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Introduction : The "autonomous sensory meridian response" (ASMR) is a neologism used to describe an internal sensation of deep relaxation and pleasant head tingling which is often stimulated by gentle sounds, light touch, and personal attention. Methods : An fMRI-based methodology was employed to examine the brain activation of subjects prescreened for ASMR-receptivity (n=10) as they watched ASMR videos and identified specific moments of relaxation and tingling. Results : Subjects who experienced ASMR showed significant activation in regions associated with both reward (NAcc) and emotional arousal (dACC and Insula/IFG). Brain activation during ASMR showed similarities to patterns previously observed in musical frisson as well as affiliative behaviors. Conclusion : This is the first study to measure the activation of various brain regions during ASMR and these results may help to reveal the mechanistic underpinnings of this sensation.
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OBJECTIVE: To describe pharmacy students' use of mobile devices in a basic health science laboratory and to report the students' perceptions on how solving cases with their mobile devices influenced their attitudes, abilities, and view on the use of mobile devices as tools for pharmacists. METHODS: First-year pharmacy students utilized mobile devices to solve clinical case studies in a basic health sciences laboratory. A pre-survey and two post-surveys were administered to assess the students' comfort, awareness, use, and perceptions on the use of their mobile devices and apps. RESULTS: The pre-survey and first post-survey each had a response rate of 99%, and the second post-survey had a response rate of 100%. In comparing the pre-survey and first post-survey data, there was a statistically significant increase in the number of students that agreed or strongly agreed that they were more comfortable utilizing their mobile device (p = 0.025), they were more aware of apps for pharmacists (p < 0.005), and they have used more apps that can be useful for pharmacists (p < 0.005). The second post-survey demonstrated that over 78% of students agreed or strongly agreed that completing the case studies influenced them to be more comfortable with their mobile devices, to be more aware of apps that can be useful for pharmacists, and to be more agreeable with mobile device utilization by pharmacists in improving patient care. In addition, the second post-survey also demonstrated that 84% of students responded that using their mobile devices to solve the cases influenced them to either use their mobile device in a clinical setting for a clinical and/or pharmacy-related purpose for the first time or to use it more frequently for this purpose. CONCLUSIONS: The use of mobile devices to solve clinical cases in a first-year basic health science laboratory course was perceived as beneficial by students and influenced them to utilize their mobile device even more in a pharmacy practice setting.
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Educación en Farmacia/métodos , Aplicaciones Móviles/normas , Percepción , Estudiantes de Farmacia/psicología , Adolescente , Adulto , Actitud del Personal de Salud , Curriculum/normas , Curriculum/tendencias , Educación en Farmacia/normas , Femenino , Humanos , Invenciones/tendencias , Masculino , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To examine pharmacy students' ownership of, use of, and preference for using a mobile device in a practice setting. METHODS: Eighty-one pharmacy students were recruited and completed a pretest that collected information about their demographics and mobile devices and also had them rank the iPhone, iPad mini, and iPad for preferred use in a pharmacy practice setting. Students used the 3 devices to perform pharmacy practice-related tasks and then completed a posttest to again rank the devices for preferred use in a pharmacy practice setting. RESULTS: The iPhone was the most commonly owned mobile device (59.3% of students), and the iPad mini was the least commonly owned (18.5%). About 70% of the students used their mobile devices at least once a week in a pharmacy practice setting. The iPhone was the most commonly used device in a practice setting (46.9% of students), and the iPod Touch was the least commonly used device (1.2%). The iPad mini was the most preferred device for use in a pharmacy practice setting prior to performing pharmacy practice-related tasks (49.4% of students), and was preferred by significantly more students after performing the tasks (70.4%). CONCLUSION: Pharmacy students commonly use their mobile devices in pharmacy practice settings and most selected the iPad mini as the preferred device for use in a practice setting even though it was the device owned by the fewest students.
