RESUMEN
BACKGROUND AND PURPOSE: To investigate final-year student pharmacists' experiences of a new module for North American Pharmacist Licensure Examination® (NAPLEX®) preparation at one college of pharmacy in the United States. EDUCATIONAL ACTIVITY AND SETTING: All student pharmacists enrolled in a new Spring 2023 module for NAPLEX preparation (n = 118) were invited to complete an electronic questionnaire and participate in a semi-structured interview. The questionnaire investigated the perceived helpfulness, grading, importance, prioritization, structure, and timing of the module in the curriculum, as well as assignment choices, confidence building, and time management using a six-point Likert scale. Semi-structured interviews investigated experiences with NAPLEX modules, time management, and course format. Questionnaire data were descriptively analyzed; interview data were thematically analyzed. FINDINGS: Forty-one completed questionnaires and seven interviews were analyzed. Median scores for questionnaire items were six (denoting strongly agree) for three items, five (denoting agree) for seven items, and four (denoting somewhat agree) for two items. Twenty-three (56%) students desired an online self-directed (asynchronous) course structure. Seventeen (42%) students desired a mixture of short and long course assignments with a greater proportion of short course assignments while another 17 (42%) desired only short course assignments. Two themes were constructed from interviews: timing (when to study for NAPLEX) and structure (how to study for NAPLEX). SUMMARY: Study findings indicated typically positive perceptions of a module for NAPLEX preparation among final-year student pharmacists at a college of pharmacy in the United States. Recommendations from students can be used to improve the module in future years.
Asunto(s)
Curriculum , Educación en Farmacia , Percepción , Estudiantes de Farmacia , Humanos , Estudiantes de Farmacia/estadística & datos numéricos , Estudiantes de Farmacia/psicología , Curriculum/tendencias , Curriculum/normas , Encuestas y Cuestionarios , Estados Unidos , Educación en Farmacia/métodos , Educación en Farmacia/normas , Educación en Farmacia/estadística & datos numéricos , Masculino , Femenino , Evaluación Educacional/métodos , Evaluación Educacional/estadística & datos numéricos , Adulto , Entrevistas como Asunto/métodos , Licencia en Farmacia/estadística & datos numéricosRESUMEN
Increasing temperature influences the habitats of various organisms, including microscopic invertebrates. To gain insight into temperature-dependent changes in tardigrades, we isolated storage cells exposed to various temperatures and conducted biochemical and ultrastructural analysis in active and tun-state Paramacrobiotus experimentalis Kaczmarek, Mioduchowska, Poprawa, & Roszkowska, 2020. The abundance of heat shock proteins (HSPs) and ultrastructure of the storage cells were examined at different temperatures (20 °C, 30 °C, 35 °C, 37 °C, 40 °C, and 42 °C) in storage cells isolated from active specimens of Pam. experimentalis. In the active animals, upon increase in external temperature, we observed an increase in the levels of HSPs (HSP27, HSP60, and HSP70). Furthermore, the number of ultrastructural changes in storage cells increased with increasing temperature. Cellular organelles, such as mitochondria and the rough endoplasmic reticulum, gradually degenerated. At 42 °C, cell death occurred by necrosis. Apart from the higher electron density of the karyoplasm and the accumulation of electron-dense material in some mitochondria (at 42 °C), almost no changes were observed in the ultrastructure of tun storage cells exposed to different temperatures. We concluded that desiccated (tun-state) are resistant to high temperatures, but not active tardigrades (survival rates of tuns after 24 h of rehydration: 93.3% at 20 °C, 60.0% at 35 °C, 33.3% at 37 °C, 33.3% at 40 °C, and 20.0% at 42 °C).
