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Intercurrent events and estimands play a key role in defining the treatment effects of interest precisely. Sometimes the median or other quantiles of outcomes in a principal stratum according to potential occurrence of intercurrent events are of interest in randomized clinical trials. Naïve analyses such as those based on the observed occurrence of the intercurrent events lead to biased results. Therefore, we propose principal quantile treatment effect estimators that can nonparametrically estimate the distribution of potential outcomes by principal score weighting without relying on the exclusion restriction assumption. Our simulation studies show that the proposed method works in situations where the median or quantiles may be regarded as the preferred population-level summary over the mean. We illustrate our proposed method by using data from a randomized controlled trial conducted on patients with nonerosive reflux disease., (© 2024 Takeda Pharmaceutical Company Limited. Statistics in Medicine published by John Wiley & Sons Ltd.)

In middle to late 2023, a sublineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron XBB, EG.5.1 (a progeny of XBB.1.9.2), is spreading rapidly around the world. We performed multiscale investigations, including phylogenetic analysis, epidemic dynamics modeling, infection experiments using pseudoviruses, clinical isolates, and recombinant viruses in cell cultures and experimental animals, and the use of human sera and antiviral compounds, to reveal the virological features of the newly emerging EG.5.1 variant. Our phylogenetic analysis and epidemic dynamics modeling suggested that two hallmark substitutions of EG.5.1, S:F456L and ORF9b:I5T are critical to its increased viral fitness. Experimental investigations on the growth kinetics, sensitivity to clinically available antivirals, fusogenicity, and pathogenicity of EG.5.1 suggested that the virological features of EG.5.1 are comparable to those of XBB.1.5. However, cryo-electron microscopy revealed structural differences between the spike proteins of EG.5.1 and XBB.1.5. We further assessed the impact of ORF9b:I5T on viral features, but it was almost negligible in our experimental setup. Our multiscale investigations provide knowledge for understanding the evolutionary traits of newly emerging pathogenic viruses, including EG.5.1, in the human population., (© 2024 The Author(s). Microbiology and Immunology published by The Societies and John Wiley & Sons Australia, Ltd.)

In late 2023, several SARS-CoV-2 XBB descendants, notably EG.5.1, were predominant worldwide. However, a distinct SARS-CoV-2 lineage, the BA.2.86 variant, also emerged. BA.2.86 is phylogenetically distinct from other Omicron sublineages, accumulating over 30 amino acid mutations in its spike protein. Here, we examined the virological characteristics of the BA.2.86 variant. Our epidemic dynamics modeling suggested that the relative reproduction number of BA.2.86 is significantly higher than that of EG.5.1. Additionally, four clinically available antivirals were effective against BA.2.86. Although the fusogenicity of BA.2.86 spike is similar to that of the parental BA.2 spike, the intrinsic pathogenicity of BA.2.86 in hamsters was significantly lower than that of BA.2. Since the growth kinetics of BA.2.86 are significantly lower than those of BA.2 both in vitro and in vivo, the attenuated pathogenicity of BA.2.86 is likely due to its decreased replication capacity. These findings uncover the features of BA.2.86, providing insights for control and treatment., Competing Interests: Declaration of interests J.I. has consulting fees and honoraria for lectures from Takeda Pharmaceutical Co. Ltd. K. Sato has consulting fees from Moderna Japan Co., Ltd. and Takeda Pharmaceutical Co. Ltd. and honoraria for lectures from Gilead Sciences, Inc., Moderna Japan Co., Ltd., and Shionogi & Co., Ltd., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Circulation of SARS-CoV-2 Omicron XBB has resulted in the emergence of XBB.1.5, a new Variant of Interest. Our phylogenetic analysis suggests that XBB.1.5 evolved from XBB.1 by acquiring the S486P spike (S) mutation, subsequent to the acquisition of a nonsense mutation in ORF8. Neutralization assays showed similar abilities of immune escape between XBB.1.5 and XBB.1. We determine the structural basis for the interaction between human ACE2 and the S protein of XBB.1.5, showing similar overall structures between the S proteins of XBB.1 and XBB.1.5. We provide the intrinsic pathogenicity of XBB.1 and XBB.1.5 in hamsters. Importantly, we find that the ORF8 nonsense mutation of XBB.1.5 resulted in impairment of MHC suppression. In vivo experiments using recombinant viruses reveal that the XBB.1.5 mutations are involved with reduced virulence of XBB.1.5. Together, our study identifies the two viral functions defined the difference between XBB.1 and XBB.1.5., (© 2024. The Author(s).)

