Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 286
Filtrar
2.
Echocardiography ; 41(6): e15860, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38889076

RESUMEN

PURPOSE: Persistent microvascular obstruction (MVO) after successful percutaneous coronary intervention (PCI) in acute ST segment elevation myocardial infarction (STEMI) has been well-described. MVO predicts lack of recovery of left ventricular function and increased mortality. Sonothrombolysis utilizing diagnostic ultrasound induced cavitation of commercially available microbubble contrast has been effective at reducing infarct size and improving left ventricular ejection fraction (LVEF) when performed both pre- and post-PCI. However, the effectiveness of post-PCI sonothrombolysis alone after successful PCI has not been demonstrated. METHODS: A prospective randomized controlled trial was performed in 50 consecutive consenting patients with anterior STEMI who underwent a continuous microbubble infusion immediately following successful PCI. Intermittent high mechanical index (MI) impulses were applied only in the sonthrombolysis group. Delayed enhancement magnetic resonance imaging (MRI) was performed at 48 h and again at 6-8 weeks to assess for differences in infarct size, LVEF, and MVO. RESULTS: There were no differences between groups in age, gender, and cardiovascular risk factors. Significant (> 2 segments) MVO following successful PCI was observed in 66% of patients. Although sonothrombolysis reduced the extent of MVO acutely, there were no differences in infarct size, LVEF, or extent of MVO by MRI at 48 h. Twenty-eight patients returned for a follow up MRI at 6-8 weeks. LVEF improved only in the sonothrombolysis group (∆LVEF 7.81 ± 4.57% with sonothrombolysis vs. 1.77 ± 7.02% for low MI only, p = .011). CONCLUSION: Post-PCI sonothrombolysis had minimal effect on reducing myocardial infarct size but improved left ventricular systolic function in patients with acute anterior wall STEMI.


Asunto(s)
Intervención Coronaria Percutánea , Humanos , Femenino , Masculino , Intervención Coronaria Percutánea/métodos , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Infarto del Miocardio con Elevación del ST/fisiopatología , Infarto del Miocardio con Elevación del ST/cirugía , Recuperación de la Función , Infarto del Miocardio/fisiopatología , Microburbujas , Ecocardiografía/métodos , Microcirculación/fisiología , Medios de Contraste , Anciano
3.
Artículo en Inglés | MEDLINE | ID: mdl-38709650

RESUMEN

OBJECTIVE: Pain is common in inpatient rehabilitation patients; however, the prevalence of pain diagnoses in this population is not well-defined. This study examines comorbid pain diagnoses in inpatient rehabilitation patients across impairment groups. DESIGN: Adult inpatient rehabilitation patients discharged from January 2016 through December 2019 were identified in the Uniform Data System for Medical Rehabilitation® database using a literature-established framework containing ICD-10-CM pain diagnoses. Demographic data, clinical data, and pain diagnoses were compared across the 17 rehabilitation impairment groups. RESULTS: Of 1,925,002 patients identified, 1,347,239 (70.0%) had at least one ICD-10 pain diagnosis. Over half of all patients in each impairment group had at least one pain diagnosis. The most common pain diagnoses were limb/extremity and joint pain, with variation between impairment groups. Female sex and being in the arthritis, major multiple trauma, and pain syndrome impairment groups were associated with a greater odds of a pain diagnosis. CONCLUSION: Over half of all patients in each rehabilitation impairment group have a pain diagnosis, which varies between impairment groups. Due to the high prevalence of pain diagnoses, a new focus on pain management in inpatient rehabilitation patients is needed. Rehabilitation outcomes may also be affected by pain.

