Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 83
Filtrar
1.
Food Chem Toxicol ; 158: 112670, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34774925

RESUMO

Since its commercial introduction in 1974, national and international regulatory agencies have consistently reported no human health concerns associated with the herbicide glyphosate when used according to label directions. However, in 2015, the International Agency for Research on Cancer (IARC) classified glyphosate as a probable human carcinogen. Despite IARC being the sole outlier in its conclusion, dietary exposure to glyphosate remains a health concern to some members of the public. While glyphosate residues have been detected in foods, it is unclear whether a specific eating pattern substantially contributes to glyphosate exposure. Therefore, dietary glyphosate intake was determined for three eating patterns recommended in the U.S. The 95th percentile of glyphosate ingestion at 2,000 calories/day for adults for the U.S.-Style, Mediterranean-Style, and Vegetarian eating patterns ranged from 38 to 960, 39 to 1100, and 39 to 880 µg/day, respectively. No significant differences were observed in glyphosate intake between the dietary styles, and the 95th percentile glyphosate intakes were well below the current U.S. EPA chronic oral reference dose (RfD) of 0.1 mg/kg/day. Our data demonstrate that ingestion of certain high residue foods, particularly grains and legumes, is a driver of total dietary glyphosate body burden regardless of dietary style.

2.
Gerontology ; : 1-11, 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34844245

RESUMO

INTRODUCTION: An early detection of impaired functional performance is critical to enhance symptom management for patients with chronic obstructive pulmonary disease (COPD). However, conventional functional measures based on walking assessments are often impractical for small clinics where the available space to administrate gait-based test is limited. This study examined the feasibility and effectiveness of an upper-extremity frailty meter (FM) in identifying digital measures of functional performance and assessing frailty in COPD patients. METHODS: Forty-eight patients with COPD (age = 68.8 ± 8.5 years, body mass index [BMI] = 28.7 ± 5.8 kg/m2) and 49 controls (age = 70.0 ± 3.0 years, BMI = 28.7 ± 6.1 kg/m2) were recruited. All participants performed a 20-s repetitive elbow flexion-extension test using a wrist-worn FM sensor. Functional performance was quantified by FM metrics, including speed (slowness), range of motion (rigidity), power (weakness), flexion and extension time (slowness), as well as speed and power reduction (exhaustion). Conventional functional measures, including timed-up-and-go test, gait and balance tests, and 5 repetition sit-to-stand test, were also performed. RESULTS: Compared to controls, COPD patients exhibited deteriorated performances in all conventional functional assessments (d = 0.64-1.26, p < 0.010) and all FM metrics (d = 0.45-1.54, p < 0.050). FM metrics had significant agreements with conventional assessment tools (|r| = 0.35-0.55, p ≤ 0.001). FM metrics efficiently identified COPD patients with pre-frailty and frailty (d = 0.82-2.12, p < 0.050). CONCLUSION: This study proposes the feasibility of using a 20-s repetitive elbow flexion-extension test and wrist-worn sensor-derived frailty metrics as an alternative and practical solution to evaluate functional performance in COPD patients. Its simplicity and low risk for test administration may also facilitate its application for remote patient monitoring. Furthermore, in settings where the administration of walking test is impractical, for example, when ventilator support is needed or space is limited, FM may be used as an alternative solution. Future studies are encouraged to use the FM to quantitatively monitor the progressive decline in functional performance and quantify outcomes of rehabilitation interventions.

3.
Adv Radiat Oncol ; 6(6): 100800, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34693079

RESUMO

Purpose: Medical assistants (MAs) occupy an increasingly prevalent role in the clinical setting. Subspecialized fields such as oncology require specific clinical knowledge; however, MAs have few requirements for continued education. Here we assess the role and effect of a pilot MA Radiation Oncology education curriculum. Methods and Materials: A needs assessment survey was conducted and reviewed to develop a comprehensive introductory oncology curriculum. A resident physician-led program was implemented in an academic cancer care center consisting of monthly, 1-hour lectures. Pre- and postlecture surveys were administered to assess learning. Quarterly surveys were conducted over the 20-month curriculum timeframe. Results: The needs assessment revealed that there were no pre-existing MA continuing education didactics, but all (100%) MAs surveyed were "very interested" in such a curriculum. Sessions were found to be clear, comprehensive, relevant, and associated with a significant increase in a sense of empowerment (P = .035). Topics in Head and Neck and Breast Cancer showed large improvements in understanding (change in median Likert score of 3-4 points each) whereas topics in Introduction to Oncology and New Patient Consultation showed the smallest change (change 0.5-1). For 20 months, there was a sustained improvement in clinical understanding within and outside the scope of the MA role and an improvement in perceived empathy for patients (from median Likert score 3.5-5). Conclusions: Dedicated education programs for MAs show the potential to improve clinical understanding and participation in patient care. Further studies may demonstrate how such programs translate to staff productivity or patient clinical outcomes. Interprofessional education may facilitate collaboration and enhanced clinical workflow.

