating Cronbach's alpha coefficients, and their validity was tested by examining correlations with existing scales, namely the Moral Competence Scale for Public Health Nurses and the Professional Identity Scale for Public Health Nurses, and years of experience as a public health nurse.Results　A total of 721 (34.8%) valid respondents were included in the analysis. Three scales, methods of community practices (three factors, nine items), perceptions of public health nurses toward community residents through community practices (three factors, 10 items), and organizational environment supporting community practices (two factors, 11 items) were developed as indicators of the implementation of public health nurses' community practices. Cronbach's alpha coefficients for the three scales were 0.896, 0.913, and 0.868, respectively. As hypothesized, each subfactor exhibited a positive correlation with the existing scales. However, certain subfactors did not demonstrate any correlation with years of experience.Conclusion　The three scales developed in this study were individually examined for reliability and validity. These scales can be used independently or in combination, allowing public health nurses to select the most suitable scale(s) based on their objective.　A notable contribution of this study is the establishment of concrete indicators for evaluating community practices, addressing the previously vague nature of this evaluation. By incorporating the scale items into daily health practices, we anticipate that these indicators can be employed to evaluate community practices at the organizational and individual levels.

A 50s woman with a stomachache was referred to our hospital with diagnosed gastric cancer. Upper endoscopy showed a type 3 tumor in the lower gastric body, and CT demonstrated a pelvic tumor 10 cm in size. Laparoscopic surgery was performed; since the pelvic tumor was found to derive from the left ovary, left oophorectomy and total gastrectomy were performed. Pathological examination revealed that the ovarian tumor was a gastric cancer metastasis. Adjuvant chemotherapy with S-1 monotherapy was introduced. Four months after the operation, metastasis was suspected due to right ovary tumor edema. Due to the possibility of obtaining R0 resection and adverse events of chemotherapy, we chose right oophorectomy. Pathological examination demonstrated signet-ring cell cancer. Fourteen months after the first operation, the patient is alive with no recurrence or metastasis.

Currently, various posterior surgical techniques are available for cervical spondylotic myelopathy. These techniques include laminoplasty and laminectomy with or without fusion, and are often used in patients with multilevel cervical stenosis. They were developed with the intent to reduce the risk of complications such as injury to the spinal cord and nerve roots, C5 palsy, postlaminectomy membrane, and postoperative kyphosis. Posterior decompression for cervical spondylotic myelopathy is effective in improving neurological function in patients with appropriate surgical indications.

Objectives　The purpose of this study was to define the terminology used in community health activities by systematically establishing agreement among public health nurses and related professionals, to aid them in effectively cooperating with other professionals.Methods　We extracted the major terms described in "Guidelines for Public Health Nurses' Activities in the Region," which was issued by the Director of Health Bureau, Ministry of Health, Labor and Welfare; and conducted 2 iterations on the proposed definition of the terms using the Delphi method. The survey targeted 800 stakeholders from the following 4 professions: public health nurses in managerial positions in local governments, clerical staff in local governments, public health nursing professors at educational institutions, and social welfare council staff. Respondents indicated their degree of agreement with the definition of the terms using a 4-point Likert scale. We tallied the answers indicating "I agree" or "Mostly agree." A 70% term agreement was considered "conformed." A free text box for each proposed definition was also available so that respondents could share their opinions and offer alternatives.Results　The first survey received 231 responses. The conformity of their definitions ranged from 83.9%-96.9% (mean=91.5%). Although all definitions exceeded the consensus level, we examined their adequacy with reference to the definitions and opinions from the free text. Various opinions were obtained from those engaged in each occupation. The second round included 117 consenting stakeholders from the first survey, yielding 90 responses. Their degree of conformity ranged from 86.7%-98.9% (mean=94.6%). Therefore, we determined the definitions had reached a robust agreement. We revised the definitions of some terms with reference to the opinions from the free texts and finalized the definitions. Finally, we defined 23 terms-such as region, community diagnosis, and policy.Conclusion　All terms had a conformity of more than 85%, thus bringing into alignment those community health terms that had varying interpretations among related occupations earlier. By including the opinions of those from the related occupations who collaborate with public health nurses, the definitions of these terms could be established and shared. These definitions can be used in public health nursing practice, education, service, and research-among those in involved these related occupations.

A 60-year-old woman was referred to our hospital because of possible miliary brain metastases of unknown primary origin. On admission, she was alert and had no apparent motor weakness. Neuroradiological examinations revealed more than 100 small enhancing lesions, some of which had undergone cystic changes, suggesting multiple metastases. However, plain chest and abdominal CT revealed no abnormalities, and fluorodeoxyglucose-positron emission tomography could not reveal the primary origin of the cancer. Blood examination revealed no apparent abnormalities, except for tumor markers, including pro-gastrin-releasing peptide and carcinoembryonic antigen. On day 22, the patient underwent a biopsy through right frontal craniotomy. Histopathological findings indicated metastases from cancer. Immunohistochemistry was positive for cytokeratin(CK)7 and thyroid transcription factor-1 while negative for CK20(-), CK5/6, and p40, resulting in the diagnosis of lung adenocarcinoma. Genetic testing showed negative for EGFR mutation and positive for ALK fusion gene. From the day 48, whole brain radiotherapy was started, and the ALK inhibitor was prescribed from day 64. Metastatic brain tumors of unknown primary are rare. Miliary brain metastases from an unknown primary origin are rare. To our knowledge, this is the first case of military brain metastases of an unknown primary origin, which was later determined to have originated from ALK fusion-positive lung cancer.

