Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 23
Filtrar
1.
J Cardiopulm Rehabil Prev ; 44(3): 157-161, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38669342

RESUMO

PURPOSE: This is a retrospective cohort study designed to evaluate the impact of having a prior COVID-19 infection on cardiac rehabilitation (CR) completion rates and outcomes. METHODS: Participants enrolled into the CR program from June 1, 2020, to March 30, 2022. They completed both physical and mental health assessments prior to enrollment and upon completion of the program. The cohort was divided into (-) COVID and (+) COVID based on whether they self-reported a prior COVID-19 infection. Outcome measures included General Anxiety Disorder-7, Patient Health Questionnaire-9, Mental Composite Score (Short Form Health Survey-36), Physical Composite Score (Short Form Health Survey-36), and exercise capacity (reported in METs). Program completion rates and outcome measures were compared between (-) COVID and (+) COVID cohorts. RESULTS: A total of 806 participants were enrolled in the study. Program completion rates were 58.7% in the (-) COVID group and 67.2% in the (+) COVID group ( P = .072). African Americans ( P = .017), diabetics ( P = .017), and current smokers ( P = .003) were less likely to complete the program. Both (-) COVID and (+) COVID groups showed significant improvement in all outcome measures after completing the CR program. However, there was no difference in outcomes between groups. CONCLUSIONS: Having a prior COVID-19 infection did not negatively impact the mental and physical health benefits obtained by completing the CR program, regardless of the American Association of Cardiovascular and Pulmonary Rehabilitation risk category.


Assuntos
COVID-19 , Reabilitação Cardíaca , Humanos , COVID-19/reabilitação , COVID-19/epidemiologia , Reabilitação Cardíaca/métodos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , SARS-CoV-2 , Tolerância ao Exercício , Cooperação do Paciente/estatística & dados numéricos
2.
Nature ; 623(7986): 296-300, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37938704

RESUMO

Systematic studies1-4 have revealed hundreds of ultra-compact dwarf galaxies (UCDs5) in the nearby Universe. With half-light radii rh of approximately 10-100 parsecs and stellar masses M* ≈ 106-108 solar masses, UCDs are among the densest known stellar systems6. Although similar in appearance to massive globular clusters7, the detection of extended stellar envelopes4,8,9, complex star formation histories10, elevated mass-to-light ratio11,12 and supermassive black holes13-16 suggest that some UCDs are remnant nuclear star clusters17 of tidally stripped dwarf galaxies18,19, or even ancient compact galaxies20. However, only a few objects have been found in the transient stage of tidal stripping21,22, and this assumed evolutionary path19 has never been fully traced by observations. Here we show that 106 galaxies in the Virgo cluster have morphologies that are intermediate between normal, nucleated dwarf galaxies and single-component UCDs, revealing a continuum that fully maps this morphological transition and fills the 'size gap' between star clusters and galaxies. Their spatial distribution and redder colour are also consistent with stripped satellite galaxies on their first few pericentric passages around massive galaxies23. The 'ultra-diffuse' tidal features around several of these galaxies directly show how UCDs are forming through tidal stripping and that this evolutionary path can include an early phase as a nucleated ultra-diffuse galaxy24,25. These UCDs represent substantial visible fossil remnants of ancient dwarf galaxies in galaxy clusters, and more low-mass remnants probably remain to be found.

