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2.
J Control Release ; 323: 361-375, 2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-32339548

RESUMO

Traumatic brain injury (TBI) is a significant medical problem with limited treatment options and is one of the main causes of life-long disability. Neuroinflammation orchestrated by activated microglia/macrophages at the site of injury plays a critical role in the onset of many pathological events following TBI, leading to blood brain barrier (BBB) dysfunction, neuronal damage and long term neuronal and behavioral deficits. Current treatment involves intravenous administration of anti-inflammatory drugs which have limited clinical outcomes only when dosed within the early time window after injury. Hence there is an urgent need to develop improved drug delivery systems which have potential to cross impaired BBB, target and deliver drugs selectively to activated microglia/macrophages at the sites of injury, and suppress the detrimental effects of acute inflammation. In this study, we have used Sinomenine (Sino), a potent anti-inflammatory and antioxidant drug conjugated to hydroxyl terminated generation-4 PAMAM dendrimer (D-Sino) as a potential therapy for attenuating early inflammation in TBI. D-Sino conjugates were synthesized using highly robust copper-catalyzed click reaction with high purity. D-Sino conjugates enhanced the intracellular availability of Sino due to their rapid cellular uptake, significantly attenuated early/acute inflammation by suppressing pro-inflammatory cytokines (TNF-α, IL-1ß, CCL-3 and IL-6), and reduced oxidative stress (iNOS and NO) in LPS activated murine macrophages (RAW 264.7) by inhibiting NF-κB activation and its nuclear translocation (the root cause for inflammation inception) significantly more as compared to the free drug. Upon systemic administration in a rabbit model of pediatric TBI, D-Sino conjugates specifically targeted activated microglia/macrophages at the site of injury in the brain. Single dose of D-Sino attenuated inflammation in the injured brain areas by suppressing inflammatory cytokines expression whereas free Sino treatment did not demonstrate a significant effect. Together, these results suggest that D-Sino conjugate may open up new avenues for increasing the therapeutic window in the treatment of early inflammation and for improving the efficacy of the drug in TBI. Moreover, this treatment can work in conjunction with current clinical practices such as therapeutic hypothermia and pharmacologically induced coma for many indications associated with TBI, where acute inflammation plays a critical role in disease progression.

3.
Proteomics ; 20(5-6): e1800407, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32068959

RESUMO

Aging biology is intimately associated with dysregulated metabolism, which is one of the hallmarks of aging. Aging-related pathways such as mTOR and AMPK, which are major targets of anti-aging interventions including rapamcyin, metformin, and exercise, either directly regulate or intersect with metabolic pathways. In this review, numerous candidate bio-markers of aging that have emerged using metabolomics are outlined. Metabolomics studies also reveal that not all metabolites are created equally. A set of core "hub" metabolites are emerging as central mediators of aging. The hub metabolites reviewed here are nicotinamide adenine dinucleotide, reduced nicotinamide dinucleotide phosphate, α-ketoglutarate, and ß-hydroxybutyrate. These "hub" metabolites have signaling and epigenetic roles along with their canonical roles as co-factors or intermediates of carbon metabolism. Together these hub metabolites suggest a central role of the TCA cycle in signaling and metabolic dysregulation associated with aging.

4.
Sci Adv ; 6(4): eaay8514, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32010790

RESUMO

Poor transport of neuropharmaceutics through central nervous system (CNS) barriers limits the development of effective treatments for CNS disorders. We present the facile synthesis of a novel neuroinflammation-targeting polyethylene glycol-based dendrimer (PEGOL-60) using an efficient click chemistry approach. PEGOL-60 reduces synthetic burden by achieving high hydroxyl surface density at low generation, which plays a key role in brain penetration and glia targeting of dendrimers in CNS disorders. Systemically administered PEGOL-60 crosses impaired CNS barriers and specifically targets activated microglia/macrophages at the injured site in diverse animal models for cerebral palsy, glioblastoma, and age-related macular degeneration, demonstrating its potential to overcome impaired blood-brain, blood-tumor-brain, and blood-retinal barriers and target key cells in the CNS. PEGOL-60 also exhibits powerful intrinsic anti-oxidant and anti-inflammatory effects in inflamed microglia in vitro. Therefore, PEGOL-60 is an effective vehicle to specifically deliver therapies to sites of CNS injury for enhanced therapeutic outcomes in a range of neuroinflammatory diseases.