(Objectives) The Enhanced Recovery After Surgery (ERAS) protocols are standardized and multimodal perioperative care pathways designed to improve surgical outcomes by minimizing stress response and inflammation following surgery. First adopted in colorectal surgery, ERAS is now being employed in various other types of surgeries, most recently in patients undergoing radical cystectomy (RC). Implementation of ERAS protocols resulted in reductions in perioperative complication rates and length of hospital stay (LOS). However, information on the adoption of ERAS in patients undergoing RC in Japan is limited. The objective of this study was to evaluate the safety and efficacy of ERAS implemented in the Toyohashi Municipal Hospital in 2017 for the management of patients with RC. (Patients and methods) This was a retrospective study of 103 patients who underwent RC and urinary diversion from January 2012 to March 2019. Of the 103 patients, 71 underwent surgery prior to the introduction of the ERAS were allocated to the 'traditional' group, while 32 were exposed to the ERAS protocol were allocated to the 'ERAS' group. In this study, ERAS included no bowel preparation, preoperative carbohydrate loading, preoperative fluid reduction, preoperative fasting, reduced drainage use, no nasogastric intubation, and early postoperative drinking and eating. A comparative analysis was performed to evaluate LOS and postoperative complication rate (Clavien classification ≥2) after RC between the 'traditional' and 'ERAS' groups. (Results) Patient characteristics and intraoperative variables such as median age, sex, body mass index, clinical and pathological cancer stage, amount of bleeding, need for transfusion, and technique of urinary diversion did not differ between groups. However, duration of surgery was significantly shorter in the ERAS group than in the traditional group (402 min vs. 470 min; P = 0.03). Further, rate of complication was significantly lower (43.8% vs. 67.6%; P=0.03) and LOS after RC was significantly shorter (21 days vs. 28 days; P<0.001) in the ERAS group compared to the traditional group. Moreover, ERAS was an independent factor affecting shorter LOS after RC (OR, 5.22; 95% CI, 1.52-17.90; P = 0.009) in multivariate analyses. (Conclusions) It is possible that the ERAS protocol adopted in this study reduced the LOS and postoperative complication rate after RC at this site in Japan.

Brain function is controlled by the balance between the excitatory and inhibitory systems. If this balance is disrupted and the excitatory system dominates, convulsions or epileptic seizures are induced. Neuronal hyperexcitability in the brain leads to marked changes in the function of the neurons, which adversely affect the stability of the neural network. Many of the currently used antiepileptic drugs are symptomatic treatments that suppress the electrical hyperexcitability of the cerebrum. Although patients with epilepsy should continuously take antiepileptic drugs to control their seizures, approximately 20% of patients are drug resistant. The brain has the ability to control neuronal functions within acceptable limits while it maintains the amount of synaptic inputs that form the basis of information accumulation. Neuronal self-regulation is known as homeostatic scaling by which the intensity of all excitatory synapses is suppressed when neuronal excitability is increased. However, the molecular mechanisms of homeostatic scaling and their pathophysiological significance in vivo remain unclear. Repeated treatment with a subconvulsive dosage of pentylenetetrazol (PTZ), a γ-aminobutyric acid (GABA) A receptor antagonist, is known to induce kindling in mice, which is a common animal model used to study epilepsy. We found that PTZ-induced kindling was potentiated in mice deficient in the transcription factor neuronal PAS domain protein 4 (Npas4), the expression of which is immediately induced in response to neuronal activity. At this symposium, we will discuss the possibility of Npas4 as a novel target molecule for epilepsy treatment.

(Purpose) Enzalutamide is one of the therapeutic options for castration-resistant prostate cancer (CRPC). However, general fatigue is frequently observed in patients after introduction of enzalutamide. Here, we used the Cancer Fatigue Scale (CFS) to monitor general fatigue after introduction of enzalutamide, and administered the Japanese herbal medicine (Kampo) drug, Hochuekkito, for management of general fatigue. (Materials and methods) Three patients with CRPC were enrolled in this retrospective observational study. The patients were all male, 72, 69, and 88 years old, respectively, and had received previous hormone therapy for CRPC. They complained of general fatigue 2-5 weeks after introduction of enzalutamide. The CFS was divided into three subcategories: physical fatigue, affective fatigue, and cognitive fatigue. Hochuekkito was prescribed for management of general fatigue. Moreover, 31 previous CRPC cases treated in our hospital were divided into a general fatigue group and a non-general fatigue group. The period of enzalutamide prescription was compared among the previous groups and the present three cases to determine the usefulness of Hochuekkito. (Results) In this series, CFS was useful to monitor general fatigue after introduction of enzalutamide. General fatigue after introduction of enzalutamide mainly consisted of physical fatigue, and improved in two of the three cases included in this study. However, enzalutamide was discontinued in one patient due to general fatigue. Fourteen of our 31 previous CRPC cases developed general fatigue after introduction of enzalutamide. The mean periods of enzalutamide prescription were 265.6, 173.2, and 193.0 days in the non-general fatigue, general fatigue, and the present three cases, respectively. The differences among the groups were not significant. (Conclusions) The CFS is useful to monitor general fatigue, including its subcategories, after introduction of enzalutamide in patients with CRPC. The Kampo medicine Hochuekkito may be useful for management of general fatigue in such cases.

