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1.
Nat Commun ; 12(1): 6764, 2021 11 19.
Artículo en Inglés | MEDLINE | ID: mdl-34799563

RESUMEN

The field of cellular microbiology, rooted in the co-evolution of microbes and their hosts, studies intracellular pathogens and their manipulation of host cell machinery. In this review, we highlight emerging technologies and infection models that recently promoted opportunities in cellular microbiology. We overview the explosion of microscopy techniques and how they reveal unprecedented detail at the host-pathogen interface. We discuss the incorporation of robotics and artificial intelligence to image-based screening modalities, biochemical mapping approaches, as well as dual RNA-sequencing techniques. Finally, we describe chips, organoids and animal models used to dissect biophysical and in vivo aspects of the infection process. As our knowledge of the infected cell improves, cellular microbiology holds great promise for development of anti-infective strategies with translational applications in human health.


Asunto(s)
Antiinfecciosos/farmacología , Técnicas Citológicas , Infecciones/tratamiento farmacológico , Técnicas Microbiológicas , Microscopía/métodos , Animales , Antiinfecciosos/uso terapéutico , Inteligencia Artificial , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos/métodos , Evaluación Preclínica de Medicamentos/tendencias , Interacciones Huésped-Patógeno , Humanos , Infecciones/microbiología , Microscopía/tendencias , Organoides , Análisis de Secuencia de ARN , Investigación Biomédica Traslacional/métodos , Investigación Biomédica Traslacional/tendencias
2.
Int J Mol Sci ; 22(8)2021 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-33918011

RESUMEN

Nanoliposomes are one of the leading potential nano drug delivery systems capable of targeting chemotherapeutics to tumor sites because of their passive nano-targeting capability through the enhanced permeability and retention (EPR) effect for cancer patients. Recent advances in nano-delivery systems have inspired the development of a wide range of nanotargeted materials and strategies for applications in preclinical and clinical usage in the cancer field. Nanotargeted 188Re-liposome is a unique internal passive radiotheranostic agent for nuclear imaging and radiotherapeutic applications in various types of cancer. This article reviews and summarizes our multi-institute, multidiscipline, and multi-functional studied results and achievements in the research and development of nanotargeted 188Re-liposome from preclinical cells and animal models to translational clinical investigations, including radionuclide nanoliposome formulation, targeted nuclear imaging, biodistribution, pharmacokinetics, radiation dosimetry, radiation tumor killing effects in animal models, nanotargeted radionuclide and radio/chemo-combination therapeutic effects, and acute toxicity in various tumor animal models. The systemic preclinical and clinical studied results suggest 188Re-liposome is feasible and promising for in vivo passive nanotargeted radionuclide theranostics in future cancer care applications.


Asunto(s)
Liposomas , Nanopartículas , Radioisótopos , Radiofármacos , Renio , Investigación Biomédica Traslacional , Animales , Estudios Clínicos como Asunto , Evaluación Preclínica de Medicamentos , Humanos , Liposomas/química , Nanopartículas/química , Neoplasias/diagnóstico por imagen , Neoplasias/mortalidad , Neoplasias/terapia , Evaluación de Resultado en la Atención de Salud , Radiometría , Radiofármacos/química , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único , Nanomedicina Teranóstica/métodos , Distribución Tisular , Tomografía Computarizada de Emisión de Fotón Único , Investigación Biomédica Traslacional/métodos
3.
Mol Oncol ; 15(5): 1277-1288, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33734563

RESUMEN

There is a persistent variation in cancer outcomes among and within European countries suggesting (among other causes) inequalities in access to or delivery of high-quality cancer care. European policy (EU Cancer Mission and Europe's Beating Cancer Plan) is currently moving towards a mission-oriented approach addressing these inequalities. In this study, we used the quantitative and qualitative data of the Organisation of European Cancer Institutes' Accreditation and Designation Programme, relating to 40 large European cancer centres, to describe their current compliance with quality standards, to identify the hallmarks common to all centres and to show the distinctive features of Comprehensive Cancer Centres. All Comprehensive Cancer Centres and Cancer Centres accredited by the Organisation of European Cancer Institutes show good compliance with quality standards related to care, multidisciplinarity and patient centredness. However, Comprehensive Cancer Centres on average showed significantly better scores on indicators related to the volume, quality and integration of translational research, such as high-impact publications, clinical trial activity (especially in phase I and phase IIa trials) and filing more patents as early indicators of innovation. However, irrespective of their size, centres show significant variability regarding effective governance when functioning as entities within larger hospitals.


