Use of the ICU Nurse-Physician Questionnaire (ICU N-P-Q): Testing reliability and validity in neonatal intensive care units in Japan

Objective: Although communication among health providers has become a critical part of improving quality of care, few studies on this topic have been conducted in Japan. This study aimed to examine the reliability and validity of the Intensive Care Unit Nurse-Physician Questionnaire (ICU N-P-Q) for use among nurses and physicians in neonatal ICUs (NICUs) in Japan. Methods: A Japanese translation of the ICU N-P-Q was administered to physicians and nurses working at 40 NICUs across Japan, which were participating in the Improvement of NICU Practice and Team Approach Cluster randomized controlled trial (INTACT). We used the principal components analysis to evaluate the factor structure of the instruments. Convergent validity was assessed by examining correlations between the subscales of Communication and Conflict Management of the ICU N-P-Q and the subscales and total score of the Nurse-Physician Collaboration Scale (NPCS). Correlations between the subscales of Communication and Conflict Management by correlation with scales that refer to performance, including Job Satisfaction and Unit Effectiveness, were calculated to test the criterion validity. Results: In total, 2006 questionnaires were completed by 316 physicians and 1690 nurses. The exploratory factor analysis revealed 15 factors in the physicians' questionnaire and 12 in the nurses' questionnaire. Convergent validity was confirmed, except for 'Between-group Accuracy' and 'Cooperativeness' in the physicians' scale, and for 'Between-group Accuracy' and 'Sharing of Patient Information' in the nurses' scale. Correlations between the subscales of communication and outcomes were confirmed in the nurses' questionnaire but were not fully supported in the physicians' questionnaire. Conclusions: Although the psychometric property behaved somewhat differently by occupation, the present findings provide preliminary support for the utility of the common item structure with the original scale, to measure the degree and quality of communication and collaboration among staff at NICUs and similar healthcare settings in Japan. Trial registration number: UMIN000007064; Pre-results

Bone marrow stroma cells are susceptible to prion infection.

Abnormal protease-resistant prion protein (PrP-res) is the only surrogate biochemical marker for prion diseases, and a sensitive technique to detect PrP-res in blood or tissues is urgently needed. Primary cultured bone marrow stromal cells (MSCs) expressed PrP and were capable of supporting stable human prion infection. Using a mouse-adapted BSE strain, we demonstrated that PrP-res can be detected in expanded MSCs. We then analyzed the bone marrow cells collected at autopsy from two individuals with sporadic Creutzfeldt-Jakob disease (CJD), and, in both cases, cultured MSCs were positive for PrP-res. These data would suggest that ex vivo MSC expansion accompanied by PrP-res analysis could be a helpful tool in the definitive diagnosis of prion disease at an earlier stage in the disease process than is currently possible, and with considerably less distress to the patient

Human papillomavirus DNA in plasma of patients with HPV16 DNA-positive uterine cervical cancer.

OBJECTIVES: The squamous cell carcinoma antigen is considered the most accurate serologic tumor marker for uterine cervical carcinoma. However, serum squamous cell carcinoma antigen levels were found to correlate significantly with clinical severity of atopic dermatitis and chronic renal failure. The present study was conducted in patients with human papillomavirus 16 DNA-positive uterine cervical cancer to determine the plasma level of human papillomavirus 16 DNA and the diagnostic values of plasma human papillomavirus DNA in these patients. METHODS: Forty-three human papillomavirus 16-positive patients with cervical intraepithelial neoplasia or uterine cervical squamous cell carcinoma were recruited in this study. The diagnosis was cervical cancer in 20 patients, high-grade squamous intraepithelial lesions in 21, low-grade squamous intraepithelial lesions in 1 and negative for intraepithelial lesion or malignancy in 3 patients. Before any treatment, blood samples were collected from all patients. For analysis of human papillomavirus DNA in plasma of patients with cervical cancer, quantitative polymerase chain reaction fluorescent assay for human papillomavirus 16 was performed using human papillomavirus 16 primers and SYBR Green dye using the LightCycler 480 SW1.5 apparatus. RESULTS: Plasma human papillomavirus 16 DNA was detected in only 30.0% of the patients with human papillomavirus 16-positive cervical cancer and in none of normal controls. The copy number of plasma human papillomavirus 16 DNA was higher in patients with invasive cancer than in those with cervical intraepithelial neoplasia (CIN3), micro-invasive cancer and in normal individuals. CONCLUSIONS: These results indicated that the plasma human papillomavirus DNA level could be potentially used as a marker of low-invasive cervical cancer tumors in patients with normal squamous cell carcinoma antigen levels before treatment

Hyperefficient PrP Sc amplification of mouse-adapted BSE and scrapie strain by protein misfolding cyclic amplification technique.