Pregnancy- and lactation-associated osteoporosis is a rare disease. Although researchers have reported a few cases, there are no established diagnostic criteria for pregnancy- and lactation-associated osteoporosis. However, a diagnosis can be easily obtained by an accurate medical interview, physical examination, imaging studies, and laboratory data, including bone mineral density measurement. This disease should be suspected when a woman presents with severe back pain in the late stages of pregnancy or the early postpartum period. An accurate and prompt diagnosis helps with appropriate treatment and prevents the progression of the disease.

The dosage of cisplatin is adjusted according to creatinine clearance (Ccr) estimated by the Cockcroft-Gault formula, which is commonly used as a marker for renal function. It is known that different serum creatinine (Scr) levels are reported depending on the analytical methods utilized such as the Scr level by the enzyme method being lower than that by the Jaffe method. Although the enzyme method is used in Japan, most drug dosages, including cisplatin, are adjusted according to the estimated Ccr using the Jaffe method-based Scr level. The purpose of this study was to investigate whether assessment of renal function with or without Scr adjustment affects cisplatin-based chemotherapy in cervical cancer patients. The patients were divided into two groups, normal (Ccr≥60 mL/min with adjusted Scr) and false normal (Ccr<60 mL/min with adjusted Scr, but Ccr≥60 mL/min with non-adjusted Scr). The false normal group had significantly higher rates of cisplatin dose reduction after the second course than the normal group (p<0.05). Leukocytopenia and Grade 2 or higher neutropenia were significantly more common in the false normal group than in the normal group (p<0.05). These results suggest that evaluation of renal function using the adjusted Scr is important for the accurate dosage of cisplatin and that it helps to improve the patient's quality of life. Further investigations may provide useful information for accurate and safe cisplatin-based chemotherapy for cancer patients.

Pregnancy-associated osteoporosis is a rare condition characterized by a transient but significant reduction in bone mineral density. To date, the underlying pathophysiological mechanisms remain unclear. Related symptoms include severe back or hip pain secondary to vertebral fractures and/or transient osteoporosis of the hip, which typically occur during the third trimester or during lactation. Although most women are managed conservatively, a few women need surgery. Prompt diagnosis and appropriate treatment is important not only for pain control, but also to improve the woman's future quality of life.

A 43-year-old woman underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy for endometrioid adenocarcinoma of the uterine body(Stage ⅢC)at 40 years of age. Screening of the adenocarcinoma samples for Lynch syndrome by immunohistochemistry for mismatch repair proteins indicated a loss of MSH2/MSH6 proteinexpression . A genetic test revealed a deletion of about 20 kb, including exons 8 and 9 of the EPCAM gene. Colonoscopy revealed a type 1 tumor in the cecum. The risk of developing metachronous colorectal cancer and postoperative survival according to the extent of colectomy(total colectomy versus segmental colectomy)and her marked obesity were considered collectively. The patient subsequently selected total colectomy with ileorectal anastomosis. Pathological findings revealed mucinous carcinoma(Stage Ⅱ). Patients with Lynch syndrome caused by deletion of EPCAM are not usually at a high risk of uterine body cancer, but the risk of developing uterine body cancer should be noted when the range of EPCAM deletion extends near to MSH2, as inthis case.

A 77-year-old man with a right kidney stone was admitted to our hospital. A ureteroscope was introduced into the ureter without dilation under direct vision. We then performed flexible transurethral lithotripsy (f-TUL) using a ureteral access sheath and successfully fragmented the stone and extracted almost all the stone fragments without any complications. Just 3 hours after the operation, he suddenly developed right abdominal pain with a decrease in hemoglobin. A CT scan showed a retroperitoneal hemorrhage around the lower ureter. We herein describe a rare complication associated with flexible transurethral lithotripsy.

Overactive bladder (OAB) is a storage symptom complex that includes urinary urgency with or without urge incontinence, urinary frequency and nocturia. OAB is common symp- tom complex and its morbidity is high and increased with age. Although many factors cause OAB, we can classify them as neurogenic or non-neurogenic. To diagnose OAB, we need to ask a patient about his condition using Overactive Bladder Symptom Score (OABSS), exam- ine physical findings and urinalysis. And we also need to exclude other urinary tract diseases that make bladder irritation. Pharmacotherapy and behavior therapy are useful for improving OAB symptoms. Anticholinergic agents are utilized for OAB treatment but we need to pay attention to the adverse effects.

Nedaplatin(NDP)is a platinum derivative anticancer drug.An NDP dose of 100mg/m2 every 4 weeks is recommended in non-elderly Japanese patient because a higher dose may lead to myelosuppression, such as thrombocytopenia.In a pharmacokinetic analysis, thrombocytopenia was significantly correlated with renal function.However, the correct dose in patients with impaired renal function remains unclear.To evaluate the usefulness of dose reduction in patients with renal dysfunction, we conducted a retrospective study.This study included Japanese solid cancer patients who received NDP monotherapy in Nagoya University Hospital between April 2011 and March 2014. Eighty three patients were evaluated and divided into 2 groups based on renal function: a creatinine clearance(Ccr; mL/min)≥60 group and a Ccr<60 group.The frequency of B Grade 3 thrombocytopenia and neutropenia was significantly higher in the Ccr<60 group than that in the Ccr≥60 group (3.4% vs 32.0%; p=0.001 and 6.8% vs 32.0%; p=0.005, respectively).In the Ccr<60 group, the frequency of BGrade 3 thrombocytopenia and neutropenia was lower in the reduced dose group than that in standard dose(100mg/m2)group (41.7% vs 23.1%; p=0.410 and 41.7% vs 23.1%; p=0.410, respectively).A multiple logistic regression analysis revealed that NDP dose and serum creatinine were risk factors for the incidence of BGrade 3 thrombocytopenia and neutropenia.These results suggest that NDP dose should be reduced to achieve safe drug treatment in patients with Ccr<60.

