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1.
Brain Commun ; 5(1): fcac329, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36601626

RESUMO

Visual hallucinations are common in Parkinson's disease and are associated with a poorer quality of life and a higher risk of dementia. An important and influential model that is widely accepted as an explanation for the mechanism of visual hallucinations in Parkinson's disease and other Lewy body diseases is that these arise due to aberrant hierarchical processing, with impaired bottom-up integration of sensory information and overweighting of top-down perceptual priors within the visual system. This hypothesis has been driven by behavioural data and supported indirectly by observations derived from regional activation and correlational measures using neuroimaging. However, until now, there was no evidence from neuroimaging for differences in causal influences between brain regions measured in patients with Parkinson's hallucinations. This is in part because previous resting-state studies focused on functional connectivity, which is inherently undirected in nature and cannot test hypotheses about the directionality of connectivity. Spectral dynamic causal modelling is a Bayesian framework that allows the inference of effective connectivity-defined as the directed (causal) influence that one region exerts on another region-from resting-state functional MRI data. In the current study, we utilize spectral dynamic causal modelling to estimate effective connectivity within the resting-state visual network in our cohort of 15 Parkinson's disease visual hallucinators and 75 Parkinson's disease non-visual hallucinators. We find that visual hallucinators display decreased bottom-up effective connectivity from the lateral geniculate nucleus to primary visual cortex and increased top-down effective connectivity from the left prefrontal cortex to primary visual cortex and the medial thalamus, as compared with non-visual hallucinators. Importantly, we find that the pattern of effective connectivity is predictive of the presence of visual hallucinations and associated with their severity within the hallucinating group. This is the first study to provide evidence, using resting-state effective connectivity, to support a model of aberrant hierarchical predictive processing as the mechanism for visual hallucinations in Parkinson's disease.

2.
Heart Rhythm ; 2023 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-36693614

RESUMO

BACKGROUND: The TYRX absorbable antibacterial envelope has been shown to stabilize implantable cardiac devices and reduce infection. A third-generation envelope was developed to reduce surface roughness with a redesigned multifilament mesh and enhanced form-factor but identical polymer coating and antibiotic concentrations as the currently available second-generation envelope. OBJECTIVE: To compare drug elution, bacterial challenge efficacy, stabilization, and absorption of second- vs. third-generation envelopes. METHODS: Antibiotic elution was assessed in vitro and in vivo. For efficacy against gram+/gram- bacteria, 40 rabbits underwent device insertions with or without third-generation envelopes. For stabilization (migration, rotation), 5 sheep were implanted with 6 devices each in second- or third-generation envelopes. Pre-specified acceptance criteria were <83 mm migration and <90 degrees rotation. Absorption was assessed via gross pathology. RESULTS: Elution curves were equivalent (similarity factors ≥50 per FDA guidance). Third-generation envelopes eluted antibiotics above minimal inhibitory concentration (MIC) in vivo at 2hr post-implant through 7d, consistent with second-generation envelopes. Bacterial challenge showed reductions (p<0.05) in infection with second- and third-generation envelopes. Device migration was 5.5±3.5 (third-generation) vs. 9.9±7.9 mm (second-generation) (p<0.05). Device rotation was 18.9±11.4 (third-generation) vs. 17.6±15.1 degrees (second-generation) and did not differ (p=0.79). Gross pathology confirmed absence of luminal mesh remainders and no differences in peri-device fibrosis at 9 or 12wks. CONCLUSION: The third-generation TYRX absorbable antibacterial envelope demonstrated equivalent pre-clinical performance to the second-generation envelope: antibiotic elution curves were similar, elution was above MIC for 7d, infections were reduced compared to no envelope, and acceptance criteria for migration, rotation, and absorption were met.

