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Progressive familial intrahepatic cholestasis (PFIC) is a liver disease that occurs during childhood and requires liver transplantation. ABCB4 is localized along the canalicular membranes of hepatocytes, transports phosphatidylcholine into bile, and its mutation causes PFIC3. Abcb4 gene-deficient mice established as animal models of PFIC3 exhibit cholestasis-induced liver injury. However, their phenotypes are often milder than those of human PFIC3, partly because of the existence of large amounts of less toxic hydrophilic bile acids synthesized by the rodent-specific enzymes Cyp2c70 and Cyp2a12. Mice with double deletions of Cyp2c70/Cyp2a12 (CYPDKO mice) have a human-like hydrophobic bile acid composition. PFIC-related gene mutations were induced in CYPDKO mice to determine whether these triple-gene-deficient mice are a better model for PFIC. To establish a PFIC3 mouse model using CYPDKO mice, we induced abcb4 gene deletion in vivo using adeno-associated viruses expressing SaCas9 under the control of a liver-specific promoter and abcb4-target gRNAs. Compared to Abcb4-deficient wild-type mice, Abcb4-deficient CYPDKO mice showed more pronounced liver injury along with an elevation of inflammatory and fibrotic markers. The proliferation of intrahepatic bile ductal cells and hematopoietic cell infiltration were also observed. CYPDKO/abcb4-deficient mice show a predominance of taurine-conjugated chenodeoxycholic acid and lithocholic acid in the liver. In addition, phospholipid levels in the gallbladder bile were barely detectable. Mice with human-like bile acids exhibit severe cholestatic liver injury when Abcb4 is knocked down using genome editing technology. This mouse model is useful for studying human cholestatic diseases and developing new treatments.
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Campylobacter jejuni is one of the major bacteria that causes diarrhea in humans. It has been associated with many cases of food poisoning in Japan caused by eating raw or undercooked chicken meat, chicken liver, and grilled chicken (Yakitori). Campylobacter jejuni is also known as the preceding infection pathogen of Guillain-Barré syndrome (GBS), which causes considerable health impact on humans. In January 2022, in a case of C. jejuni food poisoning that occurred at a restaurant in Tokyo, one of four patients with diarrhea developed GBS. The poisoning is presumed to have been caused by undercooked chicken dishes. Recently, it was one of the common cases in Japan. Moreover, C. jejuni isolates from three patients, including the patient with GBS, had the same genotype (ST22, HS19, and LOS A). This genotype was frequently detected from patients with GBS in our past surveys. Our findings confirmed that the patient developed GBS via food poisoning after consuming undercooked chicken dish.
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The prevalence of azole-resistant Aspergillus fumigatus is increasing worldwide and is speculated to be related to the use of azole pesticides. Aspergillus spp., the causative agent of aspergillosis, could be brought into domestic dwellings through food. However, studies on azole-resistant Aspergillus spp. in food products are limited. Therefore, we aimed to isolate Aspergillus spp. from processed foods and commercial agricultural products and performed drug susceptibility tests for azoles. Among 692 food samples, we isolated 99 strains of Aspergillus spp. from 50 food samples, including vegetables (22.9%), citrus fruits (26.3%), cereals (25.5%), and processed foods (1.8%). The isolates belonged to 18 species across eight sections: Aspergillus, Candidi, Clavati, Flavi, Fumigati, Nidulantes, Nigri, and Terrei. The most frequently isolated section was Fumigati with 39 strains, followed by Nigri with 28 strains. Aspergillus fumigatus and A. welwitschiae were the predominant species. Ten A. fumigatus and four cryptic strains, four A. niger cryptic strains, two A. flavus, and four A. terreus strains exceeded epidemiological cutoff values for azoles. Aspergillus tubingensis, A. pseudoviridinutans, A. lentulus, A. terreus, and N. hiratsukae showed low susceptibility to multi-azoles. Foods containing agricultural products were found to be contaminated with Aspergillus spp., with 65.3% of isolates having minimal inhibitory concentrations below epidemiological cutoff values. Additionally, some samples harbored azole-resistant strains of Aspergillus spp. Our study serves as a basis for elucidating the relationship between food, environment, and clinically important Aspergillus spp.