Bone resorption inhibitors used in Japan are bisphosphonate, selective estrogen receptor modulators(SERMs), denosumab, eldecalcitol, and calcitonin. The structural and material properties of bone quality are important factors in osteoporosis treatment. In contrast to improvements in bone density, those in bone quality are difficult to clinically determine as no simple test is available and changes are difficult to detect. Numerous reports have been published on the mechanisms by which bone resorption inhibitors increase bone density and suppress bone fractures. This paper describes the effects of each bone resorption inhibitor and focusses on burr holes, trabeculae, microdamage, collagen cross-links, and microstructures.

It-is well known that dopamine is necessary for motor function, reward-motivated behaviors. The principal target of dopamine is medium spiny neurons (MSNs), which are a special type of GABAergic inhibitory cell that represents,90% of the neurons within the striatum, including the nucleus accumbens (NAc). There is a distinct class of spatially intermixed MSNs that express dopamine type 1 or 2 receptors (DlR-MSNs or D2R-MSNs, respectively). The D1R-MSN and D2R-MSN pathways control the dynamic balance in the basal ganglia circuit. D1R is coupled -to adenylate cyclase through Golf to activate protein kinase A (PKA), whereas D2R inhibits adenylate cyclase through Gi. Although PKA has been implicated in reward signals downstream of D1Rs by pharmacological approaches, there is no direct evidence indicating that PKA in DlR-MSNs regulates neuronal excitability and reward-related behaviors. We have established the system in which enzymatic activity can be manipulated in the NAc under the control of specific promoters for DlR-MSNs using adeno-associated virus (AAV)-mediated conditional'transgenic techniques. We have also found novel PKA substrates in dopamine receptor signaling using phosphoproteomic approach. This review article focuses on the PKA and its substrates to understand dopamine-related signals in the MSNs. We discuss phosphoproteomic approaches for' comprehensively screening of dopamine signaling. Finally, we highlight RapI pathway as a novel reward signal in vivo.

We report a 27-year-old female who was diagnosed with adenocarcinoma of the uterine cervix associated with Peutz- Jeghers syndrome(PJS). She had undergone 5 surgeries for intestinal intussusception and had been diagnosed with PJS. She was referred to our hospital, complaining of watery vaginal discharge, and was diagnosed with adenocarcinoma of the uterine cervix. Following neoadjuvant chemotherapy, radical hysterectomy and small intestinal polypectomy by intraoperative endoscopy were performed. Among the third-degree relatives of her family, 10 had been diagnosed with PJS; of these 10, uterine cervical adenocarcinoma occurred in 3 relatives, pancreatic cancer in 2, cholangiocellular carcinoma in 1, and colon cancer in 1. Patients with PJS are at increased risk of developing malignant tumors in various organs. A recent review of the literature from Japan revealed that the cumulative cancer risk was estimated to be 83%by the age of 70 years, with especially high incidence rates of uterine cervical adenocarcinoma, colorectal cancer, and pancreas cancer. Surveillance for malignant neoplasms in patients with PJS is recommended, focusing on the sex and age of the patients.

Objective: Patients with childhood-onset epilepsy often need continued epilepsy treatment into adulthood. We investigated parents’ opinions of the changes in their children’s epilepsy treatment during the transition from childhood to adulthood using questionnaires and formulated agendas to build the appropriate medical treatment system for epilepsy. Methods: We distributed questionnaires to parents of patients with epilepsy who were 12 to 18 years old. Results: We distributed 176 questionnaires, and analyzed 79 (45%) questionnaires. Most parents (59%) wanted their child to continue treatment for epilepsy in the pediatrics department because of confidence in the current treatment environment. Most parents (73%) were anxious about their child not being treated in the pediatrics department during future epilepsy medical treatments because of concerns about whether a proper handover from the pediatrics department to other departments is possible. No parent was recommended the departmental transition by the primary pediatrician to other courses for future epilepsy treatment, while 19% of par-ents had a sense of incongruity regarding epilepsy treatment at the current pediatrics department. Parents who were anxious about future epilepsy treatments had significantly fewer general-school students than parents without anxiety. In addition, their children had more seizures than children of parents who were not anxious. Furthermore, they wanted their child to continue treatment for epilepsy in the pediatrics department more than the parents without anxiety. Conclusions: Approximately 70% of the parents were anxious about obtaining future epilepsy treatment in clinical departments other than the pediatrics department. To build a satisfactory medical treatment system for patients with epilepsy having different backgrounds and requiring continued treatment in adulthood, it is important to create a cooperating network consisting of pediatricians, neurologists, neurosurgeons, psychiatrists, and epileptologists.

Sporadic late-onset nemaline myopathy is an uncommon disease. Clinically, it is characterized by progressive muscle weakness that can develop in limbs or axial muscles. Asymmetrical distal weakness, facial weakness, dropped head, and dysphagia can also occur. Since the serum creatine kinase level usually remains within the normal range, patients can be misdiagnosed with motor neuron disease. Recognition of nemaline rods on muscle biopsy is crucial for accurate diagnosis. If it is associated with monoclonal gammopathy of undetermined significance, the outcome is known to be unfavorable. In spite of various immunotherapies such as corticosteroids, immunosuppressants, and plasmapheresis, most patients die of respiratory failure within 5 years. Since the efficacy of autologous stem cell transplantation following high-dose melphalan was first reported in 2008, there have been accumulating reports that showed the positive effect of this therapy for the disease.