3.
Kidney Med ; 5(2): 100585, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36712315

RESUMO

Rationale & Objective: There has been an increasing demand for the expertise provided by a renal genetics clinic. Such programs are limited in the United States and typically operate in a genomics research setting. Here we report a 3-year, real-world, single-center renal genetics clinic experience. Study Design: Retrospective cohort. Setting & Participants: Outpatient cases referred to the renal genetics clinic of the Cleveland Clinic between January 2019 and March 2022 were reviewed. Analytical Approach: Clinical and laboratory characteristics were analyzed. All genetic testing was performed in clinical labs. Results: 309 new patients referred from 15 specialties were evaluated, including 118 males and 191 females aged 35.1 ± 20.3 years. Glomerular diseases were the leading presentation followed by cystic kidney diseases, electrolyte disorders, congenital anomalies of kidneys and urinary tract, nephrolithiasis, and tubulointerstitial kidney diseases. Dysmorphic features were noted in 27 (8.7%) patients. Genetic testing was recommended in 292 (94.5%) patients including chromosomal microarray (8.9%), single-gene tests (19.5%), multigene panels (77.3%), and exome sequencing (17.5%). 80.5% of patients received insurance coverage for genetic testing. 45% (115/256) of patients had positive results, 25% (64/256) had variants of unknown significance, and 22.3% (57/256) had negative results. 43 distinct monogenic disorders were diagnosed. Family history of kidney disease was present in 52.8% of patients and associated with positive genetic findings (OR, 2.28; 95% CI, 1.40-3.74). 69% of patients with positive results received a new diagnosis and/or a change in the diagnosis. Among these, 39.7% (31/78) of patients received a significant change in disease management. Limitations: Retrospective and single-center study. Conclusions: The renal genetics clinic plays important roles in the diagnosis and management of patients with genetic kidney diseases. Multigene panels are the most frequently used testing modality with a high diagnostic yield. Family history of kidney disease is a strong indication for renal genetics clinic referral.

4.
Artigo em Inglês | MEDLINE | ID: mdl-36669898

RESUMO

BACKGROUND: Whole exome sequencing may identify rare pathogenic/likely pathogenic variants (LPVs) that are linked to atrial fibrillation (AF). The impact of LPVs associated with AF on a population level on outcomes is unclear. OBJECTIVES: This study sought to examine the association of LPVs with AF and their impact on clinical outcomes using the UK Biobank, a national repository of participants with available whole exome sequencing data. METHODS: A total of 200,631 individuals in the UK Biobank were studied. Incident and prevalent AF, comorbidities, and outcomes were identified using self-reported assessments and hospital stay operative, and death registry records. LPVs were determined using arrhythmia and cardiomyopathy gene panels with LOFTEE and ClinVar to predict variants of functional significance. RESULTS: Compared with control subjects, there was a modestly increased prevalence of LPVs among 9,585 patients with AF (2.0% vs 1.7%, respectively; P = 0.01). Among those with prevalent AF at <45 years of age, 4.2% were LPV carriers. LPVs in TTN and PKP2 were associated with AF with adjusted odds ratios of 2.69 (95% CI: 1.57-4.61) and 2.69 (95% CI: 1.54-4.68), respectively. There was no significant difference in combined ischemic stroke, heart failure hospitalization, and mortality among patients who have AF with and without LPVs (25.1% vs 23.8%; P = 0.49). Among participants with AF and available cardiac magnetic resonance imaging data, LPV carriers had lower left ventricular ejection fractions than non-LPV carriers (42% vs 52%; P = 0.027). CONCLUSIONS: Patients with AF had a modestly increased prevalence of LPVs. Among reference arrhythmia and cardiomyopathy genes, the contribution of rare variants to AF risk at a population level is modest and its impact on outcomes appears to be limited, despite an association of LPVs with reduced left ventricular ejection fraction among patients with AF.