4.
Clin J Sport Med ; 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38810121

RESUMEN

OBJECTIVE: To compare clinical outcomes following steroid injections using the anterior and posterior approaches. DESIGN: Systematic review with meta-analysis. SETTING: Embase, Web of Science, and Cochrane Center Register of Controlled Trials were searched for randomized control trials (RCTs) and prospective comparative studies. PATIENTS: Patients with adhesive capsulitis. INTERVENTIONS: Glenohumeral steroid injections using either anterior or posterior approach. MAIN OUTCOME MEASURES: Pain visual analog scale (VAS) and shoulder range of motion (ROM) at 12 weeks, accuracy, and adverse events. Standardized mean difference (SMD) for VAS and weighted mean difference (WMD) for ROMs. RESULTS: We identified 6 RCTs and one prospective comparative study with a total of 468 patients. While there was no difference in pain VAS at 12 weeks between the 2 approaches (SMD, -0.86; 95% CI, -1.76 to 0.04), the anterior approach resulted in greater improvements in external rotation (WMD, 8.08; 95% CI, 0.79-15.38) and abduction (WMD, 6.76; 95% CI, 3.05-10.48) compared with the posterior approach. Subgroup analysis with RCTs that utilized steroid injection with hydrodilatation for both approaches demonstrated greater reduction in pain VAS at 12 weeks with the anterior approach (SMD, -0.52; 95% CI, -0.98 to -0.07). Overall, procedures were well tolerated without major complications. CONCLUSIONS: While pain reduction is similar, the anterior approach may be more beneficial in restoring shoulder external rotation and abduction compared with the posterior approach at 12 weeks. Steroid injection combined with hydrodilatation may further improve pain control when performed with the anterior approach at 12 weeks.

5.
Spine (Phila Pa 1976) ; 49(10): 733-740, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38229507

RESUMEN

STUDY DESIGN: Retrospective. OBJECTIVE: We aimed to assess the frequency of facet joint inflammatory features noted in routine radiology reports of lumbar spine magnetic resonance imaging (MRI) studies among patients with chronic low back pain. SUMMARY OF BACKGROUND DATA: Facet joint arthropathy is one of the most common causes of chronic low back pain. It may encompass various inflammatory imaging characteristics, such as facet joint effusion, bone marrow edema, and soft tissue edema. The extent to which radiology reports mention inflammatory features of the lumbar facet joints and the accuracy of these reports have not been investigated. MATERIALS AND METHODS: The authors performed a chart review on 49 subjects with previous facet-related interventions ( i.e . medial branch blocks or intra-articular facet joint injection) and MRI available in the medical record. One senior musculoskeletal radiologist and a musculoskeletal radiology fellow graded the inflammatory features using a published facet joint inflammation grading system [Gold Standard (GS)]. The authors identified the inflammatory markers mentioned in the radiology reports and calculated the sensitivity and positive predictive value of the radiology reports compared with GS readings. RESULTS: Compared with the GS, the sensitivity of radiology reports for facet joint effusion, bone marrow, and soft tissue edema ranged from 6% to 22%, and the positive predictive value ranged from 25% to 100%. L4/5 had the highest number of cases with inflammatory features noted on the reports. CONCLUSION: Inflammatory findings, such as facet joint effusion, bone marrow edema, and soft tissue edema, are not commonly identified in radiology reports. Further investigations are needed to determine the clinical importance of MRI-detected lumbar facet joint inflammatory features as a potential mechanism of nociception and as a predictor of outcomes following injections or other therapies.


Asunto(s)
Inflamación , Dolor de la Región Lumbar , Vértebras Lumbares , Imagen por Resonancia Magnética , Articulación Cigapofisaria , Humanos , Dolor de la Región Lumbar/diagnóstico por imagen , Dolor de la Región Lumbar/etiología , Imagen por Resonancia Magnética/métodos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/patología , Articulación Cigapofisaria/diagnóstico por imagen , Articulación Cigapofisaria/patología , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto , Inflamación/diagnóstico por imagen , Anciano , Edema/diagnóstico por imagen
6.
Cardiovasc Revasc Med ; 61: 99-109, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37867120

