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1.
Development ; 150(2)2023 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-36628974

RESUMEN

Src kinases are important regulators of cell adhesion. Here, we have explored the function of Src42A in junction remodelling during Drosophila gastrulation. Src42A is required for tyrosine phosphorylation at bicellular (bAJ) and tricellular (tAJ) junctions in germband cells, and localizes to hotspots of mechanical tension. The role of Src42A was investigated using maternal RNAi and CRISPR-Cas9-induced germline mosaics. We find that, during cell intercalations, Src42A is required for the contraction of junctions at anterior-posterior cell interfaces. The planar polarity of E-cadherin is compromised and E-cadherin accumulates at tricellular junctions after Src42A knockdown. Furthermore, we show that Src42A acts in concert with Abl kinase, which has also been implicated in cell intercalations. Our data suggest that Src42A is involved in two related processes: in addition to establishing tension generated by the planar polarity of MyoII, it may also act as a signalling factor at tAJs to control E-cadherin residence time.


Asunto(s)
Proteínas de Drosophila , Drosophila , Animales , Uniones Adherentes/metabolismo , Cadherinas/genética , Cadherinas/metabolismo , Drosophila/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Uniones Intercelulares/metabolismo , Proteínas Proto-Oncogénicas pp60(c-src)/genética , Proteínas Proto-Oncogénicas pp60(c-src)/metabolismo , Familia-src Quinasas/genética , Familia-src Quinasas/metabolismo
2.
Development ; 148(18)2021 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-34409448

RESUMEN

Light-sheet or selective plane illumination microscopy (SPIM) is ideally suited for in toto imaging of living specimens at high temporal-spatial resolution. In SPIM, the light scattering that occurs during imaging of opaque specimens brings about limitations in terms of resolution and the imaging field of view. To ameliorate this shortcoming, the illumination beam can be engineered into a highly confined light sheet over a large field of view and multi-view imaging can be performed by applying multiple lenses combined with mechanical rotation of the sample. Here, we present a Multiview tiling SPIM (MT-SPIM) that combines the Multi-view SPIM (M-SPIM) with a confined, multi-tiled light sheet. The MT-SPIM provides high-resolution, robust and rotation-free imaging of living specimens. We applied the MT-SPIM to image nuclei and Myosin II from the cellular to subcellular spatial scale in early Drosophila embryogenesis. We show that the MT-SPIM improves the axial-resolution relative to the conventional M-SPIM by a factor of two. We further demonstrate that this axial resolution enhancement improves the automated segmentation of Myosin II distribution and of nuclear volumes and shapes.


Asunto(s)
Imagenología Tridimensional/métodos , Microscopía Fluorescente/métodos , Animales , Drosophila/metabolismo , Drosophila/fisiología , Embrión no Mamífero/metabolismo , Embrión no Mamífero/fisiología , Desarrollo Embrionario/fisiología , Miosina Tipo II/metabolismo
3.
Clin Transplant ; 38(3): e15286, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38504561

RESUMEN

BACKGROUND: The use of protocol liver biopsy to monitor liver allograft status remains controversial. There is limited data from modern transplantation populations that includes protocol biopsies to evaluate its value in predicting clinical outcomes. METHODS: All protocol liver biopsies were identified from 875 patients who underwent liver transplantation at Helsinki University Hospital between 2000 and 2019. Each histologic component was analyzed for its ability to predict long-term outcomes, especially graft survival. We determined the frequency of significant biopsy findings based on the Banff working group definition. Liver function tests (LFTs) and clinical markers were evaluated for their ability to predict significant biopsy findings. RESULTS: In total, 867 protocol liver biopsies were analyzed. Significant findings were identified in 20.1% of the biopsies. In the first protocol biopsy, steatohepatitis (hazard ratio [HR] 3.504, p = .03) and moderate or severe congestion (HR 3.338, p = .04) predicted graft loss. The presence of cholangitis (HR 2.563, p = .04), necrosis (HR 7.635, p < .001), mild congestion (HR 4.291, p = .009), and significant biopsy finding (HR 2.540, p = .02) predicted inferior death-censored graft survival. While the degree of elevation of LFTs was positively associated with significant biopsy findings, the discrimination was poor (AUC .572-.622). Combined LFTs and clinical risk factors remained suboptimal for discriminating significant biopsy findings (AUC .696). CONCLUSIONS: Our findings support the use of protocol liver biopsies after liver transplantation since they frequently revealed changes associated with long-term outcomes, even when LFTs were normal.