Asunto(s)
Tardigrada , Animales , Temperatura , Tardigrada/metabolismo , Proteínas de Choque Térmico/metabolismo , Invertebrados/metabolismo , Proteínas HSP70 de Choque Térmico , CalorRESUMEN
Calreticulin is an endoplasmic Ca2+ binding protein and molecular chaperone. As a cardiac embryonic gene, calreticulin is essential for heart development. The protein supports Ca2+-dependent signaling events that are critical to cardiomyocyte differentiation and cardiogenesis. The increased expression of calreticulin and endoplasmic reticulum/sarcoplasmic reticulum Ca2+ capacity produces cardiomyocytes with enhanced efficiency, and detrimental mechanical stretching of cardiac fibroblasts, leading to cardiac pathology. Deletion of the calreticulin gene in adult cardiomyocytes results in left ventricle dilation, an impaired electrocardiogram, and heart failure. These observations indicate that a well-adjusted endoplasmic reticulum and calreticulin-dependent Ca2+ pool in cardiomyocytes are critical for the maintenance of proper cardiac function.
Asunto(s)
Calcio , Calreticulina , Calcio/metabolismo , Calreticulina/genética , Calreticulina/metabolismo , Retículo Endoplásmico/metabolismo , Miocitos Cardíacos/metabolismo , Retículo Sarcoplasmático/metabolismoRESUMEN
We previously showed that calnexin (Canx)-deficient mice are desensitized to experimental autoimmune encephalomyelitis (EAE) induction, a model that is frequently used to study inflammatory demyelinating diseases, due to increased resistance of the blood-brain barrier to immune cell transmigration. We also discovered that Fabp5, an abundant cytoplasmic lipid-binding protein found in brain endothelial cells, makes protein-protein contact with the cytoplasmic C-tail domain of Canx. Remarkably, both Canx-deficient and Fabp5-deficient mice commonly manifest resistance to EAE induction. Here, we evaluated the importance of Fabp5/Canx interactions on EAE pathogenesis and on the patency of a model blood-brain barrier to T-cell transcellular migration. The results demonstrate that formation of a complex comprised of Fabp5 and the C-tail domain of Canx dictates the permeability of the model blood-brain barrier to immune cells and is also a prerequisite for EAE pathogenesis.
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Calnexina/metabolismo , Encefalomielitis Autoinmune Experimental/metabolismo , Proteínas de Unión a Ácidos Grasos/metabolismo , Proteínas de Neoplasias/metabolismo , Animales , Transporte Biológico/fisiología , Barrera Hematoencefálica/metabolismo , Encéfalo/metabolismo , Línea Celular , Movimiento Celular/fisiología , Modelos Animales de Enfermedad , Células Endoteliales/metabolismo , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , PermeabilidadRESUMEN
Transgenic mice with selective induction of calreticulin transgene expression in cardiomyocytes (CardiacCRT+) were analyzed. CardiacCRT+ cardiomyocytes showed increased contractility and Ca2+ transients. Yet, in vivo assessment of cardiac performance, and ischemic tolerance of CardiacCRT+ mice demonstrated right ventricle dilation and reduced cardiac output, increased QT interval and decreased P amplitude. Paradoxically, ex vivo working hearts from CardiacCRT+ mice showed enhanced ischemic cardio-protection and cardiac efficiency. Under aerobic conditions, CardiacCRT+ hearts showed less efficient cardiac function than sham control hearts due to an increased ATP production from glycolysis relative to glucose oxidation. During reperfusion, this inefficiency was reversed, with CardiacCRT+ hearts exhibiting better functional recovery and increased cardiac efficiency compared to sham control hearts. On the other hand, mechanical stretching of isolated cardiac fibroblasts activated the IRE1α branch of the unfolded protein response pathway as well as induction of Col1A2 and TGFß gene expression ex vivo, which were all suppressed by tauroursodeoxycholic acid.
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Calreticulina/metabolismo , Contracción Miocárdica , Isquemia Miocárdica/metabolismo , Miocitos Cardíacos/metabolismo , Animales , Calreticulina/genética , Células Cultivadas , Metabolismo Energético , Frecuencia Cardíaca , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Isquemia Miocárdica/genética , Isquemia Miocárdica/fisiopatología , Miocitos Cardíacos/patología , Regulación hacia ArribaRESUMEN
Chronic exposure to cyclosporine causes nephrotoxicity and organ damage. Here we show that cyclosporine nephrotoxicity in vivo is associated with the activation of the unfolded protein response (UPR) pathway to initiate tissue fibrosis. We demonstrate that cyclosporine therapy activated the IRE1α branch of the unfolded protein response (UPR) and stimulated the TGFß1 signaling pathway in the kidneys of male mice. Co-administration of the proteostasis promoter tauroursodeoxycholic acid (TUDCA) with cyclosporine inhibited the UPR pathway in the kidneys of treated male mice as well as decreased the development of renal fibrogenesis.
