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1.
Can Med Educ J ; 15(1): 68-74, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38528892

RESUMO

Background: Interviews are considered an important part of the medical school admissions process but have been critiqued based on bias and reliability concerns since the 1950s. To determine the impact of the interview, this systematic review investigated the characteristics and outcomes of medical students admitted with and without interviews. Methods: We searched four literature databases from inception through August 2022; all studies comparing medical students admitted with and without interviews were included. We excluded studies from outside the medical school setting and non-research reports. We reviewed interview type, study design, quality, and outcomes. Results: Eight studies from five institutions across five countries were included. Six reported no demographic differences between students admitted with and without interviews; one found that more men were admitted without than with semi-structured interviews, and both cohorts had similar academic and clinical performance. Structured interviews admitted students who scored higher on clinical exams and social competence and lower on academic exams. Cohorts admitted with and without structured interviews had similar mental health issues by their final year of medical school. Discussion: This review suggests that students admitted with and without unstructured and semi-structured interviews were similar demographically, academically, and clinically. Moreover, structured interviews selected more socially competent students who performed better clinically but worse academically. Further research is needed to determine the impact of the selection interview in medical school admissions.


Contexte: Les entrevues sont considérées comme une composante importante du processus d'admission dans les facultés de médecine, mais elles ont été critiquées depuis les années 1950 sur la base de préoccupations liées à la partialité et à la fiabilité. Afin de déterminer l'impact de l'entrevue, nous avons étudié dans cette revue systématique les caractéristiques et les résultats des étudiants en médecine admis ayant passé ou non une entrevue. Méthodes: Nous avons effectué des recherches dans quatre bases de données bibliographiques depuis leur création jusqu'à août 2022; toutes les études comparant les étudiants en médecine admis avec ou sans entrevue ont été incluses. Nous avons exclu les études réalisées en dehors du cadre des facultés de médecine et les rapports ne relevant pas de la recherche. Nous avons examiné le type d'entrevue, la conception de l'étude, la qualité et les résultats. Résultats: Huit études provenant de cinq établissements dans cinq pays ont été incluses. Six d'entre elles ne font état d'aucune différence démographique entre les étudiants admis avec ou sans entrevue ; l'une d'entre elles a révélé que davantage d'hommes étaient admis sans entrevue qu'avec une entrevue semi-structurée, et que les deux cohortes présentaient des rendements universitaires et cliniques similaires. Les entrevues structurées ont permis d'admettre des étudiants qui ont obtenu de meilleurs résultats aux examens cliniques et compétence sociale et de moins bons résultats aux examens universitaires. Les cohortes admises avec et sans entrevues structurées présentaient des problèmes de santé mentale similaires lors de leur dernière année d'études de médecine. Discussion: Cette étude suggère que les étudiants admis avec et sans entrevues non structurées et semi-structurées étaient similaires d'un point de vue démographique, universitaire et clinique. En outre, les entrevues structurées ont permis de sélectionner des étudiants plus compétents sur le plan social, qui ont obtenu de meilleurs résultats cliniques, mais avec une moins bonne performance sur le plan académique. D'autres recherches sont nécessaires pour déterminer l'impact de l'entrevue de sélection sur les admissions dans les facultés de médecine.

