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1.
FEBS J ; 287(3): 443-451, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31994340

RESUMEN

You have spent most of your training learning how to be successful in a research laboratory. But are you ready to step in front of a class and teach? This Words of Advice article provides guidance and resources for designing a course using backward design and for becoming an effective teacher, especially in today's new format of large, interactive classes.

2.
Int J Paleopathol ; 2020 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-31964606

RESUMEN

Andean paleopathological research has significantly enhanced knowledge about the geographical distribution and evolution of tuberculosis (TB) in pre-Columbian South America. In this paper, we review the history and progress of research on ancient tuberculosis (TB) in the Andean region, focusing on the strengths and limitations of current approaches for the molecular detection of ancient pathogens, with special attention to TB. As a case study, we describe a molecular screening approach for the detection of ancient Mycobacterium tuberculosis in individuals from Late Intermediate Period (1000-1400 CE) contexts at the site of Huari, Peru. We evaluate 34 commingled human vertebrae and combine morphological assessments of pathology with high throughput sequencing and a non-selective approach to ancient pathogen DNA screening. Our method enabled the simultaneous detection of ancient M. tuberculosis DNA and an evaluation of the environmental microbial composition of each sample. Our results show that despite the dominance of environmental DNA, molecular signatures of M. tuberculosis were identified in eight vertebrae, six of which had no observable skeletal pathology classically associated tuberculosis infection. This screening approach will assist in the identification of candidate samples for downstream genomic analyses. The method permits higher resolution disease identification in cases where pathology may be absent, or where the archaeological context may necessitate a broad differential diagnosis based on morphology alone.

3.
Acad Med ; 95(2): 194-199, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31464734

RESUMEN

An important tenet of competency-based medical education is that the educational continuum should be seamless. The transition from undergraduate medical education (UME) to graduate medical education (GME) is far from seamless, however. Current practices around this transition drive students to focus on appearing to be competitively prepared for residency. A communication at the completion of UME-an educational handover-would encourage students to focus on actually preparing for the care of patients. In April 2018, the American Medical Association's Accelerating Change in Medical Education consortium meeting included a debate and discussion on providing learner performance measures as part of a responsible educational handover from UME to GME. In this Perspective, the authors describe the resulting 5 recommendations for developing such a handover: (1) The purpose of the educational handover should be to provide medical school performance data to guide continued improvement in learner ability and performance, (2) the process used to create an educational handover should be philosophically and practically aligned with the learner's continuous quality improvement, (3) the educational handover should be learner driven with a focus on individualized learning plans that are coproduced by the learner and a coach or advisor, (4) the transfer of information within an educational handover should be done in a standardized format, and (5) together, medical schools and residency programs must invest in adequate infrastructure to support learner improvement. These recommendations are shared to encourage implementation of the educational handover and to generate a potential research agenda that can inform policy and best practices.

4.
Nat Commun ; 10(1): 4470, 2019 10 02.
Artículo en Inglés | MEDLINE | ID: mdl-31578321

RESUMEN

The second plague pandemic, caused by Yersinia pestis, devastated Europe and the nearby regions between the 14th and 18th centuries AD. Here we analyse human remains from ten European archaeological sites spanning this period and reconstruct 34 ancient Y. pestis genomes. Our data support an initial entry of the bacterium through eastern Europe, the absence of genetic diversity during the Black Death, and low within-outbreak diversity thereafter. Analysis of post-Black Death genomes shows the diversification of a Y. pestis lineage into multiple genetically distinct clades that may have given rise to more than one disease reservoir in, or close to, Europe. In addition, we show the loss of a genomic region that includes virulence-related genes in strains associated with late stages of the pandemic. The deletion was also identified in genomes connected with the first plague pandemic (541-750 AD), suggesting a comparable evolutionary trajectory of Y. pestis during both events.