Introduction: Solid and sensitive infectious disease surveillance systems need to be developed and implemented to prevent and control epidemics. Although statutory national infectious disease surveillance systems have been developed in many countries, some challenges remain, such as their limited timeliness, representativeness, and sensitivity, as well as the fact that they cannot capture all local outbreaks that occur in small communities. To overcome these limitations, local community-based infectious disease surveillance systems that meet local needs and can operate with constrained resources need to be developed, especially in remote and rural low-resource areas. This study aimed to develop, implement, and evaluate a voluntary and unique local community-based ophthalmology sentinel surveillance system in Isa city (OSSS-Isa), a remote rural area in Japan., Methods: For the development of OSSS-Isa, one hospital in Isa city assumed a leading role and developed a network with all medical institutions - 20 hospitals and clinics in the local community, including two ophthalmology clinics - as sentinel reporting sites. Surveillance was conducted on a weekly basis from Monday to Sunday. The collection, aggregation, and reporting of the surveillance data were implemented promptly on the same day, Monday, using a paper-based form and fax. For the evaluation of OSSS-Isa, the study followed the updated guidelines for evaluating public health surveillance systems proposed by the Centers for Disease Control and Prevention to select the evaluation criteria and develop a questionnaire. The questionnaires were then distributed to 20 hospitals and clinics, with the responses evaluated on a five-point Likert scale., Results: For the implementation of OSSS-Isa, the system issued alerts twice to the networked hospitals and clinics when signs of an increase in the prevalence of a target infectious eye disease appeared in Isa city. After the alerts, the number of cases decreased in the community. Regarding the evaluation survey, physicians from 18 hospitals and clinics responded to the questionnaire (response rate 90%). In contrast to flexibility, more than 75% of the respondents gave high ratings to simplicity, data quality, acceptability, timeliness, and stability in evaluating OSSS-Isa, with the mean score for these evaluation criteria higher than 3.67., Conclusion: The present results indicate that OSSS-Isa has high simplicity, data quality, acceptability, timeliness, and stability, which is highly embedded with the local healthcare providers in Isa city. OSSS-Isa contributed to the early and accurate detection of signs of infectious eye disease outbreaks emerging in a small remote rural local community. The success factors seem to include its simple well-designed implementation methods, good external factors, and active human factors suited to the characteristics of the small remote rural community. The OSSS-Isa initiative appears to be a meaningful practical example of successful health advocacy by healthcare providers by developing a system at the local social level while going beyond the boundaries of routine medical practice. If voluntary small-scale surveillance systems can complement statutory large-scale ones and work together locally, nationally, and internationally, it might be possible to detect small, unusual happenings that occur in the community, such as emerging infectious diseases, and thereby help avert global outbreaks.

Objective: Previous studies have used selective recall and descriptive dietary record methods, requiring considerable effort for assessing food and water intake. This study created a simplified lifestyle questionnaire to predict habitual water intake (SQW), accurately and quickly assessing the habitual water intake. We also evaluated the validity using descriptive dietary records as a cross-sectional study., Subjects and Methods: First, we used crowdsourcing and machine learning to collect data, predict water intake records, and create questionnaires. We collected 305 lifestyle-related questions as predictor variables and selective recall methods for assessing water intake as an outcome variable. Random forests were used for the machine learning models because of their interpretability and accurate estimation. Random forest and single regression correlation analysis were augmented by the synthetic minority oversampling that trained the model. We separated the data by sex and evaluated our model using unseen hold-out testing data, predicting the individual and overall habitual water intake from various sources, including non-alcoholic beverages, alcohol, and food., Results: We found a 0.60 Spearman's correlation coefficient for total water intake between the predicted and the selective recall method values, reflecting the target value to be achieved. This question set was then used for feasibility tests. The descriptive dietary record method helped to obtain a ground-truth value. We categorized the data by gender, season, and source: non-alcoholic beverages, alcohol, food, and total water intake, and the correlation was confirmed. Consequently, our results showed a Pearson's correlation coefficient of 0.50 for total water intake between the predicted and the selective recall method values., Conclusions: We hypothesize that dissemination of SQW can lead to better health management by easily determining the habitual water intake.

Microbubble testing using transcranial Doppler (TCD) is an important screening tool for diagnosing paradoxical cerebral embolism with high-risk PFO. However, little is known about the association between the microbubble test by TCD and the features of high-risk PFO evaluated by transesophageal echocardiography (TEE). We studied 101 consecutive patients at Showa University, from April 2019 to October 2020, who underwent both TCD and TEE with a sufficient Valsalva maneuver and who were strongly suspected by neurologists as cryptogenic stroke. According to the appearance of microbubbles as high-intensity transient signals (HITS), the TCD grade was stratified into three categories based on the criteria (A: none, no HITS, B: small; 1-10 HITS, and C: large; > 10 HITS, or an uncountable number of HITS). Among patients with RLS through the PFO in TEE, high-risk morphological features of PFO for cerebral embolism were evaluated as follows: (1) tunnel height, (2) tunnel length, (3) total excursion distance of the atrial septum into the right and left atrium, (4) existence of Eustachian valve or Chiari network, (5) angle of PFO from the inferior vena cava, and (6) large shunt (20 or more microbubbles). Of 101 patients (TCD grade; Group A = 49, Group B = 26, Group C = 26), RLS through PFO was detected in 37 patients (grade A = 8, grade B = 6, grade C = 23) by TEE. Among PFO-positive patients, tunnel height, length, total excursion distance into the right and left atria, angle of PFO from the inferior vena cava, and frequency of large shunt in TEE were significantly larger in grade C than in grade A and B (p < 0.05). Additionally, grade C patients had significantly more forms of high-risk PFOs than those in grades A and B when the six features of high-risk PFO were compared. A multivariate logistic regression demonstrated that the tunnel length of PFO and the presence of large shunt in TEE were independently associated with large HITS in TCD (odds ratio: 1.18 and 49.5, 95% confidence interval 1.043-1.337 and 10.05-244.3, p = 0.0086 and p < 0.0001, respectively). In conclusion, the existence of a large HITS detected by TCD may have a screening advantage in predicting the high-risk morphologies of PFO that can cause paradoxical cerebral embolism., (© 2022. Springer Japan KK, part of Springer Nature.)

