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Mental nerve paresthesia is a serious postoperative complication of mandibular third molar extraction. It appears that no study has examined the relationship between the surface morphology of the mandibular third molar roots and the possibility of mental nerve paresthesia following tooth extraction. Therefore, the root morphology of the mandibular third molars was examined according to age using dental cone beam computed tomography (CBCT), and the possibility of mental nerve paresthesia following tooth extraction was evaluated. The study included 1216 patients who had undergone mandibular third molar extractions. The root morphology of 1534 teeth in 791 patients who had CBCT performed before surgery was studied. Factors evaluated were age, complete or incomplete formation of the mandibular third molar roots, periodontal ligament atrophy of the mandibular third molar roots, hypercementosis, and mandibular canal deformation. Mandibular third molar root formation was completed between the ages of 19 and 30 years. Complete formation of the mandibular third molar roots (P = 0.002) and deformation of the mandibular canal (P < 0.001) were identified as risk factors for mental nerve paresthesia. These findings suggest that the risk of mental nerve paresthesia could be reduced if the extraction of third molars is performed prior to complete root formation.
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Tomografía Computarizada de Haz Cónico , Mandíbula , Nervio Mandibular , Tercer Molar , Parestesia , Extracción Dental , Raíz del Diente , Humanos , Tercer Molar/cirugía , Extracción Dental/efectos adversos , Femenino , Adulto , Masculino , Parestesia/etiología , Raíz del Diente/diagnóstico por imagen , Persona de Mediana Edad , Mandíbula/cirugía , Mandíbula/inervación , Mandíbula/diagnóstico por imagen , Factores de Riesgo , Nervio Mandibular/diagnóstico por imagen , Factores de Edad , Adolescente , Complicaciones Posoperatorias , AncianoRESUMEN
We discovered a simple regime where a near-critical plasma irradiated by a laser of experimentally available intensity can self-organize to produce positrons and accelerate them to ultrarelativistic energies. The laser pulse piles up electrons at its leading edge, producing a strong longitudinal plasma electric field. The field creates a moving gamma-ray collider that generates positrons via the linear Breit-Wheeler process-annihilation of two gamma rays into an electron-positron pair. At the same time, the plasma field, rather than the laser, serves as an accelerator for the positrons. The discovery of positron acceleration was enabled by a first-of-its-kind kinetic simulation that generates pairs via photon-photon collisions. Using available laser intensities of 10^{22} W/cm^{2}, the discovered regime can generate a GeV positron beam with a divergence angle of around 10° and a total charge of 0.1 pC. The result paves the way to experimental observation of the linear Breit-Wheeler process and to applications requiring positron beams.
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INTRODUCTION: The effects of pimobendan on the heart rhythm in cats are unknown. The purpose of this pilot study was to evaluate the effect of pimobendan on the cardiac rhythm and selected echocardiographic parameters of cats. ANIMALS, MATERIALS, AND METHODS: Six clinically healthy cats received each of four medication protocols for 15 days, with a washout period of at least one month between each protocol. The protocols were, pimobendan 0.5 mg/kg twice daily (high dosage group), pimobendan 0.25 mg/kg twice daily (standard dosage group), pimobendan 0.125 mg/kg twice daily (low dosage group), and Biofermin R, one tablet twice daily (placebo group). Twenty-four-hour ambulatory electrocardiogram recordings, blood pressure measurements, and echocardiographic examinations were performed after two weeks of each medication protocol. Electrocardiographic, echocardiographic, and blood pressure parameters were compared between the four groups. RESULTS: The total number of escape/idioventricular/idiojunctional complexes in the high dosage group was significantly higher compared with the placebo, low dosage, and standard dosage groups (p < 0.001). The blood pressure; total number of heart beats per day; and mean, minimum, and maximum heart rates were not significantly different between the groups. The longitudinal strain rate and calculated cardiac output were significantly increased in the high and standard dosage groups. CONCLUSIONS: The administration of pimobendan, especially at high doses, was associated with increased numbers of escape/idioventricular/idiojunctional complexes in some cats and echocardiographic parameters. Further studies are warranted to investigate both the mechanism underlying the observed changes and what, if any, clinical implications these changes might have in cats with heart disease.