Asunto(s)
Trasplante de Hígado , Humanos , Trasplante de Hígado/efectos adversos , Supervivencia de Injerto , Trasplante Homólogo , Hígado/patología , Biopsia , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/etiología , Rechazo de Injerto/patología
4.
BMC Med Educ ; 24(1): 285, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38486216

RESUMEN

BACKGROUND: Interprofessional collaboration is essential to maintain high-quality care in long-term care and geriatric rehabilitation. However, little is known regarding perceived factors influencing interprofessional collaboration by people involved in care. This concerns both long-term care and geriatric rehabilitation. Moreover, knowledge of using patient outcome measures to enhance interprofessional collaboration during multidisciplinary team meetings is insufficient. This study examined the perceived facilitators of and barriers to interprofessional collaboration in general and during multidisciplinary team meetings, specifically according to healthcare professionals, patients, and informal caregivers. Differences between long-term care and geriatric rehabilitation were also investigated. Finally, it was examined which patient outcome measures were used in multidisciplinary team meetings. METHODS: A constructivist qualitative study using 10 focus groups and 18 semi-structured interviews with 14 patients, 13 informal caregivers,10 managers, and 22 healthcare professionals from eight Dutch long-term care and geriatric rehabilitation facilities. A combined inductive and deductive approach to a thematic analysis was performed. RESULTS: The perceived influencing factors of interprofessional collaboration were classified into two general themes: (1) 'Involvement of patient, informal caregiver, and healthcare professional', categorised into: 'participation of patients and informal caregivers', 'behaviour and attitude of team members', 'expectations of team members towards each other', and 'exchange of information, knowledge, and reciprocity in communication'; and (2) 'A systematic approach to providing care for older people', consisting of: 'coordination of team procedures', and 'coordination of organisational procedures'. Also, one theme for multidisciplinary team meetings was identified: 'Organised participation of patient, informal caregiver, and healthcare professional in multidisciplinary team meeting, categorised into: 'team procedures', 'working systematically', and 'participation in multidisciplinary team meetings. Standardised patient outcome measures were scarcely used in multidisciplinary team meetings. CONCLUSION: People involved in long-term care and geriatric rehabilitation indicated that, apart from working systematically, being involved in care and multidisciplinary team meetings are essential factors for interprofessional collaboration. These factors must be taken into consideration to provide valuable, high-quality care to older people residing in long-term care and geriatric. TRIAL REGISTRATION: Not applicable.


Asunto(s)
Comunicación , Cuidados a Largo Plazo , Humanos , Anciano , Investigación Cualitativa , Grupos Focales , Grupo de Atención al Paciente
5.
Endoscopy ; 55(2): 150-157, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-35672016

RESUMEN

BACKGROUND: Digital single-operator pancreatoscopy (DSOP)-guided lithotripsy is a novel treatment modality for pancreatic endotherapy, with demonstrated technical success in retrospective series of between 88 % and 100 %. The aim of this prospective multicenter trial was to systematically evaluate DSOP in patients with chronic pancreatitis and symptomatic pancreatic duct stones. METHODS: Patients with symptomatic chronic pancreatitis and three or fewer stones ≥ 5mm in the main pancreatic duct (MPD) of the pancreatic head or body were included. The primary end point was complete stone clearance (CSC) in three or fewer treatment sessions with DSOP. Current guidelines recommend extracorporeal shock wave lithotripsy (ESWL) for MPD stones > 5 mm. A performance goal was developed to show that the CSC rate of MPD stones using DSOP was above what has been previously reported for ESWL. Secondary end points were pain relief measured with the Izbicki pain score (IPS), number of interventions, and serious adverse events (SAEs). RESULTS: 40 chronic pancreatitis patients were included. CSC was achieved in 90 % of patients (36/40) on intention-to-treat analysis, after a mean (SD) of 1.36 (0.64) interventions (53 procedures in total). The mean (SD) baseline IPS decreased from 55.3 (46.2) to 10.9 (18.3). Overall pain relief was achieved in 82.4 % (28/34) after 6 months of follow-up, with complete pain relief in 61.8 % (21/34) and partial pain relief in 20.6 % (7/34). SAEs occurred in 12.5 % of patients (5/40), with all treated conservatively. CONCLUSION: DSOP-guided endotherapy is effective and safe for the treatment of symptomatic MPD stones in highly selected patients with chronic pancreatitis. It significantly reduces pain and could be considered as an alternative to standard ERCP techniques for MPD stone treatment in these patients.