RESUMEN

BACKGROUND: Calcific aortic stenosis is the principal indication for transcatheter aortic valve replacement (TAVR). Comorbid mitral annular calcification (MAC) is often present in patients undergoing TAVR. Limited data exist on the impact of MAC on TAVR outcomes. We conducted a systematic review and meta-analysis to explore the effects of MAC and concomitant mitral valve dysfunction (MVD) on TAVR outcomes. METHODS: A comprehensive literature review was conducted using PubMed, Embase, Google Scholar, ClinicalTrials.gov, Scopus, and OVID for studies until March 20, 2023. Using the random-effects Mantel-Haenszel method, we calculated pooled risk ratios (RRs) and their corresponding 95 % confidence intervals (CIs) for all dichotomous variables. RESULTS: Six studies comprising 5822 patients (2541 with MAC [severe MAC (>4 mm thickness) 583; non-severe MAC 1958; 400 with MVD; and 1071 without MVD], 3281 without MAC) met inclusion criteria. At 30 days and 1 year, no significant differences were observed between the overall MAC and no MAC groups in terms of mortality, stroke, and permanent pacemaker implantation. However, MAC with MVD was associated with a higher risk of all-cause mortality compared to MAC without MVD at 30 days (RR = 3.43, 95 % CI 2.04-5.76, P < 0.00001) and at 1 year (RR = 2.44, 95 % CI 1.85-3.20, P < 0.00001). Moreover, the risk of cardiovascular mortality was higher in patients with MAC and MVD compared to those with MAC alone (RR = 2.77, 95 % CI 1.89-4.06, P < 0.00001). Additionally, patients with severe MAC had a higher risk of major bleeding at 30 days compared to the non-severe MAC group (RR = 1.33, 95 % CI 1.04-1.69, P = 0.02). CONCLUSION: TAVR appears to be safe in patients with non-severe MAC, but severe MAC is associated with a higher risk of major bleeding and concomitant MVD increases the mortality risk in patients undergoing TAVR.


Asunto(s)
Estenosis de la Válvula Aórtica , Enfermedades de las Válvulas Cardíacas , Implantación de Prótesis de Válvulas Cardíacas , Reemplazo de la Válvula Aórtica Transcatéter , Humanos , Válvula Mitral/diagnóstico por imagen , Válvula Mitral/cirugía , Resultado del Tratamiento , Enfermedades de las Válvulas Cardíacas/cirugía , Estenosis de la Válvula Aórtica/complicaciones , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/cirugía , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Hemorragia/etiología , Factores de Riesgo , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos
7.
Spine (Phila Pa 1976) ; 49(5): 332-340, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-37798843

RESUMEN

STUDY DESIGN: Retrospective. OBJECTIVE: We aimed to describe a magnetic resonance imaging (MRI)-based grading system of inflammatory features of the lumbar facet joints using an atlas and assess its reliability. SUMMARY OF BACKGROUND DATA: Chronic low back pain is often caused by facet joint arthropathy. Inflammatory features are often evident on MRI. While several grading systems of facet arthropathy have been described, there is scant data on the reliability of these systems, and none focus exclusively on inflammatory features. MATERIALS AND METHODS: We describe a grading system that assesses facet joint effusion, bone marrow edema, and soft tissue edema. Each feature was graded from 0 to 3 (facet edema) or 0 to 2 (bone marrow edema intensity and extent, soft tissue edema intensity and extent). Four spine experts graded MRIs of 50 subjects at the bilateral L3/4, L4/5, and L5/S1 levels. All subjects had symptomatic facet arthropathy and received therapeutic facet joint injections. We assessed the intra-reader and inter-reader reliability of each feature at each joint and summarized across all six joints. RESULTS: The mean age of subjects was 56 years (SD = 17), and 48% were female. The injections occurred at the L3/4 level in 12% of cases, at L4/5 in 88%, and at L5/S1 in 80% of cases. The intra-reader reliability kappa's for each feature ranged from 0.42 to 0.81. In contrast, the inter-reader reliability kappa values for each feature ranged from 0.37 to 0.54. CONCLUSION: MRI inflammatory features of the lumbar facet joints are often noted in patients with low back pain. The proposed grading system is reliable and could serve as a research tool for studies assessing the clinical relevance and prognostic value of these features.