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PURPOSE: The presence of cereulide, an emetic toxin produced by Bacillus cereus, in fried rice samples is critical evidence of food poisoning even in situations where B. cereus could not be detected. This study aims to develop a screening method for analyzing cereulide in fried rice using the QuEChERS procedure and liquid chromatography-tandem mass spectrometry (LC-MS/MS). METHODS: Cereulide was identified and quantified in fried rice samples using the QuEChERS extraction method and LC-MS/MS. The accuracies of the methods were determined by analyzing fortified blank samples at two concentrations (10 and 50 µg/kg) conducted on three samples daily for five days. RESULTS: The QuEChERS procedure removed matrix compounds from fried rice. Characteristic MS/MS spectra enabled the identification of cereulide. As the matrix effects in seven fried rice samples were within ± 6%, an external solvent calibration curve could be used for quantification. This method exhibited good accuracy ranging from 88 to 89%. The relative standard deviations for both repeatability and intra-laboratory reproducibility were < 4%. These standard deviations satisfied the criteria of the Japanese validation guidelines for residues (MHLW 2010, Director Notice, Syoku-An No. 1224-1). The limit of quantification was 2 µg/kg. The applicability of this method was confirmed using the analysis of cereulide in fried rice samples incubated with emetic Bacillus cereus. CONCLUSIONS: The QuEChERS extraction procedure described herein showed substantial promise as a reliable screening tool for cereulide in fried rice sample.
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Depsipéptidos , Oryza , Espectrometría de Masas en Tándem , Oryza/química , Oryza/microbiología , Espectrometría de Masas en Tándem/métodos , Depsipéptidos/análisis , Cromatografía Liquida/métodos , Reproducibilidad de los Resultados , Contaminación de Alimentos/análisis , Bacillus cereus/aislamiento & purificación , Toxinas Bacterianas/análisis , Toxinas Bacterianas/aislamiento & purificaciónRESUMEN
This study investigated the interpersonal coordination between the pitcher and the batter in bat-and-ball sports. Although the importance of interpersonal coordination is widely accepted in many sports, no studies have investigated it in bat-and-ball sports because the dominant task constraints surrounding the interaction between pitcher and batter make it difficult to apply conventional analytic techniques. To address the issue, this study proposes a new analytical framework to investigate interpersonal coordination in bat-and-ball sports under a real game situation with two main characteristics: asymmetric interaction and delayed coupling. First, the dynamic time warping technique was used to evaluate the stability of the head movement pattern of the pitcher and batter, and cross-correlation analysis was used to quantify the temporal relationship between them. We found that the head movement pattern of batters was significantly more unstable than that of pitchers, and approximately 60% of the variance of the change in the head movement pattern of batters could be explained by that of the pitchers. Moreover, expert batters followed a pitcher's movements with a specific time delay of approximately 250 ms. These findings highlight the characteristics of interpersonal coordination in bat-and-ball sports: the pitcher can make a pre-patterned stable motion, whereas the batter needs to follow and adjust their movement to it. Although the effects of prediction ability need to be investigated to understand its detailed mechanism, the contribution of this study is that it revealed the existence of the interpersonal coordination between the pitcher and batter of bat-and-ball sports under a real game situation.
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Béisbol , Quirópteros , Animales , Desempeño Psicomotor , Fenómenos Biomecánicos , Movimientos de la CabezaRESUMEN
BACKGROUND: Intimate and romantic relationships are important in life for individuals, irrespective of mental health status. We developed a four-hour peer-led learning program for persons with mental disorders about intimate and romantic relationships through a co-creation process with service users and examined its preliminary effectiveness and feasibility of implementing the program. METHODS: A one-group pretest-posttest trial was conducted using a mixed-method design for 45 individuals with mental disorders in Japan. Outcome data were collected at three time points: baseline, post-intervention, and one month after program completion. Mixed models for repeated measures (MMRM) were used to examine changes over time in the Rosenberg Self-Esteem Scale (RSES), Recovery Assessment Scale (RAS), Herth Hope Index (HHI), and the original items. Group interviews were conducted for process evaluation. RESULTS: MMRM showed significant changes over time on RSES, RAS, HHI, and two original items "I am able to communicate well with others about myself" and "I am able to listen to others well." In multiple comparisons, RSES and HHI were significant one month after the program. Participants reported changes during the first month after attending the program in terms of their positive attitude toward romantic relationships (n = 14), taking romantic actions (n = 11), and feeling their overall communication improved (n = 11). Although two participants had an unscheduled psychiatric visit that could be attributed to attending the program, all recovered after one month. CONCLUSIONS: The program exhibited preliminary effectiveness to a moderate extent in improving recovery, particularly regarding self-esteem and hope. The program is feasible but requires further modifications regarding inclusion criteria for participants and the training of peer facilitators. TRIAL REGISTRATION: UMIN000041743;09/09/2020.