Asunto(s)
Cálculos , Litotricia , Enfermedades Pancreáticas , Pancreatitis Crónica , Humanos , Estudios Retrospectivos , Estudios Prospectivos , Resultado del Tratamiento , Enfermedades Pancreáticas/terapia , Enfermedades Pancreáticas/complicaciones , Pancreatitis Crónica/etiología , Cálculos/complicaciones , Litotricia/efectos adversos , Litotricia/métodos , Conductos Pancreáticos/diagnóstico por imagen , Dolor/etiología , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Colangiopancreatografia Retrógrada Endoscópica/métodos
6.
Eur J Public Health ; 33(3): 448-454, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-37164632

RESUMEN

BACKGROUND: In Europe, more than 15 million people live with heart failure (HF). It imposes an enormous social, organizational and economic burden. As a reaction to impending impact on healthcare provision, different country-specific structures for HF-care have been established. The aim of this report is to provide an overview and compare the HF-care approaches of Germany, Ireland, the Netherlands and the UK, and to open the possibility of learning from each other's experience. METHODS: A mixed methods approach was implemented that included a literature analysis, interviews and questionnaires with HF-patients and caregivers, and expert interviews with representatives from healthcare, health service research and medical informatics. RESULTS: The models of HF-care in all countries analyzed are based on the European Society of Cardiology guidelines for diagnosis and treatment of HF. Even though the HF-models differed in design and implementation in practice, key challenges were similar: (i) unequal distribution of care between urban and rural areas, (ii) long waiting times, (iii) unequal access to and provision of healthcare services, (iv) information and communication gaps and (v) inadequate implementation and financing of digital applications. CONCLUSION: Although promising approaches exist to structure and improve HF-care, across the four countries, implementation was reluctant to embrace novel methods. A lack of financial resources and insufficient digitalization making it difficult to adopt new concepts. Integration of HF-nurses seems to be an effective way of improving current models of HF-care. Digital solutions offer further opportunities to overcome communication and coordination gaps and to strengthen self-management skills.


Asunto(s)
Atención a la Salud , Insuficiencia Cardíaca , Humanos , Europa (Continente) , Alemania , Insuficiencia Cardíaca/terapia , Países Bajos
7.
Proc Natl Acad Sci U S A ; 117(22): 12155-12163, 2020 06 02.
Artículo en Inglés | MEDLINE | ID: mdl-32430325

RESUMEN

Microtubule polarity in axons and dendrites defines the direction of intracellular transport in neurons. Axons contain arrays of uniformly polarized microtubules with plus-ends facing the tips of the processes (plus-end-out), while dendrites contain microtubules with a minus-end-out orientation. It has been shown that cytoplasmic dynein, targeted to cortical actin, removes minus-end-out microtubules from axons. Here we have identified Spindly, a protein known for recruitment of dynein to kinetochores in mitosis, as a key factor required for dynein-dependent microtubule sorting in axons of Drosophila neurons. Depletion of Spindly affects polarity of axonal microtubules in vivo and in primary neuronal cultures. In addition to these defects, depletion of Spindly in neurons causes major collapse of axonal patterning in the third-instar larval brain as well as severe coordination impairment in adult flies. These defects can be fully rescued by full-length Spindly, but not by variants with mutations in its dynein-binding site. Biochemical analysis demonstrated that Spindly binds F-actin, suggesting that Spindly serves as a link between dynein and cortical actin in axons. Therefore, Spindly plays a critical role during neurodevelopment by mediating dynein-driven sorting of axonal microtubules.