4.
Nat Commun ; 12(1): 6233, 2021 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-34716350

RESUMO

Acute myeloid leukemia (AML) is a hematological malignancy with an undefined heritable risk. Here we perform a meta-analysis of three genome-wide association studies, with replication in a fourth study, incorporating a total of 4018 AML cases and 10488 controls. We identify a genome-wide significant risk locus for AML at 11q13.2 (rs4930561; P = 2.15 × 10-8; KMT5B). We also identify a genome-wide significant risk locus for the cytogenetically normal AML sub-group (N = 1287) at 6p21.32 (rs3916765; P = 1.51 × 10-10; HLA). Our results inform on AML etiology and identify putative functional genes operating in histone methylation (KMT5B) and immune function (HLA).


Assuntos
Antígenos HLA/genética , Leucemia Mieloide Aguda/genética , Polimorfismo de Nucleotídeo Único , Aldeído Redutase/genética , Estudos de Casos e Controles , Grupo com Ancestrais do Continente Europeu/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Leucemia Mieloide Aguda/mortalidade , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
5.
Cancer ; 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34550601

RESUMO

BACKGROUND: Disparity in mental health care among cancer patients remains understudied. METHODS: A large, retrospective, single tertiary-care institution cohort study was conducted based on deidentified electronic health record data of 54,852 adult cancer patients without prior mental health diagnosis (MHD) diagnosed at the University of California, San Francisco between January 2012 and September 2019. The exposure of interest was early-onset MHD with or without psychotropic medication (PM) within 12 months of cancer diagnosis and primary outcome was all-cause mortality. RESULTS: There were 8.2% of patients who received a new MHD at a median of 197 days (interquartile range, 61-553) after incident cancer diagnosis; 31.0% received a PM prescription; and 3.7% a mental health-related visit (MHRV). There were 62.6% of patients who were non-Hispanic White (NHW), 10.8% were Asian, 9.8% were Hispanic, and 3.8% were Black. Compared with NHWs, minority cancer patients had reduced adjusted odds of MHDs, PM prescriptions, and MHRVs, particularly for generalized anxiety (Asian odds ratio [OR], 0.66, 95% CI, 0.55-0.78; Black OR, 0.60, 95% CI, 0.45-0.79; Hispanic OR, 0.72, 95% CI, 0.61-0.85) and selective serotonin-reuptake inhibitors (Asian OR, 0.43, 95% CI, 0.37-0.50; Black OR, 0.51, 95% CI, 0.40-0.61; Hispanic OR, 0.79, 95% CI, 0.70-0.89). New early MHD with PM was associated with elevated all-cause mortality (12-24 months: hazard ratio [HR], 1.43, 95% CI, 1.25-1.64) that waned by 24 to 36 months (HR, 1.18, 95% CI, 0.95-1.45). CONCLUSIONS: New mental health diagnosis with PM was a marker of early mortality among cancer patients. Minority cancer patients were less likely to receive documentation of MHDs or treatment, which may represent missed opportunities to identify and treat cancer-related mental health conditions.