Objective: To evaluate the efficiency of the direct tuberculosis-loop-mediated isothermal amplification (TB-LAMP) assay by using non-centrifuged sputum samples. STUDY PERIOD AND METHODS: The study was conducted between June 2013 and February 2014. We collected 111 sputum samples from patients who had been radiographically diagnosed with tuberculosis and had not received any treatments for longer than 5 days. In the direct TB-LAMP assay, a loop-mediated isothermal amplification kit and 60-μL sputum samples were used. A direct smear microscopy test was used as the smear test. Then, the same sputum samples were processed with a CCE pretreatment reagent, and 100 μL of the solution samples were cultured by using the mycobacterial growth indicator tube (MGIT) culture method., Results: Forty-six of the 111 samples were positive in the smear microscopy tests. All the smear-positive samples were positive in both the MGIT and direct TB-LAMP assay (100%). The mean positive detection time with the direct TB-LAMP assay was 13 minutes 55 seconds. Of 56 smear-negative and MGIT positive samples, 44 (78.6%) were judged to be positive using the direct TB-LAMP assay, with a mean positive detection time of 15 minutes 59 seconds., Discussion: The direct TB-LAMP assay using non-centrifuged sputum samples was demonstrated to have a high detection rate and thus may be considered useful for rapid and effective tuberculosis diagnosis.

Since the identification of JAK2 V617F mutation in patients with BCR/ABL-negative myeloproliferative neoplasms in 2005, the molecular basis of these hematological disorders has been extensively studied. Consequently, various small molecular compounds including JAK2 inhibitors have been developed. The JAK2 inhibitor ruxolitinib improves survival as well as splenomegaly and the clinical symptomatic burden in intermediate-2 or high risk myelofibrosis patients. This agent also reduces the JAK2 V617F allele burden in some patients, suggesting that it also has a certain molecular effect. Based on the results of clinical studies, ruxolitinib has been approved for treatment of myelofibrosis in the United States and Europe. Clinical and preclinical studies of several other JAK2 inhibitors are currently ongoing. Other small molecular compounds including histone deacetylase inhibitors, mTOR inhibitors and telomerase inhibitors are currently being tested in clinical trials. We also discuss the possibility of combination therapies using JAK2 inhibitors and other agents.

Abnormalities in early brain development contribute to the etiology of many neurological disorders in later life. Recent advances in genome analysis indicate that large numbers of common gene variants shape any individual's disease risk, including that for major mental illnesses. Polyriboinosinic-polyribocytidilic acid (polyI:C) is known to induce strong innate immune responses that mimic immune activation by viral infections. Our previous findings suggest that activation of the innate immune system in astrocytes results in impairments of neurite outgrowth and spine formation, which lead to behavioral abnormalities in adulthood. Although glial cells are classically thought to provide structural and metabolic support to neurons, they are now widely recognized as essential regulators of neuronal development including neuronal migration, axon and dendrite growth, formation of synapses, and synaptic plasticity. Astrocytes also play critical roles in regulating CNS immune function by responding to inflammatory mediators and producing additional cytokines and chemokines. Most of the functions of astrocytes are mediated by the release of humoral factors through a close interaction with neurons. However, the mechanism by which innate immune activation of astrocytes affects neuronal development remains to be determined. To explore the alteration in proteins secreted from murine astrocytes after polyI:C stimulation, astrocyte-conditioned medium (ACM) was analyzed by 2-dimensional fluorescence difference gel electrophoresis (2D-DIGE). We identified matrix metalloproteinase-3 (Mmp3) as a potential mediator of polyI:C/ACM-induced neurodevelopmental impairment. Here, we provide an overview of the mechanism of neurodevelopmental impairment following polyI:C-induced innate immune activation of astrocytes.

We report herein on a 52-year-old Japanese woman with acute pericarditis and glomerulonephritis associated with human parvovirus B19 infection, who had no significant medical history. The patient was admitted for progressive edema and upper abdominal pain. On physical examination, she had hypertension, generalized edema and upper abdominal tenderness. Urinalysis revealed protein (1+), and occult blood (+/-), with cellular casts. Echocardiography revealed pericardial effusion measuring 3-9mm in diameter. A serological test showed elevation of serum IgM antibodies for parvovirus B19. At the end of two weeks, generalized edema and glomerulonephritis improved spontaneously, and pericardial effusion was resolved three weeks after admission. This case would appear to be a very rare case indicating a direct relationship between human parvovirus B19 infection and acute pericarditis in a healthy adult patient.