Asunto(s)
Axones/fisiología , Proteínas de Ciclo Celular/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/crecimiento & desarrollo , Dineínas/metabolismo , Microtúbulos/fisiología , Neuronas/fisiología , Actinas/metabolismo , Animales , Transporte Biológico , Proteínas de Ciclo Celular/genética , Células Cultivadas , Corteza Cerebral/metabolismo , Dendritas/fisiología , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Cinetocoros/metabolismo , Proteínas Asociadas a Microtúbulos/metabolismo , Neuronas/citología
8.
Int J Mol Sci ; 24(15)2023 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-37569286

RESUMEN

Microtubule-Associated Serine/Threonine (MAST) kinases represent an evolutionary conserved branch of the AGC protein kinase superfamily in the kinome. Since the discovery of the founding member, MAST2, in 1993, three additional family members have been identified in mammals and found to be broadly expressed across various tissues, including the brain, heart, lung, liver, intestine and kidney. The study of MAST kinases is highly relevant for unraveling the molecular basis of a wide range of different human diseases, including breast and liver cancer, myeloma, inflammatory bowel disease, cystic fibrosis and various neuronal disorders. Despite several reports on potential substrates and binding partners of MAST kinases, the molecular mechanisms that would explain their involvement in human diseases remain rather obscure. This review will summarize data on the structure, biochemistry and cell and molecular biology of MAST kinases in the context of biomedical research as well as organismal model systems in order to provide a current profile of this field.

9.
Cancer ; 128(19): 3479-3486, 2022 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-35917201

RESUMEN

BACKGROUND: Locally advanced cervical cancer (CC) remains lethal in the United States. We investigate the effect of receiving care at an National Cancer Institute-designated cancer center (NCICC) on survival. METHODS: Data for women diagnosed with CC from 2004 to 2016 who received radiation treatment were extracted from the California Cancer Registry (n = 4250). Cox proportional hazards regression models assessed whether (1) receiving care at NCICCs was associated with risk of CC-specific death, (2) this association remained after multivariable adjustment for age, race/ethnicity, and insurance status, and (3) this association was explained by receipt of guideline-concordant treatment. RESULTS: Median age was 50 years (interquartile range [IQR] 41-61 years), with median follow-up of 2.7 years (IQR 1.3-6.0 years). One-third of patients were seen at an NCICC, and 29% died of CC. The hazard of CC-specific death was reduced by 20% for those receiving care at NCICCs compared with patients receiving care elsewhere (HR = .80; 95% CI, 0.70-0.90). Adjustment for guideline-concordant treatment and other covariates minimally attenuated the association to 0.83 (95% CI, 0.74-0.95), suggesting that the survival advantage associated with care at NCICCs may not be due to receipt of guideline-concordant treatment. CONCLUSIONS: This study demonstrates survival benefit for patients receiving care at NCICCs compared with those receiving care elsewhere that is not explained by differences in guideline-concordant care. Structural, organizational, or provider characteristics and differences in patients receiving care at centers with and without NCI designation could explain observed associations. Further understanding of these factors will promote equality across oncology care facilities and survival equity for patients with CC.


Asunto(s)
Neoplasias del Cuello Uterino , Adulto , Etnicidad , Femenino , Humanos , Persona de Mediana Edad , National Cancer Institute (U.S.) , Modelos de Riesgos Proporcionales , Sistema de Registros , Estados Unidos/epidemiología , Neoplasias del Cuello Uterino/terapia
10.
Pediatr Blood Cancer ; 69(5): e29489, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34866330

RESUMEN

PURPOSE: In growing children, craniospinal irradiation (CSI) has historically treated the entire vertebral body (VB) to avoid potential long-term spinal abnormalities. Vertebral body-sparing proton craniospinal irradiation (VBSpCSI) is a technique that spares the majority of the VB from significant irradiation, and long-term safety outcomes have been reported previously. This retrospective study reviews the acute toxicity profile of children treated with VBSpCSI in a cohort comparison with photon-based craniospinal radiotherapy (3DCRT). METHODS: Thirty-eight pediatric CSI patients treated between 2008 and 2018 were retrospectively evaluated for treatment-related toxicity. Acute toxicity outcomes and acute hematologic profiles were compared according to treatment modality, either VBSpCSI or 3DCRT. Statistical analysis was performed using Fisher's exact test for toxicity. RESULTS: Twenty-five patients received VBSpCSI and 13 patients received photon CSI. Mean patient age at treatment was 7.5 years (range 2-16). The cohorts were well matched with respect to gender, age, and CSI dose. Patients receiving VBSpCSI had lower rates of grade 2+ gastrointestinal (GI) toxicity (24% vs. 76.5%, p = .005), grade 2+ nausea (24% vs. 61.5%, p = .035), and any-grade esophagitis (0% vs. 38%, p = .0026). Patients treated with VBSpCSI had lower red blood cell transfusion rates (21.7% vs. 60%, p = .049) and grade 4+ lymphopenia (33.3% vs. 77.8%, p = .046). CONCLUSIONS: VBSpCSI in children is a volumetric de-escalation from traditional volumes, which irradiate the entire VB to full or intermediate doses. In our study, VBSpCSI was associated with lower rates of acute GI and hematologic toxicities. Long-term growth outcomes and disease control outcomes are needed for this technique.