Asunto(s)
Instituciones Oncológicas , Neoplasias/terapia , Calidad de la Atención de Salud , Academias e Institutos/normas , Academias e Institutos/estadística & datos numéricos , Investigación Biomédica/organización & administración , Investigación Biomédica/normas , Investigación Biomédica/estadística & datos numéricos , Instituciones Oncológicas/organización & administración , Instituciones Oncológicas/estadística & datos numéricos , Estudios de Cohortes , Europa (Continente)/epidemiología , Humanos , Oncología Médica/normas , Oncología Médica/estadística & datos numéricos , Neoplasias/epidemiología , Grupo de Atención al Paciente/organización & administración , Grupo de Atención al Paciente/normas , Grupo de Atención al Paciente/estadística & datos numéricos , Atención Dirigida al Paciente/organización & administración , Atención Dirigida al Paciente/normas , Atención Dirigida al Paciente/estadística & datos numéricos , Investigación Biomédica Traslacional/métodos , Investigación Biomédica Traslacional/organización & administración , Investigación Biomédica Traslacional/estadística & datos numéricos
4.
Clin Nutr ; 40(3): 936-945, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-32747205

RESUMEN

BACKGROUND & AIMS: In hospital nutrition care the difficulty of translating knowledge to action often leads to inadequate management of patients with malnutrition. nutritionDay, an annual cross-sectional survey has been assessing nutrition care in healthcare institutions in 66 countries since 2006. While initial efforts led to increased awareness of malnutrition, specific local remedial actions rarely followed. Thus, reducing the Knowledge-to-action (KTA) gap in nutrition care requires more robust and focused strategies. This study describes the strategy, methods, instruments and experience of developing and implementing nutritionDay 2.0, an audit and feedback intervention that uses quality and economic indicators, feedback, benchmarking and self-defined action strategies to reduce the KTA gap in hospital nutrition care. METHODS: We used an evidence based multi-professional mixed-methods approach to develop and implement nutritionDay 2.0 This audit and feedback intervention is driven by a Knowledge-to-Action framework complemented with robust stakeholder analysis. Further evidence was synthesized from the literature, online surveys, a pilot study, World Cafés and individual expert feedback involving international health care professionals, nutrition care scientists and patients. RESULTS: The process of developing and implementing nutritionDay 2.0 over three years resulted in a new audit questionnaire based on 36 nutrition care quality and economic indicators at hospital, unit and patient levels, a new action-oriented feedback and benchmarking report and a unit-level personalizable action plan template. The evaluation of nutritionDay 2.0 is ongoing and will include satisfaction and utility of nutritionDay 2.0 tools and short-, mid- and long-term effects on the KTA gap. CONCLUSION: In clinical practice, nutritionDay 2.0 has the potential to promote behavioural and practice changes and improve hospital nutrition care outcomes. In research, the data generated advances knowledge about institutional malnutrition and quality of hospital nutrition care. The ongoing evaluation of the initiative will reveal how far the KTA gap in hospital nutrition care was addressed and facilitate the understanding of the mechanisms needed for successful audit and feedback. TRIAL REGISTRATION: Registration in clinicaltrials.gov: Identifier: NCT02820246.


Asunto(s)
Servicios Dietéticos/normas , Encuestas de Atención de la Salud/métodos , Auditoría Médica/métodos , Terapia Nutricional/normas , Investigación Biomédica Traslacional/métodos , Estudios Transversales , Implementación de Plan de Salud , Humanos , Garantía de la Calidad de Atención de Salud/métodos , Participación de los Interesados
5.
Tumori ; 107(2): 150-159, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32522106