Asunto(s)
Artropatías , Dolor de la Región Lumbar , Articulación Cigapofisaria , Humanos , Femenino , Persona de Mediana Edad , Masculino , Dolor de la Región Lumbar/patología , Articulación Cigapofisaria/patología , Estudios Retrospectivos , Reproducibilidad de los Resultados , Vértebras Lumbares/patología , Imagen por Resonancia Magnética/métodos , Edema
8.
Clin Imaging ; 106: 110030, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38150854

RESUMEN

OBJECTIVE: As indications for sub-lobar resections increase, it will become more important to identify risk factors for postsurgical recurrence. We investigated retrospectively the association between local recurrence after sub-lobar resection of neoplastic lung lesions and pre- and post-operative CT imaging and pathologic features. MATERIALS AND METHODS: We reviewed retrospectively neoplastic lung lesions with postoperative chest CT surveillance of sub-lobar resections in 2006-2016. We defined "suspicious" findings as nodularity ≥3 mm or soft tissue thickening ≥4 mm along the suture line and/or progression and explored their association with local recurrence. Primary lung cancer stage, tumoral invasion of lymphatics, visceral pleura or large vessels, bronchial and vascular margin distance were also assessed. RESULTS: Our study group included 45 cases of sub-lobar resection took for either primary (n = 37) or metastatic (n = 8) lung tumors. Local recurrence was observed in 16 of those patients. New nodularity ≥3 mm or soft tissue thickening ≥4 mm along the suture line on surveillance CT was significantly associated with local recurrence (p = 0.037). Additionally, solid nodule (p = 0.005), age at surgery ≤60 years (p = 0.006), two or more sites of invasion (p < 0.0001) and poor histologic differentiation (p = 0.0001) were also significantly associated with local tumor recurrence. Of 16 patients with surveillance post-surgical PET-CT, 15 had elevated FDG uptake. CONCLUSION: The postoperative changes along the suture line should follow a predictable time course demonstrating a pattern of stability, thinning or resolution on CT surveillance. New or increasing postoperative nodularity ≥3 mm or soft tissue thickening ≥4 mm along the suture line requires close diagnostic work-up. Surgical pathology characteristics added prognostic value on postoperative recurrence surveillance.


Asunto(s)
Neoplasias Pulmonares , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Persona de Mediana Edad , Fluorodesoxiglucosa F18 , Pulmón/patología , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/patología , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos
9.
Chem Commun (Camb) ; 59(86): 12851-12854, 2023 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-37807841

RESUMEN

We introduced Ni Apt as the first aptamer with a characterized dissociation constant for recognizing Ni-NTA. Serving as a nucleic acid analog of the His-tag commonly employed for protein purification using Ni-NTA resin, Ni Apt displays a remarkable binding affinity (Kd = 106 nM) towards Ni-NTA. Furthermore, it can be eluted from the resin using imidazole or EDTA, similar to the removal of His-tag from Ni-NTA resin. The versatile capabilities of Ni Apt make it a valuable molecular tool in nucleic acid purification and recognition applications.


Asunto(s)
ADN , Oligonucleótidos
11.
Spine (Phila Pa 1976) ; 48(20): 1455-1463, 2023 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-37470372