Asunto(s)
ADN Bacteriano/genética , Genoma Bacteriano/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Pandemias , Peste/epidemiología , Yersinia pestis/genética , Arqueología/métodos , ADN Bacteriano/química , ADN Bacteriano/clasificación , Europa Oriental/epidemiología , Fósiles , Humanos , Filogenia , Filogeografía , Peste/microbiología , Polimorfismo de Nucleótido Simple , Factores de Tiempo , Virulencia/genética , Yersinia pestis/patogenicidad
5.
Acad Med ; 94(9): 1332-1336, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31460928

RESUMEN

PROBLEM: Despite prominent calls to incorporate value-based health care (VBHC) into medical education, there is still a global need for robust programs to teach VBHC concepts throughout health professions training. APPROACH: In June 2017, Dell Medical School released the first collection (three modules) of a set of free interactive online learning modules, which aim to teach the basic foundations of VBHC to health professions learners at any stage of training and can be incorporated across diverse educational settings. These modules were designed by an interprofessional team based on principles of cognitive engagement for active learning. OUTCOMES: From June 2017 to September 2018, the website received 130,098 pageviews from 8,546 unique users (2,072 registered users), representing 45 states in the United States and 10 foreign countries. As of October 15, 2018, 568 (27%) of registered users completed modules 1-3. Five-hundred thirty-five of these users completed a survey (94% response rate). Nearly all (484/535; 90%) reported overall satisfaction with the curriculum, 522/535 (98%) agreed "after completing the modules, I can define value in health care," and 520/535 (97%) agreed "after completing the modules, I can provide examples of low- and high-value care." Second-year Dell Medical School students reported that they have incorporated value into their clinical clerkships (e.g., by discussing VBHC with peers [43/45; 96%]) as a result of completing the modules. NEXT STEPS: Future plans for the curriculum include the release of additional modules, more robust knowledge assessment, and an expanded learning platform that allows for further community engagement.

6.
PLoS One ; 14(7): e0219312, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31276481

RESUMEN

Ebolaviruses continue to inflict horrific disease and instill fear. The 2013-2016 outbreak in Western Africa caused unfathomable morbidity and mortality (over 11,000 deaths), and the second largest outbreak is on-going in the Democratic Republic of the Congo. The first stage of an Ebolavirus infection is entry, culminating in delivery of the viral genome into the cytoplasm to initiate replication. Among enveloped viruses, Ebolaviruses use a complex entry pathway: they bind to attachment factors on cell surfaces, are engulfed by macropinocytosis, and traffic through the endosomal system. En route, the receptor binding subunit of the glycoprotein (GP) is reduced from ~130 to ~19 kDa by cathepsins. This event allows cleaved GP (GPcl) to bind to Niemann-Pick C1 (NPC1), its endosomal receptor. The virus then fuses with a late endosomal membrane, but how this occurs remains a subject of debate. An early, but standing, observation is that entry of particles bearing GPcl is inhibited by agents that raise endosomal pH or inhibit cysteine proteases, suggesting the need for an additional factor(s). Yet, some have concluded that NPC1 is sufficient to trigger the fusion activity of GPcl. Here, we re-examined this question using sensitive cell-cell and pseudovirus-cell fusion assays. We did not observe detectable GPcl-mediated fusion with NPC1 or its GPcl binding domain at any pH tested, while robust fusion was consistently observed with GP from lymphocytic choriomeningitis virus at low pH. Addition of proposed fusion-enhancing factors-cations (Ca++ and K+), a reducing agent, the anionic lipid Bis(Monoacylglycero)Phosphate, and a mixture of cathepsins B and L-did not induce detectable fusion. Our findings are in line with the earlier proposal that an additional factor is required to trigger the full fusion activity of GPcl after binding to NPC1. We discuss caveats to our study and what the missing factor(s) might be.

7.
Annu Rev Microbiol ; 73: 639-666, 2019 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-31283430

RESUMEN

The last century has witnessed progress in the study of ancient infectious disease from purely medical descriptions of past ailments to dynamic interpretations of past population health that draw upon multiple perspectives. The recent adoption of high-throughput DNA sequencing has led to an expanded understanding of pathogen presence, evolution, and ecology across the globe. This genomic revolution has led to the identification of disease-causing microbes in both expected and unexpected contexts, while also providing for the genomic characterization of ancient pathogens previously believed to be unattainable by available methods. In this review we explore the development of DNA-based ancient pathogen research, the specialized methods and tools that have emerged to authenticate and explore infectious disease of the past, and the unique challenges that persist in molecular paleopathology. We offer guidelines to mitigate the impact of these challenges, which will allow for more reliable interpretations of data in this rapidly evolving field of investigation.

