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1.
Med Educ ; 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33772840

RESUMO

Research has shown that taking "timeouts" in medical practice improves performance and patient safety. However, the benefits of taking timeouts, or pausing, is not sufficiently acknowledged in workplaces and training programs. To promote this acknowledgment, we suggest a systematic conceptualization of the medical pause, focusing on its importance, processes, and implementation in training programs. By employing insights from educational and cognitive psychology, we first identified pausing as an important skill to interrupt negative momentum and bolster learning. Subsequently, we categorized constituent cognitive processes for pausing skills into two phases: the decision-making phase (determining when and how to take pauses) and the executive phase (applying relaxation or reflection during pauses). We present a model that describes how relaxation and reflection during pauses can optimize cognitive load in performance. Several strategies to implement pause training in medical curricula are proposed: intertwining pause training with training of primary skills, providing second-order scaffolding through shared control, and employing auxiliary tools such as computer-based simulations with a pause function.

2.
Environ Manage ; 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33710388

RESUMO

Regionally scaled assessments of hydrologic alteration for small streams and its effects on freshwater taxa are often inhibited by a low number of stream gages. To overcome this limitation, we paired modeled estimates of hydrologic alteration to a benthic macroinvertebrate index of biotic integrity data for 4522 stream reaches across the Chesapeake Bay watershed. Using separate random-forest models, we predicted flow status (inflated, diminished, or indeterminant) for 12 published hydrologic metrics (HMs) that characterize the main components of flow regimes. We used these models to predict each HM status for each stream reach in the watershed, and linked predictions to macroinvertebrate condition samples collected from streams with drainage areas less than 200 km2. Flow alteration was calculated as the number of HMs with inflated or diminished status and ranged from 0 (no HM inflated or diminished) to 12 (all 12 HMs inflated or diminished). When focused solely on the stream condition and flow-alteration relationship, degraded macroinvertebrate condition was, depending on the number of HMs used, 3.8-4.7 times more likely in a flow-altered site; this likelihood was over twofold higher in the urban-focused dataset (8.7-10.8), and was never significant in the agriculture-focused dataset. Logistic regression analysis using the entire dataset showed for every unit increase in flow-alteration intensity, the odds of a degraded condition increased 3.7%. Our results provide an indication of whether altered streamflow is a possible driver of degraded biological conditions, information that could help managers prioritize management actions and lead to more effective restoration efforts.

3.
Dev Dyn ; 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33522040

RESUMO

Before limbs or fins, can be patterned and grow they must be initiated. Initiation of the limb first involves designating a portion of lateral plate mesoderm along the flank as the site of the future limb. Following specification, a myriad of cellular and molecular events interact to generate a bud that will grow and form the limb. The past three decades has provided a wealth of understanding on how those events generate the limb bud and how variations in them result in different limb forms. Comparatively, much less attention has been given to the earliest steps of limb formation and what impacts altering the position and initiation of the limb have had on evolution. Here, we first review the processes and pathways involved in these two phases of limb initiation, as determined from amniote model systems. We then broaden our scope to examine how variation in the limb initiation module has contributed to biological diversity in amniotes. Finally, we review what is known about limb initiation in fish and amphibians, and consider what mechanisms are conserved across vertebrates.

4.
Pharmacogenomics J ; 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33589791

RESUMO

This study examined rates of genetic testing in two cohorts of publicly insured individuals who have newly prescribed medication with FDA pharmacogenomic labeling guidance. Genetic testing was rare (4.4% and 10.5% in Medicaid and Medicare cohorts, respectively) despite the fact that all participants selected were taking medications that contained pharmacogenomic labeling information. When testing was conducted it was typically done before the initial use of a target medication. Factors that emerged as predictors of the likelihood of undergoing genetic testing included White ethnicity (vs. Black), female gender, and age. Cost analyses indicated higher expenditures in groups receiving genetic testing vs. matched comparators with no genetic testing, as well as disparities between proactively and reactively tested groups (albeit in opposite directions across cohorts). Results are discussed in terms of the possible reasons for the low base rate of testing, mechanisms of increased cost, and barriers to dissemination and implementation of these tests.