Unlabelled: OBJECTIVE; The COBAS TaqMan real-time polymerase chain reaction (PCR) assay (TaqMan assay) is a well-accepted and widely distributed molecular-based diagnostic test for tuberculosis. In the present study, we evaluated the efficacy of the LAMP assay (loopamp MTBC detection kit) as an alternative molecular-based diagnostic kit for tuberculosis, through comparison with the TaqMan assay. STUDY PERIOD AND METHODS: This study was conducted over a period of approximately 2 months, between May and July 2012. We collected 48 samples (43 sputum, 2 gastric fluid, 2 pleural fluid, and 1 pus fluid samples) from patients who had been diagnosed with tuberculosis through the culture method, but had not received any treatment for more than one week. All samples were processed using the CC-E pre-treatment reagent (Japan BCG) prior to performing the TaqMan and LAMP assay. For the TaqMan assay, 100 microL of supernatant was used after centrifugation at 1,000 rpm for 1 minute, whereas 60 microL of the precipitate in the same sample was used for the LAMP assay., Results: In total, 23 out of 48 samples were identified as positive for tuberculosis according to smear microscopy tests, among which 15, 4, and 4 samples had smear test scores or 1+, 2+, and 3+, respectively. All the samples that tested positive in the smear test, regardless of the score, also tested positive in both the TaqMan and TB-LAMP assays (100%). Of the 25 smear-negative samples, we noted that 16 tested positive by the TaqMan assay (64%), whereas 20 tested positive by the LAMP assay (80%)., Discussion: Compared with the TaqMan assay, the LAMP assay showed a higher positive rate among the smear-negative samples. We believe that this is because substances in the samples acted as co-precipitating agents, resulting in the presence of a larger number of bacteria in the precipitates than in the supernatants. Thus, the findings indicate that the application of the LAMP method to precipitates obtained following CC-E pre-treatments may lead to prompt diagnosis of tuberculosis, with a level of sensitivity comparable to that of culture tests.

Development of animal models is a crucial issue in biological psychiatry for the search of novel drug targets as well as the screening of candidate compounds. Epidemiologic studies suggest that environmental insults, such as prenatal infection and perinatal complication, are involved in the development of schizophrenia. Recently, we have developed a novel mouse model of viral infection during the perinatal stage by injecting polyriboinosinic-polyribocytidilic acid (polyI:C) into neonatal mice. Neonatal treatment of mice with polyI:C, an inducer of innate immune responses via toll-like receptor 3, caused a significant increase in interferon-induced transmembrane protein 3 (IFITM3) levels in the astrocytes of the hippocampus, which resulted in long-lasting brain dysfunction, including cognitive and emotional impairments as well as a deficit in depolarization-evoked glutamate release in the hippocampus in adulthood. Neonatal polyI:C-induced neuronal impairments have not been observed in IFITM3-KO mice. These findings suggest that the induction of IFITM3 expression in astrocytes by the activation of the innate immune system during the early stages of neurodevelopment has non-cell autonomous effects that affect subsequent neurodevelopment, leading to neuropathological impairments and brain dysfunction, by impairing endocytosis in astrocytes.

Advance in the live imaging technology revealed that cells display a variety of Ca(2 +) dynamics, such as the wave, oscillation, blip, puff and spark. Accumulating evidences suggest that not only Ca(2 +) itself, but its spatio-temporal dynamics are the important information carrier in the physiological responses. Here, we will introduce the pattern of Ca(2 +) dynamics along with the latest version of high-performance Ca(2 +) probes.

People with epilepsy have a high incidence of mood disorders that may affect their quality of life. Lamotrigine(LTG)is one of the antiepileptic drugs that are commercially available in Japan these days and its mood-stabilizing qualities were well known. First, 66 outpatients with epilepsy were evaluated for changes in mood states by the Profile of Mood States(POMS)and the Japanese-edition Beck Depression Inventory-Second Edition(BDI-II)on self report. The POMS questionnaire includes 30 items that address six components of mood. At baseline, one third of the outpatients with epilepsy had mood problems compared by POMS health reference. The mean BDI-II baseline score was 14.9±10.1, and one third of these epilepsy patients exhibited moderate or severe depression. Second, in the twelve patients with epilepsy, LTG was added to other antiepileptic drugs, and the POMS and BDI-II were administered at baseline and after addiction to LTG. 4 out of 8(50%)patients with simple partial seizure and 5 out of 8(62.5%)patients after the adjunctive therapy experienced at least a 50% reduction in the number of seizures compared with the self-reported baseline before the adjunctive therapy. The component scores of Depression-Dejection, Anger-Hostility and Confusion-Bewilderment in POMS were statistically improved in these patients completing adjunctive LTG(pared t-test, p<0.05). In these patients, the mean BDI-II baseline score was 25.8±13.1. Following administration of LTG, there was a significant decrease in the mean BDI-II scores(15.0±6.6)between baseline and the end of adjunctive LTG. This study suggests that, in addition to seizure control, LTG may have a mood-stabilizing effect and improve the quality of life in patients with epilepsy.

We report a case of a 15-year-old girl with relapsing-remitting multiple sclerosis (MS) who received cyclophosphamide pulse therapy. At the age of 5 years, she displayed symptoms such as headache and unconsciousness after varicella infection as the first episode of MS. She had been treated with methylprednisolone pulse therapy, intravenous immunoglobulin, interferon-beta1b, and azathioprine. However, she had relapsed 12 times by the age of 15 years. At this time, she showed weakness and severe paralysis of her left leg, and even 1 month after methylprednisolone pulse therapy, she still had gait impairment and showed gadolinium-enhanced lesion on brain magnetic resonance imaging. We then started cyclophosphamide pulse therapy (600 mg/m2) once a month for 12 months combined with interferon-beta1a. She had no serious side effects and she could walk again after 4 months on cyclophosphamide treatment. She has been free from relapse for 2 years and 8 months until the present time. Although only a few studies have indicated the efficacy of cyclophosphamide pulse therapy for childhood MS, we consider careful use of cyclophosphamide could be one of the options for refractory childhood MS.

