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1.
Antimicrob Resist Infect Control ; 9(1): 192, 2020 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-33287908

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents an unprecedented healthcare challenge. Various SARS-CoV-2 outbreaks in healthcare facilities have been reported. Healthcare workers (HCWs) may play a critical role in the spread of the virus, particularly when asymptomatic. We examined four healthcare-associated outbreaks of SARS-CoV-2 infections that occurred at a university hospital in Berlin, Germany. We aimed to describe and analyze the spread of the virus in order to draw conclusions for effective containment of SARS-CoV-2 in healthcare facilities. METHODS: Healthcare-associated outbreaks of SARS-CoV-2 infections were defined as two or more laboratory confirmed infections with SARS-CoV-2 where an epidemiological link within the healthcare setting appeared likely. We focused our analysis on one of three sites of the Charité-University Medicine hospital within a 2 month period (March and April 2020). RESULTS: We observed four healthcare-associated outbreaks of SARS-CoV-2 infections, with a total of 24 infected persons (23 HCWs and one patient). The outbreaks were detected in the departments of nephrology and dialysis (n = 9), anesthesiology (n = 8), surgical pediatrics (n = 4), and neurology (n = 3). Each outbreak showed multiple unprotected contacts between infected HCWs. A combination of contact tracing, testing, physical distancing and mandatory continuous wearing of face masks by all HCWs was able to contain all four outbreaks. CONCLUSIONS: HCW to HCW transmission represented the likely source of the four outbreaks. Ensuring proper physical distancing measures and wearing of protective equipment, also when interacting with colleagues, must be a key aspect of fighting COVID-19 in healthcare facilities.

2.
Int J Implant Dent ; 6(1): 65, 2020 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-33099690

RESUMO

BACKGROUND: An effective biomaterial for bone replacement should have properties to avoid bacterial contamination and promote bone formation while inducing rapid cell differentiation simultaneously. Bone marrow stem cells are currently being investigated because of their known potential for differentiation in osteoblast lineage. This makes these cells a good option for stem cell-based therapy. We have aimed to analyze, in vitro, the potential of pure titanium (Ti), Ti-35Nb-7Zr alloy (A), niobium (Nb), and zirconia (Zr) to avoid the microorganisms S. aureus (S.a) and P. aeruginosa (P.a). Furthermore, our objective was to evaluate if the basic elements of Ti-35Nb-7Zr alloy have any influence on bone marrow stromal cells, the source of stem cells, and observe if these metals have properties to induce cell differentiation into osteoblasts. METHODS: Bone marrow stromal cells (BMSC) were obtained from mice femurs and cultured in osteogenic media without dexamethasone as an external source of cell differentiation. The samples were divided into Ti-35Nb-7Zr alloy (A), pure titanium (Ti), Nb (niobium), and Zr (zirconia) and were characterized by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS). After predetermined periods, cell interaction, cytotoxicity, proliferation, and cell differentiation tests were performed. For monotypic biofilm formation, standardized suspensions (106 cells/ml) with the microorganisms S. aureus (S.a) and P. aeruginosa (P.a) were cultured for 24 h on the samples and submitted to an MTT test. RESULTS: All samples presented cell proliferation, growth, and spreading. All groups presented cell viability above 70%, but the alloy (A) showed better results, with statistical differences from Nb and Zr samples. Zr expressed higher ALP activity and was statistically different from the other groups (p < 0.05). In contrast, no statistical difference was observed between the samples as regards mineralization nodules. Lower biofilm formation of S.a and P.a. was observed on the Nb samples, with statistical differences from the other samples. CONCLUSION: Our results suggest that the basic elements present in the alloy have osteoinductive characteristics, and Zr has a good influence on bone marrow stromal cell differentiation. We also believe that Nb has the best potential for reducing the formation of microbial biofilms.