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Cardiotónicos , Gatos , Piridazinas , Animales , Cardiotónicos/farmacología , Cardiotónicos/uso terapéutico , Ecocardiografía/veterinaria , Proyectos Piloto , Piridazinas/farmacologíaRESUMEN
A 6-month-old, female, domestic shorthair cat weighing 1.8 kg presented with cardiomegaly seen on radiographs taken at a primary care veterinary center. Echocardiography revealed a single enlarged vessel overriding a ventricular septal defect and severe hypertrophy of the right ventricular free wall. There was no evidence of a pulmonary arterial trunk originating from the heart. The blood flow through the ventricular septal defect exhibited right-to-left shunting. The cat suddenly experienced dyspnea and died at home, and a postmortem examination was performed. A single large vessel was noted leaving the heart, from which the right and left pulmonary arteries arose separately; a main pulmonary artery was absent. There was only one single anomalous coronary ostium that arose from the brachiocephalic artery and divided into two branches. The walls of the extracardiac coronary artery were thick, but neither infarcts nor narrowing was observed within the coronary arteries. There were no abnormalities in the intracardiac coronary artery. These findings revealed a persistent truncus arteriosus with an anomalous coronary artery. A combination of these anomalies might have contributed to the early death of the cat.
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Anomalías de los Vasos Coronarios , Defectos del Tabique Interventricular , Tronco Arterial Persistente , Animales , Gatos , Anomalías de los Vasos Coronarios/diagnóstico por imagen , Anomalías de los Vasos Coronarios/veterinaria , Vasos Coronarios , Femenino , Defectos del Tabique Interventricular/veterinaria , Arteria Pulmonar/diagnóstico por imagen , Tronco Arterial Persistente/diagnóstico por imagen , Tronco Arterial Persistente/veterinariaRESUMEN
Genebanks provide access to diverse materials for crop improvement. To utilize and evaluate them effectively, core collections, such as the World Rice Core Collection (WRC) in the Genebank at the National Agriculture and Food Research Organization, have been developed. Because the WRC consists of 69 accessions with a high degree of genetic diversity, it has been used for >300 projects. To allow deeper investigation of existing WRC data and to further promote research using Genebank rice accessions, we performed whole-genome resequencing of these 69 accessions, examining their sequence variation by mapping against the Oryza sativa ssp. japonica Nipponbare genome. We obtained a total of 2,805,329 single nucleotide polymorphisms (SNPs) and 357,639 insertion-deletions. Based on the principal component analysis and population structure analysis of these data, the WRC can be classified into three major groups. We applied TASUKE, a multiple genome browser to visualize the different WRC genome sequences, and classified haplotype groups of genes affecting seed characteristics and heading date. TASUKE thus provides access to WRC genotypes as a tool for reverse genetics. We examined the suitability of the compact WRC population for genome-wide association studies (GWASs). Heading date, affected by a large number of quantitative trait loci (QTLs), was not associated with known genes, but several seed-related phenotypes were associated with known genes. Thus, for QTLs of strong effect, the compact WRC performed well in GWAS. This information enables us to understand genetic diversity in 37,000 rice accessions maintained in the Genebank and to find genes associated with different phenotypes. The sequence data have been deposited in DNA Data Bank of Japan Sequence Read Archive (DRA) (Supplementary Table S1).
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Variación Genética , Genoma de Planta , Estudio de Asociación del Genoma Completo , Oryza/genética , Secuenciación Completa del Genoma , Ecotipo , Flores/genética , Genes de Plantas , Haplotipos/genética , Mutación/genética , Fenotipo , Filogenia , Análisis de Componente Principal , Carácter Cuantitativo HeredableRESUMEN
In metals, orbital motions of conduction electrons on the Fermi surface are quantized in magnetic fields, which is manifested by quantum oscillations in electrical resistivity. This Landau quantization is generally absent in insulators. Here, we report a notable exception in an insulator-ytterbium dodecaboride (YbB12). The resistivity of YbB12, which is of a much larger magnitude than the resistivity in metals, exhibits distinct quantum oscillations. These unconventional oscillations arise from the insulating bulk, even though the temperature dependence of the oscillation amplitude follows the conventional Fermi liquid theory of metals with a large effective mass. Quantum oscillations in the magnetic torque are also observed, albeit with a lighter effective mass.