5.
Gerontologist ; 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33598713

RESUMO

BACKGROUND AND OBJECTIVES: Important decisions about the future care of people living with dementia are routinely made in hospitals. Very little is known about how the care needs of hospitalized people with dementia are understood, or how the perspectives of the person, families, and staff intersect to inform decision-making. This study explores how the care needs of people with dementia are understood by the person, their family, and hospital staff (the care triad), and how these perspectives shape decision-making. RESEARCH DESIGN AND METHODS: Ethnographic data were collected from 2 care-of-older-people general hospital wards via observations, conversations, and interviews with people with dementia, families, and staff. In total, 400 hr of observation and 46 interviews were conducted across two 7- to 9-month periods. RESULTS: The person's care needs were often understood differently between and within arms of the care triad. A lack of consistent engagement with families and people with dementia reduced opportunities to recognize and integrate this range of views, leading to delays or difficulties in decision-making. People with dementia, particularly those lacking capacity, were most likely to have their perspectives overlooked. DISCUSSION AND IMPLICATIONS: Early engagement with people with dementia and their families is required to ensure that all perspectives on the person's current and future care needs are understood and represented during decision-making. Particular attention should be paid to involving people living with dementia in discussions and decisions about their care, and to the assessment and involvement of people who may lack capacity.

6.
Conserv Biol ; 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33471375

RESUMO

Many questions relevant to conservation decision-making are characterized by extreme uncertainty due to lack of empirical data and complexity of the underlying ecologic processes, leading to a rapid increase in the use of structured protocols to elicit expert knowledge. Published ecologic applications often employ a modified Delphi method, where experts provide judgments anonymously and mathematical aggregation techniques are used to combine judgments. The Sheffield elicitation framework (SHELF) differs in its behavioral approach to synthesizing individual judgments into a fully specified probability distribution for an unknown quantity. We used the SHELF protocol remotely to assess extinction risk of three subterranean aquatic species that are being considered for listing under the U.S. Endangered Species Act. We provided experts an empirical threat assessment for each known locality over a video conference and recorded judgments on the probability of population persistence over four generations with online submission forms and R-shiny apps available through the SHELF package. Despite large uncertainty for all populations, there were key differences between species' risk of extirpation based on spatial variation in dominant threats, local land use and management practices, and species' microhabitat. The resulting probability distributions provided decision makers with a full picture of uncertainty that was consistent with the probabilistic nature of risk assessments. Discussion among experts during SHELF's behavioral aggregation stage clearly documented dominant threats (e.g., development, timber harvest, animal agriculture, and cave visitation) and their interactions with local cave geology and species' habitat. Our virtual implementation of the SHELF protocol demonstrated the flexibility of the approach for conservation applications operating on budgets and time lines that can limit in-person meetings of geographically dispersed experts.

7.
Sci Rep ; 11(1): 1691, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33462281

RESUMO

Fish adaption behaviors in complex environments are of great importance in improving the performance of underwater vehicles. This work presents a numerical study of the adaption behaviors of self-propelled fish in complex environments by developing a numerical framework of deep learning and immersed boundary-lattice Boltzmann method (IB-LBM). In this framework, the fish swimming in a viscous incompressible flow is simulated with an IB-LBM which is validated by conducting two benchmark problems including a uniform flow over a stationary cylinder and a self-propelled anguilliform swimming in a quiescent flow. Furthermore, a deep recurrent Q-network (DRQN) is incorporated with the IB-LBM to train the fish model to adapt its motion to optimally achieve a specific task, such as prey capture, rheotaxis and Kármán gaiting. Compared to existing learning models for fish, this work incorporates the fish position, velocity and acceleration into the state space in the DRQN; and it considers the amplitude and frequency action spaces as well as the historical effects. This framework makes use of the high computational efficiency of the IB-LBM which is of crucial importance for the effective coupling with learning algorithms. Applications of the proposed numerical framework in point-to-point swimming in quiescent flow and position holding both in a uniform stream and a Kármán vortex street demonstrate the strategies used to adapt to different situations.