3.
JMIR Mhealth Uhealth ; 8(6): e15517, 2020 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-32442150

RESUMO

BACKGROUND: Comprehensive exams such as the Dean-Woodcock Neuropsychological Assessment System, the Global Deterioration Scale, and the Boston Diagnostic Aphasia Examination are the gold standard for doctors and clinicians in the preliminary assessment and monitoring of neurocognitive function in conditions such as neurodegenerative diseases and acquired brain injuries (ABIs). In recent years, there has been an increased focus on implementing these exams on mobile devices to benefit from their configurable built-in sensors, in addition to scoring, interpretation, and storage capabilities. As smartphones become more accepted in health care among both users and clinicians, the ability to use device information (eg, device position, screen interactions, and app usage) for subject monitoring also increases. Sensor-based assessments (eg, functional gait using a mobile device's accelerometer and/or gyroscope or collection of speech samples using recordings from the device's microphone) include the potential for enhanced information for diagnoses of neurological conditions; mapping the development of these conditions over time; and monitoring efficient, evidence-based rehabilitation programs. OBJECTIVE: This paper provides an overview of neurocognitive conditions and relevant functions of interest, analysis of recent results using smartphone and/or tablet built-in sensor information for the assessment of these different neurocognitive conditions, and how human-device interactions and the assessment and monitoring of these neurocognitive functions can be enhanced for both the patient and health care provider. METHODS: This survey presents a review of current mobile technological capabilities to enhance the assessment of various neurocognitive conditions, including both neurodegenerative diseases and ABIs. It explores how device features can be configured for assessments as well as the enhanced capability and data monitoring that will arise due to the addition of these features. It also recognizes the challenges that will be apparent with the transfer of these current assessments to mobile devices. RESULTS: Built-in sensor information on mobile devices is found to provide information that can enhance neurocognitive assessment and monitoring across all functional categories. Configurations of positional sensors (eg, accelerometer, gyroscope, and GPS), media sensors (eg, microphone and camera), inherent sensors (eg, device timer), and participatory user-device interactions (eg, screen interactions, metadata input, app usage, and device lock and unlock) are all helpful for assessing these functions for the purposes of training, monitoring, diagnosis, or rehabilitation. CONCLUSIONS: This survey discusses some of the many opportunities and challenges of implementing configured built-in sensors on mobile devices to enhance assessments and monitoring of neurocognitive functions as well as disease progression across neurodegenerative and acquired neurological conditions.

4.
Am J Emerg Med ; 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32059934

RESUMO

STUDY OBJECTIVES: The American Heart Association (AHA) recently established the Resuscitation Quality Improvement (RQI) program, which requires physicians to perform quarterly cardiopulmonary resuscitation (CPR) skill checks. The aim of this study was to determine if timing of last training impacted skill performance of emergency physicians. METHODS: A convenience sample of emergency medicine (EM) physicians was asked to complete a Basic Life Support (BLS) scenario on a manikin. Participants passed the scenario if they successfully performed high-quality CPR. Participants completed a survey to assess clinical experience and timing of prior BLS training. Outcomes were comparisons of skills check pass rates for physicians recently trained in BLS (≤90 days) and those trained >90 days ago and those trained >2 years ago. RESULTS: A total of 113 individuals were included in the study: 87 attending physicians and 26 residents. Overall 92.9% correctly performed CPR with the proper assessment, compression rate, compression depth and rescue breaths. There was no difference between success rates in EM physicians who had BLS training within 90 days (91.7%) and physicians who had not had BLS within 90 days, (93.1%). (p = 1.00) There was no difference in the pass rate of those trained within 90 days (91.7%) to those trained >2 years ago (90.9%) (95CI 0.088, 0.096). CONCLUSION: There was no difference between delivery of high-quality CPR in EM physicians who had recent BLS training and those who did not.