8.
Int J Paleopathol ; 26: 48-60, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31228793

RESUMEN

OBJECTIVE: To carefully assess skeletal lesions in close environment context in order to evaluate whether skeletal fluorosis was present in individuals living in the prehistoric Midwest, USA. MATERIALS: Skeletal remains from minimally 117 individuals recovered from the Ray Site, located in western Illinois (USA) and dated to the Middle/early Late Woodland periods (50 BC-AD 400). METHODS: Macroscopic evaluation of all recovered skeletal elements. RESULTS: Eight individuals display a constellation of abnormal bony changes, including osteosclerosis, a high frequency of fractures, and dental abnormalities. CONCLUSIONS: The osteosclerotic changes along with the naturally high fluoride content of west central Illinois soil and water suggests the presence of skeletal fluorosis. SIGNIFICANCE: This is the first report of skeletal fluorosis from archaeologically recovered human remains from North America. LIMITATIONS: The ambiguous nature of the skeletal changes associated with fluorosis, especially in the less severe stages of the disease, renders determination of the etiology difficult. SUGGESTIONS FOR FURTHER RESEARCH: The continuation of paleopathological investigations of fluoride toxicity within archaeological communities recovered from this region with emphasis on the incorporation of biomedical and environmental data. Furthermore, complementary analyses of the chemical composition and the histological presentation of the skeletons could provide support for this diagnosis.


Asunto(s)
Enfermedades Óseas/etiología , Enfermedades Óseas/historia , Exposición a Riesgos Ambientales/historia , Intoxicación por Flúor/historia , Enfermedades Óseas/patología , Niño , Femenino , Intoxicación por Flúor/patología , Fluorosis Dental/historia , Fluorosis Dental/patología , Historia Antigua , Humanos , Illinois , Masculino , Persona de Mediana Edad , Paleopatología
9.
J Virol ; 93(12)2019 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-30918081

RESUMEN

Influenza virus is an RNA virus encapsulated in a lipid bilayer derived from the host cell plasma membrane. Previous studies showed that influenza virus infection depends on cellular lipids, including the sphingolipids sphingomyelin and sphingosine. Here we examined the role of a third sphingolipid, glucosylceramide, in influenza virus infection following clustered regularly interspaced short palindromic repeats with Cas9 (CRISPR-Cas9)-mediated knockout (KO) of its metabolizing enzyme glucosylceramidase (GBA). After confirming GBA knockout of HEK 293 and A549 cells by both Western blotting and lipid mass spectrometry, we observed diminished infection in both KO cell lines by a PR8 (H1N1) green fluorescent protein (GFP) reporter virus. We further showed that the reduction in infection correlated with impaired influenza virus trafficking to late endosomes and hence with fusion and entry. To examine whether GBA is required for other enveloped viruses, we compared the results seen with entry mediated by the glycoproteins of Ebola virus, influenza virus, vesicular stomatitis virus (VSV), and measles virus in GBA knockout cells. Entry inhibition was relatively robust for Ebola virus and influenza virus, modest for VSV, and mild for measles virus, suggesting a greater role for viruses that enter cells by fusing with late endosomes. As the virus studies suggested a general role for GBA along the endocytic pathway, we tested that hypothesis and found that trafficking of epidermal growth factor (EGF) to late endosomes and degradation of its receptor were impaired in GBA knockout cells. Collectively, our findings suggest that GBA is critically important for endocytic trafficking of viruses as well as of cellular cargos, including growth factor receptors. Modulation of glucosylceramide levels may therefore represent a novel accompaniment to strategies to antagonize "late-penetrating" viruses, including influenza virus.IMPORTANCE Influenza virus is the pathogen responsible for the second largest pandemic in human history. A better understanding of how influenza virus enters host cells may lead to the development of more-efficacious therapies against emerging strains of the virus. Here we show that the glycosphingolipid metabolizing enzyme glucosylceramidase is required for optimal influenza virus trafficking to late endosomes and for consequent fusion, entry, and infection. We also provide evidence that promotion of influenza virus entry by glucosylceramidase extends to other endosome-entering viruses and is due to a general requirement for this enzyme, and hence for optimal levels of glucosylceramide, for efficient trafficking of endogenous cargos, such as the epidermal growth factor (EGF) receptor, along the endocytic pathway. This work therefore has implications for the basic process of endocytosis as well as for pathogenic processes, including virus entry and Gaucher disease.