RESUMEN

STUDY DESIGN: A scoping review. OBJECTIVE: We aimed to identify and describe the factors associated with the patient-reported response after lumbar intra-articular facet joint (FJ) injections or medial branch blocks (MBBs). SUMMARY OF BACKGROUND DATA: FJ osteoarthritis is among the most common causes of chronic low back pain. Management often includes FJ intra-articular injection and MBBs (which may be followed by radiofrequency ablation of the nerves innervating these joints). However, the success of these approaches is variable, prompting interest in identifying patient characteristics (imaging features, clinical signs, and among others) associated with response to these types of facet injections. MATERIALS AND METHODS: We performed a literature search on factors associated with patient-reported outcomes after lumbar FJ intra-articular injections or MBBs for patients with low back pain published in English or Spanish between 2000 and 2023. We excluded duplicate papers that did not describe factors associated with outcomes or those describing other interventions. We collected data on the association of these factors with patient-reported outcomes. RESULTS: Thirty-seven studies met the inclusion criteria and were analyzed. These studies evaluated factors, such as age, depression, and single photon emission computed tomography (SPECT), and among variables. Age and imaging findings of facet arthropathy were the most frequently described factors. Imaging findings of FJ arthropathy and positive SPECT were often associated with positive results after intra-articular FJ injections or MBBs. In contrast, younger age and smoking were frequently associated with less favorable clinical outcomes. CONCLUSION: Numerous factors were considered in the 37 studies included in this review. Imaging findings of facet arthropathy, duration of pain, and positive SPECT were consistently associated with favorable results after facet interventions.


Asunto(s)
Dolor de la Región Lumbar , Bloqueo Nervioso , Articulación Cigapofisaria , Humanos , Dolor de la Región Lumbar/diagnóstico por imagen , Dolor de la Región Lumbar/tratamiento farmacológico , Dolor de la Región Lumbar/etiología , Bloqueo Nervioso/métodos , Articulación Cigapofisaria/diagnóstico por imagen , Inyecciones Intraarticulares/efectos adversos , Región Lumbosacra
12.
Trends Parasitol ; 39(8): 622-625, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37302957

RESUMEN

Protein disulfide isomerases (PDIs) ensure that specific substrate proteins are correctly folded. PDI activity plays an essential role in malaria transmission. Here we provide an overview of the role of PDIs in malaria-causing Plasmodium parasites and outline why PDI inhibition could be a novel way to treat malaria and prevent transmission.


Asunto(s)
Malaria , Plasmodium , Humanos , Proteína Disulfuro Isomerasas/metabolismo , Malaria/tratamiento farmacológico , Malaria/prevención & control , Plasmodium/metabolismo
13.
Spine (Phila Pa 1976) ; 48(9): 636-644, 2023 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-36856452

RESUMEN

STUDY DESIGN: A scoping review. OBJECTIVE: We aimed to identify and characterize grading systems of the inflammatory features of the lumbar facet joints (FJs) noted on magnetic resonance imaging and summarize their reliability. SUMMARY OF BACKGROUND DATA: Chronic low back pain is one of the most common causes of disability worldwide and is frequently accompanied by FJ osteoarthritis. Inflammatory changes in the lumbar FJs are commonly noted in imaging studies of patients with FJ osteoarthritis and low back pain. Several grading systems for these inflammatory changes have been developed. However, these grading system's features and reliability have yet to be reviewed. MATERIALS AND METHODS: We performed a literature search of studies reporting grading systems for FJ inflammatory changes published in English or Spanish between 1985 and 2022. We collected data on reported interreader reliability measures of each grading system. Finally, we compared the features of inflammation described by each system. RESULTS: Six studies met the inclusion criteria and were used in our analysis. Features commonly graded in these systems are the hyperintensity signal noted within the FJ, bone marrow edema, and the extent of the soft-tissue edema surrounding the FJs. We found that the interreader reliability measures ranged from 0.56 to 0.96. CONCLUSIONS: Only 6 studies have reported methods for documenting inflammation in the FJs. Studies varied in the precise tissues and phenomena included in the grading systems. However, the systems were generally reliable. Future studies should document the reliability of these methods when independent investigators are not involved in developing the classification schemes. Further work might combine one or more of these measures to establish a standard and reliable grading system for inflammatory changes in the FJs, including signal intensity within the joint, bone marrow edema, and soft-tissue inflammation.