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Actitud del Personal de Salud , Actitud hacia los Computadores , Instrucción por Computador/instrumentación , Computadoras de Mano , Educación en Farmacia/métodos , Teléfono Inteligente , Estudiantes de Farmacia/psicología , Estudios Cruzados , Curriculum , Humanos , Encuestas y CuestionariosRESUMEN
BACKGROUND: Warfarin is the most frequently prescribed anticoagulant in North America and Europe. It is administered as a racemate, but S-warfarin is principally responsible for its anticoagulant activity. Cytochrome P450 (CYP) 2C9 is the enzyme primarily responsible for the metabolism of S-warfarin. Numerous variant alleles of CYP2C9 have been identified. The CYP2C9*12 (rs9332239) allele harbors a P489S substitution in CYP2C9 which has been shown to result in a 40% decline in catalytic activity in vitro. CASES: Four Caucasian patients with a low mean weekly warfarin dose (MWWD) were genotyped for CYP2C9, VKORC1 and APOE variant alleles. None of the four patients carried the common CYP2C9 variant alleles (*2, *3, *5, *6, *7, *8, *9, *11, *13) despite a relatively low MWWD (23.4±7.94 mg) compared to 208 patients carrying the CYP29C9*1 genotype (32.2±12.65 mg). Given that CYP2C9*12 confers decreased in vitro activity to the enzyme, we investigated whether these patients carried this allele. All four patients were CYP2C9*12 CT heterozygotes. Individual comparisons with patients possessing the same VKORC1 and APOE genotypes also demonstrated lower dose requirements in the patients that possessed CYP2C9*12 allele. CONCLUSIONS: There are no reports of the clinical impact of rs9332239 on CYP2C9 substrates. This is the first report of patients with the rare CYP2C9*12 genotype and lower warfarin dose requirements.
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Anticoagulantes/metabolismo , Hidrocarburo de Aril Hidroxilasas/genética , Mutación , Tromboembolia/genética , Warfarina/metabolismo , Anciano , Anciano de 80 o más Años , Alelos , Sustitución de Aminoácidos , Anticoagulantes/uso terapéutico , Apolipoproteínas E/genética , Hidrocarburo de Aril Hidroxilasas/metabolismo , Secuencia de Bases , Biotransformación , Citocromo P-450 CYP2C9 , Cálculo de Dosificación de Drogas , Femenino , Genotipo , Técnicas de Genotipaje , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Tromboembolia/enzimología , Tromboembolia/patología , Tromboembolia/prevención & control , Vitamina K Epóxido Reductasas/genética , Warfarina/uso terapéuticoRESUMEN
AIM: Identifying the factors responsible for reducing the proliferation, syncytialization, and invasiveness of trophoblast tissues, as seen with preeclampsia, intrauterine growth restriction, and spontaneous miscarriage, is a current challenge in reproductive biology. These factors, transforming growth factor (TGF)-beta as an example, can work by altering trophoblast differentiation or proliferation. We therefore investigated and compared specific markers of trophoblast proliferation and differentiation in three commonly used trophoblast tissue cell models, and also investigated the influence of TGF-beta on these markers. METHODS: In this study, we isolated human trophoblasts from first trimester and term placentas, and additionally used human choriocarcinoma cells (JEG-3). Baseline values of human chorionic gonadotropin (hCG) secretion and relative mRNA levels of cell cycle regulators (cyclin E, p21, p27, and p57) were investigated for each cell type. We also investigated the influence of TGF-beta on these parameters. RESULTS: Quantitative and longitudinal production of hCG differed between the three cell types. Significantly different amounts of cyclin E, p21, p27, and p57 mRNA were demonstrated within each cell type, as well as between all the cell types, throughout the culture time period. Each trophoblast type demonstrated a reduction of hCG secretion in response to TGF-beta. TGF-beta did not show a consistent effect on the cell cycle mRNA of any of the cell types. CONCLUSION: We were able to characterize and compare the differential production of hCG, as well as the differential expression of cell cycle-associated mRNA of early trophoblasts, term trophoblasts, and choriocarcinoma cells. The production of hCG was altered by TGF-beta, although mRNA levels were not markedly altered by TGF-beta.
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Gonadotropina Coriónica/fisiología , Genes cdc , ARN Mensajero/metabolismo , Factor de Crecimiento Transformador beta/farmacología , Trofoblastos/fisiología , Proteínas de Ciclo Celular/biosíntesis , Proteínas de Ciclo Celular/genética , Línea Celular Tumoral , Coriocarcinoma , Femenino , Humanos , Placenta/citología , Embarazo , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Trofoblastos/efectos de los fármacosRESUMEN
The native form of human chorionic gonadotropin (hCG) is a heterodimer protein with two asparagine (Asn)-linked carbohydrate chains on each subunit. Removal of the Asn-linked carbohydrate chains from hCG has resulted in hCG variants with consistent antagonistic properties on isolated murine cells. Specific and direct enzymatic removal of these carbohydrate chains from native hCG with resultant antagonistic properties has not been reported. An antagonist to the hCG/luteinising hormone (LH) receptor could be used as an anticancer therapy, emergency contraceptive or for therapeutic resolution of ectopic pregnancies. Therefore, our aim was to use enzymes to specifically remove Asn-linked carbohydrate chains from hCG in the heterodimer form and analyse the resultant bioactivity. Native hCG was treated with endoglycosidases, carbohydrate removal was analysed with electrophoresis and the hCG variants were tested for altered bioactivity with human and murine cells. Endoglycosidases were able to cleave most of the Asn-linked carbohydrate chains from the native hCG. The deglycosylated hCG demonstrated a 75% reduction in bioactivity on a murine Leydig cell line and a 65% reduction in bioactivity on human granulosa cells. These results exemplify a simple and efficient method for creating deglycosylated hCG and provide the most direct evidence for the importance of Asn-linked carbohydrate chains in maintaining hCG bioactivity.