2.
Graefes Arch Clin Exp Ophthalmol ; 261(10): 2755-2762, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37017740

RESUMO

PURPOSE: The published information on virtual supervision (VS) in ophthalmology is not well described. This scoping review describes the evidence and potential role for VS in ophthalmic practice and education. METHODS: A literature search strategy was developed in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). We included full-text articles published in an English-language peer-reviewed journal that involved physician-physician or physician-trainee VS in ophthalmology. We excluded studies with direct (in-person) supervision. Two investigators independently extracted from each article the year of publication and study location, design, participant characteristics, sample size, and outcomes. We appraised the methodological quality of the studies using the Mixed Methods Appraisal Tool (MMAT). RESULTS: Seven articles were included in our qualitative synthesis. Supervisees ranged from physicians such as an ophthalmic surgeon and a general practitioner to medical trainees such as ophthalmology residents, vitreoretinal fellows, and emergency medicine residents. Study settings included emergency departments, operating rooms, eye clinics, and a rural hospital. All studies reported successful transmission of real-time images or videos of clinical examinations and surgical or in-office procedures. Various methods were used to ensure high image and video quality during VS, although some technical challenges remained. MMAT ratings revealed limitations in outcome measurement, statistical analysis, sampling strategy, and inclusion of confounding factors. CONCLUSION: Virtual supervision in ophthalmology is technologically feasible and permits synchronous communication and transmission of clinical data, which can be used to formulate diagnostic and management plans and learn new surgical skills. Future studies with larger sample sizes and robust study designs should investigate factors that make VS effective in ophthalmic practice and education.


Assuntos
Oftalmologia , Humanos , Oftalmologia/educação
3.
Brain Tumor Res Treat ; 10(3): 135-143, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35929110

RESUMO

Over the last two decades, numerous studies have investigated the presence of human cytomegalovirus (CMV) within glioblastoma or gliomas; however, the results are severely conflicting. While a few researchers have suggested the potential benefits of cytotoxic T lymphocyte or dendritic cell-based vaccines for recurrent or newly diagnosed glioblastoma patients, several studies did not at all agree with the existence of CMV in glioblastoma cells. In this review, we summarized the conflicting results and issues about the detection of CMV in glioblastoma or glioma patients. We also provided the clinical data of published and unpublished clinical trials using CMV-specific immunotherapy for glioblastomas.

4.
ACG Case Rep J ; 9(1): e00687, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35097148

RESUMO

Peripheral facial nerve palsy is a prevalent type of mononeuropathy that can have a variety of etiologies. Facial nerve damage because of esophagogastroduodenoscopy, however, is exceedingly rare and has only been reported in 1 patient. We report the first case in the United States of a patient who developed left-sided facial nerve palsy after a routine esophagogastroduodenoscopy, with little meaningful recovery of nerve function. We hope to bring awareness to gastroenterologists of this rare complication with potential long-term detrimental effects that can be avoided with the adjustment of equipment and patient position before the procedure.

5.
Radiol Case Rep ; 16(7): 1643-1645, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34007375

RESUMO

Atypical or unilateral polycystic kidney disease is a rare entity that is found incidentally and is characterized on imaging as asymmetric or unilateral distribution of cysts confined to the kidneys. We present a case of an incidental finding of atypical polycystic kidney disease in a 72-year-old male. Computed tomography imaging showed asymmetric distribution of cysts only in the kidneys and the patient had no genitourinary symptoms, had normal renal function, and did not have a family history of renal disease. Although considered to be benign, rare cases of progression of atypical polycystic kidney disease to bilateral polycystic kidney disease has been documented in the literature, which portends a worse prognosis. It is important for clinicians to be aware of this entity so that patients can be monitored periodically for progression of disease.

6.
Radiol Case Rep ; 15(4): 420-423, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32071663

RESUMO

Epididymoorchitis is a relatively common urologic condition involving the scrotum which presents with unilateral pain and swelling. It is typically treated with antibiotics but can progress to complications such as scrotal pyocele. Global testicular infarction is an exceedingly rare but devastating complication of epididymoorchitis. Grey scale and color Doppler ultrasound demonstrate testicular hypovascularity with subsequent hypoechoic changes of the testicular parenchyma. Scrotal MRI shows T2 hyperintense changes through the testicle with nonenhancement of the testicular parenchyma post contrast, consistent with infarction. The cause of global infarction in epididymitis is uncertain but may be due to mixed arterial and venous insufficiency. This case illustrates a 41-year-old male that developed acute left testicular pain. Initial ultrasound showed an enlarged left testicle with hyperemia. The patient's symptoms progressed and a scrotal MRI demonstrated a lack of left testicular enhancement consistent with global infarction, as well as an adjacent pyocele.