Asunto(s)
Dolor de la Región Lumbar , Osteoartritis , Articulación Cigapofisaria , Humanos , Dolor de la Región Lumbar/etiología , Articulación Cigapofisaria/diagnóstico por imagen , Articulación Cigapofisaria/patología , Reproducibilidad de los Resultados , Imagen por Resonancia Magnética/efectos adversos , Osteoartritis/complicaciones , Osteoartritis/patología , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/patología , Espectroscopía de Resonancia Magnética , Inflamación/diagnóstico por imagen , Inflamación/patología
14.
BMJ Open ; 13(3): e069929, 2023 03 23.
Artículo en Inglés | MEDLINE | ID: mdl-36958772

RESUMEN

INTRODUCTION: Parkinson's disease (PD) is the second most common neurological disease globally, for which currently no one definitive cause or cure exists. Estimates suggest that 145 000 people with Parkinson's (PwP) live in the UK. PD presents with motor and non-motor symptoms fluctuating significantly in and between individuals continually throughout the day. PD adversely affects activities of daily living, quality of life and well-being. Self-efficacy is an important belief to improve for PwP as it enables the individual to develop confidence in their ability to exert control over their own motivation, behaviour and social environment. This scoping review aims to identify digital technologies which have been shown to positively impact on promoting self-efficacy in PwP. METHODS AND ANALYSES: Six bibliographic databases MEDLINE, PsycINFO, Web of Science, CINAHL, EMBASE and IEEE Xplore will be searched from the date of their inception to the May 2023. The primary outcome will be to identify interventions which are associated with a change in self-efficacy in PwP to enable positive and negative outcomes, as well as safety to be evaluated. The secondary outcomes of this review will focus on the intervention's proposed mechanisms for success, particularly looking at the impact they had on positive behaviour change(s) or modification(s) on study participants. ETHICS AND DISSEMINATION: This scoping review will not require ethical approval as it will use data collected from previously published primary studies. The findings of this review will be published in peer-reviewed journals and widely disseminated.


Asunto(s)
Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/complicaciones , Autoeficacia , Actividades Cotidianas , Calidad de Vida , Tecnología Digital , Literatura de Revisión como Asunto
15.
J Surg Case Rep ; 2023(2): rjad041, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36789377

RESUMEN

A 49-year-old female with a background of stage IV diffuse large B-cell lymphoma and subsequent graft-versus-host disease from a bone marrow transplant presented to a rural hospital in New South Wales, Australia with 12-h history of painless per rectal bleeding and fever. On examination she had a soft, but distended abdomen. Laboratory investigations revealed thrombocytopenia and hypokalaemia. Computed tomography of the abdomen and pelvis had a bizarre appearance due to pneumatosis cystoides coli extending from the ileocaecal junction to the mid-transverse colon. Given her benign abdominal examination, her management was initially supportive with intravenous antibiotics, intravenous fluid resuscitation and correction of electrolyte abnormalities.

16.
Comput Struct Biotechnol J ; 20: 5873-5885, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36382181

RESUMEN

Metastatic and locally advanced prostate cancer is treated by pharmacological targeting of androgen synthesis and androgen response via androgen signaling inhibitors (ASI), most of which target the androgen receptor (AR). However, ASI therapy invariably fails after 1-2 years. Emerging clinical evidence indicates that in response to ASI therapy, the AR-positive prostatic adenocarcinoma can transdifferentiate into AR-negative neuroendocrine prostate cancer (NEPC) in 17-25 % treated patients, likely through a process called neuroendocrine differentiation (NED). Despite high clinical incidence, the epigenetic pathways underlying NED and ASI therapy-induced NED remain unclear. By utilizing a combinatorial single cell and bulk mRNA sequencing workflow, we demonstrate in a time-resolved manner that following AR inhibition with enzalutamide, prostate cancer cells exhibit immediate loss of canonical AR signaling activity and simultaneous morphological change from epithelial to NE-like (NEL) morphology, followed by activation of specific neuroendocrine (NE)-associated transcriptional programs. Additionally, we observed that activation of NE-associated pathways occurs prior to complete repression of epithelial or canonical AR pathways, a phenomenon also observed clinically via heterogenous AR status in clinical samples. Our model indicates that, mechanistically, ASI therapy induces NED with initial morphological change followed by deactivation of canonical AR target genes and subsequent de-repression of NE-associated target genes, while retaining AR expression and transcriptional shift towards non-canonical AR activity. Coupled with scRNA-seq and CUT&RUN analysis, our model system can provide a platform for screening of potential therapeutic agents that may prevent ASI-induced NED or reverse the NED process.