3.
Cancer Treat Res ; 184: 75-85, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36449189

RESUMO

About 1-10% of all serious adverse drug reactions (sADRs) are reported to the Food and Drug Administration (FDA) ( Moore T, Bennett C. Underreporting of Hemorrhagic and Thrombotic Complications of Pharmaceuticals to the U.S. Food and Drug Administration: Empirical Findings for Warfarin, Clopidogrel, Ticlopidine, and Thalidomide from the Southern Network on Adverse Reactions (SONAR). Semin Thromb Hemost. 2012;38(08):905-907. https://doi.org/10.1055/s-0032-1328890 ). Prevailing opinion suggests that low reporting rates reflect time constraints.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Imunoterapia , Estados Unidos , Humanos , Clopidogrel , Talidomida , Ticlopidina
5.
EClinicalMedicine ; 31: 100693, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33554084

RESUMO

BACKGROUND: Adverse drug/device reactions (ADRs) can result in severe patient harm. We define very serious ADRs as being associated with severe toxicity, as measured on the Common Toxicity Criteria Adverse Events (CTCAE)) scale, following use of drugs or devices with large sales, large financial settlements, and large numbers of injured persons. We report on impacts on patients, clinicians, and manufacturers following very serious ADR reporting. METHODS: We reviewed clinician identified very serious ADRs published between 1997 and 2019. Drugs and devices associated with reports of very serious ADRs were identified. Included drugs or devices had market removal discussed at Food and Drug Advisory (FDA) Advisory Committee meetings, were published by clinicians, had sales > $1 billion, were associated with CTCAE Grade 4 or 5 toxicity effects, and had either >$1 billion in settlements or >1,000 injured patients. Data sources included journals, Congressional transcripts, and news reports. We reviewed data on: 1) timing of ADR reports, Boxed warnings, and product withdrawals, and 2) patient, clinician, and manufacturer impacts. Binomial analysis was used to compare sales pre- and post-FDA Advisory Committee meetings. FINDINGS: Twenty very serious ADRs involved fifteen drugs and one device. Legal settlements totaled $38.4 billion for 753,900 injured persons. Eleven of 18 clinicians (61%) reported harms, including verbal threats from manufacturer (five) and loss of a faculty position (one). Annual sales decreased 94% from $29.1 billion pre-FDA meeting to $4.9 billion afterwards (p<0.0018). Manufacturers of four drugs paid $1.7 billion total in criminal fines for failing to inform the FDA and physicians about very serious ADRs. Following FDA approval, the median time to ADR reporting was 7.5 years (Interquartile range 3,13 years). Twelve drugs received Box warnings and one drug received a warning (median, 7.5 years following ADR reporting (IQR 5,11 years). Six drugs and 1 device were withdrawn from marketing (median, 5 years after ADR reporting (IQR 4,6 years)). INTERPRETATION: Because very serious ADRs impacts are so large, policy makers should consider developing independently funded pharmacovigilance centers of excellence to assist with clinician investigations. FUNDING: This work received support from the National Cancer Institute (1R01 CA102713 (CLB), https://www.nih.gov/about-nih/what-we-do/nih-almanac/national-cancer-institute-nci; and two Pilot Project grants from the American Cancer Society's Institutional Grant Award to the University of South Carolina (IRG-13-043-01) https://www.cancer.org/ (SH; BS).

6.
Artigo em Inglês | MEDLINE | ID: mdl-33455912

RESUMO

OBJECTIVE: This study aimed to assess if there is secondary care medical inertia towards coeliac disease (CD). DESIGN: Group (1): Time from primary care presentation to diagnostic endoscopy was quantified in 151 adult patients with a positive endomysial antibody test and compared with 92 adult patients with histologically proven inflammatory bowel disease (IBD). Group (2): Across four hospitals, duodenal biopsy reports for suspected CD were reviewed (n=1423). Group (3): Clinical complexity was compared between known CD (n=102) and IBD (n=99) patients at their respective follow-up clinic appointments. Group (4): 50 gastroenterologists were questioned about their perspective on CD and IBD. RESULTS: Group (1): Suspected coeliac patients waited significantly longer for diagnostic endoscopy following referral (48.5 (28-89) days) than suspected patients with IBD (34.5 (18-70) days; p=0.003). Group (2): 1423 patients underwent diagnostic endoscopy for possible CD, with only 40.0% meeting guidelines to take four biopsies. Increased diagnosis of CD occurred if guidelines were followed (10.1% vs 4.6% p<0.0001). 12.4% of newly diagnosed CD patients had at least one non-diagnostic gastroscopy in the 5 years prior to diagnosis. Group (4): 32.0% of gastroenterologists failed to identify that CD has greater prevalence in adults than IBD. Moreover, 36.0% of gastroenterologists felt that doctors were not required for the management of CD. CONCLUSION: Prolonged waiting times for endoscopy and inadequacies in biopsy technique were demonstrated suggesting medical inertia towards CD. However, this has to be balanced against rationalising care accordingly. A Coeliac UK National Patient Charter may standardise care across the UK.