RESUMEN

BACKGROUND: No predictive markers for chemotherapy activity have been validated in gastric cancer (GC). The potential value of class III ß-tubulin (TUBB3) as biomarker for prognosis and resistance to taxane-based therapy was reported. METHODS: We analyzed GC samples of patients enrolled in the Intergroup Trial of Adjuvant Chemotherapy in Adenocarcinoma of the Stomach (ITACA-S), a randomized adjuvant study comparing 5-fluorouracil/leucovorin (5-FU/LV) and docetaxel-based sequential chemotherapy. TUBB3 was quantitated by selected reaction monitoring mass spectrometry and patients were stratified using a threshold of 750 attomoles per microgram (amol/µg). Cox proportional modeling and Kaplan-Meier survival analysis were used to assess the impact of TUBB3 expression on overall survival (OS) and disease-free survival. RESULTS: Patients with TUBB3 protein levels >750 and <750 amol/µg were 21.9% and 78.1%, respectively, and were well-balanced between treatment arms. TUBB3 protein levels were not prognostic. Whereas no survival differences according to the 2 arms were observed in the subgroup with low TUBB3 expression (5-year OS 47% vs 40%; p = 0.44), patients with high TUBB3 had a clinically meaningful poorer OS when receiving docetaxel-based versus 5-FU/LV chemotherapy (5-year OS 31% vs 54%; p = 0.09), with a statistically significant interaction between TUBB3 and treatment (p = 0.049). CONCLUSIONS: The quantification of TUBB3 might be considered as a negative predictive biomarker of benefit from taxane-based therapy in GC. Studies are needed to evaluate its role in the neoadjuvant setting.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resistencia a Antineoplásicos/efectos de los fármacos , Neoplasias Gástricas/tratamiento farmacológico , Tubulina (Proteína)/metabolismo , Adenocarcinoma/metabolismo , Biomarcadores de Tumor/metabolismo , Quimioterapia Adyuvante/métodos , Cisplatino/administración & dosificación , Docetaxel/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Estimación de Kaplan-Meier , Leucovorina/administración & dosificación , Masculino , Pronóstico , Neoplasias Gástricas/metabolismo , Investigación Biomédica Traslacional/métodos
6.
Drug Discov Today ; 25(10): 1855-1864, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32693162

RESUMEN

Increasingly, new drug development by major pharmaceutical companies relies on in-licensing of innovative therapies. Often there are limited data accompanying these novel entities. By focusing on scientific principles and generating key preclinical and clinical data, discovery companies can improve their valuations. From the lens of a large pharmaceutical company, we highlight key scientific aspects that are assessed to mitigate risk in valuations and deal terms. Our focus is on clinical development aspects for oncology drugs by stage of development. However, these lessons apply equally to other therapeutic areas.


Asunto(s)
Antineoplásicos/farmacología , Desarrollo de Medicamentos/métodos , Investigación Biomédica Traslacional/métodos , Animales , Descubrimiento de Drogas/métodos , Evaluación Preclínica de Medicamentos/métodos , Industria Farmacéutica/métodos , Humanos
7.
Fam Syst Health ; 38(2): 99-104, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32525346

RESUMEN

Entrepreneurs in integrated care face some of the same challenges in empirically demonstrating impact, regardless of the model of care they espouse. In this editorial, 2 leading model developers reflect on the state of the science in primary care integration, including research gaps and promising research underway. We asked these leaders to discuss conceptual areas of shared concern, and we present those with reference to the metaphor of the translational research bridge. Their insights resonate with one another and suggest a role for collaboration to advance empirical support for the implementation of integrated care. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Asunto(s)
Liderazgo , Investigación Biomédica Traslacional/métodos , Prestación Integrada de Atención de Salud/tendencias , Humanos , Atención Primaria de Salud/métodos , Investigación Biomédica Traslacional/tendencias
8.
Trends Cancer ; 6(9): 730-732, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32430152

RESUMEN

Given extensive reports of anticancer nanomedicines in preclinical studies, why is there such a paucity of clinical trials using these therapies? Nanotechnology can certainly deliver, but we need to tackle the limitations that are impeding the translation of nanomedicines into the clinic and start benefiting from their full potential.


Asunto(s)
Materiales Biocompatibles/uso terapéutico , Ensayos Clínicos como Asunto , Nanomedicina/métodos , Neoplasias/terapia , Investigación Biomédica Traslacional/métodos , Animales , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos/tendencias , Humanos , Nanomedicina/tendencias , Nanopartículas/uso terapéutico , Proyectos de Investigación/tendencias , Investigación Biomédica Traslacional/tendencias
9.
Pflugers Arch ; 472(5): 527-545, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32415463