7.
Cardiol Rev ; 28(6): 312-318, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32040019

RESUMO

Exposure to heavy metals is common. This exposure is related to environmental contamination of air, water and soil, occupational exposure, accumulation in food, tobacco, and other factors. Cadmium and lead are notable for their widespread contamination, long-lasting effects in the body, and renal as well as cardiovascular toxicity. Acute toxicity due to high-level exposure, as well as chronic low-level exposure are now well-established pathogenic entities. Both chronic renal failure and ischemic heart disease patients have been treated separately in recent studies with ethylenediaminetetraacetic acid (EDTA) chelation therapy. In patients with chronic kidney disease (serum creatinine: 1.5-4.0 mg/dL) and increased body lead burden, weekly low-dose chelation with calcium EDTA slowed the rate of decline in renal function in patients with diabetes and in non-diabetic patients. In patients with a history of myocardial infarction, the Trial to Assess Chelation Therapy study showed that EDTA chelation decreased the likelihood of cardiovascular events, particularly in patients with diabetes. However, heavy metal levels were not measured in this study. It is clear that more research is needed in this area. There is also a need to more frequently consider and test for the possibility of cadmium and lead toxicity in patients with increased risk, such as those with hypertension, diabetes mellitus, and chronic renal disease.


Assuntos
Intoxicação por Cádmio/terapia , Doenças Cardiovasculares , Ácido Edético/farmacologia , Intoxicação por Chumbo/terapia , Intoxicação por Cádmio/etiologia , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/terapia , Quelantes/farmacologia , Terapia por Quelação/métodos , Humanos , Intoxicação por Chumbo/etiologia , Metais Pesados/toxicidade
8.
Biochem Biophys Res Commun ; 512(3): 517-523, 2019 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-30904161

RESUMO

Invasive aspergillosis (IA) is a life-threatening disease impacting immunocompromised individuals. Standard treatments of IA, including polyenes and azoles, suffer from high toxicity and emerging resistance, leading to the need to develop new antifungal agents with novel mechanisms of action. Ergosterol biosynthesis is a classic target for antifungals, and squalene synthase (SQS) catalyzes the first committed step in ergosterol biosynthesis in Aspergillus spp. making SQS of interest in the context of antifungal development. Here, we cloned, expressed, purified and characterized SQS from the pathogen Aspergillus flavus (AfSQS), confirming that it produced squalene. To identify potential leads targeting AfSQS, we tested known squalene synthase inhibitors, zaragozic acid and the phosphonosulfonate BPH-652, finding that they were potent inhibitors. We then screened a library of 744 compounds from the National Cancer Institute (NCI) Diversity Set V for inhibition activity. 20 hits were identified and IC50 values were determined using dose-response curves. 14 compounds that interfered with the assay were excluded and the remaining 6 compounds were analyzed for drug-likeness, resulting in one compound, celastrol, which had an AfSQS IC50 value of 830 nM. Enzyme inhibition kinetics revealed that celastrol binds to AfSQS in a noncompetitive manner, but did not bind covalently. Since celastrol is also known to inhibit growth of the highly virulent Aspergillus fumigatus by inhibiting flavin-dependent monooxygenase siderophore A (SidA, under iron starvation conditions), it may be a promising multi-target lead for antifungal development.


Assuntos
Antifúngicos/farmacologia , Aspergillus flavus/enzimologia , Inibidores Enzimáticos/farmacologia , Farnesil-Difosfato Farnesiltransferase/antagonistas & inibidores , Farnesil-Difosfato Farnesiltransferase/metabolismo , Aspergilose/tratamento farmacológico , Aspergilose/microbiologia , Aspergillus flavus/genética , Aspergillus flavus/metabolismo , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Clonagem Molecular , Farnesil-Difosfato Farnesiltransferase/genética , Humanos , Modelos Moleculares , Terapia de Alvo Molecular , Triterpenos Pentacíclicos , Ácidos Tricarboxílicos/farmacologia , Triterpenos/farmacologia
9.
J Am Chem Soc ; 140(24): 7568-7578, 2018 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-29787268