11.
J Infect Dis ; 218(suppl_5): S672-S678, 2018 11 22.
Artículo en Inglés | MEDLINE | ID: mdl-29939303

RESUMEN

Background: A need to develop therapeutics to treat Ebola virus disease patients in remote and resource-challenged settings remains in the wake of the 2013-2016 epidemic in West Africa. Toward this goal, we screened drugs under consideration as treatment options and other drugs of interest, most being small molecules approved by the Food and Drug Administration. Drugs demonstrating in vitro antiviral activity were advanced for evaluation in combinations because of advantages often provided by drug cocktails. Methods: Drugs were screened for blockade of Ebola virus infection in cultured cells. Twelve drugs were tested in all (78 pair-wise) combinations, and 3 were tested in a subset of combinations. Results: Multiple synergistic drug pairs emerged, with the majority comprising 2 entry inhibitors. For the pairs of entry inhibitors studied, synergy was demonstrated at the level of virus entry into host cells. Highly synergistic pairs included aripiprazole/piperacetazine, sertraline/toremifene, sertraline/bepridil, and amodiaquine/clomiphene. Conclusions: Our study shows the feasibility of identifying pairs of approved drugs that synergistically block Ebola virus infection in cell cultures. We discuss our findings in terms of the theoretic ability of these or alternate combinations to reach therapeutic levels. Future research will assess selected combinations in small-animal models of Ebola virus disease.


Asunto(s)
Antivirales/administración & dosificación , Ebolavirus/efectos de los fármacos , Animales , Antivirales/uso terapéutico , Aprobación de Drogas , Sinergismo Farmacológico , Quimioterapia Combinada , Células Vero , Virión/efectos de los fármacos , Internalización del Virus/efectos de los fármacos
12.
J Vet Emerg Crit Care (San Antonio) ; 28(4): 361-365, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29898249

RESUMEN

OBJECTIVE: To describe the successful management of acute kidney injury (AKI) secondary to oak intoxication using hemodialysis in a miniature zebu. CASE SUMMARY: A 1-year-old male intact miniature zebu was presented for evaluation of a 2-day history of lethargy, anorexia, decreased urine production, and dry, firm stool. Initial diagnostics revealed severe azotemia and the bull was presumptively diagnosed with AKI secondary to oak intoxication due to free access to oak trees in the pasture. Despite conventional management with IV fluids and supportive therapy, the degree of azotemia progressively worsened, and the bull became oliguric and fluid overloaded. Two treatments with hemodialysis resulted in reduction of azotemia and ketonemia, and resolution of fluid overload and oliguria. The zebu was discharged from the hospital after 10 days of hospitalization. NEW OR UNIQUE INFORMATION PROVIDED: To the authors' knowledge, this is the first reported case using hemodialysis for AKI in a bovid. Treatment with hemodialysis was effective in this case resulting in rapid resolution of azotemia, fluid overload, and oliguria. Hemodialysis may hasten the recovery and decrease morbidity and mortality in bovids with AKI.