RESUMEN

Paralysis is a frequent phenomenon in many diseases, and to date, only functional electrical stimulation (FES) mediated via the innervating nerve can be employed to restore skeletal muscle function in patients. Despite recent progress, FES has several technical limitations and significant side effects. Optogenetic stimulation has been proposed as an alternative, as it may circumvent some of the disadvantages of FES enabling cell type-specific, spatially and temporally precise stimulation of cells expressing light-gated ion channels, commonly Channelrhodopsin2. Two distinct approaches for the restoration of skeletal muscle function with optogenetics have been demonstrated: indirect optogenetic stimulation through the innervating nerve similar to FES and direct optogenetic stimulation of the skeletal muscle. Although both approaches show great promise, both have their limitations and there are several general hurdles that need to be overcome for their translation into clinics. These include successful gene transfer, sustained optogenetic protein expression, and the creation of optically active implantable devices. Herein, a comprehensive summary of the underlying mechanisms of electrical and optogenetic approaches is provided. With this knowledge in mind, we substantiate a detailed discussion of the advantages and limitations of each method. Furthermore, the obstacles in the way of clinical translation of optogenetic stimulation are discussed, and suggestions on how they could be overcome are provided. Finally, four specific examples of pathologies demanding novel therapeutic measures are discussed with a focus on the likelihood of direct versus indirect optogenetic stimulation.


Asunto(s)
Terapia por Estimulación Eléctrica/métodos , Músculo Esquelético/metabolismo , Optogenética/métodos , Investigación Biomédica Traslacional/métodos , Animales , Humanos , Contracción Muscular , Músculo Esquelético/fisiología
10.
J Contin Educ Health Prof ; 40(1): 11-18, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32149944

RESUMEN

INTRODUCTION: The Accreditation Council for Graduate Medical Education provided guidelines, in 2013, regarding 13 clinical procedures pediatric residents should learn. Previous studies show that, when asked, general pediatricians (GPeds) self-report performing these procedures infrequently. When examined using the knowledge translation model, this low procedural performance frequency, especially by GPeds, may indicate a problem within the primary care landscape. METHODS: This was a descriptive study using the Partners For Kids, an accountable care organization, database to obtain how frequently each of the procedures was performed for a geographically representative sample of GPeds in central Ohio. RESULTS: A total of 296 physicians participated in Partners For Kids. Nearly one-third practiced for more than 15 years (n = 83, 28%) and one-third also lived in a rural region (n = 78, 26.4%). The most commonly billed procedure was administering immunizations (n = 79,292, 92.3%); the least was peripheral intravenous catheter placement (n = 2, 0.002%). Most procedures were completed in the office-based setting. DISCUSSION: General pediatricians in central Ohio do not frequently perform the 13 recommended procedures of Accreditation Council for Graduate Medical Education. Evaluation of this problem using the knowledge translation model shows that potential barriers could be inadequate training during or after residency or more likely that these procedures are not necessary in GPeds' current scope of practice. The next step should be to see, from the practitioner's perspective, what procedures are important to their daily practice. Adapting this knowledge to the local context will help target continuing medical education/continuing professional development interventions.


Asunto(s)
Acreditación/métodos , Métodos , Pediatras/normas , Acreditación/estadística & datos numéricos , Competencia Clínica/normas , Competencia Clínica/estadística & datos numéricos , Humanos , Ohio , Organización y Administración , Pediatras/estadística & datos numéricos , Investigación Biomédica Traslacional/instrumentación , Investigación Biomédica Traslacional/métodos , Investigación Biomédica Traslacional/estadística & datos numéricos
11.
Rheum Dis Clin North Am ; 46(1): 1-19, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31757278

RESUMEN

Lectures, a form of passive learning, are a modality of teaching used in medical education. Active learning strategies allow learners and teachers to interact and be more engaged with the subject matter in a manner that encourages discussion, critical thinking, and advanced clinical reasoning skills. Learning to be effective requires vigilance, which promotes memory retention and should afford a way for learners to build on preexisting knowledge via scaffolding and concept mapping that uses critical thinking. Educators should also to use evaluation models that seek to improve patient care, health care systems, and community health.


Asunto(s)
Educación de Postgrado en Medicina , Aprendizaje Basado en Problemas/métodos , Reumatología/educación , Investigación Biomédica Traslacional/métodos , Competencia Clínica , Educación de Postgrado en Medicina/métodos , Educación de Postgrado en Medicina/normas , Humanos , Atención Plena , Reumatología/normas , Pensamiento
12.
J Ethnopharmacol ; 247: 112255, 2020 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-31568819