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The synthesis and crystal structure of the perfluorinated metal-organic framework (MOF) CFA-14 (Coordination Framework Augsburg University-14), CoII2(tfpb)(OH)2 (H2-tfpb = 1,4-bis(3,5-bis(trifluoromethyl)-1H-pyrazole-4-yl)benzene) are described. The cobalt-containing MOF crystallizes in the tetragonal crystal system within the space group I41/acd (no. 142) and the unit cell parameters are as follows: a = 20.3213(11) Å, c = 12.4045(8) Å, V = 5122.5(6) Å3. CFA-14 features a porous two-fold interpenetrated 3-D microporous structure constructed from 1-D chains of cobalt(ii) ions expanding in the c-direction, bridged by OH- groups and tfpb2- ligands. The structure exhibits quadratic channels running along the c-axis. CFA-14 is fully characterized by synchrotron single crystal X-ray diffraction, thermogravimetric analysis, variable temperature powder X-ray diffraction, IR- and UV-Vis spectroscopy, photoluminescence and gas sorption measurements. Moreover, the magnetic properties of CFA-14 are examined via SQUID measurements.
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BACKGROUND: Although autoimmune gastritis (AIG) is generally considered relatively rare, we frequently encounter AIG among patients at to our hospital who have experienced at least two episodes of Helicobacter pylori eradication failure. AIMS: We investigated the incidence of AIG in consecutive patients who consulted our department for H. pylori eradication with reference to eradication history. METHODS: A total of 404 consecutive patients who visited the H. pylori-specific out-patient unit of our hospital from June 2015 to June 2017 were enrolled. Of these, 137 were treatment-naive, 47 had failed treatment once (single failure), and 220 had failed treatment twice or more (multiple failures) by 13 C-UBT. Gastroscopy was performed in all patients. Culture tests of gastric mucosal samples were performed for H. pylori and other bacteria positive for urease activity. Anti-parietal cell antibody (APCA) was measured. Patients with severe atrophy in the gastric corpus and positivity for APCA were diagnosed as having AIG. RESULTS: A total of 43 patients were diagnosed as having AIG, of whom two were treatment-naive (1.5%, 2/137), 1 failed eradication once (2.1% 1/47), and 40 failed treatment at least twice (18.2%, 40/220). The incidence of AIG was significantly higher in the multiple failure group than in the single failure or treatment-naive groups. Urease-positive bacteria, such as Klebsiella pneumoniae and alpha-streptococcus, were identified in 33 of the 35 AIG patients who underwent culture testing. CONCLUSION: AIG patients were often misdiagnosed as refractory to eradication therapy, probably because achlorhydria in AIG might allow urease-positive bacteria other than H. pylori to colonise the stomach, causing positive 13 C-UBT results.
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Enfermedades Autoinmunes/epidemiología , Errores Diagnósticos/estadística & datos numéricos , Gastritis/epidemiología , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/epidemiología , Adulto , Anciano , Antibacterianos/uso terapéutico , Atrofia , Enfermedades Autoinmunes/diagnóstico , Farmacorresistencia Bacteriana/inmunología , Femenino , Mucosa Gástrica/diagnóstico por imagen , Mucosa Gástrica/patología , Gastritis/diagnóstico , Gastritis/microbiología , Gastroscopía , Helicobacter pylori/efectos de los fármacos , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Inhibidores de la Bomba de Protones/uso terapéutico , Inducción de Remisión , Insuficiencia del TratamientoRESUMEN
Motivation: In the new release of pymzML (v2.0), we have optimized the speed of this established tool for mass spectrometry data analysis to adapt to increasing amounts of data in mass spectrometry. Thus, we integrated faster libraries for numerical calculations, improved data retrieving algorithms and have optimized the source code. Importantly, to adapt to rapidly growing file sizes, we developed a generalizable compression scheme for very fast random access and applied this concept to mzML files to retrieve spectral data. Results: pymzML performs at par with established C programs when it comes to processing times. However, it offers the versatility of a scripting language, while adding unprecedented fast random access to compressed files. Additionally, we designed our compression scheme in such a general way that it can be applied to any field where fast random access to large data blocks in compressed files is desired. Availability and implementation: pymzML is freely available on https://github.com/pymzML/pymzML under GPL license. pymzML requires Python3.4+ and optionally numpy. Documentation available on http://pymzml.readthedocs.io.