Objective: We have previously reported the modified parent training of smaller groups and shorter schedules (PTSS). In this study, we applied PTSS to the mothers of children with pervasive developmental disorder (PDD) and revealed the new evidence for its effectiveness., Methods: The participants were 30 mothers of children with PDD aged from 4.2 to 9.6 years. The effectiveness of PTSS was assessed with the confidence degree questionnaire (CDQ) and the child behavior checklist (CBCL), before and after each PTSS course. The recorded interviews were qualitatively analyzed using the KJ (Kawakita Jiro) methods., Results: Average CDQ scores were clearly improved as previously reported. In addition, the CBCL total T-score was significantly improved, which was not observed in the previous study. About KJ methods, six factors that change of mothers recognition were identified., Conclusions: Our findings provides additional evidence for the usefulness of PTSS for children with PDD.

Schizophrenia is associated with enormous morbidity, mortality, personal disability, and social cost. Although considerable research on schizophrenia has been performed, the etiology of this disease has not been fully elucidated. In recent years, imaging and genetic technologies have been developed dramatically. Disturbances in glutamate and GABAergic neurotransmission may underlie the pathophysiology of schizophrenia. We attempted an integrative review, of studies pertaining to recent advances of schizophrenia research with a focus on neuroimaging and genetic studies. Additionally, we present the preliminary findings of the clinical research in our outpatient unit, specialized for early intervention, at the University of Tokyo Hospital.

We report a case of fulminant brachial plexopathy with radicular involvement. A 25-year-old man developed acute total monoplegia in the left upper limb. Needle electromyography showed extensive acute denervation in the C5-T1 spinal segments, and peripheral sensory nerve conduction was normal, mimicking a pre-ganglionic lesion. However, left median somatosensory evoked potentials revealed abnormal Erb's point potential, suggesting a brachial plexus lesion. Corticosteroid treatment resulted in good recovery. These findings suggest that the primary pathophysiology was conduction block and this can explain the good clinical recovery in this patient.

A 69-year-old woman was admitted because of unconsciousness and multiple cranial neuropathy. She had suffered diarrhea 2 weeks previously. On examination, she was noted to have total external and internal ophthalmoplegia, bilateral facial palsy, dysphagia, dysarthria, neck weakness, distal motor weakness of all limbs, and ataxia. She had also presented with hyporeflexia and hypoesthesia, but with a bilateral pyramidal tract sign. A study of her cerebrospinal fluid revealed albuminocytologic dissociation, and nerve conduction study revealed demyelination of her peripheral nerves. Moreover, electroencephalography findings were abnormal and anti-GQ1b antibody was positive. We diagnosed Fisher syndrome with Guillain-Barré syndrome and Bickerstaff brainstem encephalitis. We administered intravenous immunoglobulin treatment for 5 days and her symptoms gradually improved. However, her external ophthalmoplegia continued for several months.

Schizophrenia affects nearly 1% of the population and is clinically characterized by positive symptoms (e.g. delusions and hallucinations), negative symptoms (e.g. affective flattening, apathy and social withdrawal) and cognitive dysfunction. Genetic susceptibility factors for schizophrenia, such as neuregulinl, dysbindin and disrupted-in-schizophrenia 1 (DISC1), have recently been reported, some of which play a role in neurodevelopment. Furthermore, epidemiologic studies suggest that environmental insults, such as prenatal infection and perinatal complication, are involved in the development of schizophrenia. The possible interaction between environment and genetic susceptibility factors is proposed as a promising disease etiology of schizophrenia. Polyriboinosinic-polyribocytidylic acid (polyI:C), a toll-like receptor 3 ligand, induces a strong innate immune response. Maternal immune activation by polyI:C exposure in rodents induces a wide spectrum of behavioral and neurochemical abnormalities in adult offspring. We have reported that neonatal injection of polyI:C in mice results in schizophrenia-like behavioral abnormalities in adulthood. In this review, we show how gene-environment interactions during neurodevelopment result in phenotypic changes in adulthood, by injecting polyI:C into transgenic mice that express a dominant-negative form of human DISC1 (DN-DISC1). Our findings suggest that polyI:C-treated DN-DISC1 mice are a validated animal model for schizophrenia with gene-environment interactions.

Valproate sodium (VPA) is a commonly used antiepileptic drug. However, various side effects, including liver dysfunction, thrombocytopenia, anorexia, hyperammonemia, and pancreatitis have been reported in association with the administration of VPA. Recently, renal Fanconi syndrome associated with VPA treatment has occasionally been reported. However, the mechanisms and detailed characteristics of this adverse effect remain unknown. We herein report three cases of Fanconi syndrome associated with VPA treatment. All of these patients were severely disabled children, who had been previously treated with multiple antiepileptic drugs, and also required tube feeding. The possible risk factors of Fanconi syndrome in these three cases were similar to those previously reported in the literature. In addition, all three patients developed Fanconi syndrome after the onset of bacterial infections. Before developing Fanconi syndrome, hypouricemia was observed in all three and an increased urinary level of beta2 microglobulin (beta2MG) was also noted in one of the patients. None of these patients had hypophosphatemia. Two patients had an appropriate serum VPA level, while the other had an inappropriately high level. We therefore recommend that severely disabled children receiving multiple antiepileptic drugs and tube feeding be periodically checked for urinary beta2MG and uric acid, especially during the course of any infectious episodes.