The mammarenavirus Lassa virus (LASV) causes a life-threatening acute febrile disease, Lassa fever (LF). To date, no US Food and Drug Administration (FDA)-licensed medical countermeasures against LASV are available. This underscores the need for the development of novel anti-LASV drugs. Here, we screen an FDA-approved drug library to identify novel anti-LASV drug candidates using an infectious-free cell line expressing a functional LASV ribonucleoprotein (vRNP), where levels of vRNP-directed reporter gene expression serve as a surrogate for vRNP activity. Our screen identified the pan-ErbB tyrosine kinase inhibitor afatinib as a potent inhibitor of LASV vRNP activity. Afatinib inhibited multiplication of lymphocytic choriomeningitis virus (LCMV) a mammarenavirus closely related to LASV. Cell-based assays revealed that afatinib inhibited multiple steps of the LASV and LCMV life cycles. Afatinib also inhibited multiplication of Junín virus vaccine strain Candid#1, indicating that afatinib can have antiviral activity against a broad range of human pathogenic mammarenaviruses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: School refusal occurs in about 1-2% of young people. Anxiety and depression are considered to be the most common emotional difficulties for children who do not attend school. However, at present, no definitive treatment has been established for school refusal, although interventions such as cognitive behavioral therapy have been used. This paper reports a protocol for a cluster-randomized controlled trial of a mindfulness yoga intervention for children with school refusal., Methods: This study is a multicenter, exploratory, open cluster-randomized controlled trial. This study will recruit children aged 10-15 years with school refusal. After a 2-week baseline, participants for each cluster will be randomly assigned to one of two groups: with or without mindfulness yoga for 4 weeks. Mindfulness yoga will be created for schoolchildren for this protocol and distributed to the participants on DVD. The primary outcome is anxiety among children with school refusal using the Spence Children's Anxiety Scale-Children., Discussion: For this study, we developed a mindfulness yoga program and protocol, and examine whether mindfulness yoga can improve anxiety in children with school refusal. Our mindfulness yoga program was developed based on the opinions of children of the same age, and is a program that children can continue to do every day without getting bored. In this way, we believe that we can contribute to the smooth implementation of support to reduce the anxiety of children with school refusal, and to the reduction of the number of children who refuse to go to school., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Amitani, Amitani, Owaki, Monuki, Adachi, Kawazu, Fukumoto, Suzuki, Yoshimura, Mizuma, Nishida, Watanabe, Hirose, Funakoshi, Ota, Murotani and Asakawa.)

Background: The purpose of this study was to develop an objective, content-valid, and reliable assessment method for Kampo medicine using an objective structured clinical examination (OSCE) for the assessment of clinical competence in Kampo medicine., Methods: We developed a blueprint followed by a list of 47 assessment items and three task scenarios related to clinical competence in Kampo medicine. An eight-member test committee checked the relevance of the assessment items on a Likert scale. We calculated a content validity index and content validity ratio, and used the Angoff method to set the passing threshold. We trained a total of nine simulated patients with three assigned to each scenario. We conducted an OSCE for 11 candidates with varying medical abilities, and conducted three stations per person, which were evaluated by one evaluator in one room by direct observation. We used video recordings to test the inter-rater reliability of the three raters. We used the test results to verify the reliability of the assessment chart., Results: The inter-rater reliability (intraclass correlation coefficient [2,1]) was 0.973. The reliability of the assessment chart for each scenario (Cronbach's α) was 0.86, 0.89, and 0.85 for Scenarios 1, 2, and 3, respectively. The reliability of the assessment chart for the whole OSCE (Cronbach's α) was 0.90., Conclusions: We developed a content-valid new OSCE assessment method for Kampo medicine and obtained high inter-rater and test reliabilities. Our findings suggest that this is one of the most reliable evaluation methods for assessing clinical competence in Kampo medicine., (© 2022. The Author(s).)

The increasing burden of tick-borne orthonairovirus infections, such as Crimean-Congo hemorrhagic fever, is becoming a global concern for public health. In the present study, we identify a novel orthonairovirus, designated Yezo virus (YEZV), from two patients showing acute febrile illness with thrombocytopenia and leukopenia after tick bite in Hokkaido, Japan, in 2019 and 2020, respectively. YEZV is phylogenetically grouped with Sulina virus detected in Ixodes ricinus ticks in Romania. YEZV infection has been confirmed in seven patients from 2014-2020, four of whom were co-infected with Borrelia spp. Antibodies to YEZV are found in wild deer and raccoons, and YEZV RNAs have been detected in ticks from Hokkaido. In this work, we demonstrate that YEZV is highly likely to be the causative pathogen of febrile illness, representing the first report of an endemic infection associated with an orthonairovirus potentially transmitted by ticks in Japan., (© 2021. The Author(s).)