RESUMO

Bisphosphonates are a major class of drugs used to treat osteoporosis, Paget's disease, and cancer. They have been proposed to act by inhibiting one or more targets including protein prenylation, the epidermal growth factor receptor, or the adenine nucleotide translocase. Inhibition of the latter is due to formation in cells of analogs of ATP: the isopentenyl ester of ATP (ApppI) or an AppXp-type analog of ATP, such as AMP-clodronate (AppCCl2p). We screened both ApppI as well as AppCCl2p against a panel of 369 kinases finding potent inhibition of some tyrosine kinases by AppCCl2p, attributable to formation of a strong hydrogen bond between tyrosine and the terminal phosphonate. We then synthesized bisphosphonate preprodrugs that are converted in cells to other ATP-analogs, finding low nM kinase inhibitors that inhibited cell signaling pathways. These results help clarify our understanding of the mechanisms of action of bisphosphonates, potentially opening up new routes to the development of bone resorption, anticancer, and anti-inflammatory drug leads.


Assuntos
Trifosfato de Adenosina/análogos & derivados , Difosfonatos/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Transdução de Sinais/efeitos dos fármacos , Trifosfato de Adenosina/síntese química , Trifosfato de Adenosina/química , Trifosfato de Adenosina/farmacologia , Linhagem Celular Tumoral , Difosfonatos/síntese química , Difosfonatos/química , Humanos , Ligação de Hidrogênio , Modelos Químicos , Pró-Fármacos/síntese química , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Proteínas Tirosina Quinases/antagonistas & inibidores
10.
Inorg Chem ; 56(13): 7558-7565, 2017 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-28631925

RESUMO

We synthesized a series of polyoxometalate-bisphosphonate complexes containing MoVIO6 octahedra, zoledronate, or an N-alkyl (n-C6 or n-C8) zoledronate analogue, and in two cases, Mn as a heterometal. Mo6L2 (L = Zol, ZolC6, ZolC8) and Mo4L2Mn (L = Zol, ZolC8) were characterized by using single-crystal X-ray crystallography and/or IR spectroscopy, elemental and energy dispersive X-ray analysis and 31P NMR. We found promising activity against human nonsmall cell lung cancer (NCI-H460) cells with IC50 values for growth inhibition of ∼5 µM per bisphosphonate ligand. The effects of bisphosphonate complexation on IC50 decreased with increasing bisphosphonate chain length: C0 ≈ 6.1×, C6 ≈ 3.4×, and C8 ≈ 1.1×. We then determined the activity of one of the most potent compounds in the series, Mo4Zol2Mn(III), against SK-ES-1 sarcoma cells in a mouse xenograft system finding a ∼5× decrease in tumor volume than found with the parent compound zoledronate at the same compound dosing (5 µg/mouse). Overall, the results are of interest since we show for the first time that heteropolyoxomolybdate-bisphosphonate hybrids kill tumor cells in vitro and significantly decrease tumor growth, in vivo, opening up new possibilities for targeting both Ras as well as epidermal growth factor receptor driven cancers.


Assuntos
Antineoplásicos/farmacologia , Difosfonatos/farmacologia , Compostos Organometálicos/farmacologia , Compostos de Tungstênio/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Difosfonatos/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Modelos Moleculares , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Relação Estrutura-Atividade , Compostos de Tungstênio/química
11.
Chembiochem ; 18(11): 985-991, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28340291

RESUMO

Many organisms contain head-to-head isoprenoid synthases; we investigated three such types of enzymes from the pathogens Neisseria meningitidis, Neisseria gonorrhoeae, and Enterococcus hirae. The E. hirae enzyme was found to produce dehydrosqualene, and we solved an inhibitor-bound structure that revealed a fold similar to that of CrtM from Staphylococcus aureus. In contrast, the homologous proteins from Neisseria spp. carried out only the first half of the reaction, yielding presqualene diphosphate (PSPP). Based on product analyses, bioinformatics, and mutagenesis, we concluded that the Neisseria proteins were HpnDs (PSPP synthases). The differences in chemical reactivity to CrtM were due, at least in part, to the presence of a PSPP-stabilizing arginine in the HpnDs, decreasing the rate of dehydrosqualene biosynthesis. These results show that not only S. aureus but also other bacterial pathogens contain head-to-head prenyl synthases, although their biological functions remain to be elucidated.