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Piper longum, commonly referred as 'Pippali', has found its traditional use in India, Malaysia, Singapore and other South Asian countries as an analgesic, carminative, anti-diarrhoeic, immunostimulant, post childbirth to check postpartum hemorrhage and to treat asthma, insomnia, dementia, epilepsy, diabetes, rheumatoid arthritis, asthma, spleen disorder, puerperal fever, leprosy etc. AIM OF THE REVIEW: This review offers essential data focusing on the traditional use, phytochemistry and pharmacological profile of Piper longum thereby identifying research gaps and future opportunities for investigation on this plant. MATERIALS AND METHODS: This systematic survey was accomplished as per the PRISMA guidelines. The information was collected from books, and electronic search (PubMed, Science Direct, Lilca and Scielo) during 1967-2019. RESULTS: Many phytochemicals have been identified till date, including alkaloids as its major secondary metabolites (piperine and piperlongumine), essential oil, flavonoids and steroids. These exhibit a wide range of activities including anti-inflammatory, analgesic, anti-oxidant, anti-microbial, anti-cancer, anti-parkinsonian, anti-stress, nootropic, anti-epileptic, anti-hyperglycemic, hepatoprotective, anti-hyperlipidemic, anti-platelet, anti-angiogenic, immunomodulatory, anti-arthritic, anti-ulcer, anti-asthmatic, anthelmintic action, anti-amebic, anti-fungal, mosquito larvicidal and anti-snake venom. CONCLUSION: Amongst various activities, bioscientific clarification in relation to its ethnopharmacological perspective has been evidenced mainly for anti-amebic, anthelminthic, anti-tumor and anti-diabetic activity. However, despite traditional claims, insufficient scientific validation for the treatment of insomnia, dementia, epilepsy, rheumatoid arthritis, asthma, spleen disorder, puerperal fever and leprosy, necessitate future investigations in this direction. It is also essential and critical to generate toxicological data and pharmacokinetics on human subjects so as to confirm its conceivable bio-active components in the body.


Asunto(s)
Etnofarmacología/métodos , Medicina Tradicional/métodos , Piper/química , Extractos Vegetales/farmacología , Investigación Biomédica Traslacional/métodos , Etnofarmacología/tendencias , Humanos , India , Malasia , Extractos Vegetales/uso terapéutico , Singapur , Investigación Biomédica Traslacional/tendencias
13.
Rev Bras Enferm ; 72(suppl 3): 220-226, 2019 Dec.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-31851257

RESUMEN

OBJECTIVE: create and validate a musical educational technology for lactation physiology learning for professional training in health. METHOD: methodological study with application of a conceptual framework of Knowledge Translation. In the creation cycle, the knowledge of the physiology of lactation was synthetized in key points to create the lyrics and the melody. In the action cycle, the content of the musical educational technology was validated by judges experts in breast feeding, in the period from September to December 2017. RESULTS: 18 judges from all Brazilian regions participated in the validation. The content of the technology obtained a global Content Validity Index of 0.94 with one round of validation. CONCLUSION: the musical educational technology is validated to introduce the content of the physiology of lactation in the learning process of students, mediated by the teacher.


Asunto(s)
Lactancia/fisiología , Musicoterapia/métodos , Fisiología/educación , Investigación Biomédica Traslacional/instrumentación , Adulto , Brasil , Tecnología Educacional , Femenino , Humanos , Lactancia/metabolismo , Musicoterapia/instrumentación , Musicoterapia/tendencias , Encuestas y Cuestionarios , Investigación Biomédica Traslacional/métodos
14.
Semin Reprod Med ; 37(3): 119-124, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-31869839

RESUMEN

Kisspeptin and neurokinin B (NKB) are hypothalamic neuropeptides that are vital for reproductive health. An absence of either kisspeptin or NKB signaling results in hypogonadotrophic hypogonadism and a failure to proceed through puberty. In recent years, several studies have demonstrated potential avenues for the clinical utility of medications that act through these pathways in the assessment and treatment of reproductive disorders. Kisspeptin acts to stimulate hypothalamic gonadotrophic-releasing hormone (GnRH) secretion from the hypothalamus. Kisspeptin induces gonadotrophin secretion in both healthy men and women, and in women with reproductive disorders such as hypothalamic amenorrhea (HA). Kisspeptin-based treatments hold promise for use during in vitro fertilization (IVF) treatment; a bolus of kisspeptin-54 induces an LH surge of 12 to 14 hours of duration sufficient to induce oocyte maturation, but with markedly reduced rates of the most significant complication of IVF treatment, ovarian hyperstimulation syndrome (OHSS). Kisspeptin could also be used chronically to restore reproductive health in patients with functional hypogonadism, such as those with HA. Furthermore, kisspeptin has potential as a diagnostic test of hypothalamic function; a "kisspeptin test" could be used in children with delayed puberty to identify the subset with genetically determined deficits in hypothalamic pathways (congenital hypogonadotrophic hypogonadism [CHH]). In addition to its role in hypothalamic GnRH pulse generation, NKB plays a critical role in the occurrence of one of the most troubling symptoms of the menopause, the "hot flush." Neurokinin-3 receptor (NK3R) antagonists are highly effective as treatments for hot flushes in postmenopausal women, with several compounds now in late-phase development. Furthermore, NK3R antagonism leads to a reduction in LH secretion by reducing GnRH pulsatility in the hypothalamus and has been shown to reduce androgen levels in women with polycystic ovary syndrome (PCOS) (in whom GnRH pulsatility is often increased). In summary, although further detailed evaluation in several clinical settings is ongoing, medications based on kisspeptin and NKB pathways have prodigious potential in the assessment and treatment of reproductive disorders.