This study aimed to estimate the water intake of Japanese people from food moisture. For this purpose, we described a water conversion factor for cooking (WCFC) that focuses on how cooking changes the water content of complete dishes and not food ingredients, and investigated methods for calculating the water content of cooked dishes. In this study, we utilized 129 dishes commonly consumed by Japanese people. We measured the water content of the dishes before and after cooking and calculated the percentage of residual water after cooking. The dishes were divided into staple foods or side dishes, and categorized based on residual percentage in water content and cooking method. The percentage of residual water after cooking change in water content in each category was expressed in terms of the WCFC, which is the water content of the cooked dish relative to the uncooked dish. In total, there were 43 categories with a WCFC range of 0.40 to 1.33. Our results revealed that the water content of food is not simply changed by heating-based cooking methods, but by a complex combination of cooking operations. Furthermore, by fitting WCFC to a culinary structuralism theory, it can potentially be utilized for all cuisines and not just dishes in Japan. Additionally, we found that the water content of a day's worth of food calculated using WCFC and actual measurements barely differed, indicating that WCFC could potentially be used to estimate water intake from food moisture. PRACTICAL APPLICATION: This research can be used in nutrition surveys to estimate water intake from food moisture., (© 2021 Institute of Food Technologists®.)

Comprehensive discharge planning provided by interprofessional collaboration is critical for discharging patients from hospitals to home. For effective interprofessional discharge planning, the evaluation that clarifies the differences in assessment viewpoints between various healthcare professionals is needed. This study aimed to clarify the assessment viewpoints of multiple healthcare professional groups when discharging patients from a long-term care hospital (LTCH) to home. We reviewed 102 medical records from an LTCH in Japan, extracted descriptions of discharge planning assessments written by 3 doctors, 13 nurses, 3 physical therapists, 13 care workers, and 2 social workers, linked these to the International Classification of Functioning, Disability and Health, and conducted the statistical analysis. Doctors and nurses significantly focused on "Body Functions". Physical therapists and care workers significantly focused on "Activities and Participation". Social workers significantly focused on "Environmental Factors". We also identified the factors less or missing from assessments in the clinical field of the LTCH. Our findings could be contributed as a base of knowledge to foster a better understanding of different healthcare professionals' assessment viewpoints. The further development of comprehensive discharge planning assessment tools, service programs, and research on discharge planning methods that could contribute to effective interprofessional discharge planning is needed., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The recent emergence of novel tick-borne RNA viruses has complicated the epidemiological landscape of tick-borne infectious diseases, posing a significant challenge to public health systems that seek to counteract tick-borne diseases. The identification of two novel tick-borne phleboviruses (TBPVs), severe fever with thrombocytopenia syndrome virus (SFTSV) and Heartland virus (HRTV), as causative agents of severe illness in humans has accelerated the investigation and discoveries of novel TBPVs. In the present study, we isolated a novel TBPV designated Mukawa virus (MKWV) from host-questing Ixodes persulcatus females captured in Japan. Genetic characterization revealed that MKWV is a member of the genus Phlebovirus in the family Phenuiviridae Interestingly, MKWV is genetically distinct from other known TBPVs and shares a most recent common ancestor with mosquito/sandfly-borne (insect-borne) phleboviruses. Despite its genetic similarity to insect-borne phleboviruses, the molecular footprints of its viral proteins and its biological characteristics define MKWV as a tick-borne virus that can be transmitted to mammals. A phylogenetic ancestral-state reconstruction for arthropod vectors of phleboviruses including MKWV based on viral L segment sequences indicated that ticks likely harbored ancestral phleboviruses that evolved into both the tick-borne and MKWV/insect-borne phlebovirus lineages. Overall, our findings suggest that most of the phlebovirus evolution has occurred in hard ticks to generate divergent viruses, which may provide a seminal foundation for understanding the mechanisms underlying the evolution and emergence of pathogenic phleboviruses, such as Rift Valley fever virus and SFTSV/HRTV. IMPORTANCE The emergence of novel tick-borne RNA viruses causing severe illness in humans has complicated the epidemiological landscape of tick-borne diseases, requiring further investigation to safeguard public health. In the present study, we discovered a novel tick-borne phlebovirus from Ixodes persulcatus ticks in Japan. While its viral RNA genome sequences were similar to those of mosquito/sandfly-borne viruses, molecular and biological footprints confirmed that this is a tick-borne virus. The unique evolutionary position of the virus allowed us to estimate the ancestral phlebovirus vector, which was likely a hard tick. Our findings may provide a better understanding of the evolution and emergence of phleboviruses associated with emerging infectious diseases, such as severe fever with thrombocytopenia syndrome (SFTS) and Heartland virus disease., (Copyright © 2018 Matsuno et al.)

With our aging society, more people hope for a long and healthy life. In recent years, researchers have focused on healthy longevity factors. In particular, calorie restriction delays aging, reduces mortality, and extends life. Ghrelin, which is secreted during fasting, is well known as an orexigenic peptide. Because ghrelin is increased by caloric restriction, ghrelin may play an important role in the mechanism of longevity mediated by calorie restriction. In this review, we will discuss the role of orexigenic peptides with a particular focus on ghrelin. We conclude that the ghrelin-growth hormone secretagogue-R signaling pathway may play an important role in the anti-aging mechanism., Competing Interests: No author has relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.