Asunto(s)
Irradiación Craneoespinal , Terapia de Protones , Adolescente , Niño , Preescolar , Irradiación Craneoespinal/efectos adversos , Irradiación Craneoespinal/métodos , Humanos , Terapia de Protones/efectos adversos , Terapia de Protones/métodos , Protones , Dosificación Radioterapéutica , Estudios Retrospectivos , Cuerpo Vertebral
11.
Cancer ; 127(3): 403-411, 2021 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-33036065

RESUMEN

BACKGROUND: Population-based studies demonstrate that Black men in the United States have an increased risk of death from prostate cancer. Determinants of racial disparities are multifactorial, including socioeconomic and biologic factors. METHODS: The authors conducted a pooled analysis of patients derived from 152 centers within the Veterans Health Administration. The cohort included men who had nonmetastatic prostate diagnosed between 2001 and 2015 and received definitive radiation therapy. The primary endpoint was prostate cancer-specific mortality (PCSM). Secondary endpoints included all-cause mortality (ACM) and the time from a prostate-specific antigen level ≥4 ng/mL to biopsy and radiation therapy. A Cox regression model was performed to adjust for differences between clinical parameters. RESULTS: Among the 31,131 patients included in the cohort, 9584 (30.8%) were Black. The 10-year cumulative incidence of death from prostate cancer was lower in Black men compared with White men (4.0% vs 4.8%; P = .004). In a competing risk model, Black race was associated with a decreased risk of PCSM (subdistribution hazard ratio, 0.79; 95% CI, 0.69-0.92; P = .002). Similarly, the 10-year cumulative incidence of death from any cause was lower in Black men (27.6% vs 31.8%; P < .001). In multivariable analysis, Black men had a 10% decreased risk of ACM (hazard ratio, 0.90; 95% CI, 0.85-0.95; P < .001). CONCLUSIONS: The current results indicate relatively lower PCSM and ACM among Black men who were included in a large Veterans Health Administration cohort and received radiation therapy as primary treatment for nonmetastatic prostate cancer. There is an ongoing need to continue to understand and mitigate the factors associated with disparities in health care outcomes.


Asunto(s)
Neoplasias de la Próstata/radioterapia , Adulto , Negro o Afroamericano , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/etnología , Neoplasias de la Próstata/mortalidad , Salud de los Veteranos
12.
PLoS Biol ; 16(12): e3000082, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30517095

RESUMEN

Multicellular animals face the principle challenge to deal with two distinct compartments: the internal organismal compartment and the external environment. This challenge is met by the differentiation of cell sheets into epithelia, which provide a dynamic barrier in tissues, organs, and organisms. Cell polarity is key to all functions of epithelia, and compromising polarity causes many severe diseases. Within the past 20 years, research on Drosophila melanogaster discovered a conserved molecular machinery that controls epithelial polarity. Recent findings suggest that the textbook Drosophila-based paradigm of the control of epithelial polarity may not be as universal as previously assumed.