Asunto(s)
Kisspeptinas/fisiología , Neuroquinina B/fisiología , Investigación Biomédica Traslacional , Animales , Femenino , Fertilización In Vitro/métodos , Fertilización In Vitro/tendencias , Hormona Liberadora de Gonadotropina/metabolismo , Humanos , Hipotálamo/metabolismo , Masculino , Reproducción/fisiología , Investigación Biomédica Traslacional/métodos , Investigación Biomédica Traslacional/tendencias
15.
Methods Mol Biol ; 2011: 3-22, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31273690

RESUMEN

Most large pharmaceutical companies have downscaled or closed their clinical neuroscience research programs in response to the low clinical success rate for drugs that showed tremendous promise in animal experiments intended to model psychiatric pathophysiology. These failures have raised serious concerns about the role of preclinical research in the identification and evaluation of new pharmacotherapies for psychiatry. In the absence of a comprehensive understanding of the neurobiology of psychiatric disorders, the task of developing "animal models" seems elusive. The purpose of this review is to highlight emerging strategies to enhance the utility of preclinical research in the drug development process. We address this issue by reviewing how advances in neuroscience, coupled with new conceptual approaches, have recently revolutionized the way we can diagnose and treat common psychiatric conditions. We discuss the implications of these new tools for modeling psychiatric conditions in animals and advocate for the use of systematic reviews of preclinical work as a prerequisite for conducting psychiatric clinical trials. We believe that work in animals is essential for elucidating human psychopathology and that improving the predictive validity of animal models is necessary for developing more effective interventions for mental illness.


Asunto(s)
Biotecnología , Fármacos del Sistema Nervioso Central/farmacología , Desarrollo de Medicamentos , Evaluación Preclínica de Medicamentos , Investigación Biomédica Traslacional , Experimentación Animal , Animales , Biomarcadores , Fármacos del Sistema Nervioso Central/uso terapéutico , Ensayos Clínicos como Asunto , Desarrollo de Medicamentos/métodos , Evaluación Preclínica de Medicamentos/métodos , Humanos , Trastornos Mentales/diagnóstico , Trastornos Mentales/tratamiento farmacológico , Trastornos Mentales/etiología , Terapia Molecular Dirigida , Investigación Biomédica Traslacional/métodos , Resultado del Tratamiento
16.
Theranostics ; 9(11): 3365-3387, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31244958

RESUMEN

A critical step in the translational science of nanomaterials from preclinical animal studies to humans is the comprehensive investigation of their disposition (or ADME) and pharmacokinetic behaviours. Disposition and pharmacokinetic data are ideally collected in different animal species (rodent and nonrodent), at different dose levels, and following multiple administrations. These data are used to assess the systemic exposure and effect to nanomaterials, primary determinants of their potential toxicity and therapeutic efficacy. At toxic doses in animal models, pharmacokinetic (termed toxicokinetic) data are related to toxicologic findings that inform the design of nonclinical toxicity studies and contribute to the determination of the maximum recommended starting dose in clinical phase 1 trials. Nanomaterials present a unique challenge for disposition and pharmacokinetic investigations owing to their prolonged circulation times, nonlinear pharmacokinetic profiles, and their extensive distribution into tissues. Predictive relationships between nanomaterial physicochemical properties and behaviours in vivo are lacking and are confounded by anatomical, physiological, and immunological differences amongst preclinical animal models and humans. These challenges are poorly understood and frequently overlooked by investigators, leading to inaccurate assumptions of disposition, pharmacokinetic, and toxicokinetics profiles across species that can have profoundly detrimental impacts for nonclinical toxicity studies and clinical phase 1 trials. Herein are highlighted two research tools for analysing and interpreting disposition and pharmacokinetic data from multiple species and for extrapolating this data accurately in humans. Empirical methodologies and mechanistic mathematical modelling approaches are discussed with emphasis placed on important considerations and caveats for representing nanomaterials, such as the importance of integrating physiological variables associated with the mononuclear phagocyte system (MPS) into extrapolation methods for nanomaterials. The application of these tools will be examined in recent examples of investigational and clinically approved nanomaterials. Finally, strategies for applying these extrapolation tools in a complementary manner to perform dose predictions and in silico toxicity assessments in humans will be explained. A greater familiarity with the available tools and prior experiences of extrapolating nanomaterial disposition and pharmacokinetics from preclinical animal models to humans will hopefully result in a more straightforward roadmap for the clinical translation of promising nanomaterials.