Asunto(s)
Lesión Renal Aguda/veterinaria , Enfermedades de los Bovinos/terapia , Intoxicación por Plantas/veterinaria , Quercus/envenenamiento , Diálisis Renal/veterinaria , Lesión Renal Aguda/etiología , Lesión Renal Aguda/terapia , Animales , Bovinos , Enfermedades de los Bovinos/etiología , Diagnóstico Diferencial , Masculino , Intoxicación por Plantas/etiología
13.
PLoS Negl Trop Dis ; 12(6): e0006447, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29927932

RESUMEN

Treponema pallidum infections occur worldwide causing, among other diseases, syphilis and yaws. In particular sexually transmitted syphilis is regarded as a re-emerging infectious disease with millions of new infections annually. Here we present three historic T. pallidum genomes (two from T. pallidum ssp. pallidum and one from T. pallidum ssp. pertenue) that have been reconstructed from skeletons recovered from the Convent of Santa Isabel in Mexico City, operational between the 17th and 19th century. Our analyses indicate that different T. pallidum subspecies caused similar diagnostic presentations that are normally associated with syphilis in infants, and potential evidence of a congenital infection of T. pallidum ssp. pertenue, the causative agent of yaws. This first reconstruction of T. pallidum genomes from archaeological material opens the possibility of studying its evolutionary history at a resolution previously assumed to be out of reach.


Asunto(s)
Huesos/microbiología , ADN Bacteriano/aislamiento & purificación , Genoma Bacteriano , Sífilis/historia , Treponema pallidum/genética , Treponema pallidum/aislamiento & purificación , Arqueología , Historia del Siglo XVII , Historia del Siglo XVIII , Historia del Siglo XIX , Humanos , México , Sífilis/diagnóstico , Sífilis/microbiología , Factores de Virulencia/genética , Buba/diagnóstico , Buba/historia , Buba/microbiología
14.
Proc Natl Acad Sci U S A ; 114(38): E7987-E7996, 2017 09 19.
Artículo en Inglés | MEDLINE | ID: mdl-28874543

RESUMEN

Ebolavirus (EBOV), an enveloped filamentous RNA virus causing severe hemorrhagic fever, enters cells by macropinocytosis and membrane fusion in a late endosomal compartment. Fusion is mediated by the EBOV envelope glycoprotein GP, which consists of subunits GP1 and GP2. GP1 binds to cellular receptors, including Niemann-Pick C1 (NPC1) protein, and GP2 is responsible for low pH-induced membrane fusion. Proteolytic cleavage and NPC1 binding at endosomal pH lead to conformational rearrangements of GP2 that include exposing the hydrophobic fusion loop (FL) for insertion into the cellular target membrane and forming a six-helix bundle structure. Although major portions of the GP2 structure have been solved in pre- and postfusion states and although current models place the transmembrane (TM) and FL domains of GP2 in close proximity at critical steps of membrane fusion, their structures in membrane environments, and especially interactions between them, have not yet been characterized. Here, we present the structure of the membrane proximal external region (MPER) connected to the TM domain: i.e., the missing parts of the EBOV GP2 structure. The structure, solved by solution NMR and EPR spectroscopy in membrane-mimetic environments, consists of a helix-turn-helix architecture that is independent of pH. Moreover, the MPER region is shown to interact in the membrane interface with the previously determined structure of the EBOV FL through several critical aromatic residues. Mutation of aromatic and neighboring residues in both binding partners decreases fusion and viral entry, highlighting the functional importance of the MPER/TM-FL interaction in EBOV entry and fusion.


Asunto(s)
Ebolavirus/química , Proteínas del Envoltorio Viral/química , Proteínas Virales de Fusión/química , Membrana Celular/química , Membrana Celular/metabolismo , Membrana Celular/virología , Ebolavirus/fisiología , Dominios Proteicos , Estructura Secundaria de Proteína , Relación Estructura-Actividad , Proteínas del Envoltorio Viral/metabolismo , Proteínas Virales de Fusión/metabolismo , Internalización del Virus
15.
PLoS Negl Trop Dis ; 11(4): e0005540, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-28403145