5.
J Clin Oncol ; 38(7): 674-685, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31841383

RESUMO

PURPOSE: To estimate age-specific relative and absolute cancer risks of breast cancer and to estimate risks of ovarian, pancreatic, male breast, prostate, and colorectal cancers associated with germline PALB2 pathogenic variants (PVs) because these risks have not been extensively characterized. METHODS: We analyzed data from 524 families with PALB2 PVs from 21 countries. Complex segregation analysis was used to estimate relative risks (RRs; relative to country-specific population incidences) and absolute risks of cancers. The models allowed for residual familial aggregation of breast and ovarian cancer and were adjusted for the family-specific ascertainment schemes. RESULTS: We found associations between PALB2 PVs and risk of female breast cancer (RR, 7.18; 95% CI, 5.82 to 8.85; P = 6.5 × 10-76), ovarian cancer (RR, 2.91; 95% CI, 1.40 to 6.04; P = 4.1 × 10-3), pancreatic cancer (RR, 2.37; 95% CI, 1.24 to 4.50; P = 8.7 × 10-3), and male breast cancer (RR, 7.34; 95% CI, 1.28 to 42.18; P = 2.6 × 10-2). There was no evidence for increased risks of prostate or colorectal cancer. The breast cancer RRs declined with age (P for trend = 2.0 × 10-3). After adjusting for family ascertainment, breast cancer risk estimates on the basis of multiple case families were similar to the estimates from families ascertained through population-based studies (P for difference = .41). On the basis of the combined data, the estimated risks to age 80 years were 53% (95% CI, 44% to 63%) for female breast cancer, 5% (95% CI, 2% to 10%) for ovarian cancer, 2%-3% (95% CI females, 1% to 4%; 95% CI males, 2% to 5%) for pancreatic cancer, and 1% (95% CI, 0.2% to 5%) for male breast cancer. CONCLUSION: These results confirm PALB2 as a major breast cancer susceptibility gene and establish substantial associations between germline PALB2 PVs and ovarian, pancreatic, and male breast cancers. These findings will facilitate incorporation of PALB2 into risk prediction models and optimize the clinical cancer risk management of PALB2 PV carriers.

6.
Biol Cell ; 112(2): 39-52, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31845361

RESUMO

BACKGROUND INFORMATION: Primary cilia are highly conserved multifunctional cell organelles that extend from the cell membrane. A range of genetic disorders, collectively termed ciliopathies, is attributed to primary cilia dysfunction. The archetypical ciliopathy is the Bardet-Biedl syndrome (BBS), patients of which display virtually all symptoms associated with dysfunctional cilia. The primary cilium acts as a sensory organelle transmitting intra- and extracellular signals thereby transducing various signalling pathways facilitated by the BBS proteins. Growing evidence suggests that cilia proteins also have alternative functions in ciliary independent mechanisms, which might be contributing to disease etiology. RESULTS: In an attempt to gain more insight into possible differences in organ specific roles, we examined whether relative gene expression for individual Bbs genes was constant across different tissues in mouse, in order to distinguish possible differences in organ specific roles. All tested tissues show differentially expressed Bbs transcripts with some tissues showing a more similar stoichiometric composition of transcripts than others do.  However, loss of Bbs6 or Bbs8 affects expression of other Bbs transcripts in a tissue-dependent way. CONCLUSIONS AND SIGNIFICANCE: Our data support the hypothesis that in some organs, BBS proteins not only function in a complex but might also have alternative functions in a ciliary independent context. This significantly alters our understanding of disease pathogenesis and development of possible treatment strategies.