Assuntos
Doença Celíaca , Gastroenterologistas , Adulto , Biópsia , Doença Celíaca/diagnóstico , Humanos , Atenção Secundária à Saúde , Reino Unido/epidemiologia
7.
Ultrasound J ; 12(1): 52, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33284363

RESUMO

Undifferentiated abdominal pain is a common presentation often requiring immediate medical or surgical intervention. Providing an accurate diagnosis involves a detailed patient history and thorough physical exam. Point of care ultrasound is gaining acceptance as a rapid diagnostic tool that can be used to accurately detect life-threatening conditions while potentially avoiding unnecessary radiation exposure and facilitating rapid treatment. Detection of pneumoperitoneum with point-of-care ultrasound is a simple procedure that relies heavily on the experience of the investigating practitioner. Standard technique involves placing a high-frequency linear-array transducer in the right upper quadrant, where abdominal free air is most likely to accumulate. Detection of the 'gut point', which is the transition of abdominal wall sliding to lack thereof in a single image, is the pathognomonic finding of pneumoperitoneum. If visualization is difficult, moving the patient to the left lateral decubitus position or using the scissors technique can provide additional image views. This representative case report and review highlights the use of abdominal POCUS for the diagnosis of pneumoperitoneum. Ultrasound should continue to be explored by clinicians to narrow the differential diagnosis of acute abdominal pain.

8.
Lancet Oncol ; 21(12): e575-e588, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33271114

RESUMO

The EU, the USA, and Japan account for the majority of biological pharmacotherapy use worldwide. Biosimilar regulatory approval pathways were authorised in the EU (2006), in Japan (2009), and in the USA (2015), to facilitate approval of biological drugs that are highly similar to reference products and to encourage market competition. Between 2007 and 2020, 33 biosimilars for oncology were approved by the European Medicines Agency (EMA), 16 by the US Food and Drug Administration (FDA), and ten by the Japan Pharmaceuticals and Medical Devices Agency (PMDA). Some of these approved applications were initially rejected because of manufacturing concerns (four of 36 [11%] with the EMA, seven of 16 [44%] with the FDA, none of ten for the PMDA). Median times from initial regulatory submission before approval of oncology biosimilars were 1·5 years (EMA), 1·3 years (FDA), and 0·9 years (PMDA). Pharmacists can substitute biosimilars for reference biologics in some EU countries, but not in the USA or Japan. US regulation prohibits substitution, unless the biosimilar has been approved as interchangeable, a designation not yet achieved for any biosimilar in the USA. Japan does not permit biosimilar substitution, as prescribers must include the product name on each prescription and that specific product must be given to the patient. Policy Reviews published in 2014 and 2016 in The Lancet Oncology focused on premarket and postmarket policies for oncology biosimilars before most of these drugs received regulatory approval. In this Policy Review from the Southern Network on Adverse Reactions, we identify factors preventing the effective launch of oncology biosimilars. Introduction to the market has been more challenging with therapeutic than for supportive care oncology biosimilars. Addressing region-specific competition barriers and educational needs would improve the regulatory approval process and market launches for these biologics, therefore expanding patient access to these products in the EU, the USA, and Japan.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Medicamentos Biossimilares/uso terapêutico , Aprovação de Drogas , Hematínicos/uso terapêutico , Neoplasias/tratamento farmacológico , United States Food and Drug Administration , Antineoplásicos Imunológicos/efeitos adversos , Bevacizumab/uso terapêutico , Medicamentos Biossimilares/efeitos adversos , Aprovação de Drogas/legislação & jurisprudência , Substituição de Medicamentos , Eritropoetina/análogos & derivados , Eritropoetina/uso terapêutico , Europa (Continente) , Filgrastim/uso terapêutico , Hematínicos/efeitos adversos , Humanos , Japão , Neoplasias/imunologia , Neoplasias/mortalidade , Segurança do Paciente , Formulação de Políticas , Polietilenoglicóis/uso terapêutico , Medição de Risco , Rituximab/uso terapêutico , Trastuzumab/uso terapêutico , Resultado do Tratamento , Estados Unidos , United States Food and Drug Administration/legislação & jurisprudência
9.
Apoptosis ; 25(3-4): 217-232, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32006189