RESUMEN

Phosphatidylinositol-3-phosphate 5-kinase (PIKfyve) is a lipid kinase involved in endosome maturation that emerged from a haploid genetic screen as being required for Ebola virus (EBOV) infection. Here we analyzed the effects of apilimod, a PIKfyve inhibitor that was reported to be well tolerated in humans in phase 2 clinical trials, for its effects on entry and infection of EBOV and Marburg virus (MARV). We first found that apilimod blocks infections by EBOV and MARV in Huh 7, Vero E6 and primary human macrophage cells, with notable potency in the macrophages (IC50, 10 nM). We next observed that similar doses of apilimod block EBOV-glycoprotein-virus like particle (VLP) entry and transcription-replication competent VLP infection, suggesting that the primary mode of action of apilimod is as an entry inhibitor, preventing release of the viral genome into the cytoplasm to initiate replication. After providing evidence that the anti-EBOV action of apilimod is via PIKfyve, we showed that it blocks trafficking of EBOV VLPs to endolysosomes containing Niemann-Pick C1 (NPC1), the intracellular receptor for EBOV. Concurrently apilimod caused VLPs to accumulate in early endosome antigen 1-positive endosomes. We did not detect any effects of apilimod on bulk endosome acidification, on the activity of cathepsins B and L, or on cholesterol export from endolysosomes. Hence by antagonizing PIKfyve, apilimod appears to block EBOV trafficking to its site of fusion and entry into the cytoplasm. Given the drug's observed anti-filoviral activity, relatively unexplored mechanism of entry inhibition, and reported tolerability in humans, we propose that apilimod be further explored as part of a therapeutic regimen to treat filoviral infections.


Asunto(s)
Antivirales/farmacología , Ebolavirus/efectos de los fármacos , Marburgvirus/efectos de los fármacos , Morfolinas/farmacología , Triazinas/farmacología , Internalización del Virus/efectos de los fármacos , Animales , Transporte Biológico , Línea Celular , Ebolavirus/fisiología , Fiebre Hemorrágica Ebola/tratamiento farmacológico , Humanos , Lisosomas/metabolismo , Macrófagos/virología , Marburgvirus/fisiología , Nocodazol/farmacología , Toremifeno/farmacología , Células Vero
16.
Med Educ Online ; 22(1): 1289315, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28219315

RESUMEN

BACKGROUND: Accrediting bodies require medical schools to teach patient safety and residents to develop teaching skills in patient safety. We created a patient safety course in the preclinical curriculum and used continuous quality improvement to make changes over time. OBJECTIVE: To assess the impact of resident teaching on student perceptions of a Patient Safety course. DESIGN: Using the Institute for Healthcare Improvement patient safety curriculum as a frame, the course included the seven IHI modules, large group lectures and small group facilitated discussions. Applying a social action methodology, we evaluated the course for four years (Y1-Y4). RESULTS: In Y1, Y2, Y3 and Y4, we distributed a course evaluation to each student (n = 184, 189, 191, and 184, respectively) and the response rate was 96, 97, 95 and 100%, respectively. Overall course quality, clarity of course goals and value of small group discussions increased in Y2 after the introduction of residents as small group facilitators. The value of residents and the overall value of the course increased in Y3 after we provided residents with small group facilitation training. CONCLUSIONS: Preclinical students value the interaction with residents and may perceive the overall value of a course to be improved based on near-peer involvement. Residents gain valuable experience in small group facilitation and leadership.


Asunto(s)
Educación de Pregrado en Medicina/métodos , Seguridad del Paciente , Grupo Paritario , Competencia Clínica , Curriculum , Educación de Pregrado en Medicina/normas , Humanismo , Humanos , Internado y Residencia , Mejoramiento de la Calidad , Rol , Estudiantes de Medicina , Enseñanza
17.
MedEdPORTAL ; 13: 10595, 2017 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-30800797