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Trastornos Mentales , Humanos , Estudios de Factibilidad , Japón , AutoimagenRESUMEN
This study aimed to investigate the prevalence and antimicrobial sensitivity of Campylobacter jejuni and Campylobacter coli in retail meat (chicken, beef, pork, venison, wild boar, horse, lamb and mutton) in Tokyo (Japan) from 2010 to 2019. Furthermore, the resistance mechanism of erythromycin (EM)-resistant strains was analysed. C. jejuni had a highly positive rate in domestic chicken meat (53.4%, 334/626 samples), domestic chicken offal (49.3%, 34/69 samples), and domestic beef offal (28.3%, 47/166 samples), while C. coli had a high positivity rate in domestic pork offal (31.7%, 44/139 samples). The positive rate of C. jejuni was significantly higher in offal than that in meat in domestic beef, while the positive rate of C. coli was significantly higher in offal than that in meat in domestic beef and domestic pork (p<0.05). In the isolates, 1.0% (6/631 strains) of C. jejuni and 36.2% (55/152 strains) of C. coli were EM resistant, with 41.5% (262/631 strains) of C. jejuni and 65.1% (99/152 strains) of C. coli being ciprofloxacin resistant. A2075G mutation of the 23S rRNA gene was confirmed in all EM-resistant strains.
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Antiinfecciosos , Campylobacter coli , Campylobacter jejuni , Bovinos , Animales , Ovinos , Caballos , Campylobacter coli/genética , Antibacterianos/farmacología , Campylobacter jejuni/genética , Japón/epidemiología , Tokio , Prevalencia , Farmacorresistencia Bacteriana/genética , Macrólidos/farmacología , Carne , Eritromicina/farmacología , Pollos , Pruebas de Sensibilidad MicrobianaRESUMEN
ObjectivesãPolicies promoting community integration of individuals with mental disabilities have increased the need for community advocacy. This study aimed to identify situations in which individuals with mental disabilities perceive the need for advocacy support and how to deal with them.MethodsãIn this qualitative descriptive study, group interviews were conducted with 13 peer advocates and 12 individuals with mental disabilities. A verbatim transcript of the interviews was created. Categories were generated by raising the level of abstraction from the perspective of "Situations where individuals with mental disabilities require advocacy support and how to address them."ResultsãSituations requiring advocacy support occurred in outpatient psychiatry settings, psychiatric hospitalizations, welfare facilities, schools, neighborhoods, and places of employment; among family and relatives; and at consultation services. In outpatient psychiatry, "difficulties in accessing medical care" were reported. In psychiatric hospitalizations, participants felt "pressured and unable to escape the environment." In welfare facilities, "romantic relationships between users were discouraged." Regarding familial difficulties, "limited understanding and acceptance of the disease," "relationship deterioration due to poor hospitalization conditions and forced hospitalization," and "marital difficulties due to mental illness" were prevalent. Participants in schools experienced "isolation due to their illness," and in the local community, there were "problems related to reasonable accommodation of individuals with disabilities in neighborhood association activities." Employed participants faced "inadequate consideration despite disclosing their illness to co-workers." At counseling institutions, participants felt "forced to endure without resolution when consulting." Individuals with disabilities coped with these situations by "transferring to a different clinic" or "changing facilities," but in the case of psychiatric hospitalization, they gave up and "did not go against the staff."ConclusionãIndividuals with mental disabilities need advocacy support for psychiatric care and diverse situations such as family, school, and community engagement. Efforts should be made to introduce an advocacy system in psychiatric hospitals and to disseminate accurate information about mental illness to high-risk age groups. Moreover, it is necessary to disseminate knowledge of reasonable accommodation and appropriate responses to individuals with mental illness. Peer advocates should educate individuals with disabilities about their rights and encourage proactive measures.