6.
Front Robot AI ; 9: 1064853, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36530497

RESUMO

Road infrastructure is one of the most vital assets of any country. Keeping the road infrastructure clean and unpolluted is important for ensuring road safety and reducing environmental risk. However, roadside litter picking is an extremely laborious, expensive, monotonous and hazardous task. Automating the process would save taxpayers money and reduce the risk for road users and the maintenance crew. This work presents LitterBot, an autonomous robotic system capable of detecting, localizing and classifying common roadside litter. We use a learning-based object detection and segmentation algorithm trained on the TACO dataset for identifying and classifying garbage. We develop a robust modular manipulation framework by using soft robotic grippers and a real-time visual-servoing strategy. This enables the manipulator to pick up objects of variable sizes and shapes even in dynamic environments. The robot achieves greater than 80% classified picking and binning success rates for all experiments; which was validated on a wide variety of test litter objects in static single and cluttered configurations and with dynamically moving test objects. Our results showcase how a deep model trained on an online dataset can be deployed in real-world applications with high accuracy by the appropriate design of a control framework around it.

7.
Artigo em Inglês | MEDLINE | ID: mdl-36571159

RESUMO

INTRODUCTION: Left bundle branch area pacing (LBBP) has emerged as an alternative method for conduction system pacing. While initial experience with delivery systems for stylet-driven and lumenless lead implantation for LBBP has been described, data comparing outcomes of stylet-driven versus lumenless lead implantation for LBBP are limited. In this study, we compare success rates and outcomes of LBBP with stylet-driven versus lumenless lead delivery systems. METHODS: Eighty-three consecutive patients (mean age 74.1 ± 11.2 years; 56 [68%] male) undergoing attempted LBBP at a single institution were identified. Cases were grouped by lead delivery systems used: stylet-driven (n = 53) or lumenless (n = 30). Baseline characteristics and procedural findings were recorded and compared between the cohorts. Intermediate term follow-up data on ventricular lead parameters were also compared. RESULTS: Baseline characteristics were similar between groups. Successful LBBP was achieved in 77% of patients, with similar success rates between groups (76% in stylet-driven, 80% in lumenless, p = 0.79), and rates of adjudicated LBB capture and other paced QRS parameters were also similar. Compared with the lumenless group, the stylet-driven group had significantly shorter procedure times (90 ± 4 vs. 112 ± 31 min, p = 0.004) and fluoroscopy times (10 ± 5 vs. 15 ± 6 min, p = 0.003). Ventricular lead parameters at follow-up were similar, and rates of procedural complications and need for lead revision were low in both groups. CONCLUSION: Delivery systems for stylet-driven and for lumenless leads for LBBP have comparable acute success rates. Long-term follow-up of lead performance following use of the various delivery systems is warranted.

8.
Heart Rhythm O2 ; 3(5): 501-508, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36340480

RESUMO

Background: Limited real-world data exist on early outcomes in patients with heart failure with preserved ejection fraction (HFpEF) undergoing atrial fibrillation (AF) ablation. Objectives: The purpose of this study was to examine and compare rates of index procedural complications and 30-day readmissions after AF ablation in patients with HFpEF, with heart failure with reduced ejection fraction (HFrEF), and without heart failure. Methods: Using the Nationwide Readmissions Database (NRD), we examined 50,299 admissions of adults with heart failure undergoing AF catheter ablation between 2010 and 2014. Using ICD-9-CM codes, we identified procedural complications and causes of readmission after AF ablation. Results: From 2010 to 2014, the prevalence of HFpEF among patients undergoing AF ablation increased from 3.05% to 7.35% (P for trend <.001). Compared to patients without heart failure, patients with HFpEF had significantly increased procedural complications and index mortality (8.4% vs 6.2% and 0.30% vs 0.08%, respectively; P = .016 and P = .010, respectively). Index complication rates between patients with HFpEF and HFrEF were similar. All-cause 30-day readmissions occurred in 18.3% of patients with HFpEF compared to 9.5% of patients without heart failure (P <.001). Compared to no heart failure, the presence of HFpEF was independently associated with all-cause readmissions (adjusted odds ratio 1.52; 95% confidence interval 1.15-1.96; P = .002), but not with procedural complications, cardiac readmissions, or early mortality. Conclusion: Rates of 30-day readmissions after AF ablation are high in patients with HFpEF. However, after adjustment for age and comorbidities, complications and early mortality after AF ablation between patients with HFpEF and those without heart failure are comparable.