5.
Neuroscience ; 428: 70-75, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31917354

RESUMO

Permanently stored memories become labile through a process called reactivation. Once reactivated, these memories need reconsolidation to become permanent. Sleep is critical for memory consolidation. Is sleep necessary for memory reconsolidation? We hypothesized that sleep loss immediately after fear reactivation (FR) will prevent memory reconsolidation. To test our hypothesis, two experiments were performed in adult male C57BL/6J mice exposed to contextual fear conditioning paradigm with inescapable foot shock as unconditional stimulus (US) and contextual cage as conditional stimulus (CS). Sleep loss was achieved either by 5 h of sleep deprivation (SD; Experiment 1) or by systemic infusion of modafinil (200 mg/Kg, ip), an FDA approved wake-promoting agent (Experiment 2). One hour after light-onset, fear memory acquisition (FMA) was performed on Day 1. Mice were allowed to explore CS for 5 min followed by presentation of US (7 foot-shocks; 0.5 mA, 2.0 s duration) at pseudorandom intervals. Controls were exposed to similar CS but no shocks were delivered. On Day 2, mice were exposed to CS for 2 min (without US; for FR) followed by either sleep loss or no sleep loss. On Day 3, fear memory recall (FMR) was performed by exposing mice to CS (without US) for 12 min. Percent time spent in freezing was monitored during FC, FR and FMR. Our results suggested that as compared to sleeping controls, mice with sleep loss immediately after FR displayed a significant reduction in percent time freezing during FMR. These results suggest that sleep loss may prevent memory reconsolidation.

6.
J Clin Neurophysiol ; 37(1): 68-73, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31274707

RESUMO

PURPOSE: We present a unique technique applying F-wave latencies to assist in the diagnosis of peripheral neuropathy within the pediatric age group. METHODS: We calculated an F-wave estimated deviance adjusted for limb length measurements, distal motor conduction velocity, and distal motor latencies. We compared the F-wave estimated deviance from the normal subjects with those with peripheral neuropathy (both axonal and demyelinating) to establish diagnostic accuracy in pediatric patients. RESULTS: The normal range for the F-wave estimated deviance in the upper limb was -1 to +6 ms and in the lower limb was -8 to +5 ms. When compared with 82 subjects with peripheral neuropathy, there was a significant difference between the normal subjects and those with neuropathy (P values between 0.002 and 0.0005 for each of the individual nerves tested). CONCLUSIONS: The F-wave estimated deviance is independent of age and can be accurately applied to the electrodiagnostic testing of pediatric patients with suspected neuropathy.

8.
BMJ Open ; 9(9): e030092, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511287

RESUMO

INTRODUCTION: Chronic Myeloid Leukaemia (CML) constitutes 15% of new adult leukaemia cases as well as 2%-3% of leukaemia in children under 15% and 9% of leukaemias in adolescents 15-19 years of age annually. The introduction of Tyrosine Kinase Inhibitors (TKI) therapy has dramatically improved survival in these patients, yet the off-target effects of this treatment may have long-term health impacts on CML survivors. The risk of adverse health outcomes is especially important in children, where TKI exposure may occur during critical windows of growth and puberty, and patients require treatment for prolonged periods of time. The aim of this systematic review protocol is to report on the methods used to conduct a systematic review to investigate the endometabolic and bone health effects of TKI therapy in CML. METHODS AND ANALYSIS: Searches will be conducted in the Cochrane Central Register of Controlled Trials, EMBASE and MEDLINE from inception on August 1st, 2019. Searches may be updated while performing the systematic review to ensure new evidence is included if applicable. Grey literature search will include ClinicalTrials.gov and ProQuest Dissertations and Theses A&I. We will perform a meta-analysis if there are at least two studies reporting similar populations, interventions, methods and tracking the same outcome measures. The studies should also have similar age and sex distributions. ETHICS AND DISSEMINATION: As this is a systematic review protocol, it does not include patient data; therefore, Research Ethics Board approval is not indicated. The systematic review will be published in a peer-reviewed journal and presented at international conferences. PROSPERO REGISTRATION NUMBER: CRD42018091175.