Asunto(s)
Proteínas de Drosophila , Drosophila , Animales , Polaridad Celular , Drosophila melanogaster , Células Epiteliales
13.
Eur J Public Health ; 30(6): 1062-1066, 2020 12 11.
Artículo en Inglés | MEDLINE | ID: mdl-33313817

RESUMEN

BACKGROUND: A large number of studies are devoted to medical errors, but only a few focused on the problem's victims of these errors face. Prospective comparative studies on this topic are absent. The aim of this prospective comparative study is to fill this gap of scientific knowledge that may help to improve the care for victims. METHODS: Data were collected in the Longitudinal Internet studies for the Social Sciences panel, based on a random sample of the Dutch population. Surveys were conducted in March-April 2018 (T1response = 82.1%) and March-April 2019 (T2response = 80.1%). We assessed medical errors and potentially traumatic or stressful events between T1 and T2, and mental health, work, financial, religious, family, legal/administrative and physical problems at T1 and T2 (Ntotal = 4711). RESULTS: In total, 79 respondents were affected by medical errors between T1 and T2, and 2828 were not affected by any event. Of the victims, 28% had high PTSD symptom levels at T2. Stepwise multivariate logistic regression entering all problems at T1 and demographics showed that victims compared with controls significantly more often had all assessed problems at T2, except family problems. For instance, victims more often had mental health problems (29.5% vs. 9.3%; adj. OR = 3.04, P = 0.002) and financial problems (30.4% vs. 6.6%; adj. OR = 4.82, P < 0.001) at T2. CONCLUSIONS: Victims of medical errors more often face various non-physical problems than others. Care for victims should therefore, besides physical health, also include the assessment and targeting of their problems regarding mental health, work, religion, legal issues and finance.


Asunto(s)
Trastornos por Estrés Postraumático , Humanos , Errores Médicos , Salud Mental , Estudios Prospectivos , Encuestas y Cuestionarios
14.
J Appl Clin Med Phys ; 21(8): 305-308, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32519450

RESUMEN

PURPOSE: To provide insight into the types of questions asked to medical physicists by patients during one-on-one physicist-patient consults at one institution. MATERIALS AND METHODS: Medical physicists trained in patient communication techniques met with patients to provide an overview of the treatment planning and delivery processes, discuss the patient's treatment plan, and answer any technical questions. From August 2016 to December 2019, 152 physicist-patient consults were conducted. In the initial months of the study (August 2016-December 2017), following each physicist-patient consult, all patient questions were documented by the physicists. For the remaining time period (January 2018-December 2019), any newly encountered questions were periodically added to the list. The questions were compiled into a comprehensive list and organized into categories. RESULTS: There were a total of 88 unique patient questions. These questions fit into four topical categories. Fifty-four questions (61.4%) were in the "Treatment Planning and Delivery Questions" category, 15 questions (17.1%) were in the "General Radiation Questions or Concerns" category, 13 questions (14.8%) were in the "Safety and Quality Assurance Questions" category, and 6 questions (6.8%) were in the "Medical Questions" category. Overall, patients were primarily concerned about how radiation works, the treatment planning and delivery processes, and what is being done to keep them safe throughout their treatment. CONCLUSION: Physicist-patient consults provided an opportunity to address the technical aspects of radiation therapy with patients in greater detail. The fact that patient questions could be conveniently grouped into only four topical categories indicates that it may be straightforward for other medical physicists to prepare for effectively addressing technical questions during physicist-patient consults.


Asunto(s)
Oncología por Radiación , Humanos , Derivación y Consulta
15.
JAMA ; 324(17): 1747-1754, 2020 11 03.
Artículo en Inglés | MEDLINE | ID: mdl-33141207

RESUMEN

Importance: There is concern that African American men with low-risk prostate cancer may harbor more aggressive disease than non-Hispanic White men. Therefore, it is unclear whether active surveillance is a safe option for African American men. Objective: To compare clinical outcomes of African American and non-Hispanic White men with low-risk prostate cancer managed with active surveillance. Design, Setting, and Participants: Retrospective cohort study in the US Veterans Health Administration Health Care System of African American and non-Hispanic White men diagnosed with low-risk prostate cancer between January 1, 2001, and December 31, 2015, and managed with active surveillance. The date of final follow-up was March 31, 2020. Exposures: Active surveillance was defined as no definitive treatment within the first year of diagnosis and at least 1 additional surveillance biopsy. Main Outcomes and Measures: Progression to at least intermediate-risk, definitive treatment, metastasis, prostate cancer-specific mortality, and all-cause mortality. Results: The cohort included 8726 men, including 2280 African American men (26.1%) (median age, 63.2 years) and 6446 non-Hispanic White men (73.9%) (median age, 65.5 years), and the median follow-up was 7.6 years (interquartile range, 5.7-9.9; range, 0.2-19.2). Among African American men and non-Hispanic White men, respectively, the 10-year cumulative incidence of disease progression was 59.9% vs 48.3% (difference, 11.6% [95% CI, 9.2% to 13.9%); P < .001); of receipt of definitive treatment, 54.8% vs 41.4% (difference, 13.4% [95% CI, 11.0% to 15.7%]; P < .001); of metastasis, 1.5% vs 1.4% (difference, 0.1% [95% CI, -0.4% to 0.6%]; P = .49); of prostate cancer-specific mortality, 1.1% vs 1.0% (difference, 0.1% [95% CI, -0.4% to 0.6%]; P = .82); and of all-cause mortality, 22.4% vs 23.5% (difference, 1.1% [95% CI, -0.9% to 3.1%]; P = 0.09). Conclusions and Relevance: In this retrospective cohort study of men with low-risk prostate cancer followed up for a median of 7.6 years, African American men, compared with non-Hispanic White men, had a statistically significant increased 10-year cumulative incidence of disease progression and definitive treatment, but not metastasis or prostate cancer-specific mortality. Longer-term follow-up is needed to better assess the mortality risk.