Asunto(s)
Evaluación Preclínica de Medicamentos/métodos , Nanoestructuras/administración & dosificación , Preparaciones Farmacéuticas/administración & dosificación , Distribución Tisular , Investigación Biomédica Traslacional/métodos , Animales , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Humanos , Modelos Teóricos , Nanoestructuras/efectos adversos
17.
BMC Geriatr ; 19(1): 177, 2019 06 25.
Artículo en Inglés | MEDLINE | ID: mdl-31238882

RESUMEN

BACKGROUND: Vitamin D supplement use is recommended best practice in residential aged care facilities (RACFs) for the prevention of falls, however has experienced delays in uptake. Following successful international efforts at implementing this evidence into practice, the ViDAus study sought to replicate this success for the Australian context. The aim of this paper is to report on the process outcomes of implementing this intervention. METHODS: Forty-one RACFs were engaged in a multifaceted, interdisciplinary knowledge translation intervention. This focused on raising awareness to improve knowledge on vitamin D, and supporting facilities to identify barriers and implement locally devised strategies to improve the uptake of evidence based practice (EBP). RESULTS: Staff members of participating facilities (n = 509 including nursing, care and allied health staff) were well engaged and accepting of the intervention, though engagement of servicing general practitioners (GPs) (n = 497) and pharmacists (n = 9) was poor. Facilities each identified between three and eight strategies focused on raising awareness, identifying residents to target for vitamin D and creating referral pathways depending upon their own locally identified barriers and capacity. There was variable success at implementing these over the 12-month intervention period. Whilst this study successfully raised awareness among staff, residents and their family members, barriers were identified that hindered engagement of GPs. CONCLUSIONS: The intervention was overall feasible to implement and perceived as appropriate by GPs, pharmacists, facility staff, residents and family members. More facilitation, higher-level organisational support and strategies to improve RACF access to GPs however were identified as important improvements for the implementation of vitamin D supplement use. TRIAL REGISTRATION: Retrospectively registered (ANZCTR ID: ACTRN12616000782437 ) on 15 June 2016.


Asunto(s)
Accidentes por Caídas/prevención & control , Envejecimiento/fisiología , Práctica Clínica Basada en la Evidencia/métodos , Grupo de Atención al Paciente , Investigación Biomédica Traslacional/métodos , Vitamina D/administración & dosificación , Anciano , Anciano de 80 o más Años , Envejecimiento/efectos de los fármacos , Instituciones de Vida Asistida/tendencias , Australia/epidemiología , Suplementos Dietéticos , Práctica Clínica Basada en la Evidencia/tendencias , Familia/psicología , Femenino , Personal de Salud/psicología , Personal de Salud/tendencias , Hogares para Ancianos/tendencias , Humanos , Masculino , Grupo de Atención al Paciente/tendencias , Estudios Retrospectivos , Investigación Biomédica Traslacional/tendencias
18.
BMC Pharmacol Toxicol ; 20(1): 30, 2019 05 21.
Artículo en Inglés | MEDLINE | ID: mdl-31113474