RESUMO

Glioblastoma is the most malignant and prevalent brain tumor in adults. It can grow and spread quickly causing harm to the brain health. One of the major challenges in treatment of glioblastoma is drug resistance. Use of synergistic combination of two drugs with different anti-tumor effects is nowadays highly considered in the development of effective therapeutic strategies for many malignancies. In the present study, we showed synergistic therapeutic efficacies of two chemical compounds, N-(4-hydroxyphenyl) retinamide (4HPR) and suberoylanilide hydroxamic acid (SAHA), for significant reduction in cell viability of rat C6 and human T98G glioblastoma cells. These compounds (4HPR and SAHA) were used alone or in synergistic combination for evaluating their various anti-tumor effects. The results showed that combination of 4HPR and SAHA significantly induced morphological and molecular features of astrocytic differentiation in C6 and T98G glioblastoma cells. Combination of 4HPR and SAHA proved to be an important therapeutic strategy for inhibiting cell growth and inducing differentiation in glioblastoma cells. Furthermore, combination of the two drugs showed more efficacies than either dug alone in reducing in vitro cell invasion (transwell assay), cell migration (wound healing assay), and angiogenesis (tube formation assay) due to down regulation of the molecules involved in these processes. The ultimate of goal of using this combination of drugs was induction of apoptosis. The results showed that these drugs in synergistic combination contributed highly to increases in morphological and molecular features of apoptotic death in the tumor cells. The results from molecular studies indicated that cell death occurred via activation of the extrinsic and intrinsic pathways of apoptosis in both C6 and T98G cells. The drugs in combination also contributed to dramatic inhibition of histone deacetylase 1, an important epigenetic player in promoting growth in glioblastoma cells. This novel combination of drugs should also be considered as a promising therapeutic strategy for the treatment of glioblastoma in vivo.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Fenretinida/farmacologia , Glioblastoma/patologia , Vorinostat/farmacologia , Proteínas Angiogênicas/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Glioblastoma/tratamento farmacológico , Histona Desacetilase 1/antagonistas & inibidores , Humanos , Ratos
10.
PLoS One ; 14(7): e0219521, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31365527