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Compresión de Datos/métodos , Espectrometría de Masas/métodos , Programas Informáticos , Algoritmos , Proteómica/métodosRESUMEN
OBJECTIVES: Oral symptoms such as xerostomia and burning mouth syndrome have been recognized to increase associated with menopause. The purpose of this study was to clarify the changes in oral health as well as systemic health due to menopause and their relations with hormonal change and mental status. METHODS: Ninety-seven female dental hygienists aged 40-59 years were assigned to premenopausal, menopausal and post-menopausal groups based on self-reported menstrual condition. Subjective health statuses were evaluated by questionnaire, and objective holistic and oral statuses were evaluated by measuring serum 17ß-estradiol (E2), salivary flow rate, α-amylase and secretory IgA (SIgA) and taste sensitivity. RESULTS: A significant difference among the three groups was observed in the self-rating questionnaire of depression (SRQ-D) score and serum E2 level as well as unstimulated salivary flow rate, whereas no significant difference was observed in Simplified menopausal index, Short-Form 36-Item Health Survey, General Oral Health Assessment Index, salivary α-amylase activity, salivary SIgA concentration and taste threshold. Serum E2 levels positively correlated with unstimulated salivary flow rates and negatively correlated with SRQ-D scores and α-amylase activities. CONCLUSIONS: The results demonstrated a negative correlation between E2 levels and SRQ-D scores as well as salivary α-amylase activities, suggesting an influence of E2 on mental condition. Furthermore, E2 decrease may result in reduction of salivary flow which in turn causes various problems of oral health. Since the participants were graduates from several dental hygienist schools and working at various places, these results can be generalized to Japanese dental hygienists to some extent.
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Higienistas Dentales , Menopausia , Adulto , Amilasas/metabolismo , Depresión/epidemiología , Estradiol/sangre , Femenino , Humanos , Japón/epidemiología , Persona de Mediana Edad , Saliva/metabolismo , Umbral Gustativo , Xerostomía/epidemiologíaRESUMEN
In this study, we developed a user-friendly automatic powder diffraction measurement system for Debye-Scherrer geometry using a capillary sample at beamline BL02B2 of SPring-8. The measurement system consists of six one-dimensional solid-state (MYTHEN) detectors, a compact auto-sampler, wide-range temperature control systems, and a gas handling system. This system enables to do the automatic measurement of temperature dependence of the diffraction patterns for multiple samples. We introduced two measurement modes in the MYTHEN system and developed new attachments for the sample environment such as a gas handling system. The measurement modes and the attachments can offer in situ and/or time-resolved measurements in an extended temperature range between 25 K and 1473 K and various gas atmospheres and pressures. The results of the commissioning and performance measurements using reference materials (NIST CeO2 674b and Si 640c), V2O3 and Ti2O3, and a nanoporous coordination polymer are presented.