17.
J Occup Environ Med ; 64(9): 748-753, 2022 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-35732034

RESUMEN

OBJECTIVES: We examined the associations of the metabolic syndrome severity score (MSSS) and the metabolic syndrome (MetSyn) components with central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE). METHODS: Participants in this cross-sectional study were 253 officers from the Buffalo Cardio-Metabolic Occupational Police Stress study (2011-2014). The MSSS is a z -score that represents the severity of MetSyn and was estimated using a sex/race-specific equation and the five MetSyn components. Associations of MSSS and the MetSyn with CRAE/CRVE were obtained using linear regression models or analysis of covariance. RESULTS: For every 1-standard deviation of MSSS, CRAE decreased by 2.3 µm (SE = 1.2, P = 0.0262) and CRVE increased by 3.4 µm (SE = 1.6, P = 0.0308) after adjusting for confounders. CONCLUSIONS: Officers with higher MSSS had narrower (ie, worse) arteriolar diameters and wider (ie, worse) venular diameters.


Asunto(s)
Síndrome Metabólico , Policia , Estudios Transversales , Humanos , Síndrome Metabólico/epidemiología , Retina , Vasos Retinianos
18.
Radiother Oncol ; 170: 213-223, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35227733

RESUMEN

INTRODUCTION: Radiation therapy (RT) is a major modality for the treatment of prostate cancer (PCa), especially castration-resistant PCa (CRPC). However, hypoxia, often seen in PCa tumors, leads to radiation-resistance. This work investigates the effect of a novel oxygen-generating polymer-lipid manganese dioxide nanoparticle (PLMDs) on improving RT outcomes in CRPC xenograft models by modulating the tumor microenvironment (TME) both before and after RT. MATERIALS AND METHODS: Human PC3 and DU145 PCa cells were used to investigate clonogenic inhibition and DNA repair pathways in vitro. Tumor hypoxia and post-RT angiogenesis were evaluated in a PC3-bearing SCID mouse model. PC3 and DU145 xenografts were used to study the efficacy of PLMD in combination with single or fractionated RT. RESULTS: PLMD plus RT significantly inhibited clonogenic potential, increased DNA double-strand breaks, and reduced DNA damage repair in hypoxic PC3 and DU145 cells as compared to RT alone. PLMD significantly reduced hypoxia-positive areas, hypoxia induced factor 1α (HIF-1α) expression, and protein carbonyl levels (a measure of oxidative stress). Application of PLMD with RT decreased RT-induced angiogenic biomarkers by up to 3-fold. Treatment of the human CRPC xenografts with PLMD plus RT (single or fractionated doses) significantly prolonged median survival of the host compared to RT alone resulting in up to a 40% curative rate. CONCLUSION: PLMD treatment modulated TME and sensitized hypoxic human CRPC cells to RT thus enhancing the efficacy of RT. These results confirmed the potential of PLMD as an adjuvant to RT for the treatment of hypoxic CRPC.


Asunto(s)
Nanopartículas , Neoplasias de la Próstata Resistentes a la Castración , Animales , Línea Celular Tumoral , Xenoinjertos , Humanos , Hipoxia , Masculino , Ratones , Ratones SCID , Oxidación-Reducción , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/radioterapia , Microambiente Tumoral
19.
Sleep Med ; 89: 166-175, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-35026653