Assuntos
Síndrome de Bardet-Biedl , Regulação da Expressão Gênica , Transdução de Sinais/genética , Animais , Síndrome de Bardet-Biedl/genética , Síndrome de Bardet-Biedl/metabolismo , Síndrome de Bardet-Biedl/patologia , Modelos Animais de Doenças , Camundongos , Camundongos Knockout , Especificidade de Órgãos/genética
7.
Emotion ; 20(4): 613-624, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30816742

RESUMO

One of the cardinal symptoms of major depressive disorder (MDD) is persistent sadness. Do people with MDD actually prefer sad stimuli, potentially perpetuating their depression? Millgram, Joormann, Huppert, and Tamir (2015) observed such preferences and interpreted them as reflecting a maladaptive emotion regulatory goal to upregulate sad feelings. We assessed emotional music choice among both those with MDD and healthy controls (HC), and assessed the reasons for music preferences in these two groups. Seventy-six female participants (38 per group) completed two tasks: (1) Millgram et al.'s (2015) music task wherein participants listened to happy, neutral, and sad music excerpts and chose the one they wanted to listen to most, and (2) a novel Emotional Music Selection Task (EMST) wherein participants chose preferred music clips, varying in emotion and energy level, in paired-choice trials. In the replication music task, MDD people were more likely to choose sad music. However, inconsistent with any motivation to upregulate sadness, people with MDD reported that they chose sad music because it was low in energy levels (e.g., relaxing). EMST results revealed that MDD people had a stronger preference for both low energy and sad music, relative to HC. The strong appeal of sad music to people with MDD may be related to its calming effects rather than any desire to increase or maintain sad feelings. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Assuntos
Transtorno Depressivo Maior/psicologia , Emoções/fisiologia , Música/psicologia , Tristeza/psicologia , Adulto , Feminino , Humanos , Adulto Jovem
8.
J Hosp Med ; 14(6): 340-348, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30986182

RESUMO

BACKGROUND: Differences between hospital-presenting sepsis (HPS) and emergency department-presenting sepsis (EDPS) are not well described. OBJECTIVES: We aimed to (1) quantify the prevalence of HPS versus EDPS cases and outcomes; (2) compare HPS versus EDPS characteristics at presentation; (3) compare HPS versus EDPS in process and patient outcomes; and (4) estimate risk differences in patient outcomes attributable to initial resuscitation disparities. DESIGN: Retrospective consecutive-sample cohort. SETTING: Nine hospitals from October 1, 2014, to March 31, 2016. PATIENTS: All hospitalized patients with sepsis or septic shock, as defined by simultaneous (1) infection, (2) ≥2 Systemic Inflammatory Response Syndrome (SIRS) criteria, and (3) ≥1 acute organ dysfunction criterion. EDPS met inclusion criteria while physically in the emergency department (ED). HPS met the criteria after leaving the ED. MEASUREMENTS: We assessed overall HPS versus EDPS contributions to case prevalence and outcomes, and then compared group differences. Process outcomes included 3-hour bundle compliance and discrete bundle elements (eg, time to antibiotics). The primary patient outcome was hospital mortality. RESULTS: Of 11,182 sepsis hospitalizations, 2,509 (22.4%) were hospital-presenting. HPS contributed 785 (35%) sepsis mortalities. HPS had more frequent heart failure (OR: 1.31, CI: 1.18-1.47), renal failure (OR: 1.62, CI: 1.38-1.91), gastrointestinal source of infection (OR: 1.84, CI: 1.48-2.29), euthermia (OR: 1.45, CI: 1.10-1.92), hypotension (OR: 1.85, CI: 1.65-2.08), or impaired gas exchange (OR: 2.46, CI: 1.43-4.24). HPS were admitted less often from skilled nursing facilities (OR: 0.44, CI: 0.32-0.60), had chronic obstructive pulmonary disease (OR: 0.53, CI: 0.36-0.78), tachypnea (OR: 0.76, CI: 0.58-0.98), or acute kidney injury (OR: 0.82, CI: 0.68-0.97). In a propensity-matched cohort (n = 3,844), HPS patients had less than half the odds of 3-hour bundle compliant care (17.0% vs 30.3%, OR: 0.47, CI: 0.40-0.57) or antibiotics within three hours (66.2% vs 83.8%, OR: 0.38, CI: 0.32-0.44) vs EDPS. HPS was associated with higher mortality (31.2% vs 19.3%, OR: 1.90, CI: 1.64-2.20); 23.3% of this association was attributable to differences in initial resuscitation (resuscitation-adjusted OR: 1.69, CI: 1.43-2.00). CONCLUSIONS: HPS differed from EDPS by admission source, comorbidities, and clinical presentation. These patients received markedly less timely initial resuscitation; this disparity explained a moderate proportion of mortality differences.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Mortalidade Hospitalar/tendências , Hospitais/estatística & dados numéricos , Pacientes Internados/estatística & dados numéricos , Ressuscitação , Sepse , Idoso , Comorbidade , Feminino , Humanos , Masculino , Insuficiência de Múltiplos Órgãos , Prevalência , Estudos Retrospectivos , Sepse/epidemiologia , Sepse/mortalidade
9.
Ann Emerg Med ; 73(5): e51-e65, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31029297