9.
Global Spine J ; : 21925682221139436, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36350144

RESUMO

STUDY DESIGN: Retrospective, propensity-matched analysis. OBJECTIVES: Cervical disc arthroplasty (CDA) is being increasingly utilized for cervical disc generation. Surgeon specialty has been shown to influence the risk for postoperative complications in spine surgery, but this has not yet been explored for CDA. Thus, the purpose of this study is to determine whether there is any difference in 30-day complications between patients undergoing single-level CDA by neurosurgeons vs by orthopaedic surgeons. METHODS: A retrospective, 1:1 propensity score matched analysis was performed using the NSQIP database from 2015 to 2020. Patient demographics, operative characteristics, and postoperative complications were recorded. Independent multivariate logistic regression models were constructed using the propensity-matched dataset to assess surgical specialty influence on any complication, any site complication, any operative infection, and any medical complications. RESULTS: 3179 single-level CDAs (28.8% orthopaedic surgery patients, 71.2% neurosurgery patients) were identified that met the inclusion criteria. Well-matched cohorts of 916 patients each were generated. After controlling for all possible confounders, orthopedic surgery specialty was not associated with a higher odds for any complication (OR: .87, 95% CI: .35 - 2.20, P = .7696), any site complication (OR: .32, 95% CI: .08 - 1.32, P = .1359), any operative infection (OR: .31, 95% CI: .07 - 1.34), P = .1172), nor any medical complication (OR: 2.11, 95% CI: .62 - 7.20, P = .2311) vs neurosurgery. CONCLUSION: This is the first propensity-matched analysis to show that spine surgeon specialty does not influence the risk for any complication, any site complication, any operative infection, nor any medical complication following single-level CDA within the first 30 days after surgery.

10.
Cancer Res ; 82(21): 3888-3902, 2022 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-36251389

RESUMO

Analysis of DNA methylation is a valuable tool to understand disease progression and is increasingly being used to create diagnostic and prognostic clinical biomarkers. While conversion of cytosine to 5-methylcytosine (5mC) commonly results in transcriptional repression, further conversion to 5-hydroxymethylcytosine (5hmC) is associated with transcriptional activation. Here we perform the first study integrating whole-genome 5hmC with DNA, 5mC, and transcriptome sequencing in clinical samples of benign, localized, and advanced prostate cancer. 5hmC is shown to mark activation of cancer drivers and downstream targets. Furthermore, 5hmC sequencing revealed profoundly altered cell states throughout the disease course, characterized by increased proliferation, oncogenic signaling, dedifferentiation, and lineage plasticity to neuroendocrine and gastrointestinal lineages. Finally, 5hmC sequencing of cell-free DNA from patients with metastatic disease proved useful as a prognostic biomarker able to identify an aggressive subtype of prostate cancer using the genes TOP2A and EZH2, previously only detectable by transcriptomic analysis of solid tumor biopsies. Overall, these findings reveal that 5hmC marks epigenomic activation in prostate cancer and identify hallmarks of prostate cancer progression with potential as biomarkers of aggressive disease. SIGNIFICANCE: In prostate cancer, 5-hydroxymethylcytosine delineates oncogene activation and stage-specific cell states and can be analyzed in liquid biopsies to detect cancer phenotypes. See related article by Wu and Attard, p. 3880.


Assuntos
5-Metilcitosina , Neoplasias da Próstata , Masculino , Humanos , Próstata , Biópsia
11.
Artigo em Inglês | MEDLINE | ID: mdl-36229363