8.
Sci Rep ; 11(1): 1926, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33479281

RESUMO

Borrelia spirochetes are the causative agents of Lyme borreliosis (LB) and relapsing fever (RF). Despite the steady rise in infections and the identification of new species causing human illness over the last decade, isolation of borreliae in culture has become increasingly rare. A modified Barbour-Stoenner-Kelly (BSK) media formulation, BSK-R, was developed for isolation of the emerging RF pathogen, Borrelia miyamotoi. BSK-R is a diluted BSK-II derivative supplemented with Lebovitz's L-15, mouse and fetal calf serum. Decreasing the concentration of CMRL 1066 and other components was essential for growth of North American B. miyamotoi. Sixteen B. miyamotoi isolates, originating from Ixodes scapularis ticks, rodent and human blood collected in the eastern and upper midwestern United States, were isolated and propagated to densities > 108 spirochetes/mL. Growth of five other RF and ten different LB borreliae readily occurred in BSK-R. Additionally, primary culture recovery of 20 isolates of Borrelia hermsii, Borrelia turicatae, Borrelia burgdorferi and Borrelia mayonii was achieved in BSK-R using whole blood from infected patients. These data indicate this broadly encompassing borreliae media can aid in in vitro culture recovery of RF and LB spirochetes, including the direct isolation of new and emerging human pathogens.

9.
Cell Rep ; 34(1): 108574, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33406418

RESUMO

The zinc finger transcription factor SALL4 is highly expressed in embryonic stem cells, downregulated in most adult tissues, but reactivated in many aggressive cancers. This unique expression pattern makes SALL4 an attractive therapeutic target. However, whether SALL4 binds DNA directly to regulate gene expression is unclear, and many of its targets in cancer cells remain elusive. Here, through an unbiased screen of protein binding microarray (PBM) and cleavage under targets and release using nuclease (CUT&RUN) experiments, we identify and validate the DNA binding domain of SALL4 and its consensus binding sequence. Combined with RNA sequencing (RNA-seq) analyses after SALL4 knockdown, we discover hundreds of new SALL4 target genes that it directly regulates in aggressive liver cancer cells, including genes encoding a family of histone 3 lysine 9-specific demethylases (KDMs). Taken together, these results elucidate the mechanism of SALL4 DNA binding and reveal pathways and molecules to target in SALL4-dependent tumors.

10.
Acad Med ; Publish Ahead of Print2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33410608

RESUMO

PURPOSE: Physician burnout is endemic across medical education and has numerous deleterious effects. Given the prevalence and negative effects of burnout, there is an urgent need to understand how residents experience and cope with stress and to develop explanatory models that inform the development of more effective interventions. METHOD: Using a qualitative, constructivist grounded theory approach, the authors conducted semistructured interviews from March to April 2019, in which psychiatry residents were asked about their experiences of stress and how they coped. First- through fourth-year trainees at Zucker Hillside Hospital at Northwell Health, Glen Oaks, New York, were invited. Two authors independently and inductively coded deidentified transcripts. A constant comparative approach was used to analyze data and support construction of themes. Theoretic sufficiency was observed after 14 interviews. RESULTS: The authors constructed an explanatory model for how residents cope with stress and whether they tended toward burnout or wholehearted engagement. The model included 3 themes: self-care, work relationships, and meaning making. Self-care, including time spent with others, provided connection and belonging that bolstered physicians' developing identities. Interpersonal relationships at work profoundly influenced the experience of residents. Positive peer and supervisor relationships enhanced confidence and perseverance. Negative role models and conflict engendered feelings of inadequacy. Finally, the ability to shift perspective and build meaning through examining moral values in the face of challenges was crucial for residents who reported success at coping with stress. Residents identified personal psychotherapy as an especially important strategy to facilitate meaning making. CONCLUSIONS: These findings provide guidance for how residency programs may help residents cope with stress and move away from burnout toward wholehearted engagement. Strategies may include reducing barriers to self-care and to accessing help early in training; creating spaces that promote peer connection and providing training in addressing conflict; and facilitating engagement in meaning-making activities.

11.
Acad Psychiatry ; 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33438158

RESUMO

OBJECTIVE: Since 2007, the American Board of Psychiatry and Neurology (ABPN) has required that residency programs conduct a specific clinical skills evaluation (CSE) of physician-patient interaction, psychiatric interview and mental status examination, and case presentation on a directly observed patient interview as a prerequisite for certification. The authors examined a multisite database of CSE assessments to investigate the validity of the evaluation. METHODS: The authors collected 1156 CSE assessments from 4 residency programs conducted over a 6-year period, compared scoring patterns among the programs, score improvement over 4 years of residency, time and number of CSEs required to meet ABPN requirements, and patterns of scoring for individual faculty evaluators. RESULTS: The distribution of scores within each of the 4 programs showed similar, but nonidentical patterns. The number of CSEs required to meet the ABPN standards (3.5) and the point in training at which this was completed (late PGY-2) were the same in all programs. CSE scores were highly correlated with year of training but were not correlated with performance on an unrelated cognitive examination. Individual faculty members tended to stay within a moderate range of scores over multiple residents, partially attributable to year of training. CONCLUSIONS: Taken together, these findings support the validity of the CSE as a measure of residents' clinical skills in the specified areas and demonstrate a moderate-high degree of consistency in the scoring of the CSE across these 4 programs.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33411640