Oka varicella vaccine was developed to confer active immunity to varicella-zoster virus (VZV) in immunocompromized and immunocompetent children. It is now used to prevent varicella in about 20 million people worldwide. Although VZV infectivion is relatively unstable compared to other viruses, cell-free virus is stabilized and lyophilized vaccine has been developed. Virus titers were evaluated in vaccine distributed to six clinics in 5 years. Yearly mean virus titers at the vaccine producer were 42,000-67,000 plaque-forming units per dose, corresponding to Oka varicella vaccine (Zostavax) used to prevent zoster and postherpetic neuralgia by Oxman et al. Virus titer was found to be stable during delivery to clinics. Virus titers of varicella vaccine were equivalent to Zostavax and vaccine delivered to clinics had enough virus titer to confer active immunity to VZV in this study.

The response criteria proposed by European Leukemia Net are useful to predict the prognosis of de novo chronic myeloid leukemia (CML) patients in the chronic phase (CP) treated with imatinib. However, the clinical significance of late suboptimal response, which is defined as the achievement of CCgR without MMR after 18 months, is controversial. In this study, we retrospectively analyzed the clinical courses of 16 CML-CP patients, who satisfied the criteria for late suboptimal response. The median duration of imatinib treatment was 62 (25∼87) months. The median starting dose of imatinib was 400 mg/day. Imatinib dose was escalated to 600∼800 mg/day in 10 patients for various reasons. Among 4 patients who continued high-dose imatinib for late suboptimal response, 2 patients subsequently achieved MMR, and BCR-ABL mRNA transcript levels were decreasing in 2 patients. However, imatinib was kept at 300 or 400 mg/day in 6 patients. Among these six patients, 4 patients achieved MMR, while 2 failed to achieve MMR. None of 16 patients progressed to the acute phase or blast phase. Imatinib dose escalation was effective for late suboptimal response. Furthermore, a second tyrosine kinase inhibitor such as nilotinib may be more potent to reduce the risk of disease progression by achieving earlier MMR.

Recent molecular biological analyses of leukemia cells have revealed that deregulation of various cellular signaling pathways and deregulation of epigenetic regulation are involved in the development of leukemia. Based on these findings, many kinds of small molecular compounds have been developed to inhibit the function of proteins that are involved in signaling pathways or to modify the epigenetic regulation. These reagents include tyrosine kinase inhibitors, histone deacetylase inhibitors and DNA metyltransferase inhibitors. Furthermore, a monoclonal antibody against CD33 conjugated to an anti-cancer agent is currently being used for AML treatment. Effects of combinations of these reagents have also been examined in detail. These molecular targeted therapies are expected to improve the effectiveness of leukemia therapy.

Methamphetamine is a highly addictive drug of abuse, addiction to which has increased to epidemic proportions worldwide. It has been suggested that chronic use of methamphetamine causes long-term cognitive deficits, in addition to psychiatric signs such as hallucination and delusions, which are indistinguishable from paranoid schizophrenia. Neuroimaging studies in methamphetamine abusers have demonstrated that the loss of dopamine transporters in the striatum is related to motor and cognitive impairment. In this review, we will focus on the effect of repeated treatment with methamphetamine on cognitive function in rodents. Repeated methamphetamine treatment in mice impairs long-term recognition memory after withdrawal, which is associated with the dysfunction in dopamine D1 receptor-extracellular signal-regulated kinase 1/2 (ERK1/2) pathway in the prefrontal cortex. Methamphetamine-induced impairment of recognition memory is reversed by baclofen, clozapine, minocycline and ZSET1446. Repeated methamphetamine treatment in rats also induces impairment of spatial working memory, which is accompanied by the dysfunction of ERK1/2 pathway in the hippocampus. Repeated administration of clozapine, but not haloperidol, improves methamphetamine-induced spatial working memory impairment. These findings suggest that ERK1/2 plays an important role in memory impairments induced by repeated methamphetamine treatment. These animal models of cognitive deficits may be useful to predict the clinical effects of antipsychotics in methamphetamine psychosis and other mental disorders such as schizophrenia.

Purpose: Two cases of pediatric orbital rhabdomyosarcoma leading to visual dysfunction with rapid growth., Cases: A two-year-old girl who presented with eyelid edema. MRI revealed a tumor in the orbit. The tumor grew rapidly resulting in eye ball displacement and corneal epithelium disorder, and was subsequently removed. Histopathological examination revealed randomly proliferating cells shaped from small round to spindle cells positive for myogenin, desmin and HHF 35 in immunohistochemistry. Based on histopathology and clinical examination, diagnosis of embryonal rhabdomyosarcoma was made. A nine-year-old boy presented with eyelid edema. MRI revealed a tumor under the skin of the upper palpebra extending to the orbit. The tumor grew rapidly to the extent that the eyelids could not be opened spontaneously. Hisitopathologically, spindle-shaped cells were detected proliferating randomly in myxomatous stroma, positive for myogenin and desmin in immunohistochemistry. Based on histopathology and clinical examination, diagnosis of embryonal rhabdomyosarcoma was made. Genetic analysis depicted aberration of chromosome 7 in the first case and tetraploidy in the second case. Both patients subsequently underwent chemotherapy and local radiotherapy and no recurrence has been detected over 1 year., Conclusion: Although rhabdomyosarcoma of the orbit often progresses rapidly and may cause visual disturbances, favorable outcome can be expected by proper management especially in cases with certain histopathological types. A comprehensive approach will be required to elucidate the pathogenesis of orbital rhabdomyosarcoma and genetic abnormalities.