RESUMEN

Introduction: Patient safety education is required in medical, nursing, and pharmacy training, and interprofessional education offers an ideal format for teaching the core concepts of patient safety. This training activity was developed to fulfill interprofessional education core competencies for communication and teamwork and was nested within a required patient safety course taught at a medical school. However, the activity can easily be adapted as a stand-alone offering that can be included in a preclinical doctoring course, offered as an elective, or hosted at a college of nursing or pharmacy. Our goal was to prepare learners for the clinical environment by providing a context for patient safety, communication, and teamwork. Methods: Students participate in a 1.5-hour large-group activity that explores a case from the perspectives of each discipline. Faculty from all three disciplines sequentially present and debrief the case using focused questions to guide students' reflections and interactions between team members. Results: We have presented this activity for 4 consecutive years. Students complete a questionnaire with retrospective pre-post ratings of their perspectives on the activity and its impact on their awareness of disciplinary roles and responsibilities, communication errors, and strategies for addressing interdisciplinary conflicts. Results show statistically significant increases in the items of interest. Discussion: This interprofessional education offering is effective in terms of increasing awareness and knowledge among members of three health care disciplines, improving awareness of potential kinds of communication errors, and helping students consider the role of interdisciplinary interactions.

18.
Trials ; 17(1): 416, 2016 08 19.
Artículo en Inglés | MEDLINE | ID: mdl-27542601

RESUMEN

BACKGROUND: Osteoarthritis (OA) is a leading cause of disability in developed nations. Total knee arthroplasty (TKA) is a clinically effective treatment for people with end-stage knee OA, and represents one of the highest volume medical interventions globally. However, up to one in three patients remain dissatisfied following TKA. Research indicates that the strongest predictor of patient dissatisfaction following TKA is unmet expectations. This study will use a discrete choice experiment (DCE) provided to patients to improve knowledge of the expected outcomes of TKA. This increased knowledge is based on actual outcome data and is hypothesised to optimise patient expectations of TKA outcomes, thereby increasing their satisfaction and self-reported health outcomes. METHODS/DESIGN: One hundred and thirty-two people with end-stage OA on the waiting list for TKA will be recruited and randomly allocated to one of two groups using computer-generated block randomisation. A randomised controlled trial (RCT) adhering to SPIRIT and CONSORT guidelines will evaluate the effect of administering a DCE prior to surgery on patient-reported pain and function and satisfaction following TKA. Patients in the intervention arm will complete a survey containing the DCE, compared to the control group who will complete a modified survey that does not contain the DCE activity. The DCE contains information on actual risks of postoperative complications, as well as health status after TKA. The DCE encourages patients to actively make trade-offs between risks and health outcomes to elicit their preferences. Participants in both groups will be required to complete the survey after consenting to have the procedure, but prior to surgery during their routine preadmission appointment at St. Vincent's Hospital, Melbourne, Australia (SVHM). Patients in both the intervention and control groups will also be required to complete a brief patient expectation survey 1 week prior to scheduled TKA. In addition, orthopaedic surgeons will complete a brief expectations survey for each patient consented for TKA to compare matched surgeon and patient expectations for recovery following TKA. Primary outcomes will be evaluated by a blinded examiner at 12 months post surgery using a validated self-reported pain and physical function scale, and a validated patient satisfaction scale. Secondary outcomes will include a range of validated measures of health and psychological wellbeing. All analyses will be conducted on an intention-to-treat basis using linear regression models. DISCUSSION: This study is the first of its kind to use a DCE to provide information to patients to optimise their expectations of the outcomes of surgery. Reducing the rate of patient dissatisfaction commonly seen in patients following TKA will help to reduce the burden associated with poor outcomes on the health system. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ( ACTRN12615001226594p ). Version 1; registered on 9 November 2015.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Protocolos Clínicos , Técnicas de Apoyo para la Decisión , Osteoartritis de la Rodilla/cirugía , Humanos , Satisfacción del Paciente , Tamaño de la Muestra
19.
Viruses ; 8(8)2016 08 02.
Artículo en Inglés | MEDLINE | ID: mdl-27490565