RESUMO

Type 2 diabetes mellitus (T2DM) is characterized by chronic hyperglycemia and progressive insulin resistance, leading to macro and microvascular dysfunction. Passive heating has potential to improve glucose homeostasis and act as an exercise mimetic. We assessed the effect of acute passive heating before or during an oral glucose tolerance test (OGTT) in people with T2DM. Twelve people with T2DM were randomly assigned to 3 conditions:1) 3 h OGTT (CON); 2) 1 h passive heating (40 °C water) 30 min before an OGTT (HOT-OGTT); and 3) 1 h passive heating (40 °C water) 30 min after commencing an OGTT (OGTT-HOT). Blood [glucose], insulin sensitivity, extracellular heat shock protein 70 (eHSP70), total energy expenditure (TEE), heart rate (HR), systolic (SBP) and diastolic blood pressure (DBP) were recorded. Passive heating did not alter blood [glucose] (CON, 1,677 (386) a.u.; HOT-OGTT, 1,797 (340) a.u.; OGTT-HOT, 1,662 (364) a.u.; P = 0.28), insulin sensitivity (P = 0.15), or SBP (P = 0.18), but did increase [eHSP70] in both heating conditions (CON, 203.48 (110.81) pg·mL-1; HOT-OGTT, 402.47 (79.02) pg·mL-1; OGTT-HOT, 310.00 (60.53) pg·mL-1; P < 0.001), increased TEE (via fat oxidation) in the OGTT-HOT condition (CON, 263 (33) kcal; HOT-OGTT, 278 (40) kcal; OGTT-HOT, 304 (38) kcal;P = 0.001), increased HR in both heating conditions (P < 0.001) and reduced DBP in OGTT-HOT condition (P < 0.01). Passive heating in close proximity to a glucose challenge does not alter glucose tolerance but does increase [eHSP70] and TEE, and reduce blood pressure in people with T2DM.

13.
Psychol Health ; : 1-27, 2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33499672

RESUMO

OBJECTIVE: Inflammatory Bowel Disease (IBD) is associated with higher rates of clinically significant anxiety and depression than in healthy populations. Psychosocial interventions targeting anxiety and depression in IBD have variable efficacy and disparate treatment approaches, making treatment recommendations difficult. The current study aimed to identify effective treatment components across psychosocial treatment approaches for anxiety and depression in IBD. DESIGN: A systematic review of psychosocial treatments for anxiety and depression in IBD was conducted. Based on the Distillation and Matching Model, treatments were coded and data aggregated by intervention components, or practice elements (PE), to elucidate replicable clinical techniques. MAIN OUTCOME: The percentage of studies utilizing a given PE was the primary outcome. MEASURES: Among all included studies, as well as among those finding favorable, significant effects on anxiety or depression, the percentage utilizing each PE and number of PEs utilized was determined. RESULTS: The most utilized PEs among included interventions were relaxation, IBD psychoeducation, cognitive restructuring, distraction, and social skills. Examining only interventions with favorable differences on specified outcomes (HRQoL, Anxiety, Depression, and/or Coping) indicated that relaxation, education, cognitive restructuring, and mindfulness were most utilized. CONCLUSION: Implications for clinical practice are discussed, including the development and dissemination of treatment recommendations.

14.
Ageing Res Rev ; 66: 101240, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33347992

RESUMO

Caloric restriction (CR) mimetics are molecules that produce beneficial effects on health and longevity in model organisms and humans, without the challenges of maintaining a CR diet. Conventional CR mimetics such as metformin, rapamycin and spermidine activate autophagy, leading to recycling of cellular components and improvement of physiological function. We review here novel CR mimetics and anti-aging compounds, such as 4,4'-dimethoxychalcone, fungal polysaccharides, inorganic nitrate, and trientine, highlighting their possible molecular targets and mechanisms of action. The activity of these compounds can be understood within the context of hormesis, a biphasic dose response that involves beneficial effects at low or moderate doses and toxic effects at high doses. The concept of hormesis has widespread implications for the identification of CR mimetics in experimental assays, testing in clinical trials, and use in healthy humans. We also discuss the promises and limitations of CR mimetics and anti-aging molecules for delaying aging and treating chronic diseases.