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INTRODUCTION: For the patients undergoing liver transplantation for hepatitis B virus (HBV)-related diseases, hepatitis B immunoglobulin (HBIG) should be administered to prevent reinfection. Because HBIG is highly expensive and a blood product, an alternative strategy using HBV vaccination has been made in an attempt to discontinue use of HBIG. The aim of this study was to evaluate the impact of long-term HBV vaccination for discontinuation of HBIG, paying attention to the status of active immunization using T-cell proliferation assay. PATIENTS AND METHODS: Among the 144 recipients who underwent liver transplantation in our hospital, 16 had HBV-related liver diseases; the 14 patients who had received vaccination were subjects in our study. To evaluate the status of active immunization, T-cell proliferation was examined by counting the number of T cells after adding HBV vaccine to the culture supernatant of T cells, and tumor necrosis factor α and interferon γ were measured in the culture supernatant. RESULTS: The ratio of male/female was 13/1 (median age: 55 years; range: 37 years to 67 years). The median follow-up time was 102 months (range: approximately 14 months to 148 months). All 14 patients were free of HBV recurrence. HBIG-free status could be achieved in 9 patients (64.3%) during the treatment period for more than 50 months after beginning of HBV vaccination, of whom 5 (35.7%) became HBV vaccine-free. T-cell proliferation was confirmed by fact that the stimulation index ranged from 2.34 to 5.2 in the patients who were HBIG-free. CONCLUSION: Long-term HBV vaccination after LT is a useful and effective treatment in preventing HBV recurrence, allowing the discontinuation of HBIG treatment.
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Carcinoma Hepatocelular/cirugía , Vacunas contra Hepatitis B/uso terapéutico , Hepatitis B/prevención & control , Inmunoglobulinas/uso terapéutico , Cirrosis Hepática/cirugía , Fallo Hepático Agudo/cirugía , Neoplasias Hepáticas/cirugía , Trasplante de Hígado , Complicaciones Posoperatorias/prevención & control , Prevención Secundaria , Adulto , Anciano , Carcinoma Hepatocelular/etiología , Femenino , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/complicaciones , Humanos , Cirrosis Hepática/etiología , Fallo Hepático Agudo/etiología , Neoplasias Hepáticas/etiología , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Linfocitos T , Células TH1 , Resultado del Tratamiento , VacunaciónRESUMEN
BACKGROUND: Acid inhibitory effects of proton pump inhibitors (PPIs) are influenced by CYP2C19 genotype. In contrast, the potent acid inhibition of vonoprazan is not influenced by CYP2C19 genotype. AIM: To compare the acid inhibitory effects of vonoprazan and esomeprazole in relation to CYP2C19 genotype. METHODS: Twenty-eight healthy Japanese volunteers [7 CYP2C19 poor metabolisers (PMs), 11 intermediate metabolisers (IMs) and 10 rapid metabolisers (RMs)] received four different regimens in a randomised crossover manner: (i) vonoprazan 20 mg twice daily (b.d.), (ii) vonoprazan 20 mg daily, (iii) esomeprazole 20 mg b.d. and (iv) esomeprazole 20 mg daily. The timing of each dosing was 1 h before a meal. Twenty-four-hour intragastric pH monitoring was performed on day 7 on each regimen. RESULTS: In the overall genotype group, pH ≥4 holding time ratios (pH 4 HTRs) with vonoprazan b.d., vonoprazan daily, esomeprazole b.d. and esomeprazole daily were 100%, 95%, 91%, and 68% respectively. pH 5 HTRs were 99%, 91%, 84% and 54% respectively. Vonoprazan b.d. potently suppressed acid for 24 h, and was significantly superior to other regimens irrespective of CYP2C19 genotype. Vonoprazan daily was equivalent to esomeprazole b.d. in IMs and PMs, but superior in RMs. CYP2C19 genotype-dependent differences were observed in esomeprazole daily but not in vonoprazan b.d. or daily. CONCLUSION: Vonoprazan 20 mg b.d. inhibits acid irrespective of CYP2C19 genotype, more potently than esomeprazole 20 mg b.d., pH 4 and 5 holding time ratios reached 100% and 99%, respectively.