RESUMEN

The 2014 outbreak of Ebola virus (EBOV) in Western Africa highlighted the need for anti-EBOV therapeutics. Clomiphene is a U.S. Food and Drug Administration (FDA)-approved drug that blocks EBOV entry and infection in cells and significantly protects EBOV-challenged mice. As provided, clomiphene is, approximately, a 60:40 mixture of two stereoisomers, enclomiphene and zuclomiphene. The pharmacokinetic properties of the two isomers vary, but both accumulate in the eye and male reproductive tract, tissues in which EBOV can persist. Here we compared the ability of clomiphene and its isomers to inhibit EBOV using viral-like particle (VLP) entry and transcription/replication-competent VLP (trVLP) assays. Clomiphene and its isomers inhibited the entry and infection of VLPs and trVLPs with similar potencies. This was demonstrated with VLPs bearing the glycoproteins from three filoviruses (EBOV Mayinga, EBOV Makona, and Marburg virus) and in two cell lines (293T/17 and Vero E6). Visual problems have been noted in EBOV survivors, and viral RNA has been isolated from semen up to nine months post-infection. Since the clomiphene isomers accumulate in these affected tissues, clomiphene or one of its isomers warrants consideration as an anti-EBOV agent, for example, to potentially help ameliorate symptoms in EBOV survivors.


Asunto(s)
Antivirales/farmacología , Clomifeno/farmacología , Ebolavirus/efectos de los fármacos , Ebolavirus/fisiología , Moduladores Selectivos de los Receptores de Estrógeno/farmacología , Internalización del Virus/efectos de los fármacos , Animales , Línea Celular , Fiebre Hemorrágica Ebola/tratamiento farmacológico , Humanos , Zuclomifeno/farmacología
20.
J Virol ; 90(19): 8924-33, 2016 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-27466418

RESUMEN

UNLABELLED: The highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) cause significant morbidity and morality. There is currently no approved therapeutic for highly pathogenic coronaviruses, even as MERS-CoV is spreading throughout the Middle East. We previously screened a library of FDA-approved drugs for inhibitors of coronavirus replication in which we identified Abelson (Abl) kinase inhibitors, including the anticancer drug imatinib, as inhibitors of both SARS-CoV and MERS-CoV in vitro Here we show that the anti-CoV activity of imatinib occurs at the early stages of infection, after internalization and endosomal trafficking, by inhibiting fusion of the virions at the endosomal membrane. We specifically identified the imatinib target, Abelson tyrosine-protein kinase 2 (Abl2), as required for efficient SARS-CoV and MERS-CoV replication in vitro These data demonstrate that specific approved drugs can be characterized in vitro for their anticoronavirus activity and used to identify host proteins required for coronavirus replication. This type of study is an important step in the repurposing of approved drugs for treatment of emerging coronaviruses. IMPORTANCE: Both SARS-CoV and MERS-CoV are zoonotic infections, with bats as the primary source. The 2003 SARS-CoV outbreak began in Guangdong Province in China and spread to humans via civet cats and raccoon dogs in the wet markets before spreading to 37 countries. The virus caused 8,096 confirmed cases of SARS and 774 deaths (a case fatality rate of ∼10%). The MERS-CoV outbreak began in Saudi Arabia and has spread to 27 countries. MERS-CoV is believed to have emerged from bats and passed into humans via camels. The ongoing outbreak of MERS-CoV has resulted in 1,791 cases of MERS and 640 deaths (a case fatality rate of 36%). The emergence of SARS-CoV and MERS-CoV provides evidence that coronaviruses are currently spreading from zoonotic sources and can be highly pathogenic, causing serious morbidity and mortality in humans. Treatment of SARS-CoV and MERS-CoV infection is limited to providing supportive therapy consistent with any serious lung disease, as no specific drugs have been approved as therapeutics. Highly pathogenic coronaviruses are rare and appear to emerge and disappear within just a few years. Currently, MERS-CoV is still spreading, as new infections continue to be reported. The outbreaks of SARS-CoV and MERS-CoV and the continuing diagnosis of new MERS cases highlight the need for finding therapeutics for these diseases and potential future coronavirus outbreaks. Screening FDA-approved drugs streamlines the pipeline for this process, as these drugs have already been tested for safety in humans.


Asunto(s)
Antivirales/farmacología , Mesilato de Imatinib/farmacología , Coronavirus del Síndrome Respiratorio de Oriente Medio/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , Virus del SRAS/efectos de los fármacos , Internalización del Virus/efectos de los fármacos , Animales , Línea Celular , Humanos , Coronavirus del Síndrome Respiratorio de Oriente Medio/fisiología , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Virus del SRAS/fisiología
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