10.
Am J Cardiol ; 124(8): 1171-1178, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31409450

RESUMO

The effect of normalization of serum testosterone levels with testosterone replacement therapy (TRT) in patients with a history of myocardial infarction (MI) is unknown. The objective of this study was to determine the incidence of recurrent MI and all-cause mortality in subjects with a history of MI and low total testosterone (TT) with and without TRT. We retrospectively examined 1,470 men with documented low TT levels and previous MI, categorized into Gp1: TRT with normalization of TT levels (n = 755) Gp2: TRT without normalization of TT levels (n = 542), and Gp3: no TRT (n = 173). The association of TRT with all-cause mortality and recurrent MI was compared using propensity score-weighted Cox proportional hazard models. All-cause mortality was lower in Gp1 versus Gp2 (hazard ratio [HR] 0.76, confidence interval [CI] 0.64 to 0.90, p = 0.002), and Gp1 versus Gp3 (HR 0.76, CI 0.60 to 0.98, p = 0.031). There was no significant difference in the risk of death between Gp2 versus Gp3 (HR 0.97, CI 0.76 to 1.24, p = 0.81). Adjusted regression analyses showed no significant differences in the risk of recurrent MI between groups (Gp1 vs Gp3, HR 0.79, CI 0.12 to 5.27, p = 0.8; Gp1 vs Gp2 HR 1.10, CI 0.25 to 4.77, p = 0.90; Gp2 vs Gp3 HR 0.58, CI 0.08 to 4.06, p = 0.58). In conclusion, in a large observational cohort of male veterans with previous MI, normalization of TT levels with TRT was associated with decreased all-cause mortality compared with those with non-normalized TT levels and the untreated group. Furthermore, in this high-risk population, TRT was not associated with an increased risk of recurrent MI.

11.
Neurocase ; 25(1-2): 17-20, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30968732

RESUMO

Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is an adult-onset autosomal dominant leukoencephalopathy resulting from mutations affecting the tyrosine kinase domain of the colony stimulating factor receptor 1 protein (encoded by CSF1R). The clinical phenotypes reported with CSF1R mutations are variable. We present a case of a patient with a pathogenic variant in the CSF1R gene with clinical and imaging features suggestive of Dementia with Lewy Bodies (DLB). This case expands the known clinical presentations associated with CSF1R mutations.


Assuntos
Doença por Corpos de Lewy , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/genética , Humanos , Doença por Corpos de Lewy/diagnóstico por imagem , Doença por Corpos de Lewy/genética , Doença por Corpos de Lewy/patologia , Doença por Corpos de Lewy/fisiopatologia , Masculino , Pessoa de Meia-Idade
12.
Muscle Nerve ; 60(2): 155-160, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31032944

RESUMO

INTRODUCTION: Existing normal value references for pediatric nerve conduction studies (NCS) are based on limited sample sizes with uncertain reliability, suggesting a need for better normative data. METHODS: Electronic medical records were reviewed for pediatric patients (0 to <18 years) with normal findings on electromyography and NCS during the period from January 1, 1997 through September 20, 2017. Electrodiagnostic and demographic data were collected. Gaussian and descriptive statistics were used to establish normal values by age group. RESULTS: In this study we analyzed 1,918 normal NCS on 1,849 unique pediatric patients. Patients were stratified by age: 0 to <1 month; 1 to <6 months; 6 to <12 months; 12 to <24 months; 2 to <3 years; 3 to <4 years; 4 to <5 years; 5 to <10 years; 10 to <15 years; and 15 to <18 years. Normal reference ranges for amplitude, conduction velocity, and distal latency were established for each age group for 4 motor and 4 sensory nerves. DISCUSSION: The large sample size of this study provides reliable reference values for interpreting pediatric NCS. Muscle Nerve 60: 155-160, 2019.