We report the case of a 7-month-old boy who developed hypofibrinogenemia (66.6 mg/dL; reference value, 170-405 mg/dL) during adrenocorticotropic hormone (ACTH) therapy for infantile spasms. Although the patient showed no clinical signs of a bleeding diathesis, we recommend that plasma fibrinogen levels should be monitored during ACTH therapy, which should be discontinued when fibrinogen levels fall below hemostatic levels (60.0mg/dL) or when bleeding tendencies are recognized., (Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

A 48-year-old woman with no previous neurological diseases was transferred to our hospital because of sudden-onset unconsciousness. On arrival, she showed consciousness disturbance (E1V1M3 on the Glasgow Coma Scale), tetraplegia, right conjugate deviation and bilateral pathological reflexes. These symptoms resulted in a NIH stroke scale score of 32. Brain diffusion-weighted MR imaging (DWI) showed multiple hyper-intense lesions, and MR angiography revealed occlusions of the basilar artery (BA) and superior branch of the right middle cerebral artery (MCA). Transthoracic echocardiography disclosed a 51 × 24 mm myxoma in the left atrium. These findings led to diagnosis of acute ischemic stroke due to embolization from cardiac myxoma. Thrombolytic therapy with intravenous tissue plasminogen activator (IV tPA) was started 120 min after onset because there were no contraindications for this treatment. However, the symptoms did not resolve, and thus endovascular therapy was performed immediately after IV tPA. Angiography of the left vertebral artery initially showed BA occlusion, but a repeated angiogram resulted in spontaneous recanalization of the BA. However, the left posterior cerebral artery remained occluded by a residual embolus. Subsequently, occlusion found in the superior branch of the right MCA was treated by intra-arterial local thrombolysis using urokinase and thrombectomy with a foreign body retrieval device, but the MCA remained occluded. DWI after endovascular therapy showed new hyper-intense lesions in the bilateral medial thalamus and left occipital cortex. Clinically, neurological status did not improve, with a score of 5 on the modified Rankin Scale. IV tPA can be used for stroke due to cardiac myxoma, but development of brain aneurysms and metastases caused by myxoma is a concern. Given the difficulty of predicting an embolus composite from a thrombus or tumor particle, aspiration thrombectomy may be safer and more effective for stroke due to cardiac myxoma to avoid delayed formation of brain aneurysms and metastases.

It is known that the nervous system significantly attenuates systemic inflammatory responses through the parasympathetic nervous system. Furthermore, it has been reported that the alpha 7 subunit of a nicotinic acetylcholine receptor is required for a cholinergic inhibition against cytokine synthesis in a macrophage. As antigen-presenting cells (APCs) play a central role in the generation of primary T cell responses and the maintenance of immunity, in this study, we investigated the expression level of nicotinic receptors of a p53-deficient APC cell line (JawsII) derived from a mouse bone marrow. We showed that stimulation of the JawsII cells with lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNF-alpha) led increase of CD80 and CD86 expression while diminishment of the surface nicotinic receptor. On the other hand, stimulation of nicotinic receptor had no effect on these phenomena. Furthermore, we examined the ability of the cells to release cytokine when stimulated with both nicotine and LPS and showed that the stimulation with LPS augmented the secretion of IL-1a, IL-1b, IL-6, and TNF-alpha. These results suggested that nicotinic stimulation had no effect on the diminishment of alpha 7 nicotinic acetylcholine receptor on JawsII cells by LPS stimulation.

Study Design: Prospective analysis of sagittal vertical axis (SVA) on lateral spine radiographs using 3 different arm positions., Objective: To examine whether fists-on-clavicles position represents a functional standing position., Summary of Background Data: Radiographic visualization of spinal and pelvic sagittal morphology is difficult during relaxed standing because of interference from the arms; however, standing with arms forward-flexed results in a negative shift in SVA. The fists-on-clavicles position was proposed to provide a more functional sagittal profile and adequate visualization of the spine. No existing study compares the SVA between the fists-on-clavicle and relaxed standing positions., Methods: The SVA was measured on standing lateral radiographs of 14 healthy subjects using 3 different arm positions: relaxed with arms-at-side, arms forward-flexed to 45 degrees (shoulder flexion [SF]), and fists-on-clavicles. RESULTS.: The mean SVA with relaxed standing was 1.4 +/- 1.9 cm. SF produced a significant SVA negative shift (-3.7 +/- 2.3 cm, P < 0.001). The fists-on-clavicle position resulted in a reduced but significant SVA negative shift (-2.3 +/- 2.1 cm, P < 0.001) compared with relaxed standing., Conclusion: Although the fists-on-clavicles position was better than SF in reducing the SVA negative shift, a significant negative shift did occur in the fists-on-clavicle position compared with relaxed standing.

Humans are believed to have a preferred amount of stimulus variation in their perceptual environment. Here, paired comparison tests were conducted to examine whether the fluctuation of a flickering light improves subjective preference. Sine-wave and bandpass noise acted as the light source. We have previously shown that the preferred temporal frequency of a flickering light without any fluctuation is approximately 1 Hz (Soeta et al 2002 Journal of the Optical Society of America A 19 289 - 294). This was used as the center frequency of the light source. The bandwidth was set at 1, 2, 4, 8, and 16 Hz, to control the amplitude of the first peak of the autocorrelation function, phi1. Results show that the preferred phi1 of a flickering light is 0.46.