7.
Sensors (Basel) ; 21(16)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34450734

RESUMO

Remote monitoring of physical frailty is important to personalize care for slowing down the frailty process and/or for the healthy recovery of older adults following acute or chronic stressors. Taking the Fried frailty criteria as a reference to determine physical frailty and frailty phenotypes (slowness, weakness, exhaustion, inactivity), this study aimed to explore the benefit of machine learning to determine the least number of digital biomarkers of physical frailty measurable from a pendant sensor during activities of daily living. Two hundred and fifty-nine older adults were classified into robust or pre-frail/frail groups based on the physical frailty assessments by the Fried frailty criteria. All participants wore a pendant sensor at the sternum level for 48 h. Of seventeen sensor-derived features extracted from a pendant sensor, fourteen significant features were used for machine learning based on logistic regression modeling and a recursive feature elimination technique incorporating bootstrapping. The combination of percentage time standing, percentage time walking, walking cadence, and longest walking bout were identified as optimal digital biomarkers of physical frailty and frailty phenotypes. These findings suggest that a combination of sensor-measured exhaustion, inactivity, and speed have potential to screen and monitor people for physical frailty and frailty phenotypes.


Assuntos
Fragilidade , Atividades Cotidianas , Idoso , Biomarcadores , Exercício Físico , Idoso Fragilizado , Fragilidade/diagnóstico , Avaliação Geriátrica , Humanos , Aprendizado de Máquina , Fenótipo
8.
J Diabetes Sci Technol ; : 19322968211035128, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34328024

RESUMO

BACKGROUND: Electrical stimulation (E-Stim) may offer a unique adjunctive treatment to heal complicated diabetic foot ulcers (DFU). Our primary goal is to examine the effectiveness of daily home-based E-Stim therapy to speed-up wound healing. METHODS: Patients with chronic DFUs and mild to severe peripheral arterial disease (PAD) were recruited and randomized to either control (CG) or intervention (IG) groups. The IG received 1-hour home-based E-Stim therapy on daily basis for 4 weeks (4W). E-Stim was delivered through electrical pads placed above the ankle joint using a bio-electric stimulation technology (BEST®) platform (Tennant Biomodulator® PRO). The CG was provided with an identical but non-functional device for the same period. The primary outcome included wound area reduction at 4W from baseline (BL). RESULTS: Thirty-eight patients were recruited and 5 were removed due to non-compliance or infection, leaving 33 participants (IG, n = 16; CG, n =17). At 4W, the IG showed a significant wound area reduction of 22% (BL: 7.4 ± 8.5 cm2 vs 4W: 5.8 ± 8.0 cm2, P = 0.002). Average of wound area was unchanged in the CG (P = 0.982). The self-report adherence to daily home-therapy was 93.9%. CONCLUSIONS: Daily home-based E-Stim provides early results on the feasibility, acceptability, and effectiveness of E-Stim as an adjunctive therapy to speed up wound healings in patients with chronic DFU and mild to severe PAD.

9.
Lupus ; 30(10): 1660-1670, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34219529

RESUMO

Lupus nephritis (LN) is a life-threatening manifestation of systemic lupus erythematosus (SLE) and is more common in children than adults. The epidemiology and management of childhood-onset SLE (cSLE) have changed over time, prompting the need to reassess expected outcomes. The purpose of this study is to use the Childhood Arthritis and Rheumatology Research Alliance (CARRA) prospective registry to validate historical principles of LN in a contemporary, real-world cohort. After an extensive literature review, six principles of LN in cSLE were identified. The CARRA registry was queried to evaluate these principles in determining the rate of LN in cSLE, median time from cSLE diagnosis to LN, short-term renal outcomes, and frequency of rituximab as an induction therapy. Of the 677 cSLE patients in the CARRA registry, 32% had documented LN. Decline in kidney function was more common in Black cSLE patients than non-Black patients (p = 0.04). Black race was associated with worse short-term renal outcomes. In short-term follow up, most children with LN had unchanged or improved kidney function, and end stage kidney disease (ESKD) was rare. Ongoing follow-up of cSLE patients in the CARRA registry will be necessary to evaluate long-term outcomes to inform risk, management, and prognosis of LN in cSLE.