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Gonadotropina Coriónica/química , Glicósido Hidrolasas/química , Animales , Asparagina/química , Asparagina/metabolismo , Gonadotropina Coriónica/metabolismo , Gonadotropina Coriónica/farmacología , Electroforesis en Gel de Poliacrilamida , Femenino , Glicósido Hidrolasas/metabolismo , Células de la Granulosa/efectos de los fármacos , Células de la Granulosa/metabolismo , Humanos , Células Intersticiales del Testículo/efectos de los fármacos , Células Intersticiales del Testículo/metabolismo , Masculino , Ratones , Péptido-N4-(N-acetil-beta-glucosaminil) Asparagina Amidasa/química , Péptido-N4-(N-acetil-beta-glucosaminil) Asparagina Amidasa/metabolismo , Progesterona/metabolismo , Subunidades de Proteína , Especificidad por SustratoRESUMEN
Pregnancy is characterized by the presence of generalized leukocyte activation. We used flow cytometry to investigate changes in phenotype and intracellular cytokines of circulating granulocytes, monocytes, and T lymphocytes of pregnant women during gestation. We report that peripheral circulation of pregnancy is characterized by an increased percentage of granulocytes and a decrease in lymphocytes. The proportion of monocytes remains stable throughout gestation; however, a progressive up-regulation of surface markers CD11a, CD54, and CD64 was detected. Monocytes also showed higher production of interleukin (IL)-12 and IL-1beta compared with the nonpregnant state, and granulocytes had greater potential to synthesize IL-8. All these changes were particularly marked in late gestation. T lymphocytes did not have any characteristics of the activated state and showed a decreased IL-6 production. These findings demonstrate that activation of maternal monocytes and granulocytes increases during pregnancy and support the idea that pregnancy results in an elevation of the innate immune system and suppression of the adaptive immune system.
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Monocitos/inmunología , Embarazo/inmunología , Adulto , Especificidad de Anticuerpos , Moléculas de Adhesión Celular/metabolismo , Citocinas/biosíntesis , Citocinas/inmunología , Femenino , Citometría de Flujo , Granulocitos/inmunología , Humanos , Inmunofenotipificación , Cinética , Leucocitos/clasificación , Embarazo/sangre , Estudios Prospectivos , Linfocitos T/inmunologíaRESUMEN
If depression is associated with apathy, then they should be expressed together in different dementia syndromes and should co-occur at varying levels of disease severity. The authors performed a cross-sectional comparison of neuropsychiatric symptoms in 30 Alzheimer's disease, 28 frontotemporal dementia, 40 Parkinson's disease, 34 Huntington's disease, and 22 progressive supranuclear palsy patients, using a standardized rating scale (the Neuropsychiatric Inventory). Apathy did not correlate with depression in the combined sample; apathy (r = -0.40, P < 0.0001), but not depression, correlated with lower cognitive function as measured by the Mini-Mental State Examination. The relationship of apathy to depression also varied across diagnostic groups. Apathy is a specific neuropsychiatric syndrome that is distinct from depression. Distinguishing these two syndromes has therapeutic implications.