Asunto(s)
Población Negra , Progresión de la Enfermedad , Neoplasias de la Próstata/etnología , Espera Vigilante , Población Blanca , Anciano , Biopsia , Causas de Muerte , Humanos , Masculino , Persona de Mediana Edad , Próstata/patología , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/terapia , Estudios Retrospectivos , Riesgo
16.
Phys Chem Chem Phys ; 21(11): 6071-6079, 2019 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-30810566

RESUMEN

Transition metal dichalcogenides (TMDs), such as MoS2 and WS2, are promising alternative non-noble metal catalysts to drive the electrocatalytic H2 evolution reaction (HER). However, their catalytic performance is inherently limited by the small number of active sites as well as their poor electrical conductivity. Here, we grow vertically aligned 2H-WS2 on different substrates to expose their edge sites for the HER and introduce a scalable approach to tune these active sites via defect engineering. In a thermal hydrogen treatment procedure, sulfur vacancies and metallic tungsten nanoparticles are formed. The extent of desulfurization, and thus the HER activity, can be tuned via controlling the H2 annealing conditions. The obtained W/WS2-x electrocatalysts are evaluated experimentally and theoretically to arrive at a better understanding of how to modify the inherently inert 2H-WS2 for more efficient HER.

17.
Cancer ; 124(14): 2939-2947, 2018 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-29727915

RESUMEN

BACKGROUND: Prostate-specific antigen (PSA) measurement after definitive radiotherapy (RT) and androgen deprivation therapy for localized prostate cancer has been proposed as an early prognostic biomarker. In the current study, the authors investigated the association between 3-month post-RT PSA level and biochemical progression-free survival (bPFS), prostate cancer-specific survival (PCSS), and overall survival (OS). METHODS: A total of 5783 patients with intermediate-risk or high-risk localized prostate cancer who were diagnosed between 2000 and 2015 and treated with RT and androgen deprivation therapy were identified from Veterans Affairs data. Patients were divided into groups based on 3-month post-RT PSA values: <0.10 ng/mL, 0.10 to 0.49 ng/mL, and ≥0.50 ng/mL. The effect of the 3-month PSA group on bPFS, PCSS, and OS was evaluated in multivariable Cox models adjusting for potential confounders. RESULTS: There were 2651 patients with intermediate-risk and 3132 with high-risk disease; approximately 11% had a 3-month PSA level of ≥0.50 ng/mL. A higher 3-month PSA level was found to be strongly associated with each outcome; compared with patients in the group with a 3-month PSA value <0.10 ng/mL, the authors noted greater hazards for the patients with a 3-month PSA value ≥0.50 ng/mL (hazard ratio for bPFS: 5.23; PCSS: 3.97; and OS: 1.50 [P<.001 for all]) and the patients with a 3-month PSA value of 0.10 to 0.49 ng/mL (hazard ratio for bPFS: 2.41 [P<.001]; PCSS: 2.29 [P<.001]; and OS: 1.21 [P = .003]). When analyzed separately, the 3-month PSA level was found to be predictive of OS in the high-risk group (P<.001) but not the intermediate-risk group (P = .21). CONCLUSIONS: The 3-month post-RT PSA level appears to be a strong prognostic biomarker for bPFS, PCSS, and OS in patients with intermediate-risk and high-risk prostate cancer, particularly those with high-risk disease. The 3-month PSA measurement may augment clinical decision making and holds promise as a potential surrogate endpoint in clinical trials. Cancer 2018;124:2939-47. © 2018 American Cancer Society.