10.
Sensors (Basel) ; 21(9)2021 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-34066716

RESUMO

Since conventional screening tools for assessing frailty phenotypes are resource intensive and unsuitable for routine application, efforts are underway to simplify and shorten the frailty screening protocol by using sensor-based technologies. This study explores whether machine learning combined with frailty modeling could determine the least sensor-derived features required to identify physical frailty and three key frailty phenotypes (slowness, weakness, and exhaustion). Older participants (n = 102, age = 76.54 ± 7.72 years) were fitted with five wearable sensors and completed a five times sit-to-stand test. Seventeen sensor-derived features were extracted and used for optimal feature selection based on a machine learning technique combined with frailty modeling. Mean of hip angular velocity range (indicator of slowness), mean of vertical power range (indicator of weakness), and coefficient of variation of vertical power range (indicator of exhaustion) were selected as the optimal features. A frailty model with the three optimal features had an area under the curve of 85.20%, a sensitivity of 82.70%, and a specificity of 71.09%. This study suggests that the three sensor-derived features could be used as digital biomarkers of physical frailty and phenotypes of slowness, weakness, and exhaustion. Our findings could facilitate future design of low-cost sensor-based technologies for remote physical frailty assessments via telemedicine.


Assuntos
Fragilidade , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Idoso Fragilizado , Fragilidade/diagnóstico , Avaliação Geriátrica , Humanos , Aprendizado de Máquina , Fenótipo
11.
Int J Radiat Oncol Biol Phys ; 111(3): 638-642, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34153380

RESUMO

PURPOSE: Achieving competency as educators is increasingly recognized as a critical part of residents' training in graduate medical education across specialties. In addition to teaching medical students, radiation oncology residents often play a vital role in peer and interprofessional education. We conducted a survey to identify the needs of radiation oncology residents for developing skills in teaching. METHODS AND MATERIALS: An anonymous, web-based survey was developed and distributed to resident physicians at US radiation oncology programs. Analyses describe respondent demographics, experiences with teaching, and interest in various aspects of a formal "residents-as-teachers" curriculum. RESULTS: There were 171 completed survey responses (27.5% response rate). A total of 146 residents (85.4%) reported receiving no formal training in teaching before residency, and 121 (70.8%) reported no formal training during residency. Residents who had formal training in teaching were significantly more likely to be "quite" or "extremely" confident about teaching compared with residents who had no prior formal training (76.0% vs 51.4%; P = .022). Residents most commonly taught other residents and medical students (163 [95.3%] and 160 [93.6%] respondents, respectively). The most common settings for teaching were one-on-one teaching (164 respondents [95.9%]), small-group lectures (135 respondents [78.9%]), and intradepartmental lectures (136 respondents [79.5%]). In response to open-ended questions regarding desired teaching opportunities and domains for teaching development, many residents expressed a lack of confidence in teaching and were interested in improvement across many aspects of teaching. CONCLUSIONS: Radiation oncology residents are expected and desire to teach in a multitude of settings across a wide variety of audiences. However, a significant proportion of radiation oncology residents lack formal training and rarely receive feedback for their teaching skills. The results of this national survey support the development of a residents-as-teachers curriculum for radiation oncology residents that would address the needs for and significant interest in this area.

12.
Front Immunol ; 12: 605857, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34046028

RESUMO

Aims: Latent cytomegalovirus (CMV) infection is associated with adverse cardiovascular outcomes. Virus-specific CX3CR1+ effector memory T-cells may be instrumental in this process due to their pro-inflammatory properties. We investigated the role of CX3CR1 (fractalkine receptor) in CMV-related lymphocyte kinetics and cardiac remodeling in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). Methods and Results: We retrospectively analysed lymphocyte count, troponin, and survival in 4874 STEMI/pPCI patients, evaluated lymphocyte kinetics during reperfusion in a prospective cohort, and obtained sequential cardiac MRI (cMRI) to assess remodeling. Pre-reperfusion lymphopenia independently predicted mortality at 7.5 years. Prior to reperfusion, CCR7+ T-lymphocytes appeared to be depleted. After reperfusion, T-lymphocytes expressing CX3CR1 were depleted predominantly in CMV-seropositive patients. During ischaemia/reperfusion, a drop in CX3CR1+ T-lymphocytes was significantly linked with microvascular obstruction in CMV+ patients, suggesting increased fractalkine-receptor interaction. At 12 weeks, CMV+ patients displayed adverse LV remodeling. Conclusion: We show that lymphopenia occurs before and after reperfusion in STEMI by different mechanisms and predicts long-term outcome. In CMV+ patients, increased fractalkine induction and sequestration of CX3CR1+ T-cells may contribute to adverse remodeling, suggesting a pro-inflammatory pathomechanism which presents a novel therapeutic target.