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Ciclosporina/farmacología , Fibrosis/inducido químicamente , Enfermedades Renales/prevención & control , Riñón/efectos de los fármacos , Ácido Tauroquenodesoxicólico/farmacología , Animales , Modelos Animales de Enfermedad , Riñón/patología , Masculino , Ratones , Respuesta de Proteína DesplegadaRESUMEN
In multiple sclerosis (MS), a demyelinating inflammatory disease of the CNS, and its animal model (experimental autoimmune encephalomyelitis; EAE), circulating immune cells gain access to the CNS across the blood-brain barrier to cause inflammation, myelin destruction, and neuronal damage. Here, we discovered that calnexin, an ER chaperone, is highly abundant in human brain endothelial cells of MS patients. Conversely, mice lacking calnexin exhibited resistance to EAE induction, no evidence of immune cell infiltration into the CNS, and no induction of inflammation markers within the CNS. Furthermore, calnexin deficiency in mice did not alter the development or function of the immune system. Instead, the loss of calnexin led to a defect in brain endothelial cell function that resulted in reduced T cell trafficking across the blood-brain barrier. These findings identify calnexin in brain endothelial cells as a potentially novel target for developing strategies aimed at managing or preventing the pathogenic cascade that drives neuroinflammation and destruction of the myelin sheath in MS.
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Barrera Hematoencefálica/inmunología , Calnexina/metabolismo , Encefalomielitis Autoinmune Experimental/inmunología , Esclerosis Múltiple/inmunología , Linfocitos T/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Animales , Barrera Hematoencefálica/citología , Barrera Hematoencefálica/patología , Calnexina/genética , Calnexina/inmunología , Movimiento Celular/inmunología , Encefalomielitis Autoinmune Experimental/patología , Células Endoteliales/inmunología , Células Endoteliales/patología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Ratones , Ratones Transgénicos , Persona de Mediana Edad , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/patología , Linfocitos T/metabolismo , Regulación hacia Arriba , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/inmunología , Sustancia Blanca/patologíaRESUMEN
AIMS/HYPOTHESIS: A new class of treatments termed bioelectronic medicines are now emerging that aim to target individual nerve fibres or specific brain circuits in pathological conditions to repair lost function and reinstate a healthy balance. Carotid sinus nerve (CSN) denervation has been shown to improve glucose homeostasis in insulin-resistant and glucose-intolerant rats; however, these positive effects from surgery appear to diminish over time and are heavily caveated by the severe adverse effects associated with permanent loss of chemosensory function. Herein we characterise the ability of a novel bioelectronic application, classified as kilohertz frequency alternating current (KHFAC) modulation, to suppress neural signals within the CSN of rodents. METHODS: Rats were fed either a chow or high-fat/high-sucrose (HFHSu) diet (60% lipid-rich diet plus 35% sucrose drinking water) over 14 weeks. Neural interfaces were bilaterally implanted in the CSNs and attached to an external pulse generator. The rats were then randomised to KHFAC or sham modulation groups. KHFAC modulation variables were defined acutely by respiratory and cardiac responses to hypoxia (10% O2 + 90% N2). Insulin sensitivity was evaluated periodically through an ITT and glucose tolerance by an OGTT. RESULTS: KHFAC modulation of the CSN, applied over 9 weeks, restored insulin sensitivity (constant of the insulin tolerance test [KITT] HFHSu sham, 2.56 ± 0.41% glucose/min; KITT HFHSu KHFAC, 5.01 ± 0.52% glucose/min) and glucose tolerance (AUC HFHSu sham, 1278 ± 20.36 mmol/l × min; AUC HFHSu KHFAC, 1054.15 ± 62.64 mmol/l × min) in rat models of type 2 diabetes. Upon cessation of KHFAC, insulin resistance and glucose intolerance returned to normal values within 5 weeks. CONCLUSIONS/INTERPRETATION: KHFAC modulation of the CSN improves metabolic control in rat models of type 2 diabetes. These positive outcomes have significant translational potential as a novel therapeutic modality for the purpose of treating metabolic diseases in humans.