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Trastornos Mentales , Humanos , Trastornos Mentales/terapia , Instituciones AcadémicasRESUMEN
Phytobacter diazotrophicus is an Enterobacterales species that was originally identified as a plant growth-promoting, Gram-negative bacterium. Recently, this species has been recognized as relevant to opportunistic human and nosocomial infections in clinical settings. Its frequent misidentification as other Enterobacterales species from clinical examination occasionally causes a delay in the identification of nosocomial outbreaks. Here, we report the emergence of New Delhi metallo-ß-lactamase (NDM)-producing P. diazotrophicus isolated from hospitalized pediatric patients and hospital environments in Tokyo, Japan. In our case, these isolates were found during an investigation of carbapenem-resistant Enterobacterales in relation to nosocomial infections. Whole-genome sequencing is useful for overcoming the difficulty of species identification. Furthermore, we found that bla NDM-1 was carried by an IncA/C2 plasmid (approximately 170 kbp), which was transferrable from the clinical isolates to the recipient strain Escherichia coli J53. Our study demonstrated that P. diazotrophicus behaves as a carrier of bla NDM-harboring plasmids, potentially disseminating resistance to carbapenems among Enterobacterales. IMPORTANCE Early detection of nosocomial outbreaks is important to minimize the spread of bacteria. When an outbreak is caused by multidrug-resistant bacteria such as carbapenem-resistant Enterobacterales, a delay in findings makes it difficult to control it because such bacteria often spread not only among human patients but also in hospital environments. Phytobacter diazotrophicus, an Enterobacterales species that has recently been found to be relevant to clinical settings, is often misidentified as other bacteria in clinical laboratories. Here, we found NDM-producing P. diazotrophicus in hospitalized pediatric patients and their environment in Tokyo, Japan. Given that the isolates carried bla NDM-1-harboring transferrable plasmids, the influence of such bacteria could be greater with the mediation of horizontal transfer of carbapenem resistance. Our findings suggest that P. diazotrophicus should be recognized as an NDM-carrier, for which more attention should be paid in clinical settings.
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Antibacterianos , Infección Hospitalaria , Humanos , Niño , Antibacterianos/farmacología , Japón/epidemiología , Tokio/epidemiología , Plásmidos/genética , Carbapenémicos/farmacología , Escherichia coli/genéticaRESUMEN
Extreme and long-term social withdrawal, first described in Japan as Hikikomori, has now become a globally recognized mental health problem. Intervention studies severely lag behind epidemiological and phenomenological research. We present two descriptive case reports of Japanese university students with Hikikomori who participated in an early phase test of a structured intervention involving physical activities that was developed and facilitated by clinicians and physical education specialists-Human Movement Consultation (HMC). The two recipients (19- and 29-years old at the start of treatment) completed approximately 40 consultation sessions delivered over 3 years consisting of a combination of outdoor workouts (i.e., walking, running, and cycling) and interpersonal sports (e.g., table tennis, badminton, and tennis). Changes in social withdrawal behavior were independently rated from clinical health records using a structured scale (the Glasgow Hikikomori Scale; GHS). Behavioral observations and scale data for both cases indicated improvements from pre-treatment levels of social withdrawal. At the end of the intervention, both had returned to normative levels of functioning. Case A returned to university and Case B secured a new job upon the completion of HMC. To help advance our understanding of treatment options, these case descriptions analyze potential change mechanisms in order to understand how HMC can support recovery from extreme social withdrawal. One key observation is that both outdoor workouts and interpersonal sports offer a non-threatening method of enabling Hikikomori to engage in interpersonal interactions. Such connections via structured activities may allow the reinstatement of social skills in a graded manner. In addition, an initial focus on physical experiences may help promote psychological and social connectedness without triggering the social fears and challenges that underlie the Hikikomori state. The findings from these two cases offer a framework to guide further research and the development of exercise-based interventions for this hidden and often neglected group.