The combination of nicotinic acetylcholine receptors (nAChRs) subunits connecting with the secretion of catecholamines in bovine adrenal chromaffin cells was pharmacologically investigated using selective agonists and antagonists for their nAChRs. The EC(50) values (microM) for the agonists that stimulate the catecholamine secretion and the rank order were as follows: nicotine (3.3)> or =1,1-dimethyl-4-phenylpiperazinium (3.5) > (E)-N-methyl-4-(3-pyridinyl)-3-butene-1-amine (14) > cytisine (23) > or =acetylcholine (25). However, because both the rank order and the EC(50) values differed considerably from those in the various subunits' combinations expressed in Xenopus oocytes or mammalian cells (e.g. alpha2beta2, alpha3beta4, alpha4beta4, etc.), we could not compare them. On the other hand, the IC(50) values (microM) for the antagonists that inhibit the secretion and the rank order were mecamylamine (0.08) > alpha-conotoxin-MII (alpha-CTX-MII) (0.71) > dihydro-beta-erythroidine (DHbetaE) (48) > alpha-bungarotoxin (alpha-BTX) (no effect). Mecamylamine is a highly selective antagonist for alpha3beta4 nAChRs, and alpha-CTX-MII and alpha-BTX are specific antagonists for alpha3beta2 and alpha7 nAChRs, respectively. DHbetaE is a selective antagonist for the alpha4beta2. It has already been shown that the mRNAs for alpha3, alpha5, alpha7 and beta4 subunits are expressed in the chromaffin cells. Therefore, the subunit combination of nAChRs associated with the catecholamine secretion from bovine adrenal chromaffin cells is suggested to be at least alpha3beta4 or alpha3beta4alpha5. Further, the results indicate that the utilization of the nicotinic agonists as selective ligands for the subunit combination of nAChRs may be not suitable for the characterization of nAChRs.

Trichosporin (TS) -B-VIa, a fungal alpha-aminoisobutyric acid (Aib) -containing peptide consisting of 19 amino acid residues and a phenylalaninol, produced both 45Ca2+ influx into bovine adrenal chromaffin cells and catecholamine secretion from the cells. The secretion induced by TS-B-VIa at lower concentrations (2-5 microM) was completely dependent on the external Ca2+, while that induced by TS-B-VIa at higher concentrations (10-30 microM) was partly independent of the Ca2+. The concentration-response curves (2-5 microM) for the TS-B-VIa-induced Ca2+ influx and secretion correlated well. The TS-B-VIa (at 5 microM) -induced secretion was not antagonized by diltiazem, a blocker of L-type voltage-sensitive Ca2+ channels. The treatment of fura-2-loaded C6 glioma cells with TS-B-VIa (2-5 microM) led to an increase in the intracellular free Ca2+ concentration ([Ca2+]i) in a concentration-dependent manner but the stimulatory effects of TS-B-VIa on [Ca2+]i were only slightly observed in Ca(2+)-free medium, indicating that TS-B-VIa causes Ca2+ influx from the external medium into the C6 cells. The TS-B-VIa-induced increase in [Ca2+]i in the C6 cells was not antagonized by diltiazem and by SK&F 96365, a novel blocker of receptor-mediated Ca2+ entry. High K+ increased neither [Ca2+]1 in the C6 cells nor Mn2+ influx into the cells, while TS-B-VIa increased Mn2+ influx. Also in other non-excitable cells, bovine platelets, similar results were obtained. These results strongly suggest that the mechanism of Ca2+ influx by TS-B-VIa at the lower concentrations is distinct from the event of Ca2+ influx through receptor-operated or L-type voltage-sensitive Ca2+ channels in both excitable cells (the chrornaffin cells) and non-excitable cells (the C6 cells and the platelets) and that TS-B-VIa per se may form Ca(2+)-permeable ion channels in biological membranes. On the other hand, the peptide at the higher concentrations seems to damage cell membranes.

Taste perception depends not only on the chemical and physical properties of tastants, but may also depend on the physiological and psychological conditions of those who do the tasting. In this study, the effects of mood state on taste sensitivity was evaluated in humans who were exposed to conditions of mental or physical fatigue and tension. Taste responses to quinine sulfate (bitter), citric acid (sour) and sucrose (sweet) were tested. The intensity of the taste sensations were recorded by a computerized time-intensity (Tl) on-line system. Subjects performed mental tasks by personal computer or physical tasks by ergometer for 10-40 min. Before and after these sessions, the duration of the after-taste and the intensity of the sensation of taste were recorded by the Tl system, and in addition, psychological mood states were evaluated with POMS (Profile of Mood State). Tl evaluation showed that after the mental tasks, the perceived duration of bitter, sour and sweet taste sensations was shortened relative to the control. Total amount of bitterness, sourness and sweetness was also significantly reduced. Furthermore, the maximum intensity of bitterness was significantly reduced. There were no significant differences in bitterness and sweetness sensations following physical tasks. However, relative to before the physical task, the duration of the after-taste of sourness was significantly shortened by the physical task. After the physical task, the buffering capacity of saliva was significantly increased. Thus mental and physical tasks alter taste perception in different ways; the mechanisms underlying these changes remain to be determined.