Assuntos
Receptor 1 de Quimiocina CX3C/genética , Infecções por Citomegalovirus/complicações , Linfócitos/metabolismo , Infarto do Miocárdio/complicações , Infarto do Miocárdio/metabolismo , Remodelação Ventricular , Idoso , Biomarcadores , Receptor 1 de Quimiocina CX3C/metabolismo , Citomegalovirus , Infecções por Citomegalovirus/virologia , Feminino , Testes de Função Cardíaca , Humanos , Imunofenotipagem , Linfócitos/imunologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/mortalidade , Receptores CCR7/metabolismo , Remodelação Ventricular/genética , Remodelação Ventricular/imunologia
13.
Gerontology ; : 1-7, 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33940574

RESUMO

INTRODUCTION: Parkinson's disease (PD) progressively impairs motor and cognitive performance. The current tools to detect decline in motor and cognitive functioning are often impractical for busy clinics and home settings. To address the gap, we designed an instrumented trail-making task (iTMT) based on a wearable sensor (worn on the shin) with interactive game-based software installed on a tablet. The iTMT test includes reaching to 5 indexed circles, a combination of numbers (1-3) and letters (A&B) randomly positioned inside target circles, in a sequential order, which virtually appears on a screen kept in front of the participants, by rotating one's ankle joint while standing and holding a chair for safety. By measuring time to complete iTMT task (iTMT time), iTMT enables quantifying cognitive-motor performance. PURPOSE: This study's objective is to examine the feasibility of iTMT to detect early cognitive-motor decline in PDs. METHOD: Three groups of volunteers, including 14 cognitively normal (CN) older adults, 14 PDs, and 11 mild cognitive impaireds (MCI), were recruited. Participants completed MoCA, 20 m walking test, and 3 trials of iTMT. RESULTS: All participants enabled to complete iTMT with <3 min, indicating high feasibility. The average iTMT time for CN-Older, PD, and MCI participants were 20.9 ± 0.9 s, 32.3 ± 2.4 s, and 40.9 ± 4.5 s, respectively. After adjusting for age and education level, pairwise comparison suggested large effect sizes for iTMT between CN-older versus PD (Cohen's d = 1.7, p = 0.024) and CN-older versus MCI (d = 1.57, p < 0.01). Significant correlations were observed when comparing iTMT time with the gait speed (r = -0.4, p = 0.011) and MoCA score (r = -0.56, p < 0.01). CONCLUSION: This study demonstrated the feasibility and early results supporting the potential application of iTMT to determine cognitive-motor and distinguishing individuals with MCI and PD from CN-older adults. Future studies are warranted to test the ability of iTMT to track its subtle changes over time.

14.
Sensors (Basel) ; 21(9)2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33946664

RESUMO

BACKGROUND: Social isolation during COVID-19 may negatively impact older adults' wellbeing. To assess its impact, we measured changes in physical activity and sleep among community-dwelling older adults, from pre-to post-pandemic declaration. METHOD: Physical activity and sleep in older adults (n = 10, age = 77.3 ± 1.9 years, female = 40%) were remotely assessed within 3-month pre-to 6-month post-pandemic declaration using a pendant-wearable system. Depression was assessed pre-and post-pandemic declaration using the Center for Epidemiologic Studies Depression scale and was compared with 48 h continuous physical activity monitoring data before and during pandemic. RESULTS: Compared to pre-pandemic, post-pandemic time spent in standing declined by 32.7% (Cohen's d = 0.78, p < 0.01), walking by 52.2% (d = 1.1, p < 0.01), step-counts by 55.1% (d = 1.0, p = 0.016), and postural transitions by 44.6% (d = 0.82, p = 0.017) with increase in sitting duration by 20.5% (d = 0.5, p = 0.049). Depression symptoms increased by 150% (d = 0.8, p = 0.046). Interestingly, increase in depression was significantly correlated with unbroken-prolong sitting bout (ρ = 0.677, p = 0.032), cadence (ρ = -0.70, p = 0.024), and sleep duration (ρ = -0.72, p = 0.019). CONCLUSION: This is one of the early longitudinal studies highlighting adverse effect of the pandemic on objectively assessed physical activity and sleep in older adults. Our observations showed need for timely intervention to mitigate hard to reverse consequences of decreased physical activity such as depression.