Abnormal forms of prion protein (PrP(Sc)) accumulate via structural conversion of normal PrP (PrP(C)) in the progression of transmissible spongiform encephalopathy. Under cell-free conditions, the process can be efficiently replicated using in vitro PrP(Sc) amplification methods, including protein misfolding cyclic amplification. These methods enable ultrasensitive detection of PrP(Sc); however, there remain difficulties in utilizing them in practice. For example, to date, several rounds of protein misfolding cyclic amplification have been necessary to reach maximal sensitivity, which not only take several weeks, but also result in an increased risk of contamination. In this study, we sought to further promote the rate of PrP(Sc) amplification in the protein misfolding cyclic amplification technique using mouse transmissible spongiform encephalopathy models infected with either mouse-adapted bovine spongiform encephalopathy or mouse-adapted scrapie, Chandler strain. Here, we demonstrate that appropriate regulation of sonication dramatically accelerates PrP(Sc) amplification in both strains. In fact, we reached maximum sensitivity, allowing the ultrasensitive detection of < 1 LD(50) of PrP(Sc) in the diluted brain homogenates, after only one or two reaction rounds, and in addition, we detected PrP(Sc) in the plasma of mouse-adapted bovine spongiform encephalopathy-infected mice. We believe that these results will advance the establishment of a fast, ultrasensitive diagnostic test for transmissible spongiform encephalopathies.The definitive version is available at www.blackwell-synergy.co

Antigenic mimicry-mediated anti-prion effects induced by bacterial enzyme succinylarginine dihydrolase in mice.

Prions, the causative agents of prion diseases, are immunologically tolerated because their major component, prion protein (PrP), is a host-encoded molecule. Therefore, no effective prion vaccines have been developed. We previously showed that heterologous bovine and sheep PrP immunizations of mice overcame tolerance by an antigenic mimicry mechanism to efficiently induce anti-PrP auto-antibodies (Abs), significantly prolonging incubation times in mice subsequently infected with the mouse-adapted Fukuoka-1 prion. These results prompted us to investigate if non-mammal derived molecules able to antigenically mimic anti-prion epitopes, could act as prion vaccines. We show here that immunization of mice with recombinant succinylarginine dihydrolase, a bacterial enzyme with a peptide sequence similar to an anti-prion epitope, induced anti-PrP auto-Abs with anti-prion activity and significantly retarded survival times of the mice subsequently infected with Fukuoka-1 prions. These results might open a way for development of a new type of antigenic mimicry-based prion vaccine

Relationship between the gut microbiota and bile acid composition in the ileal mucosa of Crohn\u27s disease

Background/Aims:Crosstalk between the gut microbiota and bile acid plays an important role in the pathogenesis of gastrointestinal disorders. We investigated the relationship between microbial structure and bile acid metabolism in the ileal mucosa of Crohn’s disease (CD).Methods:Twelve non-CD controls and 38 CD patients in clinical remission were enrolled. Samples were collected from the distal ileum under balloon-assisted enteroscopy. Bile acid composition was analyzed by liquid chromatography-mass spectrometry. The gut microbiota was analyzed by 16S rRNA gene sequencing.Results:The Shannon evenness index was significantly lower in endoscopically active lesions than in non-CD controls. β-Diversity, evaluated by the UniFrac metric, revealed a significant difference between the active lesions and non-CD controls (P=0.039). The relative abundance of Escherichia was significantly higher and that of Faecalibacterium and Roseburia was significantly lower in CD samples than in non-CD controls. The increased abundance of Escherichia was more prominent in active lesions than in inactive lesions. The proportion of conjugated bile acids was significantly higher in CD patients than in non-CD controls, but there was no difference in the proportion of primary or secondary bile acids. The genera Escherichia and Lactobacillus were positively correlated with the proportion of conjugated bile acids. On the other hand, Roseburia, Intestinibacter, and Faecalibacterium were negatively correlated with the proportion of conjugated bile acids.Conclusions:Mucosa-associated dysbiosis and the alteration of bile acid composition were identified in the ileum of CD patients. These may play a role in the pathophysiology of ileal lesions in CD patients

Ultrasensitive human prion detection in cerebrospinal fluid by real-time quaking-induced conversion.

The development of technologies for the in vitro amplification of abnormal conformations of prion protein (PrP(Sc)) has generated the potential for sensitive detection of prions. Here we developed a new PrP(Sc) amplification assay, called real-time quaking-induced conversion (RT-QUIC), which allows the detection of ≥1 fg of PrP(Sc) in diluted Creutzfeldt-Jakob disease (CJD) brain homogenate. Moreover, we assessed the technique first in a series of Japanese subjects and then in a blind study of 30 cerebrospinal fluid specimens from Australia, which achieved greater than 80% sensitivity and 100% specificity. These findings indicate the promising enhanced diagnostic capacity of RT-QUIC in the antemortem evaluation of suspected CJD

Sulfide Catabolism Ameliorates Hypoxic Brain Injury

The mammalian brain is highly vulnerable to oxygen deprivation, yet the mechanism underlying the brain’s sensitivity to hypoxia is incompletely understood. Hypoxia induces accumulation of hydrogen sulfide, a gas that inhibits mitochondrial respiration. Here, we show that, in mice, rats, and naturally hypoxia-tolerant ground squirrels, the sensitivity of the brain to hypoxia is inversely related to the levels of sulfide:quinone oxidoreductase (SQOR) and the capacity to catabolize sulfide. Silencing SQOR increased the sensitivity of the brain to hypoxia, whereas neuron-specific SQOR expression prevented hypoxia-induced sulfide accumulation, bioenergetic failure, and ischemic brain injury. Excluding SQOR from mitochondria increased sensitivity to hypoxia not only in the brain but also in heart and liver. Pharmacological scavenging of sulfide maintained mitochondrial respiration in hypoxic neurons and made mice resistant to hypoxia. These results illuminate the critical role of sulfide catabolism in energy homeostasis during hypoxia and identify a therapeutic target for ischemic brain injury