Assuntos
Bactérias/enzimologia , Neopreno/metabolismo , Terpenos/metabolismo , Streptococcus faecium ATCC 9790/enzimologia , Neisseria gonorrhoeae/enzimologia , Neisseria meningitidis/enzimologia , Fosfatos de Poli-Isoprenil/metabolismo , Prenilação , Esqualeno/análogos & derivados , Esqualeno/metabolismo , Staphylococcus aureus/enzimologia
12.
ChemMedChem ; 11(20): 2311-2319, 2016 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-27578312

RESUMO

We synthesized a series of benzoic acids and phenylphosphonic acids and investigated their effects on the growth of Staphylococcus aureus and Bacillus subtilis. One of the most active compounds, 5-fluoro-2-(3-(octyloxy)benzamido)benzoic acid (7, ED50 ∼0.15 µg mL-1 ) acted synergistically with seven antibiotics known to target bacterial cell-wall biosynthesis (a fractional inhibitory concentration index (FICI) of ∼0.35, on average) but had indifferent effects in combinations with six non-cell-wall biosynthesis inhibitors (average FICI∼1.45). The most active compounds were found to inhibit two enzymes involved in isoprenoid/bacterial cell-wall biosynthesis: undecaprenyl diphosphate synthase (UPPS) and undecaprenyl diphosphate phosphatase (UPPP), but not farnesyl diphosphate synthase, and there were good correlations between bacterial cell growth inhibition, UPPS inhibition, and UPPP inhibition.


Assuntos
Alquil e Aril Transferases/antagonistas & inibidores , Antibacterianos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Benzoatos/farmacologia , Inibidores Enzimáticos/farmacologia , Compostos Organofosforados/farmacologia , Monoéster Fosfórico Hidrolases/antagonistas & inibidores , Staphylococcus aureus/efeitos dos fármacos , Alquil e Aril Transferases/metabolismo , Antibacterianos/síntese química , Antibacterianos/química , Bacillus subtilis/citologia , Bacillus subtilis/enzimologia , Bacillus subtilis/crescimento & desenvolvimento , Benzoatos/síntese química , Benzoatos/química , Parede Celular/efeitos dos fármacos , Parede Celular/metabolismo , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Compostos Organofosforados/síntese química , Compostos Organofosforados/química , Monoéster Fosfórico Hidrolases/metabolismo , Staphylococcus aureus/citologia , Staphylococcus aureus/enzimologia , Staphylococcus aureus/crescimento & desenvolvimento , Relação Estrutura-Atividade
13.
Neurotherapeutics ; 9(3): 635-8, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22454323

RESUMO

Recent work exploring the use of high-molecular weight alcohols to treat essential tremor (ET) has identified octanoic acid as a potential novel tremor-suppressing agent. We used an established harmaline-based mouse model of ET to compare tremor suppression by 1-octanol and octanoic acid. The dose-related effect on digitized motion power within the tremor bandwidth as a fraction of overall motion power was analyzed. Both 1-octanol and octanoic acid provided significant reductions in harmaline tremor. An 8-carbon alkyl alcohol and carboxylic acid each suppress tremor in a pre-clinical mouse model of ET. Further studies are warranted to determine the safety and efficacy of such agents in humans with ET.


Assuntos
Caprilatos/uso terapêutico , Estimulantes do Sistema Nervoso Central/toxicidade , Tremor Essencial/induzido quimicamente , Tremor Essencial/tratamento farmacológico , Harmalina/toxicidade , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Masculino , Camundongos , Camundongos Endogâmicos ICR
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