Assuntos
Eletromiografia , Condução Nervosa/fisiologia , Nervos Periféricos/fisiopatologia , Adolescente , Criança , Pré-Escolar , Eletrodiagnóstico , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Valores de Referência
13.
Cartilage ; : 1947603519833148, 2019 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-30841716

RESUMO

OBJECTIVES:: RNA isolation is necessary for the evaluation of gene expression. Due to the nature of its extracellular matrix, RNA isolation from articular hyaline cartilage is difficult and thus the tissue is commonly enzymatically digested in order to extract RNA from the obtained chondrocytes. We hypothesized that the digestion process affects the expression levels of common cartilage-associated genes. DESIGN:: Expression of cartilage-associated genes was compared between intact cartilage and digested chondrocytes from weight bearing and non-weight bearing regions of the equine fetlock joint. RESULTS:: The gene expression of SOX9, COL1A2, COL2A1, ACAN, and COLX were analyzed. Digested cartilage showed a significant decrease in the expression of COL1A2, COL2A1, and ACAN compared to intact cartilage in both joint regions, and an increase in COLX expression in non-weight bearing cartilage only. CONCLUSIONS:: Enzymatic digestion of cartilage significantly impacts gene expression profile. We conclude that while RNA isolation from intact cartilage is more technically difficult, determination of gene expression should be conducted on intact cartilage if true representation of the in vivo processes is sought.

14.
Psychopharmacology (Berl) ; 236(4): 1199-1206, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30460515

RESUMO

RATIONALE: Lower lip retraction (LLR) in rats has been described as a distinctive effect of 5-HT1A agonists. In the course of evaluating behavioral effects of cannabinoid agonists in rats, LLR effects were evident following injection of several cannabinoid agonists. OBJECTIVES: To pharmacologically characterize cannabinoid-induced LLR in rats. METHODS: Lower lip retraction was scored using a 3-point scale for up to 6 h after injection of the cannabinoid agonists Δ9-tetrahydrocannabinol (Δ9-THC, 1-10 mg/kg), AM7499 (0.01-1.0 mg/kg), or AM2389 (0.003-0.1 mg/kg), or, for comparison, the 5-HT1A agonist 8-OH-DPAT (0.01-0.3 mg/kg). Next, antagonist effects of rimonabant (1-10 mg/kg) and WAY100635 (0.3 mg/kg) on LLR produced by cannabinoid or 5-HT1A agonists were evaluated. Lastly, effects of 8-OH-DPAT were determined following pretreatment with AM2389 (0.003-0.01 mg/kg) or Δ9-THC (1 mg/kg). RESULTS: All three cannabinoid agonists produced LLR. Effects of AM2389 were attenuated by both rimonabant and WAY100635 whereas effects of 8-OH-DPAT were antagonized by WAY 100635 but not by rimonabant. Pretreatment with 1 mg/kg Δ9-THC or 0.01 mg/kg AM2389 shifted the 8-OH-DPAT dose-effect function for LLR to the left and isobolographic analysis of the data indicates CB1 and 5-HT1A interactions can be supraadditive. CONCLUSIONS: Cannabinoid agonists produce LLR in rats, an effect heretofore ascribed only to activity at 5-HT1A receptors, via CB1 receptor-mediated actions. Co-administration of a cannabinoid agonist and the 5-HT1A agonist 8-OH-DPAT results in a synergistic effect on LLR.


Assuntos
8-Hidroxi-2-(di-n-propilamino)tetralina/farmacologia , Agonistas de Receptores de Canabinoides/farmacologia , Canabinoides/farmacologia , Lábio/efeitos dos fármacos , Lábio/fisiologia , Agonistas do Receptor de Serotonina/farmacologia , Animais , Benzopiranos/farmacologia , Relação Dose-Resposta a Droga , Dronabinol/farmacologia , Feminino , Ratos , Ratos Sprague-Dawley , Receptor CB1 de Canabinoide/agonistas , Receptor CB1 de Canabinoide/antagonistas & inibidores , Receptor CB1 de Canabinoide/metabolismo , Receptor 5-HT1A de Serotonina/metabolismo
16.
Theranostics ; 8(20): 5529-5547, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30555562