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Seno Carotídeo/inervación , Diabetes Mellitus Tipo 2/sangre , Animales , Glucemia/metabolismo , Péptido C/sangre , Corticosterona/sangre , Diabetes Mellitus Tipo 2/fisiopatología , Electromiografía , Insulina/sangre , Resistencia a la Insulina/fisiología , Masculino , Óxido Nítrico/sangre , Pletismografía , RatasRESUMEN
AIM: Approximately 20% of Australian pre-school children are overweight. Primary care providers have a crucial role in identifying children at risk of unhealthy weight gain and to offer advice and suggestions to parents. The Healthy 4 Life pilot study aimed to develop and test the feasibility of a practice nurse (PN)-led brief intervention into a healthy kid's check in general practice. METHODS: A PN intervention was developed based on a needs assessment and existing literature. A workshop was conducted, and resources were provided to enable four PNs to deliver a brief obesity prevention intervention to parents. Nurses then incorporated the Healthy 4 Life components into the healthy kid's checks they conducted on the next 10 children. Medical records were reviewed and nurses interviewed to establish the feasibility of the intervention. RESULTS: All of the nurses incorporated some Healthy 4 Life components into their healthy kid's checks. Body mass index was calculated and plotted for all children, and advice around healthy eating was offered in 60% of consultations; however, advice about limiting screen time provided in only 2% of consultations. Nurses reported that the intervention fitted well with their current practice, although time constraints were a concern for some nurses and some parents. CONCLUSION: The provision of a brief training workshop and resources can equip nurses in general practice to offer an obesity prevention intervention to parents of young children. Further research is required to examine the impact of such an intervention on parent and child behaviours and the sustainability of such practices for PNs.
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Protección a la Infancia , Medicina General/organización & administración , Educación en Salud/organización & administración , Enfermeras Practicantes/educación , Obesidad Infantil/prevención & control , Prevención Primaria/organización & administración , Australia , Índice de Masa Corporal , Lista de Verificación , Niño , Conducta Infantil/fisiología , Preescolar , Estudios de Factibilidad , Femenino , Humanos , Estilo de Vida , Masculino , Evaluación de Necesidades , Obesidad Infantil/epidemiología , Proyectos Piloto , Desarrollo de Programa , Evaluación de Programas y Proyectos de Salud , Medición de RiesgoRESUMEN
AIM: Overweight and obesity affects approximately 20% of Australian pre-schoolers. The general practice nurse (PN) workforce has increased in recent years; however, little is known of PN capacity and potential to provide routine advice for the prevention of child obesity. This mixed methods pilot study aims to explore the current practices, attitudes, confidence and training needs of Australian PNs surrounding child obesity prevention in the general practice setting. METHODS: PNs from three Divisions of General Practice in New South Wales were invited to complete a questionnaire investigating PN roles, attitudes and practices in preventive care with a focus on child obesity. A total of 59 questionnaires were returned (response rate 22%). Semi-structured qualitative interviews were also conducted with a subsample of PNs (n = 10). RESULTS: Questionnaire respondent demographics were similar to that of national PN data. PNs described preventive work as enjoyable despite some perceived barriers including lack of confidence. Number of years working in general practice did not appear to strongly influence nurses' perceived barriers. Seventy per cent of PNs were interested in being more involved in conducting child health checks in practice, and 85% expressed an interest in taking part in child obesity prevention training. CONCLUSIONS: Findings from this pilot study suggest that PNs are interested in prevention of child obesity despite barriers to practice and low confidence levels. More research is needed to determine the effect of training on PN confidence and behaviours in providing routine healthy life-style messages for the prevention of child obesity.