RESUMO

Oncology-associated adverse drug/device reactions can be fatal. Some clinicians who treat single patients with severe oncology-associated toxicities have researched case series and published this information. We investigated motivations and experiences of select individuals leading such efforts. Clinicians treating individual patients who developed oncology-associated serious adverse drug events were asked to participate. Inclusion criteria included having index patient information, reporting case series, and being collaborative with investigators from two National Institutes of Health funded pharmacovigilance networks. Thirty-minute interviews addressed investigational motivation, feedback from pharmaceutical manufacturers, FDA personnel, and academic leadership, and recommendations for improving pharmacovigilance. Responses were analyzed using constant comparative methods of qualitative analysis. Overall, 18 clinicians met inclusion criteria and 14 interviewees are included. Primary motivations were scientific curiosity, expressed by six clinicians. A less common theme was public health related (three clinicians). Six clinicians received feedback characterized as supportive from academic leaders, while four clinicians received feedback characterized as negative. Three clinicians reported that following the case series publication they were invited to speak at academic institutions worldwide. Responses from pharmaceutical manufacturers were characterized as negative by 12 clinicians. One clinician's wife called the post-reporting time the "Maalox month," while another clinician reported that the manufacturer collaboratively offered to identify additional cases of the toxicity. Responses from FDA employees were characterized as collaborative for two clinicians, neutral for five clinicians, unresponsive for negative by six clinicians. Three clinicians endorsed developing improved reporting mechanisms for individual physicians, while 11 clinicians endorsed safety activities that should be undertaken by persons other than a motivated clinician who personally treats a patient with a severe adverse drug/device reaction. Our study provides some of the first reports of clinician motivations and experiences with reporting serious or potentially fatal oncology-associated adverse drug or device reactions. Overall, it appears that negative feedback from pharmaceutical manufacturers and mixed feedback from the academic community and/or the FDA were reported. Big data, registries, Data Safety Monitoring Boards, and pharmacogenetic studies may facilitate improved pharmacovigilance efforts for oncology-associated adverse drug reactions. These initiatives overcome concerns related to complacency, indifference, ignorance, and system-level problems as barriers to documenting and reporting adverse drug events- barriers that have been previously reported for clinician reporting of serious adverse drug reactions.


Assuntos
Antineoplásicos/efeitos adversos , Editoração , Sistemas de Notificação de Reações Adversas a Medicamentos , Humanos , Entrevistas como Assunto , Oncologia , Publicações Periódicas como Assunto , Farmacovigilância , Estados Unidos , United States Food and Drug Administration
11.
Neurochem Res ; 44(7): 1715-1725, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31011879

RESUMO

This study investigated the efficacy of quercetin (QCT) in combination with sodium butyrate (NaB) in enhancing apoptosis in rat C6 and human T98G glioblastoma cells though blockage of autophagy under nutrient-starvation. The most synergistic doses of the drugs were determined to be 25 µM QCT and 1 mM NaB in both cell lines. After QCT and QCT + NaB treatments, autophagy quantification with acridine orange staining showed a drastic decrease in protective autophagy in the cells under nutrient-starvation. Decrease in autophagy was correlated with decreases in expression of Beclin-1 and LC3B II. Combination treatment increased the morphological signs of apoptosis including membrane blebbing, nuclear fragmentation, and chromatin condensation. Annexin V staining was also performed for detection and quantification of increases in apoptosis. Western blotting results showed that combination of QCT and NaB increased apoptosis by decreasing anti-apoptotic Bcl-2 and increasing pro-apoptotic Bax, decreasing survivin, activating caspase-3, and degrading poly (ADP-ribose) polymerase (PARP). This study demonstrated the therapeutic potentials of a novel combination therapy in inhibiting protective autophagy to enhance apoptosis in rat C6 and human T98G glioblastoma cells.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Ácido Butírico/farmacologia , Quercetina/farmacologia , Animais , Proteína Beclina-1/metabolismo , Caspase 3/metabolismo , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Glioblastoma/patologia , Inibidores de Histona Desacetilases/farmacologia , Humanos , Proteínas Associadas aos Microtúbulos/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Proteína X Associada a bcl-2/metabolismo
12.
Neurotoxicology ; 73: 258-264, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30980846