RESUMO

The American College of Emergency Physicians (ACEP) organized a multidisciplinary effort to create a clinical practice guideline specific to unscheduled, time-sensitive procedural sedation, which differs in important ways from scheduled, elective procedural sedation. The purpose of this guideline is to serve as a resource for practitioners who perform unscheduled procedural sedation regardless of location or patient age. This document outlines the underlying background and rationale, and issues relating to staffing, practice, and quality improvement.


Assuntos
Sedação Consciente/normas , Consenso , Humanos , Guias de Prática Clínica como Assunto , Sociedades Médicas
10.
West J Emerg Med ; 20(2): 380-385, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30881561

RESUMO

Introduction: Despite the ever-increasing numbers of mental health patients presenting to United States emergency departments, there are large gaps in knowledge about acute care of the behavioral health patient. To address this important problem, the Coalition on Psychiatric Emergencies convened a research consensus conference in December 2016 consisting of clinical researchers, clinicians from emergency medicine, psychiatry and psychology, and representatives from governmental agencies and patient advocacy groups. Methods: Participants used a standardized methodology to select and rank research questions in the order of importance to both researchers and patients. Results: Three working groups (geriatrics, substance use disorders, and psychosis) reached consensus on 26 questions within their respective domains. These questions are summarized in this document. Conclusion: The research consensus conference is the first of its kind to include non-clinicians in helping identify knowledge gaps in behavioral emergencies. It is hoped that these questions will prove useful to prioritize future research within the specialty.


Assuntos
Consenso , Medicina de Emergência/educação , Geriatria , Saúde Mental/educação , Transtornos Psicóticos , Transtornos Relacionados ao Uso de Substâncias , Medicina de Emergência/estatística & dados numéricos , Humanos , Saúde Mental/estatística & dados numéricos , Estados Unidos
11.
West J Emerg Med ; 20(2): 403-408, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30881564

RESUMO

Introduction: Emergency departments (ED) manage a wide variety of critical medical presentations. Traumatic, neurologic, and cardiac crises are among the most prevalent types of emergencies treated in an ED setting. The high volume of presentations has led to collaborative partnerships in research and process development between experts in emergency medicine (EM) and other disciplines. While psychosis is a medical emergency frequently treated in the ED, there remains a paucity of evidence-based literature highlighting best practices for management of psychotic presentations in the ED. In the absence of collaborative research, development of best practice guidelines cannot begin. A working group convened to develop a set of high-priority research questions to address the knowledge gaps in the care of psychotic patients in the ED. This article is the product of a subgroup considering "Special Populations: Psychotic Spectrum Disorders," from the 2016 Coalition on Psychiatric Emergencies first Research Consensus Conference on Acute Mental Illness. Methods: Participants were identified with expertise in psychosis from EM, emergency psychiatry, emergency psychology, clinical research, governmental agencies, and patient advocacy groups. Background literature reviews were performed prior to the in-person meeting. A nominal group technique was employed to develop group consensus on the highest priority research gaps. Following the nominal group technique, input was solicited from all participants during the meeting, questions were iteratively focused and revised, voted on, and then ranked by importance. Results: The group developed 28 separate questions. After clarification and voting, the group identified six high-priority research areas. These questions signify the perceived gaps in psychosis research in emergency settings. Questions were further grouped into two topic areas: screening and identification; and intervention and management strategies. Conclusion: While psychosis has become a more common presentation in the ED, standardized screening, intervention, and outcome measurement for psychosis has not moved beyond attention to agitation management. As improved outpatient-intervention protocols are developed for treatment of psychosis, it is imperative that parallel protocols are developed for delivery in the ED setting.