Asunto(s)
Antagonistas de Andrógenos/uso terapéutico , Biomarcadores de Tumor/sangre , Quimioradioterapia/métodos , Calicreínas/sangre , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/terapia , Anciano , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Supervivencia sin Progresión , Próstata/patología , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Factores de Riesgo , Estados Unidos/epidemiología , United States Department of Veterans Affairs/estadística & datos numéricos
19.
Gynecol Oncol ; 150(1): 73-78, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29709291

RESUMEN

PURPOSE: The treatment for locally advanced cervical cancer is external beam radiation (EBRT), concurrent chemotherapy, and brachytherapy (BT). We investigated demographic and socioeconomic factors that influence trends in BT utilization and disparities in survival. METHODS: Using the California Cancer Registry, cervical cancer patients FIGO IB2-IVA from 2004 to 2014 were identified. We collected tumor, demographic and socioeconomic (SES) factors. We used multivariable logistic regression analysis to determine predictors of use of BT. Using Cox proportional hazards, we examined the impact of BT vs EBRT boost on cause specific (CSS) and overall survival (OS). RESULTS: We identified 4783 patients with FIGO stage 11% IB2; 32% II, 54% III, 3% IVA. Nearly half (45%) of patients were treated with BT, 18% were treated with a EBRT boost, and 37% had no boost. Stage II and III were more likely to be treated with BT (p = 0.002 and p = 0.0168) vs Stage IB2. As patients aged, the use of BT decreased. Using multivariate analysis, BT impacted CCS (HR 1.16, p = 0.0330) and OS (HR 1.14, p = 0.0333). Worse CSS was observed for black patients (p = 0.0002), low SES (p = 0.0263), stage III and IVA (p < 0.0001. Black patients, low and middle SES had worse OS, (p = 0.0003). CONCLUSIONS: The utilization of BT in locally advanced cervical cancer was low at 45%, with a decrease in CSS and OS. Black patients and those in low SES had worse CSS. As we strive for outcome improvement in cervical cancer, we need to target increasing access and disparities for quality and value.


Asunto(s)
Braquiterapia/métodos , Disparidades en Atención de Salud/normas , Neoplasias del Cuello Uterino/cirugía , Anciano , Anciano de 80 o más Años , California , Femenino , Humanos , Persona de Mediana Edad , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/patología
20.
J Appl Clin Med Phys ; 19(6): 332-335, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30328675

RESUMEN

OBJECTIVES: To develop a training program designed to meet the specific needs of medical physicists as they transition into a clinical role with direct patient care responsibilities. MATERIALS AND METHODS: The training program was designed in collaboration with the faculty at the UC San Diego School of Medicine and incorporates training techniques that have been shown to be effective in improving communication skills. The program emphasizes experiential, practice-based learning over didactic presentations. RESULTS: The training program is comprised of 5 components: 1) a 1-day Clinician-Patient Communication Workshop run by the UC San Diego School of Medicine, 2) Communication Strategies for Radiation Oncology, which consists of two, 2-hour sessions designed to provide trainees with patient communication skills that are specific to patient interactions in radiation oncology, 3) Simulated Patient Interactions, in which trainees perform mock physicist-patient consults with trained patient actors, 4) Faculty-Observed Patient Consults, and 5) a Case-Based Treatment Toxicity Course. A competency assessment mechanism was also developed to provide a clear set of objectives and to guide trainer feedback. [Correction added after first online publication on November 7, 2018: The phrase ", which consists of two, 2-hour" was added above.] CONCLUSIONS: The training program that we have developed incorporates an array of established education techniques and provides a comprehensive, accessible, means of improving medical physicists' patient communication skills.


Asunto(s)
Competencia Clínica , Educación de Postgrado en Medicina/normas , Física Sanitaria/educación , Neoplasias/radioterapia , Atención al Paciente , Desarrollo de Programa , Planificación de la Radioterapia Asistida por Computador/métodos , Humanos , Dosificación Radioterapéutica
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