RESUMO

OBJECTIVE: Extranodal extension (ENE) is an important prognostic factor in oral squamous cell carcinoma (OSCC). However, ENE is only confirmed postoperatively by histologic assessment of the lymph nodes after neck dissection. Accurate identification of ENE preoperatively would help in management of OSCC. STUDY DESIGN: We determined the expression of molecular markers gamma glutamyl hydrolase (GGH), cyclin-dependent kinase inhibitor-3 (CDKN3), and chromobox homolog-7 (CBX7) using immunohistochemistry in OSCC clinical samples (n = 35). The intensity of staining was scored using a semiquantitative index (HSCORE). The association between clinicopathologic parameters and expression of molecular markers with ENE status was analyzed using chi-square test. RESULTS: The number of positive nodes and the highest anatomic level of nodal involvement significantly correlated with ENE (P < .05). High GGH expression was significantly associated with ENE (P < .05), with an increased risk for ENE (odds ratio [OR] 9.9, 95% CI 1.08-91.47, P = .04), whereas no significant association was seen for CDKN3 and CBX7 expression with ENE. However, a trend toward significance was observed with a high level of CDKN3 and a low level of CBX7 expression with ENE. CONCLUSIONS: Gamma glutamyl hydrolase offers potential as a predictor for ENE in OSCC, whereas the role of CDKN3 and CBX7 need to be validated in a larger sample.

12.
Front Immunol ; 13: 954567, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119104

RESUMO

Oral potentially malignant disorders (OPMD) are precursors of oral squamous cell carcinoma (OSCC), and the presence of oral epithelial dysplasia (OED) in OPMD confers an increased risk of malignant transformation. Emerging evidence has indicated a role for the immune system in OPMD disease progression; however, the underlying immune mechanisms remain elusive. In this study, we used immune signatures established from cancer to delineate the immune profiles of moderate and severe OED, which are considered high-risk OPMD. We demonstrated that moderate and severe OEDs exhibit high lymphocyte infiltration and upregulation of genes involved in both immune surveillance (major histocompatibility complex-I, T cells, B cells and cytolytic activity) and immune suppression (immune checkpoints, T regulatory cells, and tumor-associated macrophages). Notably, we identified three distinct subtypes of moderate and severe OED: immune cytotoxic, non-cytotoxic and non-immune reactive. Active immune surveillance is present in the immune cytotoxic subtype, whereas the non-cytotoxic subtype lacks CD8 immune cytotoxic response. The non-immune reactive subtype showed upregulation of genes involved in the stromal microenvironment and cell cycle. The lack of T cell infiltration and activation in the non-immune reactive subtype is due to the dysregulation of CTNNB1, PTEN and JAK2. This work suggests that moderate and severe OED that harbor the non-cytotoxic or non-immune reactive subtype are likely to progress to cancer. Overall, we showed that distinct immune responses are present in high-risk OPMD, and revealed targetable pathways that could lead to potential new approaches for non-surgical management of OED.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Bucais , Lesões Pré-Cancerosas , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Transformação Celular Neoplásica/genética , Humanos , Hiperplasia , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Lesões Pré-Cancerosas/genética , Microambiente Tumoral/genética
13.
Nat Commun ; 13(1): 5345, 2022 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-36109521

RESUMO

The androgen receptor (AR) signaling inhibitor enzalutamide (enza) is one of the principal treatments for metastatic castration-resistant prostate cancer (CRPC). Several emergent enza clinical resistance mechanisms have been described, including lineage plasticity in which the tumors manifest reduced dependency on the AR. To improve our understanding of enza resistance, herein we analyze the transcriptomes of matched biopsies from men with metastatic CRPC obtained prior to treatment and at progression (n = 21). RNA-sequencing analysis demonstrates that enza does not induce marked, sustained changes in the tumor transcriptome in most patients. However, three patients' progression biopsies show evidence of lineage plasticity. The transcription factor E2F1 and pathways linked to tumor stemness are highly activated in baseline biopsies from patients whose tumors undergo lineage plasticity. We find a gene signature enriched in these baseline biopsies that is strongly associated with poor survival in independent patient cohorts and with risk of castration-induced lineage plasticity in patient-derived xenograft models, suggesting that tumors harboring this gene expression program may be at particular risk for resistance mediated by lineage plasticity and poor outcomes.