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BACKGROUND: Some children of parents with mental illness need support. This study aimed to develop and test the effectiveness of an e-learning program for training elementary schoolteachers to support children of parents with mental illness. METHODS: The program, which included a 30-min video-based e-learning program, aimed to help schoolteachers gain basic knowledge about mental illness and children of parents with mental illness, recognize children in need of support, and gain confidence in supporting them. A school-based cluster randomized controlled trial was conducted, and the schools were randomly divided into intervention and control groups. The teachers at these schools signed up for the program and participated individually. The outcome measures for the schoolteachers were evaluated at three time points: baseline (T1), post (T2), and one month later (T3). Along with the Sense of Coping Difficulty subscale (primary outcome measure), the following self-developed outcome measures were used: actual behaviors and attitude toward supporting children, knowledge, and self-assessment of program goals achievement. The Sense of Coping Difficulty subscale results at T3 were compared between the groups. Effectiveness over time was assessed for all the outcome measures. The interaction between baseline and intervention effects on the Sense of Coping Difficulty subscale was analyzed. As a part of the process evaluation, open-ended text responses were analyzed qualitatively. RESULTS: Baseline responses were collected from 87 participants in the intervention group and 84 in the control group. The total score of the Sense of Coping Difficulty subscale at T3 was significantly lower in the intervention group than in the control group (p = 0.007). Over time, a significant effect was observed on the Sense of Coping Difficulty subscale, actual behavior, knowledge of onset timing and probability of onset, and achievement of all program goals. Exploratory analysis was particularly effective for those who encountered a high level of difficulty in supporting children. The participants' text responses indicated that they planned to look carefully at children's backgrounds and stay close to them in the future. CONCLUSIONS: The program was effective for schoolteachers in supporting children of parents with mental illness. TRIAL REGISTRATION: UMIN000045483; 14/09/2021.
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Instrucción por Computador , Trastornos Mentales , Humanos , Niño , Padres/educación , Trastornos Mentales/terapiaRESUMEN
BACKGROUND & AIM: The short-term effects of teduglutide (TED) for short bowel syndrome with chronic intestinal failure (SBS-IF) in patients with Crohn's disease (CD) remain unknown. The aim of this study was to investigate the effects of TED in patients with CD on home parenteral support (PS) for SBS-IF. METHODS: We retrospectively investigated the medical records of patients with CD associated with SBS-IF who initiated TED between 2020 and 2021. The primary outcomes were the change in PS volume and proportion of patients with a reduction of PS volume by ≥ 20% at week 8. Secondary outcomes were the change in PS volume in patients with CD without/with colon in continuity and adverse events during the observation period. RESULTS: Eighteen patients with CD who underwent home PS for SBS-IF were included in this study. Two patients were excluded owing to intolerable abdominal pain or vomiting within 8 weeks (11%). Sixteen patients continued TED throughout the observation period. The median PS duration was 10.5 years. The median observation period was 22 weeks after starting TED. TED significantly reduced the PS volume from 15,825.0 mL/week to 10,700.0 mL/week (p = 0.0038), and the PS volume decreased by ≥ 20% in 7 patients (43.8%) at week 8. The PS volume was significantly reduced at week 4 (p = 0.0078) in 11 patients without colon in continuity but not in 5 patients with colon in continuity. Two patients successfully stopped home PS. No serious adverse events occurred. CONCLUSIONS: TED administration significantly reduced PS volume at week 8 in patients with CD associated with SBS-IF, and at week 4 in patients without colon in continuity.
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Enfermedad de Crohn , Insuficiencia Intestinal , Síndrome del Intestino Corto , Humanos , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/tratamiento farmacológico , Síndrome del Intestino Corto/tratamiento farmacológico , Estudios Retrospectivos , Fármacos Gastrointestinales/uso terapéuticoRESUMEN
OBJECTIVES: Given the differences in clinical and biological characteristics between cervical adenocarcinoma and squamous cell carcinoma, this study aimed to conduct an exploratory analysis to examine the molecular characteristics of cervical adenocarcinoma in a Japanese population. METHODS: This study explored the simultaneous testing of multiple mutations targeting cervical adenocarcinoma using next-generation sequencing (NGS). The following genes were analyzed: BCAR4, CD274, PDCD1LG2, KRAS, ARID1A, PTEN, ALK, EGFR, ROS1, BRAF, PIK3CA, EP300, EBXW7, SHCBP1, TGFBR2, SMAD4, ERBB2, ERBB3, and KLF5. Tumor tissue and blood samples were obtained at the time of primary treatment. The NGS-based molecular profiles obtained from Tokai University (49 specimens) were compared with the registered data in The Cancer Genome Atlas (TCGA) database (133 specimens). RESULTS: The study cohort had higher rates of adenocarcinoma than the TCGA cohort (44.9% vs. 18.0%; P = 0.001). The adenocarcinomas in the study cohort had more alterations in ROS1, EGFR, EP300, SHCBP1, ALK, and PIK3CA than those in the TCGA cohort. Among them, ROS1 had the highest number of gene alterations (median, 7.00 ± 2.63). In the study cohort, patients with a high number of ROS1 alterations had a significantly higher recurrence rate (5-year recurrence rate, 48.8% vs. 14.6%; hazard ratio [HR], 4.32; 95% confidence interval [CI], 1.20-15.50; P = 0.014) and lower overall survival than those with low alterations (5-year survival rate, 70.7% vs. 93.1%; HR, 7.15; 95% CI, 1.08-58.22; P = 0.032). CONCLUSION: The current exploratory analysis suggests that ROS1 gene alteration may be a prognostic biomarker in cervical adenocarcinoma in Japanese patients.