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Conocimientos, Actitudes y Práctica en Salud , Rol de la Enfermera , Obesidad/prevención & control , Padres/educación , Atención Primaria de Salud/métodos , Adulto , Niño , Femenino , Encuestas de Atención de la Salud , Humanos , Masculino , Persona de Mediana Edad , Nueva Gales del Sur , Padres/psicología , Proyectos Piloto , Investigación Cualitativa , Adulto JovenRESUMEN
BACKGROUND: Calreticulin, a Ca(2+)-buffering chaperone of the endoplasmic reticulum, is highly expressed in the embryonic heart and is essential for cardiac development. After birth, the calreticulin gene is sharply down regulated in the heart, and thus, adult hearts have negligible levels of calreticulin. In this study we tested the role of calreticulin in the adult heart. METHODOLOGY/PRINCIPAL FINDINGS: We generated an inducible transgenic mouse in which calreticulin is targeted to the cardiac tissue using a Cre/loxP system and can be up-regulated in adult hearts. Echocardiography analysis of hearts from transgenic mice expressing calreticulin revealed impaired left ventricular systolic and diastolic function and impaired mitral valve function. There was altered expression of Ca(2+) signaling molecules and the gap junction proteins, Connexin 43 and 45. Sarcoplasmic reticulum associated Ca(2+)-handling proteins (including the cardiac ryanodine receptor, sarco/endoplasmic reticulum Ca(2+)-ATPase, and cardiac calsequestrin) were down-regulated in the transgenic hearts with increased expression of calreticulin. CONCLUSIONS/SIGNIFICANCE: We show that in adult heart, up-regulated expression of calreticulin induces cardiomyopathy in vivo leading to heart failure. This is due to an alternation in changes in a subset of Ca(2+) handling genes, gap junction components and left ventricle remodeling.
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Calreticulina/metabolismo , Cardiomiopatía Dilatada/metabolismo , Cardiomiopatía Dilatada/patología , Animales , Señalización del Calcio , Calsecuestrina/genética , Calsecuestrina/metabolismo , Cardiomiopatía Dilatada/diagnóstico por imagen , Cardiomiopatía Dilatada/genética , Pollos , Conexinas/genética , Conexinas/metabolismo , Regulación hacia Abajo , Electrocardiografía , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Miocardio/metabolismo , Miocardio/patología , Cadenas Pesadas de Miosina/metabolismo , Especificidad de Órganos , Regiones Promotoras Genéticas/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Retículo Sarcoplasmático/metabolismo , UltrasonografíaRESUMEN
BACKGROUND: A common feature of preclinical models of colitis is that the time-course, magnitude, and persistence of inflammation vary considerably within the experimental animal group. Accordingly, noninvasive, serial quantification of colonic inflammation could advantageously guide dosing regimens and assess drug efficacy, thus enhancing the value of colitis models in research. This investigation using magnetic resonance imaging (MRI) was therefore undertaken to objectively determine inflammatory progression, variability, and response to therapy associated with trinitrobenzene sulfonic acid (TNBS)-induced colitis in Wistar rats. METHODS: Rats underwent TNBS treatment on Day 0 and received sulfasalazine or vehicle (methylcellulose) orally, daily, from Day -1 (prophylactically) or Day 2 (therapeutically). T2-weighted and semidynamic T1-weighted contrast-enhanced MRI (CE-MRI) was repeated over 7-10 days to measure colon wall thickness and perfusion-related aspects of inflammation. Rectal bleeding, stool consistency, and disease activity were scored throughout and colon pathology determined terminally. RESULTS: Principal component analysis of the CE-MRI time-series highlighted colon wall and mesenteric inflammation, which increased by 6-8x naïve values. Peristaltic artifacts were distinguished from perfusion changes using the normalized temporal standard deviation. MRI correlated strongly with terminal colon weight (mean correlation r = 0.8), well with body weight change (r = -0.7), but little with conventional clinical scores. Sulfasalazine reduced inflammation administered prophylactically and therapeutically. CONCLUSIONS: Inflammation and therapeutic efficacy can be sensitively quantified noninvasively using MRI in TNBS-treated rats. This methodology provides unique and objective in vivo measures of inflammation that can guide dosing strategies, enhancing colitis research effectiveness and the assessment of potential IBD therapeutics.