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Citocromo P-450 CYP2C19/genética , Esomeprazol/farmacología , Ácido Gástrico/metabolismo , Inhibidores de la Bomba de Protones/farmacología , Pirroles/farmacología , Sulfonamidas/farmacología , Adulto , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Esomeprazol/administración & dosificación , Esomeprazol/farmacocinética , Femenino , Genotipo , Humanos , Concentración de Iones de Hidrógeno , Japón , Masculino , Inhibidores de la Bomba de Protones/administración & dosificación , Inhibidores de la Bomba de Protones/farmacocinética , Pirroles/administración & dosificación , Pirroles/farmacocinética , Sulfonamidas/administración & dosificación , Sulfonamidas/farmacocinéticaRESUMEN
Intravascular large B-cell lymphoma (IVLBCL) is a distinct disease entity with the peculiar characteristic that tumor cells proliferate within vessels. Despite recent advances in understanding the disease from clinical aspects, the underlying pathogenesis remains unknown. Here we demonstrate analyses of IVLBCL biology using four xenograft mouse models established from primary IVLBCL samples. In all four models, the main characteristic of IVLBCL tumor cell proliferation within vessels was retained. Time-lapse engraftment analyses revealed that the tumor cells initially engrafted and proliferated in the sinusoids and vessels in the liver and then engrafted and proliferated in multiple organs. Intriguingly, serial passage of tumor cells from the adrenal gland of a transplanted mouse developed from primary patient bone marrow cells into a second mouse showed that the tumor cells mainly distributed into the adrenal gland in the second mouse, implying the existence of clonal selection and/or evolution at engraftment of a specific organ. Gene expression profiling analyses demonstrated that the gene set associated with cell migration was enriched for normal peripheral blood B cells, indicating that inhibition of cell migration might be involved in IVLBCL pathogenesis. In conclusion, the mouse xenograft models described here are essential tools for uncovering IVLBCL biology.
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Xenoinjertos/patología , Linfoma de Células B Grandes Difuso/patología , Neoplasias Vasculares/patología , Anciano , Animales , Movimiento Celular , Proliferación Celular , Femenino , Supervivencia de Injerto , Humanos , Cadenas Pesadas de Inmunoglobulina/análisis , Hígado/irrigación sanguínea , Masculino , Ratones , Persona de Mediana Edad , Especificidad de ÓrganosRESUMEN
Elevation of the posterior part of the tongue is important for normal deglutition and speech. The purpose of this study was to develop a new surface electromyography (EMG) method to non-invasively and objectively evaluate activity in the muscles that control lifting movement in the posterior tongue. Neck surface EMG (N-EMG) was recorded using differential surface electrodes placed on the neck, 1 cm posterior to the posterior border of the mylohyoid muscle on a line orthogonal to the lower border of the mandible. Experiment 1: Three healthy volunteers (three men, mean age 37·7 years) participated in an evaluation of detection method of the posterior tongue lifting up movement. EMG recordings from the masseter, temporalis and submental muscles and N-EMG revealed that i) N-EMG was not affected by masseter muscle EMG and ii) N-EMG activity was not observed during simple jaw opening and tongue protrusion, revealing the functional difference between submental surface EMG and N-EMG. Experiment 2: Seven healthy volunteers (six men and one woman, mean age 27·9 years) participated in a quantitative evaluation of muscle activity. Tongue-lifting tasks were perfor-med, exerting a prescribed force of 20, 50, 100 and 150 gf with visual feedback. For all subjects, a significant linear relationship was observed bet-ween the tongue-lifting force and N-EMG activity (P < 0·01). These findings indicate that N-EMG can be used to quantify the force of posterior tongue lifting and could be useful to evaluate the effect of tongue rehabilitation in future studies.