RESUMEN

BACKGROUND: Experimental pharmacology deals with effects of various test substances studied on different animal species which is aimed at finding out safe therapeutic agent suitable for public health as well as mechanism and site of action of a test substance. It is the basic step in the discovery of new drugs or studying the pharmacological actions of already developed one using both preclinical and clinical study designs in a stepwise phase of investigations. However, the investigations in the first phase of experimental pharmacology are usually concluded with assumption hypothesis without any adequate validation of the scientific evidence. Single dose acute toxicology had been conducted on Balb c mice with three different level of doses prepared from each of three different test chemicals (Dichlorvos, Chlorpyrifos and Cypermethrin) with known median lethal dose (LD50) to define the fundamental principles, cause of toxicity and investigation timeframe in the first phase of experimental pharmacology. METHODS: The methods used for data collection were: procurement of test chemicals, investigation of single dose acute toxicity on Balb c mice and quantitative immunoglobulins test. Data was thematically compiled for validation of the findings from each of the sources. RESULTS: The result showed that the dose had never limited the toxic property of tested chemicals but the magnitude of adverse effect and length of time at which adverse effect was manifested on treated Balb c mice. The toxicity of tested chemicals was however limited by the toxic reaction rate of a dose in the biological process of exposed Balb c mice. The toxic effect of tested chemicals became magnified within a short period of time when large amount administered orally. It also remained after a long period of time when small amount administered in the same route. CONCLUSION: Adequate investigation time for acute toxicity study was therefore essential for comprehensive analysis of pharmacological property of tested chemicals at different level of doses.


Asunto(s)
Relación Dosis-Respuesta a Droga , Pruebas de Toxicidad Aguda/métodos , Animales , Cloropirifos/administración & dosificación , Cloropirifos/toxicidad , Diclorvos/administración & dosificación , Diclorvos/toxicidad , Evaluación Preclínica de Medicamentos/métodos , Femenino , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Insecticidas/administración & dosificación , Insecticidas/toxicidad , Ratones Endogámicos BALB C , Piretrinas/administración & dosificación , Piretrinas/toxicidad , Investigación Biomédica Traslacional/métodos
19.
World J Gastroenterol ; 25(16): 1913-1927, 2019 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-31086460

RESUMEN

Understanding the occurrence, development, and treatment of liver diseases is the main goal of hepatopathology research. Liver diseases are not only diverse but also highly heterogeneous among individuals. At present, research on liver diseases is conducted mainly through cell culture, animal models, pathological specimens, etc. However, these methods cannot fully reveal the pathogenic mechanism and therapeutic characteristics of individualized liver diseases. Recent advances in three-dimensional cell culture technology (organoid culture techniques) include pluripotent stem cells and adult stem cells that are cultured in vitro to form self-organizing properties, making it possible to achieve individualized liver disease research. This review provides a comprehensive overview of the development of liver organoids, the existing and potential applications of liver regenerative medicine, the pathogenesis of liver disease heterogeneity, and drug screening.


Asunto(s)
Técnicas de Cultivo de Célula/métodos , Hepatopatías/terapia , Organoides/efectos de los fármacos , Animales , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos/métodos , Humanos , Hígado/citología , Hígado/patología , Hepatopatías/patología , Medicina Regenerativa/métodos , Investigación Biomédica Traslacional/métodos
20.
Epilepsy Behav ; 93: 60-64, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30831404

RESUMEN

INTRODUCTION: Arts-based knowledge translation (ABKT) strategies represent an innovative approach to disseminate results of qualitative studies, especially to tackle social issues, such as stigma and prejudice, due to knowledge gaps. Epilepsy affects 1% of the world population and brings a strong psychosocial impact to the patient, family members, and caregivers. People with epilepsy have difficulties to establish social relationships due to stigma. METHODS: In this study, we narrate the construction of an aerial and contemporary dance based on the results of a qualitative study with patients with epilepsy, their families, and health professionals, called "'Dialogue with Emotions' to overcome barriers and to improve quality of life in epilepsy". Under the ABKT classification, this study is defined as a strategy of subjective key messages, which are presented as active performances (contemporary dance and aerial acrobacies). RESULTS: In this sense, the choreography called "Perspective" presented elements that relate to suffering, pain, fear, social isolation, followed by mutual support, resilience, adaptation, and happiness. Through its scenic poetry and acrobatics combined with special lighting effect and soundtrack, this choreography represents the potential to overcome suffering and experience happiness if people embrace a different perspective over epilepsy. CONCLUSION: This presentation conveyed perceptions on epilepsy in a way to create an experience for its audience. It represented an opportunity to stimulate reflection, discussion, and knowledge construction between members of the academy, as well as patients and caregivers. Thus, this artistic presentation was able to promote discussions about epilepsy, disseminating research results, promoting empathy and compassion.


Asunto(s)
Concienciación , Danzaterapia/métodos , Epilepsia/psicología , Epilepsia/terapia , Seda , Adulto , Cuidadores/psicología , Familia/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prejuicio/psicología , Calidad de Vida/psicología , Aislamiento Social/psicología , Estigma Social , Investigación Biomédica Traslacional/métodos
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