Assuntos
COVID-19 , Dispositivos Eletrônicos Vestíveis , Idoso , Depressão/diagnóstico , Depressão/epidemiologia , Feminino , Humanos , Pandemias , SARS-CoV-2
15.
Gerontology ; : 1-10, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33971647

RESUMO

BACKGROUND: Cognitive frailty (CF), defined as the simultaneous presence of cognitive impairment and physical frailty, is a clinical symptom in early-stage dementia with promise in assessing the risk of dementia. The purpose of this study was to use wearables to determine the most sensitive digital gait biomarkers to identify CF. METHODS: Of 121 older adults (age = 78.9 ± 8.2 years, body mass index = 26.6 ± 5.5 kg/m2) who were evaluated with a comprehensive neurological exam and the Fried frailty criteria, 41 participants (34%) were identified with CF and 80 participants (66%) were identified without CF. Gait performance of participants was assessed under single task (walking without cognitive distraction) and dual task (walking while counting backward from a random number) using a validated wearable platform. Participants walked at habitual speed over a distance of 10 m. A validated algorithm was used to determine steady-state walking. Gait parameters of interest include steady-state gait speed, stride length, gait cycle time, double support, and gait unsteadiness. In addition, speed and stride length were normalized by height. RESULTS: Our results suggest that compared to the group without CF, the CF group had deteriorated gait performances in both single-task and dual-task walking (Cohen's effect size d = 0.42-0.97, p < 0.050). The largest effect size was observed in normalized dual-task gait speed (d = 0.97, p < 0.001). The use of dual-task gait speed improved the area under the curve (AUC) to distinguish CF cases to 0.76 from 0.73 observed for the single-task gait speed. Adding both single-task and dual-task gait speeds did not noticeably change AUC. However, when additional gait parameters such as gait unsteadiness, stride length, and double support were included in the model, AUC was improved to 0.87. CONCLUSIONS: This study suggests that gait performances measured by wearable sensors are potential digital biomarkers of CF among older adults. Dual-task gait and other detailed gait metrics provide value for identifying CF above gait speed alone. Future studies need to examine the potential benefits of gait performances for early diagnosis of CF and/or tracking its severity over time.

16.
FASEB J ; 35(5): e21604, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33913566

RESUMO

Myocardial infarction leads to a rapid innate immune response that is ultimately required for repair of damaged heart tissue. We therefore examined circulating monocyte dynamics immediately after reperfusion of the culprit coronary vessel in STEMI patients to determine whether this correlated with level of cardiac injury. A mouse model of cardiac ischemia/reperfusion injury was subsequently used to establish the degree of monocyte margination to the coronary vasculature that could potentially contribute to the drop in circulating monocytes. We retrospectively analyzed blood samples from 51 STEMI patients to assess the number of non-classical (NC), classical, and intermediate monocytes immediately following primary percutaneous coronary intervention. Classical and intermediate monocytes showed minimal change. On the other hand, circulating numbers of NC monocytes fell by approximately 50% at 90 minutes post-reperfusion. This rapid decrease in NC monocytes was greatest in patients with the largest infarct size (P < .05) and correlated inversely with left ventricular function (r = 0.41, P = .04). The early fall in NC monocytes post-reperfusion was confirmed in a second prospective study of 13 STEMI patients. Furthermore, in a mouse cardiac ischemia model, there was significant monocyte adhesion to coronary vessel endothelium at 2 hours post-reperfusion pointing to a specific and rapid vessel margination response to cardiac injury. In conclusion, rapid depletion of NC monocytes from the circulation in STEMI patients following coronary artery reperfusion correlates with the level of acute cardiac injury and involves rapid margination to the coronary vasculature.