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Demencia/diagnóstico , Trastorno Depresivo/diagnóstico , Motivación , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/psicología , Comorbilidad , Estudios Transversales , Demencia/psicología , Trastorno Depresivo/psicología , Femenino , Lóbulo Frontal , Humanos , Enfermedad de Huntington/diagnóstico , Enfermedad de Huntington/psicología , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Lóbulo Parietal , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/psicología , Parálisis Supranuclear Progresiva/diagnóstico , Parálisis Supranuclear Progresiva/psicologíaRESUMEN
Clinical criteria for dementia with Lewy bodies (DLB) have been proposed, but their formulation, reliability, and validity require further study. Pathologic criteria for DLB are also undergoing evolution. Two studies were conducted with the goal of identifying the components of these evolving criteria that may benefit from further refinement; one study evaluated the components of the clinical criteria and another study operationalized the pathologic criteria for DLB. Twenty-four patients with a premorbid diagnosis of probable or possible Alzheimer's disease (AD) (n = 18), Parkinson's disease (PD) (n = 5), or progressive supranuclear palsy (PSP) (n = 1) were studied. Inter-rater reliability and validity of the clinical criteria were determined by a retrospective chart review, done by five neurologists, and a blinded pathologic evaluation. The Consortium on dementia with Lewy bodies (CDLB) pathologic criteria were operationalized to compare past criteria and test the validity of the evolving clinical criteria on the dementia patients. Three or more cortical fields (at 250 x magnification) with many (four or more) Lewy bodies (LBs) on ubiquitin immunoreactive sections were required to meet the CDLB neocortical score of > 6. Fifteen of the AD patients had at least one LB in a cortical section, four had many LBs, while three had no LBs; all patients with movement disorder had at least one LB in a cortical section. The sensitivity/specificity ratio of the CDLB probable DLB clinical criteria based upon many LBs being present was 75%/79%. Reformulated clinical criteria that require the presence of extrapyramidal signs significantly predicted those patients with many LBs versus those with few or no LBs (chi 2 = 5.48, p = 0.02) and increased clinical specificity to 100%. This preliminary study identifies components of the evolving clinical and pathologic criteria for DLB that require further refinement.
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Enfermedad de Alzheimer/patología , Cuerpos de Lewy/patología , Anciano , Anciano de 80 o más Años , Encéfalo/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Apathy is a pervasive noncognitive neuropsychiatric disturbance in Alzheimer disease, which causes significant caregiver distress. The neuroanatomical substrate of apathy is not well understood. OBJECTIVE: To study the relationship between regional cerebral blood flow and the presence and severity of the personality disturbance, apathy, in individuals with Alzheimer disease. DESIGN: Analysis of the relationship between regional cerebral blood flow as measured by single photon emission computed tomography and severity of apathy as measured by the Neuropsychiatric Inventory using an analysis of variance design. We examined regional cerebral perfusion alterations as measured by xenon 133Xecalibrated technetium Tc 99m hexamethyl-propyleneamine-oxime single photon emission computed tomography in relation to the presence and severity of apathy. SETTING: The neurology clinics of the University of California, Los Angeles, UCLA School of Medicine, and Harbor-UCLA Medical Center. PARTICIPANTS: Thirty-one community-dwelling patients fulfilling National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association diagnostic criteria for probable Alzheimer disease who had a single photon computed tomographic scan performed within 3 months of administration of the Neuropsychiatric Inventory. RESULTS: The presence of apathy was associated with more severe prefrontal and anterior temporal dysfunction. These regional cerebral perfusion relationships with apathy were independent of cognitive decline except in the dorsolateral prefrontal cortex. CONCLUSIONS: These results demonstrate the association of apathetic syndromes with prefrontal and anterior temporal regional brain dysfunction and are consistent with similar findings previously reported in other disorders.
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Enfermedad de Alzheimer/fisiopatología , Circulación Cerebrovascular/fisiología , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/psicología , Femenino , Lóbulo Frontal/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Lóbulo Temporal/fisiopatología , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
Methodological problems which affect the assessment of humoral effects on mitogenic reactivity include: (1) the source and concentration of serum used to support cell cultures; (2) the day to-day variability of inhibitory effects and (3) the specific activity of [3H]thymidine added to the culture. These problems were alleviated by addition of half concentration (7-5%) of pooled normal human serum to all cultures, the intoruction of anti-lymphocyte serum as a suitable internal control for monitoring the suppressability of lymphocytes and a reduction of specific activity of the [3H]thymidine to 1-3 C2/mM. Inhibitory factors were loosely bound to the lymphocyte surface and eluted off after incubation at 37 degrees C for 1 hr. Cells from twenty-five subjects and paired controls were cultured simultaneously in medium containing either 15% normal human serum (NHS) or 7-5% patient and 7-5% NHS. The cells were stimulated with various dilutions of phytohaemagglutinin, Con A or pokeweed mitogen. Lupus serums suppressed the reactivity of autologous lymphocytes to PHA and pokeweed mitogen. Serums from subjects with RA and scleroderma did not significantly inhibit blastogenesis of autologous lymphocytes. One-half of the lupus serums significantly inhibited the reactivity of homologous lymphocytes to two of three mitogens. Only one of eight scleroderma serums and none of twelve RA serums and none of twelve RA serums had this effect. All patients serums were examined for antilymphocyte antibodies by microcytotoxicity and immunofluorescent techniques. These antibodies were usually found in SLE, and were often observed in subjects with rheumatoid arthritis but not scleroderma. A firm relationship between serum suppressors of lymphocyte blastogenesis and anti-lymphocyte antibodies was not found.