Assuntos
Fator de Transcrição E2F1 , Neoplasias de Próstata Resistentes à Castração , Antagonistas de Receptores de Andrógenos/farmacologia , Benzamidas , Biópsia , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Fator de Transcrição E2F1/metabolismo , Humanos , Masculino , Nitrilas , Feniltioidantoína , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/metabolismo , RNA , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo
14.
Res Sports Med ; : 1-8, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36111698

RESUMO

In order to reduce shoulder, upper arm and elbow injury rates in American football, identifying injury risk factors and any underlying associations is needed. No prior study has done such characterization at the high school level. A descriptive epidemiology study was performed using data from the National Athletic Treatment, Injury, and Outcomes Network Surveillance Program (NATION-SP) from the years 2011/12 to 2013/14 on high school football athletes. Four hundred and sixty total injuries were found in the dataset. Acromioclavicular (AC) sprains had the highest incidence of all injuries (0.060 injuries per 1000 exposures). Fractures lead to the greatest time lost (42.24 days). Most injuries occurred in older athletes (juniors and seniors, 30% and 32%, respectively), were related to tackling (31%), and in running back and linebacker positions (15% each). Orthopaedic surgeons and other sports medicine specialists can use these findings to educate players, coaches and families about injury risks and for improving injury prevention guidelines.

15.
World J Microbiol Biotechnol ; 38(11): 213, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36053362

RESUMO

The soils of Lakshadweep Islands are formed as a result of the fragmentation of coral limestone, that is carbonate-rich, with neutral pH, but poor in plant nutrients. Coconut palm (Cocos nucifera L.) is the main crop cultivated, supporting the life and livelihood of the islanders. No external fertilizer application or major plant protection measures are adopted for their cultivation as the Islands were declared to go organic decades back. Yet, Lakshadweep has one of the highest productivity of coconut compared with other coconut growing areas in India. Therefore, a question arises: how is such a high coconut productivity sustained? We try to answer by estimating in three main islands (i) the nutrients added to the soil via the litter generated by coconut palms and (ii) the role of soil microbiota, including arbuscular mycorrhizae, for the high productivity. Our results indicated that, besides adding a substantial quantum of organic carbon, twice the needed amount of nitrogen, extra 20% phosphorus to the already P-rich soils, 43-45% of potassium required by palms could be easily met by the total coconut biomass residues returned to the soil. Principal Component Analysis showed that soil organic carbon %, potassium, and organic carbon added via the palm litter and AM spore load scored >± 0.95 in PC1, whereas, available K in the soil, bacteria, actinomycetes, phosphate solubilizers and fluorescent pseudomonads scored above >± 0.95 in PC2. Based on our analysis, we suggest that the autochthonous nutrients added via the coconut biomass residues, recycled by the soil microbial communities, could be one of the main reasons for sustaining a high productivity of the coconut palms in Lakshadweep Islands, in the absence of any external fertilizer application, mimicking a semi-closed-loop forest ecosystem.


Assuntos
Fertilizantes , Microbiota , Carbono/análise , Cocos , Fertilizantes/análise , Nitrogênio/análise , Nutrientes/análise , Plantas , Potássio/análise , Solo/química , Microbiologia do Solo
16.
Anat Rec (Hoboken) ; 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-36054304

RESUMO

The growth and development of long bones are of considerable interests in the fields of comparative anatomy and palaeoanthropology, as evolutionary changes and adaptations to specific physical activity patterns are expected to be revealed during bone ontogeny. Traditionally, the cross-sectional geometry of long bones has been examined at discrete locations usually placed at set intervals or fixed percentage distances along the midline axis of the bone shaft. More recently, the technique of morphometric mapping has enabled the continuous analysis of shape variation along the shaft. Here we extend this technique to the full sequence of late fetal and postnatal development of the humeral shaft in a modern human population sample, with the aim of establishing the shape changes during growth and their relationship with the development of the arm musculature and activity patterns. A sample of modern human humeri from individuals of age ranging from 24 weeks in utero to 18 years was imaged using microtomography at multiple resolutions and custom Matlab scripts. Standard biomechanical properties, cortical thickness, surface curvature, and pseudo-landmarks were extracted along radial vectors spaced at intervals of 1° at each 0.5% longitudinal increment measured along the shaft axis. Heat maps were also generated for cortical thickness and surface curvature. The results demonstrate that a whole bone approach to analysis of cross-sectional geometry is more desirable where possible, as there is a continuous pattern of variation along the shaft. It is also possible to discriminate very young individuals and adolescents from other groups by relative cortical thickness, and also by periosteal surface curvature.