Assuntos
Traumatismos Cardíacos/sangue , Traumatismos Cardíacos/patologia , Monócitos/patologia , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Animais , Feminino , Traumatismos Cardíacos/etiologia , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos
17.
J Exp Med ; 218(5)2021 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-33822843

RESUMO

Triple-negative breast cancers (TNBCs) are associated with poor survival mediated by treatment resistance. TNBCs are fibrotic, yet little is known regarding how the extracellular matrix (ECM) evolves following therapy and whether it impacts treatment response. Analysis revealed that while primary untreated TNBCs are surrounded by a rigid stromal microenvironment, chemotherapy-resistant residual tumors inhabit a softer niche. TNBC organoid cultures and xenograft studies showed that organoids interacting with soft ECM exhibit striking resistance to chemotherapy, ionizing radiation, and death receptor ligand TRAIL. A stiff ECM enhanced proapoptotic JNK activity to sensitize cells to treatment, whereas a soft ECM promoted treatment resistance by elevating NF-κB activity and compromising JNK activity. Treatment-resistant residual TNBCs residing within soft stroma had elevated activated NF-κB levels, and disengaging NF-κB activity sensitized tumors in a soft matrix to therapy. Thus, the biophysical properties of the ECM modify treatment response, and agents that modulate stiffness-dependent NF-κB or JNK activity could enhance therapeutic efficacy in patients with TNBC.


Assuntos
Matriz Extracelular/metabolismo , NF-kappa B/metabolismo , Neoplasias de Mama Triplo Negativas/terapia , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Quimiorradioterapia , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/efeitos da radiação , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/efeitos da radiação , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Camundongos Endogâmicos NOD , Camundongos Nus , Camundongos SCID , Terapia Neoadjuvante , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/efeitos da radiação
18.
Artigo em Inglês | MEDLINE | ID: mdl-33656524

RESUMO

BACKGROUND: While numerous studies suggest the benefit of electrical stimulation (E-Stim) therapy to accelerate wound healing, the underlying mechanism of action is still debated. In this pilot study, we examined the potential effectiveness of lower extremity E-Stim therapy to improve tissue perfusion in patients with diabetic foot ulcers (DFUs). METHODS: Thirty-eight patients with DFUs were recruited. Participants underwent 60-minutes of active E-Stim therapy provided on acupuncture points above the level of the ankle joint using a bio-electric stimulation technology® (BEST) platform (Tennant Biomodulator® PRO). As primary outcome, changes in perfusion in response to E-Stim were assessed by measuring skin perfusion pressure (SPP) at baseline, 30-, and 60-min during therapy. In addition, retention was assessed 10-min post-therapy. As secondary outcome, tissue oxygen saturation (SatO2) was measured using a non-invasive near-infrared camera (Snapshot NIR, KENT Imaging Inc). RESULTS: SPP increased in response to E-Stim therapy (p = 0.02) with maximum improvement observed at 60-min (11%, p = 0.007) compared to baseline. SPP reduced at 10-min post therapy, but remained higher than baseline (9%, p = 0.1). Magnitude of improvement at 60-min was negatively correlated with baseline SPP values (r = -0.45, p = 0.01) suggesting those with lower perfusion could benefit more from E-Stim therapy. Similar trends were observed for SatO2 with statistically significant improvement for a sub-sample (n=16) with moderate-severe peripheral arterial disease (Ankle brachial index < 0.8 or > 1.4). CONCLUSIONS: This study provides early results on the feasibility and effectiveness of E-Stim therapy to improve skin perfusion and SatO2. The magnitude of benefit is higher among those with poorer skin perfusion. Results also suggest the effects of E-Stim could be washed out after stopping therapy and thus regular daily application may be required for the effective benefit for wound healing.

19.
J Surg Res ; 263: 130-139, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33652175

RESUMO

BACKGROUND: Traditional physical frailty (PF) screening tools are resource intensive and unsuitable for remote assessment. In this study, we used five times sit-to-stand test (5×STS) with wearable sensors to determine PF and three key frailty phenotypes (slowness, weakness, and exhaustion) objectively. MATERIALS AND METHODS: Older adults (n = 102, age: 76.54 ± 7.72 y, 72% women) performed 5×STS while wearing sensors attached to the trunk and bilateral thigh and shank. Duration of 5×STS was recorded using a stopwatch. Seventeen sensor-derived variables were analyzed to determine the ability of 5×STS to distinguish PF, slowness, weakness, and exhaustion. Binary logistic regression was used, and its area under curve was calculated. RESULTS: A strong correlation was observed between sensor-based and manually-recorded 5xSTS durations (r = 0.93, P < 0.0001). Sensor-derived variables indicators of slowness (5×STS duration, hip angular velocity range, and knee angular velocity range), weakness (hip power range and knee power range), and exhaustion (coefficient of variation (CV) of hip angular velocity range, CV of vertical velocity range, and CV of vertical power range) were different between the robust group and prefrail/frail group (P < 0.05) with medium to large effect sizes (Cohen's d = 0.50-1.09). The results suggested that sensor-derived variables enable identifying PF, slowness, weakness, and exhaustion with an area under curve of 0.861, 0.865, 0.720, and 0.723, respectively. CONCLUSIONS: Our study suggests that sensor-based 5×STS can provide digital biomarkers of PF, slowness, weakness, and exhaustion. The simplicity, ease of administration in front of a camera, and safety of 5xSTS may facilitate a remote assessment of PF, slowness, weakness, and exhaustion via telemedicine.