Assuntos
Envelhecimento , Restrição Calórica , Autofagia , Hormese , Humanos , Longevidade
15.
BMJ Open ; 10(12): e040732, 2020 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-33318118

RESUMO

OBJECTIVES: To pilot a complex intervention to support healthcare and improve early detection and treatment for common health conditions experienced by nursing home (NH) residents. DESIGN: Pilot cluster randomised controlled trial. SETTING: 14 NHs (7 intervention, 7 control) in London and West Yorkshire. PARTICIPANTS: NH residents, their family carers and staff. INTERVENTION: Complex intervention to support healthcare and improve early detection and treatment of urinary tract and respiratory infections, chronic heart failure and dehydration, comprising: (1) 'Stop and Watch (S&W)' early warning tool for changes in physical health, (2) condition-specific care pathway and (3) Situation, Background, Assessment and Recommendation tool to enhance communication with primary care. Implementation was supported by Practice Development Champions, a Practice Development Support Group and regular telephone coaching with external facilitators. OUTCOME MEASURES: Data on NH (quality ratings, size, ownership), residents, family carers and staff demographics during the month prior to intervention and subsequently, numbers of admissions, accident and emergency visits, and unscheduled general practitioner visits monthly for 6 months during intervention. We collected data on how the intervention was used, healthcare resource use and quality of life data for economic evaluation. We assessed recruitment and retention, and whether a full trial was warranted. RESULTS: We recruited 14 NHs, 148 staff, 95 family carers and 245 residents. We retained the majority of participants recruited (95%). 15% of residents had an unplanned hospital admission for one of the four study conditions. We were able to collect sufficient questionnaire data (all over 96% complete). No NH implemented intervention tools as planned. Only 16 S&W forms and 8 care pathways were completed. There was no evidence of harm. CONCLUSIONS: Recruitment, retention and data collection processes were effective but the intervention not implemented. A full trial is not warranted. TRIAL REGISTRATION NUMBER: ISRCTN74109734 (https://doi.org/10.1186/ISRCTN74109734). ORIGINAL PROTOCOL: BMJ Open. 2019;9(5):e026510. doi:10.1136/bmjopen-2018-026510.


Assuntos
Instituição de Longa Permanência para Idosos , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Medicina Baseada em Evidências , Feminino , Hospitais , Humanos , Londres , Masculino , Casas de Saúde , Projetos Piloto
16.
Am Psychol ; 75(8): 1158-1174, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33252952

RESUMO

Clinical psychological science has developed many efficacious treatments for diverse emotional and behavioral difficulties encountered by children and adolescents, although randomized trials investigating these treatments have disproportionally been conducted by American, university-based research labs. The subsection of the world population involved in these studies, however, represents very few people among those in need of psychological services whose voices, perspectives, and orientations to therapy have not generally been reflected in well-funded research trials. Dissemination and implementation of evidence-based services designed to meet the needs of this broader global population, therefore, may require cultural and contextual adaptation to be successful. The current article describes the implementation of Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) in 3 separate low-resourced settings (rural South Carolina, Puerto Rico, and El Salvador) utilizing the Exploration, Preparation, Implementation, and Sustainment (EPIS) framework and guided by a community-based participatory research framework. Emphasis is placed on description of program development, building collaborative and responsive partnerships, and the use of implementation strategies to guide continuous quality improvement. Program evaluation data comparing baseline to posttreatment trauma symptoms and treatment completion rates for all sites are also presented, which suggests that treatment was associated with a large reduction in symptoms, exceeding that noted in many TF-CBT randomized trials. The implications of attention to context, adaptation, and methods of building partnerships with global communities are discussed, with a particular focus on propelling more refined models and controlled studies in the future. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