Assuntos
Medicina de Emergência/organização & administração , Serviço Hospitalar de Emergência/organização & administração , Transtornos Psicóticos/diagnóstico , Consenso , Pesquisa sobre Serviços de Saúde , Humanos , Programas de Rastreamento
12.
Cell Mol Life Sci ; 76(4): 757-775, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30446775

RESUMO

Primary cilia are conserved organelles that mediate cellular communication crucial for organogenesis and homeostasis in numerous tissues. The retinal pigment epithelium (RPE) is a ciliated monolayer in the eye that borders the retina and is vital for visual function. Maturation of the RPE is absolutely critical for visual function and the role of the primary cilium in this process has been largely ignored to date. We show that primary cilia are transiently present during RPE development and that as the RPE matures, primary cilia retract, and gene expression of ciliary disassembly components decline. We observe that ciliary-associated BBS proteins protect against HDAC6-mediated ciliary disassembly via their recruitment of Inversin to the base of the primary cilium. Inhibition of ciliary disassembly components was able to rescue ciliary length defects in BBS deficient cells. This consequently affects ciliary regulation of Wnt signaling. Our results shed light onto the mechanisms by which cilia-mediated signaling facilitates tissue maturation.


Assuntos
Cílios/metabolismo , Chaperoninas do Grupo II/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Animais , Cílios/genética , Proteínas do Citoesqueleto , Embrião de Mamíferos/embriologia , Embrião de Mamíferos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Chaperoninas do Grupo II/genética , Células HEK293 , Desacetilase 6 de Histona/genética , Desacetilase 6 de Histona/metabolismo , Humanos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Associadas aos Microtúbulos/genética , Interferência de RNA , Epitélio Pigmentado da Retina/embriologia , Epitélio Pigmentado da Retina/ultraestrutura , Via de Sinalização Wnt/genética
13.
Oncotarget ; 9(78): 34794-34809, 2018 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-30410678

RESUMO

A proof-of-concept study was conducted to assess whether patients with advanced stage IV cancer for whom predominantly no standard therapy was available could benefit from comprehensive molecular profiling of their tumor tissue to provide targeted therapy. Tumor samples of 83 patients were collected under highly standardized conditions and analyzed using immunohistochemistry, next-generation sequencing and phosphoprotein profiling. Expression and phosphorylation of key oncogenic pathways were measured to identify targets at the (phospho-) proteomic level. At genomic level, 50 oncogenes and tumor suppressor genes were analyzed. Based on molecular profiling, targeted therapies were decided by the attending oncologist. Accordingly, 28 patients who met the defined criteria fell in two equal-sized groups. One group received targeted therapies while the other did not. Following six months of treatment, disease control was achieved by 49% of patients receiving targeted therapy (complete remission, 14%; partial remission, 21%; stable disease, 14%; disease progression, 36%; death, 14%) and 21% of patients receiving non-targeted therapy (stable disease, 21%; disease progression, 64%; death, 14%). Individual patients experienced dramatic responses to a therapy which otherwise would not have been applied. This approach clarifies the value of multi-omic molecular profiling for cancer diagnostics.