Assuntos
Fragilidade/diagnóstico , Avaliação Geriátrica/métodos , Exame Físico/instrumentação , Tecnologia de Sensoriamento Remoto/instrumentação , Dispositivos Eletrônicos Vestíveis , Idoso , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Feminino , Idoso Fragilizado , Humanos , Masculino , Exame Físico/métodos , Curva ROC , Tecnologia de Sensoriamento Remoto/métodos , Postura Sentada , Posição Ortostática , Fatores de Tempo
20.
JAMA Netw Open ; 3(11): e2020161, 2020 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-33211104

RESUMO

Importance: Physical frailty is a key risk factor associated with higher rates of major adverse events (MAEs) after surgery. Assessing physical frailty is often challenging among patients with chronic limb-threatening ischemia (CLTI) who are often unable to perform gait-based assessments because of the presence of plantar wounds. Objective: To test a frailty meter (FM) that does not rely on gait to determine the risk of occurrence of MAEs after revascularization for patients with CLTI. Design, Setting, and Participants: This cohort study included 184 consecutively recruited patients with CLTI at 2 tertiary care centers. After 32 individuals were excluded, 152 participants were included in the study. Data collection was conducted between May 2018 and June 2019. Exposures: Physical frailty measurement within 1 week before limb revascularization and incidence of MAEs for as long as 1 month after surgery. Main Outcomes and Measures: The FM works by quantifying weakness, slowness, rigidity, and exhaustion during a 20-second repetitive elbow flexion-extension exercise using a wrist-worn sensor. The FM generates a frailty index (FI) ranging from 0 to 1; higher values indicate progressively greater severity of physical frailty. Results: Of 152 eligible participants (mean [SD] age, 67.0 [11.8] years; 59 [38.8%] women), 119 (78.2%) were unable to perform the gait test, while all could perform the FM test. Overall, 53 (34.9%), 58 (38.1%), and 41 (27.0%) were classified as robust (FI <0.20), prefrail (FI ≥0.20 to <0.35), or frail (FI ≥0.35), respectively. Within 30 days after surgery, 24 (15.7%) developed MAEs, either major adverse cardiovascular events (MACE; 8 [5.2%]) or major adverse limb events (MALE; 16 [10.5%]). Baseline demographic characteristics were not significantly different between frailty groups. In contrast, the FI was approximately 30% higher in the group that developed MAEs (mean [SD] score, 0.36 [0.14]) than those who were MAE free (mean [SD] score, 0.26 [0.13]; P = .001), with observed MAE rates of 4 patients (7.5%), 7 patients (12.1%), and 13 patients (31.7%) in the robust, prefrail and frail groups, respectively (P = .004). The FI distinguished individuals who developed MACE and MALE from those who were MAE free (MACE: mean [SD] FI score, 0.38 [0.16]; P = .03; MALE: mean [SD] FI score, 0.35 [0.13]; P = .004) after adjusting by body mass index. Conclusions and Relevance: In this cohort study, measuring physical frailty using a wrist-worn sensor during a short upper extremity test was a practical method for stratifying the risk of MAEs following revascularization for CLTI when the administration of gait-based tests is often challenging.


Assuntos
Idoso Fragilizado/estatística & dados numéricos , Fragilidade/diagnóstico , Avaliação Geriátrica/estatística & dados numéricos , Extremidade Inferior/cirurgia , Monitorização Fisiológica/instrumentação , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Dispositivos Eletrônicos Vestíveis/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Avaliação Geriátrica/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/estatística & dados numéricos , Estados Unidos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...