17.
Antiviral Res ; : 104972, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33242518

RESUMO

Inhibition of the host RNA polyadenylating polymerases, PAPD5 and PAPD7 (PAPD5/7), with dihydroxyquinoline (DHQ), a small orally available, molecule, results in a rapid and selective degradation of hepatitis B virus (HBV) RNA, and hence reduction in the amounts of viral gene products. DHQ, is a first in class investigational agent and could represent an entirely new category of HBV antivirals. PAPD5 and PAPD7 are non-canonical, cell specified, polyadenylating polymerases, also called terminal nucleotidyl transferases 4B and 4A (TENT4B/A), respectively. They are involved in the degradation of poor-quality cell transcripts, mostly non-coding RNAs and in the maturation of a sub-set of transcripts. They also appear to play a role in shielding some mRNA from degradation. The results of studies with DHQ, along with other recent findings, provide evidence that repression of the PAPD5/7 arm of the cell "RNA quality control" pathway, causes a profound (multi-fold) reduction rather than increase, in the amount of HBV pre-genomic, pre-core and HBsAg mRNA levels in tissue culture and animal models, as well. In this review we will briefly discuss the need for new HBV therapeutics and provide background about HBV transcription. We also discuss cellular degradation of host transcripts, as it relates to a new family of anti-HBV drugs that interfere with these processes. Finally, since HBV mRNA maturation appears to be selectively sensitive to PAPD5/7 inhibition in hepatocytes, we discuss the possibility of targeting host RNA "quality control" as an antiviral strategy.

18.
J Alzheimers Dis Rep ; 4(1): 365-371, 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-33163897

RESUMO

One unexplained feature of Alzheimer's disease (AD) is that the lateral entorhinal cortex undergoes neurodegeneration before other brain areas. However, this brain region does not have elevated levels of amyloid peptides in comparison with undamaged regions. What is the cause of this special vulnerability of the entorhinal cortex? One special feature of the lateral entorhinal cortex is that it projects to newborn neurons that have undergone adult neurogenesis in the dentate gyrus of the hippocampus. Neurogenesis is abnormal in human AD brains, and modulation of neurogenesis in experimental animals influences the course of AD. This complex process of neurogenesis may expose axon terminals originating from neurons of the entorhinal cortex to a unique combination of molecules that can enhance toxic effects of amyloid. Retrograde degeneration of neurons with axons terminating in the dentate gyrus provides a likely explanation for the spatial patterns of neuronal cell death seen in AD. Specialized astrocytes in the dentate gyrus participate in adult neurogenesis and produce fatty acid binding protein7 (FABP7). These FABP7+ cells undergo an aging-related mitochondrial pathology that likely impairs their functions. This age-related abnormality may contribute to the impairment in neurogenesis seen in aging and Alzheimer's disease. Also, a compromised function of these astrocytes likely results in local elevations of palmitic acid, iron, copper, and glucose, which all enhance the toxicity of amyloid peptides. Treatments that modulate neurogenesis or diminish the production of these toxic substances may prove more successful than treatments that are solely aimed at reducing the amyloid burden alone.

19.
Artigo em Inglês | MEDLINE | ID: mdl-33214192

RESUMO

Forensic psychiatry as a subspecialty discipline is presently experiencing a broad and essentially constructive conversation concerning its foundations and their implications for teaching and practice. The essay by Griffith and Greenidge proposes developing the art of consultation to include bringing out the contextual realities often invisible at first to the quarreling parties. Often enough they can thus be spared embarrassment as they come to recognize that their shared values matter more than any differences. This outcome may prove especially broadly true in the religious arena.

20.
Cell Host Microbe ; 28(5): 638-645, 2020 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-33152278

RESUMO

When SARS-CoV-2 emerged at the end of 2019, no approved therapeutics or vaccines were available. An urgent need for countermeasures during this crisis challenges the current paradigm of traditional drug discovery and development, which usually takes years from start to finish. Approaches that accelerate this process need to be considered. Here we propose the minimum data package required to move a compound into clinical development safely. We further define the additional data that should be collected in parallel without impacting the rapid path to clinical development. Accelerated paths for antivirals, immunomodulators, anticoagulants, and other agents have been developed and can serve as "roadmaps" to support prioritization of compounds for clinical testing. These accelerated paths are fueled by a skewed risk-benefit ratio and are necessary to advance therapeutic agents into human trials rapidly and safely for COVID-19. Such paths are adaptable to other potential future pandemics.


Assuntos
Antivirais , Betacoronavirus , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Vacinas , Antivirais/uso terapêutico , Humanos
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