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Adenocarcinoma , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Proteínas Tirosina Quinasas/genética , Proteínas Tirosina Quinasas/uso terapéutico , Pronóstico , Proteínas Proto-Oncogénicas/genética , Adenocarcinoma/genética , Mutación , Proteínas Tirosina Quinasas Receptoras/genética , Receptores ErbB/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Fosfatidilinositol 3-Quinasa Clase I/genética , Biomarcadores , Proteínas Adaptadoras de la Señalización Shc/genéticaRESUMEN
In this study, we seek to clarify whether the present-day experience of psychological distress among adults whose parents suffered from mental illness is related to their childhood experiences of abuse and neglect and their provision of emotional care for their parents during their school-age years. To this end, a web-based cross-sectional study was conducted. A total of 120 participants over the age of 20 who attended a self-help group responded (50% response rate); of these, 94 had a parent diagnosed with a mental illness, and these participants were included for data analysis purposes. Of the 94 respondents, 65 (69.2%) were highly distressed, as measured by a Kessler (K) 6 measure of ≥5. A logistic regression analysis revealed that the experience of providing emotional care for parents during school-age childhood was significantly related to high levels of distress in adulthood (OR = 3.48; 95% CI 1.21-9.96). For children of parents with mental illnesses, the effects of providing emotional care for parents during childhood may include long-term psychological distress. For this reason, mentally ill parents raising children need visiting community nurses or other professionals to provide emotional care on behalf of their children.
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Salmonella foodborne disease outbreaks have markedly decreased in recent years, and different Salmonella serovars have been isolated. To clarify the characteristics of Salmonella strains causing annual epidemics and to estimate the source, we conducted a serotyping test on 1,132 human-derived Salmonella isolates in the 1990s and 2010s, and 1,061 food-derived Salmonella isolates in the 2010s in Tokyo. The serovars commonly isolated from human feces in the 1990s and after 2012 were S. Enteritidis, S. Typhimurium, S. Infantis, S. Thompson, and S. Agona. The new main serovars isolated after 2012 were S. Schwarzengrund, S. Enterica serovar 4:i:-, and S. Chester. In contrast, the main serovars detected from foods after 2012 were S. Infantis, S. Schwarzengrund, S. Agona, S. Manhattan, S. Typhimurium, and S. enterica serovar UT: r:1,5. S. Schwarzengrund has recently been frequently isolated. These strains were mainly isolated from chicken meat and offal. It was suggested that the same serovars of human-derived isolates were also isolated from foods, especially chicken meat and offal, and that these were recently an important causative food of Salmonellosis.
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Infecciones por Salmonella , Salmonella enterica , Humanos , Animales , Serogrupo , Tokio/epidemiología , Salmonella , Infecciones por Salmonella/epidemiología , Heces , PollosRESUMEN
BACKGROUND: Supporting parents with severe and persistent mental illness (SPMI) requires knowledge, skills, and a positive attitude toward parenthood. We developed a Japanese e-learning program for public health nurses (PHNs) to enable them to support parents with SPMI and their family members. This study aimed to evaluate the effectiveness of the program in improving the knowledge, skills, attitudes, and self-efficacy of PHNs in supporting them. METHODS: A three-hour video-based e-learning program was developed. A randomized controlled trial was conducted with 176 PHNs responsible for maternal and child health in Japan. The outcome measures included the Sense of Coping Difficulty/Possibility Scale, skills to support people with SPMI, and achievement of program goals. Outcome data were collected at three time points during the study: baseline (T1), post-intervention (T2), and one month after T2 (T3) using self-administered electronic questionnaires. Outcome measures were assessed by comparing the two groups at the endpoint (T3) using t-tests and ANOVA. Effectiveness over time was assessed using a mixed model for repeated measures, with group and time interactions as fixed effects. RESULTS: The study participants were randomly allocated to two groups:89 in the intervention group, and 87 in the control group. The total score and the scores in the two subscales of the Sense of Coping Difficulty/Possibility Scale in the intervention group at T3 were significantly higher than those in the control group, as shown by the t-test and ANOVA (all p<0.001). The Sense of Coping Difficulty subscale had a large effect size (Cohen's d=1.27). The analysis of the results of a mixed model for repeated measures showed that the group and time interactions on all outcome measures were not significantly different at T1 but were significantly different at T2 and T3. CONCLUSIONS: The program was effective one month after its completion, particularly in reducing PHNs' difficulties in supporting parents with SPMI. TRIAL REGISTRATION: UMIN000045765, November 1, 2021.