RESUMO

Traditional approaches (e.g., neurobehavior, neuropathology) can detect alterations in apical endpoints indicative of developmental neurotoxicity (DNT). However, there is an increasing desire to understand mode-of-action (MOA) for DNT effects; thus, this short communication describes initial work on a neuronal differentiation assay. Basically, our laboratory used the human NT2/D1 cell line to develop an assay to evaluate toxicants for effects on all-trans retinoic acid (RA)-induced neuronal differentiation. Based on literature reports, we selected a neuronal protein, neuronal class III ß-tubulin (ß3-tubulin), as a marker of differentiation. For this assay, cultured RA-treated NT2 cells were trypsinized to individual cells, methanol fixed, and labeled with a ß3-tubulin specific monoclonal antibody (TUJ1). Characterization studies using 100,000 cells/sample showed that NT2 cells had appreciable expression of ß3-tubulin starting around day 7 of the differentiation process with a peak expression noted around day 12. Methylmercury, 22(R)-hydroxycholesterol, N-(4-hydroxyphenol)retinamide (4HPR), and 9-cis retinoic acid were selected as initial test compounds. Of these, only 9-cis RA, which is known to affect the RA pathway, was positive for specific impacts on differentiation. These results demonstrate the feasibility of using a flow cytometry method targeting specific cellular biomarkers for evaluating effects on neuronal differentiation. Additional assays are needed to detect compounds targeting other (non-RA) neuronal differentiation pathways. Ultimately, a battery of in vitro assays would be needed to evaluate the potential MOAs involved in altered neuronal differentiation.


Assuntos
Alitretinoína/toxicidade , Neurogênese/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Testes de Toxicidade , Tretinoína/farmacologia , Biomarcadores/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Fenretinida/toxicidade , Citometria de Fluxo , Humanos , Hidroxicolesteróis/toxicidade , Compostos de Metilmercúrio/toxicidade , Neurônios/metabolismo , Neurônios/patologia , Medição de Risco , Transdução de Sinais , Fatores de Tempo , Tubulina (Proteína)/metabolismo
13.
Biomed Instrum Technol ; 53(2): 102-109, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30901247

RESUMO

Electrosurgical units (ESUs) developed by different manufacturers use varying terminology and icons to label the same components, which can result in confusion among users and the potential for erroneous ESU configuration. The objective of the current study was to identify nurse-preferred terms and icons for labeling ESU components. A total of 165 operating room (OR) nurses from Veterans Health Administration facilities across the United States were surveyed regarding terms and icons found on 25 ESU models. The results showed that 81% of OR nurses preferred ESUs that included both a term and an icon for labeling each component. In addition, greater consensus existed among OR nurses regarding preferred terms, rather than preferred icons, for representing each component. These findings on OR nurses' preferred terms and icons can be leveraged to improve ESU labeling practices and inform the development of a standardized, user-centered set of labels for ESU components.


Assuntos
Eletrocirurgia , Enfermeiras e Enfermeiros , Inquéritos e Questionários
14.
Artigo em Inglês | MEDLINE | ID: mdl-33869674

RESUMO

Individuals having sustained traumatic spinal cord injury (TSCI) in the United States are living longer as compared to historical trends, thanks to an ever-evolving understanding of the nature of this injury. Despite this, multiple barriers to care for TSCI patients remain including variations in government-issued veteran insurance, privatized insurance, and among uninsured individuals. The United States alone experiences 12,000 new TSCI cases every year, many of these are found to occur in a growing proportion of elderly individuals. It is crucial to understand both the short-term direct costs as wells as the long-term rehabilitation costs required by these TSCI patients. The lifetime financial burden for those having sustained a TSCI can be immense for patients, insurance companies, and hospital systems alike. Among those with TSCI, re-hospitalization rates are high, leading to increased healthcare resource utilization within this specific patient population. Costs can quickly balloon into hundreds of thousands of dollars and cause a profound financial burden for these patients. This review article seeks to communicate an understanding of the current financial landscape surrounding TSCI patients. The authors will also examine the costs of acute emergency room surgical care such as American spinal injury association grade, hospital length of stay, as well as the timing delay between injury and surgical decompression. Long-term costs associated with TSCI such as rehabilitation, care of secondary comorbidities, and post-injury employment prospects will be examined as well. These costs will be framed from the patient's perspective as well as from both the hospital and insurance company's perspectives. It is hoped a complete understanding as to what makes TSCI such a medically and financially burdensome injury will allow for improved healthcare resource utilization in this population.