14.
PLoS One ; 13(11): e0207222, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30440011

RESUMO

The retinal pigment epithelium (RPE) is an epithelial monolayer in the back of the vertebrate eye. RPE dysfunction is associated with retinal degeneration and blindness. In order to fully understand how dysregulation affects visual function, RPE-specific gene knockouts are indispensable. Since the currently available RPE-specific Cre recombinases show lack of specificity or poor recombination, we sought to generate an alternative. We generated a tamoxifen-inducible RPE-specific Cre transgenic mouse line under transcriptional control of an RPE-specific Tyrosinase enhancer. We characterized the Cre-mediated recombinant expression by crossing our RPE-Tyrosinase-CreErT2 mouse line with the tdTomato reporter line, Ai14. Detected fluorescence was quantified via high-content image analysis. Recombination was predominantly observed in the RPE and adjacent ciliary body. RPE flatmount preparations revealed a high level of recombination in adult mice (47.25-69.48%). Regional analysis of dorsal, ventral, nasal and temporal areas did not show significant changes in recombination. However, recombination was higher in the central RPE compared to the periphery. Higher levels of Cre-mediated recombinant expression was observed in embryonic RPE (~83%). Compared to other RPE-specific Cre transgenic mouse lines, this newly generated RPE-Tyrosinase-CreErT2 line shows a more uniform and higher level of recombination with the advantage to initiate recombination in both, prenatal and postnatal animals. This line can serve as a valuable tool for researches exploring the role of individual gene functions, in both developing and differentiated RPE.


Assuntos
Camundongos Transgênicos , Epitélio Pigmentado da Retina/metabolismo , Animais , Feminino , Integrases , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Modelos Animais , Monofenol Mono-Oxigenase/metabolismo , Epitélio Pigmentado da Retina/citologia , Epitélio Pigmentado da Retina/crescimento & desenvolvimento , Epitélio Pigmentado da Retina/ultraestrutura
15.
Annu Int Conf IEEE Eng Med Biol Soc ; 2018: 3962-3966, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30441227

RESUMO

Verbal speech of children diagnosed with ASD is explored in order to identify patterns autism has left in speech, and to model such patterns for implementing automatic diagnostic and screening frameworks. In this study, we identify the deviations of acoustic low-level descriptors (LLDs) in voice of an autistic adolescent from her typically developing triplet siblings. The goal is to identify the atypicality in voice introduced by autism under minimum gender, age, genetic, and language bias and use the gained insights to build a more generalized model by adding more subjects hierarchically. We report the most significant LLDs that describe the deviations of acoustic features due to autism for categories of utterances and feature groups.


Assuntos
Transtorno Autístico , Voz , Acústica , Feminino , Humanos , Idioma , Fala
16.
J Exp Psychol Appl ; 24(4): 440-458, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30299128

RESUMO

We propose that a mismatch in problem presentation and question structures may promote errors on Bayesian reasoning problems. In this task, people determine the likelihood that a positive test actually indicates the presence of a condition. Research has shown that people routinely fail to correctly identify this positive predictive value (PPV). We point out that the typical problem structure is likely to confuse reasoners by focusing on the incorrect reference class for answering this diagnostic question; instead, providing the anchor needed to address the diagnostic question about sensitivity (SEN). Results of two experiments are described in which participants answer diagnostic questions using problems presented with congruent or incongruent reference classes. Aligning reference classes eases both representational and computational difficulties, increasing the proportion who were consistently accurate to an unprecedented 93% on PPV questions, and 69% on SEN questions. Analysis of response components from incongruent problems indicated that many errors reflect difficulties in identifying and applying appropriate values from the problem, which are prerequisite processes that contribute to computational errors. We conclude with a discussion of the need, especially in applied settings and on initial exposure, to adopt problem presentations to guide, rather than confuse, the organization and use of diagnostic information. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Assuntos
Julgamento , Resolução de Problemas , Teorema de Bayes , Feminino , Humanos , Masculino
17.
Cell ; 174(6): 1571-1585.e11, 2018 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-30193114

RESUMO

Metabolic diseases are often characterized by circadian misalignment in different tissues, yet how altered coordination and communication among tissue clocks relate to specific pathogenic mechanisms remains largely unknown. Applying an integrated systems biology approach, we performed 24-hr metabolomics profiling of eight mouse tissues simultaneously. We present a temporal and spatial atlas of circadian metabolism in the context of systemic energy balance and under chronic nutrient stress (high-fat diet [HFD]). Comparative analysis reveals how the repertoires of tissue metabolism are linked and gated to specific temporal windows and how this highly specialized communication and coherence among tissue clocks is rewired by nutrient challenge. Overall, we illustrate how dynamic metabolic relationships can be reconstructed across time and space and how integration of circadian metabolomics data from multiple tissues can improve our understanding of health and disease.