RESUMEN

BACKGROUND: Adverse Childhood Experiences (ACEs) are associated with numerous adverse health outcomes in adulthood. Our objective was to investigate associations between ACEs and sleep measures among 206 police officers from the Buffalo Cardio-Metabolic Occupational Police Stress study. METHODS: ACEs (independent variable) was assessed using the ACE questionnaire. Sleep measures were assessed using the Pittsburgh Sleep Quality Index and actigraphy. ANOVA/ANCOVA were used to investigate associations between ACEs and sleep measures. RESULTS: The mean self-reported sleep duration was significantly lower among participants who reported ≥1 ACEs compared to those who reported no ACEs (6.0 ± 0.11 vs. 6.4 ± 0.14 h; multivariate-adjusted p = 0.035). Sleep efficiency was significantly lower among participants who reported ≥1 ACEs compared to those who reported none (mean = 88.7%, 95% CI = 87.7-89.6 vs. 90.2%, 89.2-91.2; unadjusted p = 0.031) but was slightly attenuated and lost statistical significance after multivariate-adjustment (88.8%, 87.8-89.7 vs. 90.1%, 88.9-91.1; p = 0.094). Compared to participants who reported no ACEs, those who reported ≥1 ACEs had a higher mean activity index score (36.9 ± 0.96 vs. 31.2 ± 1.25; multivariate-adjusted p = 0.001); a higher mean wake after sleep onset (WASO) (44.3 ± 2.24 vs. 35.3 ± 2.92 min; multivariate-adjusted p = 0.019); and a higher sleep fragmentation index (3.8 ± 1.65 vs. 3.3 ± 1.20 unadjusted p = 0.044 and 3.8 ± 0.13 vs. 3.3 ± 0.18; multivariate-adjusted p = 0.062). Among men (but not women) who reported ≥1 ACEs, self-reported sleep duration was significantly lower (5.9 ± 0.13 vs. 6.4 ± 0.15 h; multivariate-adjusted p = 0.025) and activity index was significantly higher (39.1 ± 1.3 vs. 33.2 ± 1.51; multivariate-adjusted p = 0.004) compared to those who reported no ACEs. CONCLUSION: Exposure to ≥1 ACE was associated with worse sleep measures.


Asunto(s)
Experiencias Adversas de la Infancia , Estrés Laboral , Trastornos del Inicio y del Mantenimiento del Sueño , Adulto , Humanos , Sueño , Privación de Sueño
20.
J Sleep Res ; 31(4): e13543, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-34967055

RESUMEN

Police officers experience exposures associated with increased inflammation, such as the stress associated with shiftwork and poor-quality diet, both of which have been shown to affect sleep duration and quality. This study examined the longitudinal and cross-sectional effects of the Energy-density Dietary Inflammatory Index (E-DII™) on objectively and subjectively measured sleep among police officers. Data were derived from the Buffalo Cardio-Metabolic Occupational Police Stress Cohort (n = 464 at baseline), with longitudinal data collected from 2004 to 2019. A food frequency questionnaire obtained estimated dietary intake from which E-DII scores were calculated. Dependent variables were objectively (Micro Motion Logger Sleep Watch™) and subjectively (Pittsburgh Sleep Quality Index) measured sleep quality and quantity. The analyses included a series of linear mixed-effects models used to examine cross-sectional and longitudinal associations between the E-DII and sleep quantity and quality. Cross-sectionally, more pro-inflammatory diets were associated with higher wake-after-sleep-onset but improved subjective sleep quality. In models accounting for both longitudinal and cross-sectional effects, for every 1-unit increase in the E-DII scores over time (representing a pro-inflammatory change), wake-after-sleep-onset increased by nearly 1.4 min (p = 0.07). This result was driven by officers who primarily worked day shifts (ß = 3.33, p = 0.01). Conversely, for every 1-unit increase in E-DII score, the Pittsburgh Sleep Quality Index global score improved. More pro-inflammatory diets were associated with increased wake-after-sleep-onset, an objective measure of sleep quality. Intervention studies to reduce dietary inflammatory potential may provide greater magnitude of effect for changes in sleep quality.


Asunto(s)
Estrés Laboral , Trastornos del Sueño-Vigilia , Estudios Transversales , Dieta , Humanos , Inflamación , Policia , Sueño
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...