15.
Apoptosis ; 23(11-12): 563-575, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30171377

RESUMO

Autophagy is an evolutionarily conserved catabolic process that plays an essential role in maintaining cellular homeostasis by degrading unneeded cell components. When exposed to hostile environments, such as hypoxia or nutrient starvation, cells hyperactivate autophagy in an effort to maintain their longevity. In densely packed solid tumors, such as glioblastoma, autophagy has been found to run rampant due to a lack of oxygen and nutrients. In recent years, targeting autophagy as a way to strengthen current glioblastoma treatment has shown promising results. However, that protective autophagy inhibition or autophagy overactivation is more beneficial, is still being debated. Protective autophagy inhibition would lower a cell's previously activated defense mechanism, thereby increasing its sensitivity to treatment. Autophagy overactivation would cause cell death through lysosomal overactivation, thus introducing another cell death pathway in addition to apoptosis. Both methods have been proven effective in the treatment of solid tumors. This systematic review article highlights scenarios where both autophagy inhibition and activation have proven effective in combating chemoresistance and radioresistance in glioblastoma, and how autophagy may be best utilized for glioblastoma therapy in clinical settings.


Assuntos
Antineoplásicos/uso terapêutico , Autofagia , Neoplasias Encefálicas/terapia , Resistencia a Medicamentos Antineoplásicos , Glioblastoma/terapia , Antineoplásicos/farmacologia , Autofagossomos/metabolismo , Autofagia/efeitos dos fármacos , Autofagia/efeitos da radiação , Neoplasias Encefálicas/patologia , Morte Celular/efeitos dos fármacos , Morte Celular/efeitos da radiação , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos da radiação , Glioblastoma/patologia , Humanos , Radiossensibilizantes/farmacologia , Radiossensibilizantes/uso terapêutico , Temozolomida/farmacologia , Temozolomida/uso terapêutico
16.
AORN J ; 107(1): 72-82, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29341077

RESUMO

Medical device use errors, such as instrument connection errors made with electrosurgical units (ESUs), can lead to adverse events. Current device acquisition processes at health care facilities do not typically include a proactive evaluation of use-error risk before device purchase. We conducted an evaluation to identify ESU user interface design features that can help prevent or mitigate instrument connection errors during clinical care. Thirty-six current ESU users participated in the evaluation. We used a randomized crossover design in which each participant used two ESU models in a simulated OR scenario. We compared participants' instrument connection accuracy, efficiency, and subjective feedback regarding the user interface design across the two ESU models. Overall, we found that the ESU model that incorporated more user interface design principles resulted in better performance and increased acceptance from users. Based on the results, we designed a decision-support tool to assess the risk of instrument connection errors before ESU purchase.


Assuntos
Eletrocirurgia/efeitos adversos , Eletrocirurgia/instrumentação , Desenho de Equipamento , Equipamentos e Provisões/efeitos adversos , Erros Médicos , Humanos , Competência Profissional
17.
Science ; 357(6356): 1138-1142, 2017 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-28912242

RESUMO

Three-dimensional (3D) microstructures created by microfabrication and additive manufacturing have demonstrated value across a number of fields, ranging from biomedicine to microelectronics. However, the techniques used to create these devices each have their own characteristic set of advantages and limitations with regards to resolution, material compatibility, and geometrical constraints that determine the types of microstructures that can be formed. We describe a microfabrication method, termed StampEd Assembly of polymer Layers (SEAL), and create injectable pulsatile drug-delivery microparticles, pH sensors, and 3D microfluidic devices that we could not produce using traditional 3D printing. SEAL allows us to generate microstructures with complex geometry at high resolution, produce fully enclosed internal cavities containing a solid or liquid, and use potentially any thermoplastic material without processing additives.