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CRISPR tools can generate knockout and knock-in animal models easily, but the models can contain off-target genomic lesions or random insertions of donor DNAs. Simpler methods to identify off-target lesions and random insertions, using tail or earpiece DNA, are unavailable. We develop CRISPR-KRISPR (CRISPR-Knock-ins and Random Inserts Searching PRotocol), a method to identify both off-target lesions and random insertions. CRISPR-KRISPR uses as little as 3.4 µg of genomic DNA; thus, it can be easily incorporated as an additional step to genotype founder animals for further breeding.
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Sistemas CRISPR-Cas , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Ratones , Animales , Técnicas de Sustitución del Gen , ADN/genética , Genoma , Edición Génica/métodosRESUMEN
The authors would like to make the following correction to the published paper [...].
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This study aimed to clarify whether genetic mutations participate in renal cell carcinoma (RCC) metastasis to the adrenal gland (AG). Our study analyzed whole mitochondrial gene and ribonucleic acid sequencing (RNA-seq) data from a male patient in his 60s with metastatic RCC. We confirmed common mutation sites in the mitochondrial gene and carried out Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis using RNA-seq data for RCC and adrenal carcinoma. Furthermore, we confirmed the common mutation sites of mitochondrial genes in which the T3394Y (p.H30Y) site transitioned from histidine (His.; H) to tyrosine (Tyr.; Y) in the NADH dehydrogenase subunit 1 (ND1) gene. The R11,807G (p.T350A) site transitioned from threonine (Thr.; T) to alanine (Ala.; A). Additionally, the G15,438R or A (p.G231D) site transitioned from glycine (Gly.; G) to aspartic acid (Asp.; D) in cytochrome b (CYTB). Furthermore, pathway analysis, using RNA-seq, confirmed the common mutant pathway between RCC and adrenal carcinoma as cytokine-cytokine receptor (CCR) interaction. Confirmation of the original mutation sites suggests that transfer to AG may be related to the CCR interaction. Thus, during metastasis to the AG, mitochondria DNA mutation may represent the initial origin of the metastasis, followed by the likely mutation of the nuclear genes.
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Conventionally, hitting movements in response to different advanced kinematic information have been investigated from the perspective of chronometric analysis, such as measuring the timing of movements. This is the first study to investigate the effect of manipulating advanced kinematic information on the hitting movement pattern organization based on both kinematics and kinetic analyses in addition to the conventional chronometric analysis. Specifically, the hitting movement of experienced batters in response to visual stimuli consisting of different pitching movement speeds with the same ball trajectory information was measured by an optical motion capture camera system and a foot force sensor inside the shoes. The occurrence timings of specific events (e.g., movement initiation), some kinematic parameters (e.g., maximum rotate angle of the shoulder and hip), and the balance of the ground reaction force between the ball of the big and small toes of both feet were compared between experimental conditions. This was done to test the hypothesis that the hitting movement is coupled with the visual information given to batters based on an expert anticipatory model. The results indicated that for a faster pitching speed, the batter tended to react with a significantly smaller preparatory movement (e.g., smaller weight shift and shoulder rotate angle during backswing) and put significantly larger weight on the rear foot during the swing execution phase. The situation was exactly reverse in the case of a slower pitching movement. These results suggest for the first time that manipulating advanced kinematic information not only affects the timing of the movement, but also the whole-body kinematics and lower body kinetics. The results also indicate that the hitting movement pattern of experienced batters is highly dependent on the advanced kinematic information.