RESUMO

Mitochondrial oxidative stress is associated with many neurodegenerative diseases, such as traumatic brain injury (TBI). Targeted delivery of antioxidants to mitochondria has failed to translate into clinical success due to their nonspecific cellular localization, poor transport properties across multiple biological barriers, and associated side effects. These challenges, coupled with the complex function of the mitochondria, create the need for innovative delivery strategies. Methods: Neutral hydroxyl-terminated polyamidoamine (PAMAM) dendrimers have shown significant potential as nanocarriers in multiple brain injury models. N-acetyl cysteine (NAC) is a clinically used antioxidant and anti-inflammatory agent which has shown significant potency when delivered in a targeted manner. Here we present a mitochondrial targeting hydroxyl PAMAM dendrimer-drug construct (TPP-D-NAC) with triphenyl-phosphonium (TPP) for mitochondrial targeting and NAC for targeted delivery to mitochondria in injured glia. Co-localization and mitochondrial content of mitochondria-targeted and unmodified dendrimer were assessed in microglia and macrophages in vitro via immunohistochemistry and fluorescence quantification. Therapeutic improvements of TPP-D-NAC over dendrimer-NAC conjugate (D-NAC) and free NAC were evaluated in vitro in microglia under oxidative stress challenge. In vivo neuroinflammation targeting was confirmed in a rabbit model of TBI. Results: TPP-conjugated dendrimer co-localized significantly more with mitochondria than unmodified dendrimer without altering overall levels of cellular internalization. This targeting capability translated to significant improvements in the attenuation of oxidative stress by TPP-D-NAC compared to D-NAC and free NAC. Upon systemic administration in a rabbit TBI model, TPP-conjugated dendrimer co-localized specifically with mitochondria in activated microglia and macrophages in the white matter of the ipsilateral/injured hemisphere, confirming its BBB penetration and glial targeting capabilities. Conclusion: D-NAC has shown promising efficacy in many animal models of neurodegeneration, and this work provides evidence that modification for mitochondrial targeting can further enhance its therapeutic efficacy, particularly in diseases where oxidative stress-induced glial cell death plays a significant role in disease progression.


Assuntos
Dendrímeros/metabolismo , Dendrímeros/farmacologia , Mitocôndrias/metabolismo , Cromatografia Líquida de Alta Pressão , Dendrímeros/química , Difusão Dinâmica da Luz , Imuno-Histoquímica , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Microglia/efeitos dos fármacos , Microglia/metabolismo , Estresse Oxidativo/efeitos dos fármacos
17.
Echocardiography ; 35(10): 1626-1634, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30296350

RESUMO

BACKGROUND: Cardiac imaging is the cornerstone of the pretranscatheter aortic valve replacement (TAVR) assessment. Multi-detector computed tomography (MDCT) is considered the conventional imaging modality. However, there is still no definitive gold standard. Targeted cohort of inoperable high-risk patients with underlying comorbidities, particularly renal impairment, makes apparent the need for MDCT alternative. We aimed to demonstrate the correlation extent between MDCT and three-dimensional transesophageal echocardiography (3DTEE) aortic annular area measures and to answer the question: Is 3DTEE a good alternative to MDCT? METHODS: A systematic literature search and meta-analysis were conducted to evaluate the degree of correlation and agreement between 3DTEE and MDCT aortic annular sizing. A thorough assessment of EMBASE, PubMed, and Cochrane Central Register of Controlled Trials (CENTRAL) was performed. All studies comparing 3DTEE and MDCT in relation to aortic annular sizing were included. RESULTS: Thirteen studies were included (N = 1228 patients). A strong linear correlation was found between 3DTEE and MDCT measurements of aortic annulus area (r = 0.84, P < 0.001), mean perimeter (r = 0. 0.85, P < 0.001), and mean diameter (r = 0.80, P < 0.001). Bland-Altman plots revealed smaller mean 3DTEE values in comparison to MDCT for aortic annular area, the mean difference being -2.22 mm2 with 95% limits of agreement -12.79 to 8.36. CONCLUSION: Aortic annulus measurements obtained by 3DTEE demonstrated a high level of correlation with those evaluated by MDCT. This makes 3DTEE a feasible choice for aortic annulus assessment, with advantage of real time assessment, lack of contrast, and no radiation exposure.