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Deglución/fisiología , Electromiografía , Contracción Muscular/fisiología , Músculos del Cuello/fisiología , Habla/fisiología , Lengua/fisiología , Adulto , Estudios Transversales , Voluntarios Sanos , Humanos , Masculino , Músculo Masetero/fisiología , Paladar Duro/fisiología , Reproducibilidad de los Resultados , Músculo Temporal/fisiologíaRESUMEN
STUDY QUESTION: How do the temperature and duration of storage affect ovaries during transportation? SUMMARY ANSWER: Fertility is reduced with the extension of the storage duration. WHAT IS KNOWN ALREADY: Live birth has been reported after ovarian transport overnight on ice before freezing ovarian tissue, but there have been no basic investigations of ovarian storage conditions focused on fertility. There are no guidelines on optimal ovarian storage conditions and the maximum storage time during transportation. STUDY DESIGN, SIZE AND DURATION: Experiments were performed using C57BL/6J mice. Ovaries of 4-week-old mice were harvested, stored at 4, 14, 37 °C or room temperature (RT) for 24 h, and subjected to histological examination. Next, ovaries were stored at 4 °C for 4, 8 or 24 h and subjected to histological examination. Then orthotopic transplantation of ovaries, stored at 4 °C for 4, 8 or 24 h, was performed in 6-week-old C57BL/6J mice, and fertility was assessed by in vitro fertilization and embryo transfer. Freshly harvested ovaries were used as controls for comparison with ovaries stored under the above-mentioned conditions and experiments were repeated at least three times. PARTICIPANTS/MATERIALS, SETTING AND METHODS: In experiments on the ovarian storage temperature, haematoxylin-eosin (HE) staining was performed for histological examination. In experiments on the storage duration, HE staining, the terminal deoxynucleotidyl transferase dUTP nick end labelling assay, Ki-67 staining and electron microscopy were performed, and the numbers of follicles were counted. Fertility was assessed from the number of oocytes, and the rates of fertilization, embryo development, implantation and live birth. MAIN RESULTS AND THE ROLE OF CHANCE: Histological changes were minimal after storage of ovaries at 4 °C for up to 24 h. At 4 °C, there were no significant changes in the number of MII oocytes, fertilization rate or blastocyst development rate with storage up to 24 h. The implantation rate was 82.7 ± 17.3% in the control group, while it was 82.2 ± 7.7, 14.6 ± 14.6 and 4.4 ± 4.4% after storage for 4, 8 or 24 h, respectively. After 8 or 24 h of storage, the implantation rate was significantly lower in than in the control group (P< 0.05). The rate of live pups was 24.8 ± 13.2% in the control group, while it was 23.9 ± 6.6, 4.2 ± 4.2 and 4.4 ± 4.4% after storage for 4, 8 or 24 h, respectively. After 8 or 24 h of storage, the rate of live pups was significantly lower than in the control group (P< 0.05). LIMITATIONS, REASONS FOR CAUTION: Further investigations are needed in mammals with ovaries of a similar size to human ovaries, and should include the assessment of fertility following transplantation of frozen and thawed ovaries. WIDER IMPLICATION OF THE FINDINGS: The present results suggest that prolonging the ovarian storage time reduces fertility in mice. Thus, ovaries should be frozen immediately after harvesting or transported as rapidly as possible to minimize damage. To allow young cancer patients to preserve fertility, regional medical centres need adequate ovarian tissue cryopreservation techniques. STUDY FUNDING/COMPETING INTERESTS: This study supported by Department of Obstetrics and Gynecology, St. Marianna University School of Medicine. The authors have no competing interests to declare.
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Criopreservación/veterinaria , Ovario/trasplante , Transportes , Animales , Cesárea/veterinaria , Frío/efectos adversos , Criopreservación/métodos , Transferencia de Embrión/veterinaria , Femenino , Fertilización In Vitro/veterinaria , Japón , Nacimiento Vivo/veterinaria , Ratones Endogámicos C57BL , Ratones Endogámicos ICR , Microscopía Electrónica de Transmisión/veterinaria , Ovario/citología , Ovario/metabolismo , Ovario/ultraestructura , Factores de TiempoRESUMEN