The effects of dimethylsulfoxide used as a solvent on the suppressive effects of lidocaine on synaptic transmission were examined in the bullfrog sympathetic ganglion. Compound action potentials (CAP) in response to orthodromic stimulation of the presynaptic nerve trunk were recorded extracellularly from the bullfrog sympathetic ganglion. Application of lidocaine dissolved in normal Ringer's solution significantly decreased the amplitude of CAP. This suppressive effect of lidocaine was markedly potentiated when lidocaine was dissolved in 0.1% DMSO solution. A similar potentiating effect of DMSO was observed on the suppressive action of lidocaine on acetylcholine (ACh)-induced depolarizing response recorded intracellularly from the sympathetic ganglion cell. On the other hand, 0.1% DMSO solution alone had no effect on synaptic transmission, resting membrane potential, resting membrane resistance or ACh receptor activity. The present findings suggest that DMSO as solvent should be used carefully because of its potentiating effect on drug actions. Since the effect of lidocaine is due to the suppression of nicotinic ACh receptor at the postsynaptic membrane, DMSO may allosterically act on the nicotinic ACh receptor causing an increase in efficacy of lidocaine.

Trichosporin (TS)-B-VIa, a peptide consisting of 19 amino acid residues and an amino alcohol, causes Ca(2+)-dependent secretion of catecholamines from bovine adrenal chromaffin cells. The TS-B-VIa-induced secretion was greater under alkaline conditions and at a temperature of 37 degrees C compared with that at 21 degrees or 30 degrees C. It was not observed when the peptide was eliminated from the incubation medium. These results strongly suggest that the stimulatory effect of TS-B-VIa on the secretion is reversible and dependent on the temperature and pH of the incubation medium.

SK&F 96365 (1-[3-(4-methoxyphenyl)propoxyl]-1-(4-methoxyphenyl)ethyl-1H- imidazole HCl) (1-50 microM), an inhibitor of receptor-mediated Ca2+ entry, reduced both acetylcholine (ACh)- and 56 mM K+ (high K+)-induced 45Ca2+ influxes and catecholamine secretion in bovine adrenal chromaffin cells. However, SK&F 96365 at lower concentrations (1-3 microM) inhibited only ACh-induced 45Ca2+ influx and secretion but not their high K(+)-induction. In Na(+)-free medium, ACh-induced 45Ca2+ influx and secretion were also considerably decreased by SK&F 96365 at low concentrations (1-3 microM). These results suggest that in the chromaffin cells, not only voltage-sensitive calcium channels but also ACh receptor-operated calcium channels at least in part contribute to the influx of Ca2+ which triggers the catecholamine secretion from the cells when the cells are exposed by ACh.

The effects of the antiallergic drugs, oxatomide, ibudilast, and tranilast on catecholamine secretion from bovine adrenal chromaffin cells stimulated by acetylcholine were examined. Both oxatomide (2-100 microM) and ibudilast (10-100 microM) resulted in the inhibition of the secretion of catecholamines from the cells in a concentration-dependent manner, whereas tranilast (100 nM-100 microM) did not. Oxatomide and ibudilast also reduced the acetylcholine-induced 45Ca2+ influx into the cells. The concentration-response curves for oxatomide and ibudilast inhibiting 45Ca2+ influx were quite similar to those for drugs inhibiting the secretion. Oxatomide similarly reduced both high K(+)-induced 45Ca2+ influx and secretion. However, the oxatomide inhibition of acetylcholine-induced secretion was not overcome by increasing the concentrations of acetylcholine or Ca2+. Oxatomide also inhibited histamine-induced secretion and the inhibition was almost overcome by increasing histamine concentration. These results indicate that oxatomide and ibudilast inhibit catecholamine secretion from bovine adrenal chromaffin cells stimulated by acetylcholine. The inhibition is due to the suppression of Ca2+ influx into the cells through voltage-dependent Ca2+ channels. The results further suggest that oxatomide competitively antagonizes histamine receptors and inhibits the secretion stimulated by histamine.

Long-term pretreatment (12-120 h) of cultured bovine adrenal chromaffin cells with cis-diamminedichloroplatinum (cisplatin, Pt(NH3)2Cl2) (33 microM), an antineoplastic drug, resulted in a decrease in the secretion of catecholamines from the cells stimulated by acetylcholine. Acetylcholine-induced 45Ca2+ influx into the cells was also reduced in the cells pretreated with cisplatin for 48 h. The concentration-response curves (3-66 microM) for cisplatin inhibition of the secretion and 45Ca2+ influx were quite similar. Pretreatment of cells with 33 microM Pt4+ or carboplatin, an analog of cisplatin, for 48 h also led to a decrease in acetylcholine-evoked secretion, but not with 33 microM Pt2+ or other metals (Au+, Au3+, Ni2+, Os3+, Pd2+, Ir3+, and Ir4+) that have properties similar to Pt4+. These results strongly suggest that in bovine adrenal chromaffin cells, cisplatin (3-66 microM) inhibits catecholamine secretion by the suppression of the Ca2+ influx into the cells evoked by acetylcholine and that the inhibitory effect of cisplatin is attributable to the tetravalent platinum ion in its molecule.

The loop-breaking strength of various suture materials was tested over a period of 14 days during which time the sutures were incubated in vitro in saline or canine serum, bile, activated or nonactivated pancreatic juice. Under the conditions of the study, silk and nylon maintained their strength in each environment. Polyglycolic acid maintained its strength in saline, bile or serum, but gradually lost much of its strength when exposed to pancreatic juice. Catgut, both plain and chromic, disintegrated almost completely within 24-48 hours respectively when exposed to enterokinase activated pancreatic juice. Inhibition of trypsin by aprotinin (Trasylol) resulted in preservation of catgut strength but inhibition by soybean inhibitor did not. The latter findings suggest that proteolytic enzymes, other than trypsin, may be responsible for the disintegration.