18.
J Safety Res ; 60: 125-136, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28160807

RESUMO

PROBLEM: Roadway incidents are the leading cause of work-related death in the United States. METHODS: The objective of this research was to evaluate whether two types of feedback from a commercially available in-vehicle monitoring system (IVMS) would reduce the incidence of risky driving behaviors in drivers from two companies. IVMS were installed in 315 vehicles representing the industries of local truck transportation and oil and gas support operations, and data were collected over an approximate two-year period in intervention and control groups. In one period, intervention group drivers were given feedback from in-cab warning lights from an IVMS that indicated occurrence of harsh vehicle maneuvers. In another period, intervention group drivers viewed video recordings of their risky driving behaviors with supervisors, and were coached by supervisors on safe driving practices. RESULTS: Risky driving behaviors declined significantly more during the period with coaching plus instant feedback with lights in comparison to the period with lights-only feedback (ORadj=0.61 95% CI 0.43-0.86; Holm-adjusted p=0.035) and the control group (ORadj=0.52 95% CI 0.33-0.82; Holm-adjusted p=0.032). Lights-only feedback was not found to be significantly different than the control group's decline from baseline (ORadj=0.86 95% CI 0.51-1.43; Holm-adjusted p>0.05). CONCLUSIONS: The largest decline in the rate of risky driving behaviors occurred when feedback included both supervisory coaching and lights. PRACTICAL APPLICATIONS: Supervisory coaching is an effective form of feedback to improve driving habits in the workplace. The potential advantages and limitations of this IVMS-based intervention program are discussed.


Assuntos
Acidentes de Trabalho/prevenção & controle , Acidentes de Trânsito/prevenção & controle , Veículos Automotores , Comportamento de Redução do Risco , Gestão da Segurança/métodos , Tutoria/métodos , Assunção de Riscos
19.
J Safety Res ; 59: 97-104, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27847004

RESUMO

INTRODUCTION: The effects of training content consisting of examples and/or non-examples was studied on the acquisition of safety-related skills. METHOD: Participants (N=160) were randomly assigned to first receive computer-based training on office ergonomics that included either no examples of safe or at-risk postures, safe examples only, at-risk examples only, or both safe and at-risk examples. Participants then attempted to classify as safe or at-risk various postures depicted in short video clips and demonstrate with their own posture the range of safe postures. RESULTS: Groups that were trained with both safe and at-risk examples showed greater classification accuracy and less error in their demonstration of safe postures. Training with only safe or at-risk examples resulted in a moderate amount of error and a consistent underestimation of risk. CONCLUSION: Training content consisting of both examples and non-examples improved acquisition of safety-related skills. PRACTICAL APPLICATIONS: The strategic selection of training content may improve identification of risks and safe work practices.


Assuntos
Ergonomia , Disseminação de Informação/métodos , Perna (Membro) , Postura , Segurança/estatística & dados numéricos , Humanos , Distribuição Aleatória
20.
J Appl Behav Anal ; 47(1): 83-100, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24127380

RESUMO

A simulation study was conducted to provide a more thorough account of measurement error associated with interval sampling methods. A computer program simulated the application of momentary time sampling, partial-interval recording, and whole-interval recording methods on target events randomly distributed across an observation period. The simulation yielded measures of error for multiple combinations of observation period, interval duration, event duration, and cumulative event duration. The simulations were conducted up to 100 times to yield measures of error variability. Although the present simulation confirmed some previously reported characteristics of interval sampling methods, it also revealed many new findings that pertain to each method's inherent strengths and weaknesses. The analysis and resulting error tables can help guide the selection of the most appropriate sampling method for observation-based behavioral assessments.


Assuntos
Comportamento , Simulação por Computador , Modelos Teóricos , Fatores de Tempo , Humanos , Observação
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...