17.
Kidney360 ; 3(7): 1253-1262, 2022 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-35919535

RESUMO

Background: Adjudication of inpatient AKI in the Systolic Blood Pressure Intervention Trial (SPRINT) was based on billing codes and admission and discharge notes. The purpose of this study was to evaluate the effect of intensive versus standard BP control on creatinine-based inpatient and outpatient AKI, and whether AKI was associated with cardiovascular disease (CVD) and mortality. Methods: We linked electronic health record (EHR) data from 47 clinic sites with trial data to enable creatinine-based adjudication of AKI. Cox regression was used to evaluate the effect of intensive BP control on the incidence of AKI, and the relationship between incident AKI and CVD and all-cause mortality. Results: A total of 3644 participants had linked EHR data. A greater number of inpatient AKI events were identified using EHR data (187 on intensive versus 155 on standard treatment) as compared with serious adverse event (SAE) adjudication in the trial (95 on intensive versus 61 on standard treatment). Intensive treatment increased risk for SPRINT-adjudicated inpatient AKI (HR, 1.51; 95% CI, 1.09 to 2.08) and for creatinine-based outpatient AKI (HR, 1.40; 95% CI, 1.15 to 1.70), but not for creatinine-based inpatient AKI (HR, 1.20; 95% CI, 0.97 to 1.48). Irrespective of the definition (SAE or creatinine based), AKI was associated with increased risk for all-cause mortality, but only creatinine-based inpatient AKI was associated with increased risk for CVD. Conclusions: Creatinine-based ascertainment of AKI, enabled by EHR data, may be more sensitive and less biased than traditional SAE adjudication. Identifying ways to prevent AKI may reduce mortality further in the setting of intensive BP control.


Assuntos
Injúria Renal Aguda , Doenças Cardiovasculares , Hipertensão , Injúria Renal Aguda/epidemiologia , Anti-Hipertensivos/efeitos adversos , Pressão Sanguínea , Doenças Cardiovasculares/epidemiologia , Creatinina/farmacologia , Registros Eletrônicos de Saúde , Humanos , Hipertensão/complicações , Fatores de Risco , Resultado do Tratamento
19.
J Proteome Res ; 21(9): 2237-2245, 2022 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-35916235

RESUMO

Formalin-fixed, paraffin-embedded (FFPE) tissues are banked in large repositories to cost-effectively preserve valuable specimens for later study. With the rapid growth of spatial proteomics, FFPE tissues can serve as a more accessible alternative to more commonly used frozen tissues. However, extracting proteins from FFPE tissues is challenging due to cross-links formed between proteins and formaldehyde. Here, we have adapted the nanoPOTS sample processing workflow, which was previously applied to single cells and fresh-frozen tissues, to profile protein expression from FFPE tissues. Following the optimization of extraction solvents, times, and temperatures, we identified an average of 1312 and 3184 high-confidence master proteins from 10 µm thick FFPE-preserved mouse liver tissue squares having lateral dimensions of 50 and 200 µm, respectively. The observed proteome coverage for FFPE tissues was on average 88% of that achieved for similar fresh-frozen tissues. We also characterized the performance of our fully automated sample preparation and analysis workflow, termed autoPOTS, for FFPE spatial proteomics. This modified nanodroplet processing in one pot for trace samples (nanoPOTS) and fully automated processing in one pot for trace sample (autoPOTS) workflows provides the greatest coverage reported to date for high-resolution spatial proteomics applied to FFPE tissues. Data are available via ProteomeXchange with identifier PXD029729.


Assuntos
Proteômica , Espectrometria de Massas em Tandem , Animais , Formaldeído , Camundongos , Inclusão em Parafina/métodos , Proteoma/análise , Proteômica/métodos , Espectrometria de Massas em Tandem/métodos , Fixação de Tecidos
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