Assuntos
Aorta/anatomia & histologia , Ecocardiografia Tridimensional/métodos , Ecocardiografia Transesofagiana/métodos , Tomografia Computadorizada Multidetectores/métodos , Pesos e Medidas Corporais , Humanos , Substituição da Valva Aórtica Transcateter
18.
Bioeng Transl Med ; 3(2): 87-101, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-30065965

RESUMO

Dendrimer-N-acetyl cysteine (D-NAC) conjugate has shown significant promise in multiple preclinical models of brain injury and is undergoing clinical translation. D-NAC is a generation-4 hydroxyl-polyamidoamine dendrimer conjugate where N-acetyl cysteine (NAC) is covalently bound through disulfide linkages on the surface of the dendrimer. It has shown remarkable potential to selectively target and deliver NAC to activated microglia and astrocytes at the site of brain injury in several animal models, producing remarkable improvements in neurological outcomes at a fraction of the free drug dose. Here we present a highly efficient, scalable, greener, well-defined route to the synthesis of D-NAC, and validate the structure, stability and activity to define the benchmarks for this compound. This newly developed synthetic route has significantly reduced the synthesis time from three weeks to one week, uses industry-friendly solvents/reagents, and involves simple purification procedures, potentially enabling efficient scale up.

19.
J Control Release ; 283: 175-189, 2018 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-29883694

RESUMO

Neurotherapeutics for the treatment of central nervous system (CNS) disorders must overcome challenges relating to the blood-brain barrier (BBB), brain tissue penetration, and the targeting of specific cells. Neuroinflammation mediated by activated microglia is a major hallmark of several neurological disorders, making these cells a desirable therapeutic target. Building on the promise of hydroxyl-terminated generation four polyamidoamine (PAMAM) dendrimers (D4-OH) for penetrating the injured BBB and targeting activated glia, we explored if conjugation of targeting ligands would enhance and modify brain and organ uptake. Since mannose receptors [cluster of differentiation (CD) 206] are typically over-expressed on injured microglia, we conjugated mannose to the surface of multifunctional D4-OH using highly efficient, atom-economical, and orthogonal Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC) click chemistry and evaluated the effect of mannose conjugation on the specific cell uptake of targeted and non-targeted dendrimers both in vitro and in vivo. In vitro results indicate that the conjugation of mannose as a targeting ligand significantly changes the mechanism of dendrimer internalization, giving mannosylated dendrimer a preference for mannose receptor-mediated endocytosis as opposed to non-specific fluid phase endocytosis. We further investigated the brain uptake and biodistribution of targeted and non-targeted fluorescently labeled dendrimers in a maternal intrauterine inflammation-induced cerebral palsy (CP) rabbit model using quantification methods based on fluorescence spectroscopy and confocal microscopy. We found that the conjugation of mannose modified the distribution of D4-OH throughout the body in this neonatal rabbit CP model without lowering the amount of dendrimer delivered to injured glia in the brain, even though significantly higher glial uptake was not observed in this model. Mannose conjugation to the dendrimer modifies the dendrimer's interaction with cells, but does not minimize its inherent inflammation-targeting abilities.


Assuntos
Paralisia Cerebral/metabolismo , Dendrímeros/administração & dosagem , Manose/administração & dosagem , Animais , Animais Recém-Nascidos , Lesões Encefálicas/metabolismo , Dendrímeros/farmacocinética , Modelos Animais de Doenças , Feminino , Manose/farmacocinética , Camundongos , Células RAW 264.7 , Coelhos , Distribuição Tecidual
20.
Adv Med Educ Pract ; 9: 335-343, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29780265

RESUMO

Background: General practitioners (GPs) are key members of the health care profession who are required to have a considerable breadth of knowledge to manage and treat patients effectively in the community. Their skills and experience varies depending on the medical school they attended and their foundation training and specialist GP training schemes. Exposure to ear, nose, and throat (ENT)-specific pathology is often insufficient due to the lack of formal otolaryngology rotations, minimal relevant teaching opportunities, and inconsistencies in curricula, despite ENT-related pathology presentations being one of the commonest consultations in primary care. Methods: We undertook a learning needs assessment among Watford general practice vocational training scheme trainees to assess whether they lacked confidence in managing typical ENT pathology, as well as to ascertain whether they felt a formal and focused ENT teaching session would be beneficial to them. Results: The results suggested they were interested in such a session, and therefore we organized a formal program on the assessment and management of acute and common ENT pathologies with a postteaching questionnaire to evaluate participant confidence in these domains. The results showed an improvement in participant knowledge and confidence regarding the assessment and management of ENT pathologies following the teaching session intervention. In addition, most attendees were overall very satisfied with the session. Conclusion: This study highlights the need for teaching specifically tailored to the learning needs of general practice vocational training scheme trainees, particularly in niche specialties, in order to prepare them adequately for clinical practice in the community setting.

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