Assuntos
Relógios Circadianos/fisiologia , Metaboloma , Animais , Dieta Hiperlipídica , Metabolismo Energético , Fígado/metabolismo , Masculino , Redes e Vias Metabólicas , Metabolômica , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/metabolismo , Córtex Pré-Frontal/metabolismo , Núcleo Supraquiasmático/metabolismo , Proteína Desacopladora 1/metabolismo
19.
Nat Genet ; 50(7): 1021-1031, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29892014

RESUMO

We demonstrate that a Drosophila Golgi protein, Gorab, is present not only in the trans-Golgi but also in the centriole cartwheel where, complexed to Sas6, it is required for centriole duplication. In addition to centriole defects, flies lacking Gorab are uncoordinated due to defects in sensory cilia, which lose their nine-fold symmetry. We demonstrate the separation of centriole and Golgi functions of Drosophila Gorab in two ways: first, we have created Gorab variants that are unable to localize to trans-Golgi but can still rescue the centriole and cilia defects of gorab null flies; second, we show that expression of C-terminally tagged Gorab disrupts Golgi functions in cytokinesis of male meiosis, a dominant phenotype overcome by mutations preventing Golgi targeting. Our findings suggest that during animal evolution, a Golgi protein has arisen with a second, apparently independent, role in centriole duplication.


Assuntos
Centríolos/genética , Complexo de Golgi/genética , Proteínas de Transporte Vesicular/genética , Animais , Animais Geneticamente Modificados/genética , Ciclo Celular/genética , Proteínas de Ciclo Celular/genética , Cílios/genética , Drosophila/genética , Proteínas de Drosophila/genética , Feminino , Humanos , Masculino , Proteínas Associadas aos Microtúbulos/genética , Proteínas Serina-Treonina Quinases/genética
20.
West J Emerg Med ; 19(3): 606-612, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29760863

RESUMO

Introduction: The use of research associates (RA) programs to facilitate study enrollment in the emergency department was initiated during the mid-1990s. The University of Rochester Medical Center (URMC) was an early adopting site for this model, which has experienced considerable growth and development over the past 20 years. Methods: Our goal was to detail the Emergency Department Research Associates (EDRA) program processes developed at the URMC that has led to our program's sustainability and productivity. These processes, and the lessons learned during their development, can assist institutions seeking to establish an RA program or refine an existing program. Results: Defined procedures for selecting, training, and monitoring EDRAs have been created and refined with the goal of maximizing study enrollment and minimizing protocol deviations. Our EDRA program functions as a paid service center for investigators, and our EDRAs engage in a variety of study-related activities including screening and enrolling patients, administering surveys, collecting bio-specimens, and making follow-up calls. Over the past two years, our program has averaged 222 enrollments/month (standard deviation = 79.93), gathering roughly 25 participants per study per month. Conclusion: Our EDRA model has consistently resulted in some of the highest number of enrollments across a variety of recently funded, multi-center studies. Maintaining a high-quality EDRA program requires continual investment on the part of the leadership team, though the benefits to investigators within and outside the department outweigh these costs.


Assuntos
Medicina de Emergência/educação , Serviço Hospitalar de Emergência , Avaliação de Programas e Projetos de Saúde/tendências , Projetos de Pesquisa , Estudantes/estatística & dados numéricos , Educação Médica/métodos , Hospitais , Humanos , Universidades
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