We investigated intestinal blood circulation after re-opening of a fixed-time occlusion of the superior mesenteric artery (SMA) in rabbits. The SMA root was occluded for 60 minutes, after which blood pressure and SMA flow were monitored for one hundred minutes under the administration with fluid infusion of three anti-shock agents; dopamine, phenoxybenzamine and dexamethasone. The intestinal wall tissue circulation in parallel with SMA flow was also studied. Blood pressure and SMA flow decreased after release of the SMA occlusion (SMAO), as compared those during pre-occlusive time in the control group. Fluid infusion alone did not improve blood pressure and SMA flow. Pre-administration of dexamethasone with fluid infusion improved blood pressure, SMA flow and the survival rate. Phenoxybenzamine with fluid infusion improved SMA flow, despite the low blood pressure. Circulatory damage to the intestinal wall was more extensive than that to SMA flow. These findings suggest that the severity and mortality of SMAO shock was not caused by plasma loss but rather by toxic metabolites and endotoxin from the ischemic intestine.

Mezlocillin (2 g) was administered by a single intravenous injection to 32 male patients with gonorrheal urethritis and to five female patients with gonorrheal cervicitis, none of whom had received any pre-treatment or had had any complications. The results of the treatment were "good" in 32 cases (86.5%), "fair" in three (8.1%) and "poor" in two patients (5.4%). One of the two "poor" cases showed no sensitivity to any penicillin derivative. Nausea during injection was observed twice, but the patients recovered immediately after the injection.

Anastomotic leakage and fistula of alimentary tract are accompanied by peritonitis because of exudation of contents in the digestive canal. In order to inquire about metabolism of protein and amino acids in surgical infection, this study was performed by the method of a time related cross-over trial, comparing high branched chain amino acids (BCAA) solution with low BCAA solution. The following results were obtained. When metabolism is physiologically compensated in infection, it was suggested that there appeared to be gluconeogenesis, ureagenesis and a liver disturbance accompanied in the early phase of sepsis. Administration of BCAA leads to an inhibition of muscle protein break down and a promotion of visceral protein synthesis in the case of severe infection. Administration of BCAA enriched amino acids solution have an important therapeutic measure under severe stressed condition and a significant role in medicine.

A case of carcinoid of the stomach is described and a review of 100 patients with carcinoid of the stomach reported in Japan up to 1980 is made. Of the 100 cases, the male to female ratio was 2.54. Typical clinical manifestations of the carcinoid syndrome were quite rare. Metastases to the liver were observed in 76% of cases with tumours larger than 5 cm in diameter. The liver and lymph nodes were common sites of metastases. Carcinoids arising from the anterior wall of the stomach also showed a high incidence of metastasis. As a result of histochemical examinations, it was revealed that the nonreactive cell type was found in 31% of cases, while the argentaffin cell type was found in only 10%. Confirmation of the diagnosis of carcinoid is sometimes difficult. Occasionally, therefore, electron-microscopic demonstration of specific secretory granules becomes essential for the final diagnosis.

To investigate the etiology of hyperlipemia induced by total pancreatectomy in rats, the authors determined lipoprotein lipase (LPL) activity and performed the intravenous fat loading test (IVFLT). LPL activity was remarkably reduced after total pancreatectomy, but recovered almost completely with administration of 4 i.u./Kg of insulin. The results of IVFLT showed positive correlation with LPL activity changes. The elimination rate K of IVFLT also recovered with the administration of insulin. On the other hand, in our previous reports no evidence of increase in lipid synthesis in the liver of depancreatectomized rats was found. From these results, the authors tentatively concluded that the main cause of pancreatectomy-induced hyperlipemia was a delay in the removal of lipids from the blood, due to decreased LPL activity caused by a lack of insulin.

Serum activities of amylase, lipase, phospholipase A2 and transaminases were measured in mice with diet-induced acute pancreatitis. To study the role of choline deficiency, one control group received only a choline-deficient diet (CD diet), another group received the choline-deficient diet with 0.5% DL-ethionine (CDE), and a third group received the choline-deficient diet and was given ethionine intraperitoneally. Serum amylase activities increased after 1 day of treatment in all experimental groups. In contrast, lipase activity rose later in the groups receiving ethionine either in the diet or intraperitoneally. In the CDE group there were significant changes in phospholipase A2 on the fourth day after test feeding was started, but no rise was seen in the other groups. Correspondingly, in the group receiving the CD diet alone and the group receiving intraperitoneal ethionine the mortality was significantly lower than in the group receiving ethionine in the diet. In all experimental groups there was a significant rise in serum transaminases (ASAT, ALAT). The rise in ALAT on day 4 was significantly higher in the CDE group than in the other two groups. The mortality rate in the CDE diet group on day 4 was 91%. In the animals to which ethionine was given intraperitoneally the corresponding mortality was 21%. In the CD diet group all animals survived for more than 4 days. The present results suggest that serum lipase and phospholipase A2 activities correlate better with the severity of diet-induced pancreatitis than do serum amylase levels. The most severe cases of the disease seemed to be associated with a rise in serum phospholipase A2 activity.(ABSTRACT TRUNCATED AT 250 WORDS)