iPS cells are attractive for the regenerative medicine. The creation of pluripotent cells from somatic cells has great potential for basic and clinical research and application. Retroviral transduction of four or three transfection factors has been shown to initiate a reprogramming process. Here, we describe the effect of transcription factors regarding the growth and differentiation of mouse iPS cells in normoxia or hypoxia. Furthermore, we introduce the function of hypoxia-inducible factors (HIFs) in mouse iPS cells in hypoxia using RT-PCR and western blotting together with HIFs knockdown techniques.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/fisiología , Técnicas de Cultivo de Célula/métodos , Técnicas de Reprogramación Celular/métodos , Reprogramación Celular , Subunidad alfa del Factor 1 Inducible por Hipoxia/fisiología , Células Madre Pluripotentes Inducidas/citología , Interferencia de ARN , ARN Interferente Pequeño/genética , Factores de Transcripción/fisiología , Transfección/métodos , Animales , Proteínas Reguladoras de la Apoptosis , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/antagonistas & inhibidores , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Western Blotting/métodos , Hipoxia de la Célula , Células Cultivadas , Regulación de la Expresión Génica , Subunidad alfa del Factor 1 Inducible por Hipoxia/antagonistas & inhibidores , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Células Madre Pluripotentes Inducidas/efectos de los fármacos , Ratones , Oxígeno/farmacología , Oxígeno/fisiología , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Proteínas Represoras , Factores de Transcripción/antagonistas & inhibidores , Factores de Transcripción/biosíntesis , Factores de Transcripción/genéticaRESUMEN
AIMS: The protective association of pioglitazone with cardiovascular events and death was investigated over 6-years in large-scale type 2 diabetic subjects without established cardiovascular disease in a primary care setting. METHODS: A six-year observational cohort study including 2864 subjects with type 2 diabetes without established cardiovascular disease was performed. The primary endpoint was a composite of first occurrence of cardiovascular disease or death. The effect of pioglitazone use at a baseline year with a Cox proportional hazard model and the time-dependent use in each one-year examination interval with a pooled logistic regression model were analyzed. RESULTS: Baseline use of pioglitazone (n=493) did not show a statistically protective effect on the primary endpoint (n=175), although it tended to reduce the risk (adjusted hazard ratio 0.67 [95% CI: 0.43-1.05]). However, pooled logistic regression analysis indicated a significant protective association of pioglitazone with the primary endpoint (0.58 [0.38 to 0.87] and cardiovascular disease (0.54 [0.33-0.88]), independent of concurrent levels of blood glucose, blood pressure, lipids, albuminuria, and renal function. In particular, this protective association was observed in those with diabetic nephropathy regardless of the daily dose of pioglitazone. Among a total of 898 subjects who took pioglitazone during the period, 43% experienced a discontinuation at least once; however, serious adverse effects were rare. CONCLUSIONS: This observational study indicated a protective association of pioglitazone with cardiovascular disease and death in type 2 diabetic subjects without established vascular disease, particularly those with nephropathy.
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Enfermedades Cardiovasculares/epidemiología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Tiazolidinedionas/uso terapéutico , Anciano , Albuminuria/sangre , Albuminuria/complicaciones , Albuminuria/epidemiología , Albuminuria/mortalidad , Glucemia/efectos de los fármacos , Glucemia/fisiología , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/mortalidad , Causas de Muerte , Estudios de Cohortes , Diabetes Mellitus Tipo 2/sangre , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/epidemiología , Nefropatías Diabéticas/mortalidad , Femenino , Humanos , Hipoglucemiantes/uso terapéutico , Masculino , Persona de Mediana Edad , PioglitazonaRESUMEN
In allo-stem cell transplantation (SCT), it is unclear whether donor-specific anti-HLA Abs (DSAs) can actually mediate graft rejection or if they are simply surrogate markers for the cellular immunity that causes graft rejection. Here, we first analyzed a case of cord blood allograft rejection in which DSA and cytotoxic T lymphocyte (CTL) specific for donor HLA-B*54:01 were detected at the time of graft rejection. Both the DSA and CTL inhibited colony formation by unrelated bone marrow mononuclear cells sharing HLA-B*54:01, suggesting that the humoral and cellular immune responses were involved in the graft rejection. Interestingly, the DSA and CTL were also detected in cryopreserved pre-transplant patient blood, raising a hypothesis that the presence of anti-HLA Abs could be an indicator for corresponding HLA-specific T cells. We then evaluated the existence of HLA-specific CD8(+) T cells in other patient blood specimens having anti-HLA class I Abs. Interferon-γ enzyme-linked immunospot assays clearly confirmed the existence of corresponding HLA-specific T-cell precursors in three of seven patients with anti-HLA Abs. In conclusion, our data demonstrate that integrated humoral and cellular immunity recognizing the same alloantigen of the donor can mediate graft rejection in DSA-positive patients undergoing HLA-mismatched allo-SCT. Further studies generalizing our observation are warranted.