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Starch degradation in chloroplasts requires ß-amylase (BAM) activity, which is encoded by a multigene family. Of nine Arabidopsis (Arabidopsis thaliana) BAM genes, six encode plastidic enzymes, but only four of these are catalytically active. In vegetative plants, BAM1 acts during the day in guard cells, whereas BAM3 is the dominant activity in mesophyll cells at night. Plastidic BAMs have been difficult to assay in leaf extracts, in part because of a cytosolic activity encoded by BAM5. We generated a series of double mutants lacking BAM5 and each of the active plastidic enzymes (BAM1, BAM2, BAM3, and BAM6) and found that most of the plastidic activity in 5-week-old plants was encoded by BAM1 and BAM3. Both of these activities were relatively constant during the day and the night. Analysis of leaf extracts from double mutants and purified BAM1 and BAM3 proteins revealed that these proteins have distinct properties. Using soluble starch as the substrate, BAM1 and BAM3 had optimum activity at pH 6.0 to 6.5, but at high pH, BAM1 was more active than BAM3, consistent with its known daytime role in the guard cell stroma. The optimum temperature for BAM1, which is transcriptionally induced by heat stress, was about 10°C higher than that of BAM3, which is transcriptionally induced by cold stress. The amino acid composition of BAM1 and BAM3 orthologs reflected differences that are consistent with known adaptations of proteins from heat- and cold-adapted organisms, suggesting that these day- and night-active enzymes have undergone thermal adaptation.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/enzimología , Regulación Enzimológica de la Expresión Génica , Proteínas Serina-Treonina Quinasas/metabolismo , Arabidopsis/genética , Arabidopsis/fisiología , Proteínas de Arabidopsis/genética , Cloroplastos/enzimología , Citosol/metabolismo , Regulación de la Expresión Génica de las Plantas , Calor , Concentración de Iones de Hidrógeno , Familia de Multigenes , Mutación , Hojas de la Planta/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Almidón/metabolismo , Estrés FisiológicoRESUMEN
OBJECTIVE: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and globus pallidus interna (GPi) have differential therapeutic effects for Parkinson's disease (PD) that drive patient selection. For example, GPi DBS is preferred for dystonic features and dyskinesia, whereas STN DBS has shown faster tremor control and medication reduction. Connectivity studies comparing these two targets, using patient-specific data, are still lacking. The objective was to find STN and GPi structural connectivity patterns in order to better understand differences in DBS-activated brain circuits between these two stimulation targets and to guide optimal contact selection. METHODS: The authors simulated DBS activation along the main axis of both the STN and GPi by using volume of activated tissue (VAT) modeling with known average stimulation parameters (2.8 V and 60 µsec for STN; 3.3 V and 90 µsec for GPi). The authors modeled VATs in the anterior, middle, and posterior STN and the anterior, midanterior, midposterior, and posterior GPi. The authors generated maps of the connections shared by the patients for each VAT by using probabilistic tractography of diffusion-weighted imaging data obtained in 46 PD patients who underwent DBS (26 with STN and 20 with GPi targeting), and differences between VATs for whole-brain and distal regions of interest (prefrontal cortex, supplementary motor area, primary motor cortex, primary sensory cortex, caudate, motor thalamus, and cerebellum) were generated from structural atlases. Differences between maps were quantified and compared. RESULTS: VATs across the STN and GPi had different structural connectivity patterns. The authors found significant connectivity differences between VATs for all regions of interest. Posterior and middle STN showed stronger connectivity to the primary motor cortex and supplementary motor area (SMA) (p < 0.001). Posterior STN had the strongest connectivity to the primary sensory cortex and motor thalamus (p < 0.001). Posterior GPi showed stronger connectivity to the primary motor cortex (p < 0.001). Connectivity to the SMA was similar for the posterior and midposterior GPi (p > 0.05), which was greater than that for the anterior GPi (p < 0.001). When both nuclei were compared, posterior and middle STN had stronger connectivity to the SMA, cerebellum, and motor thalamus than GPi (all p < 0.001). Posterior GPi and STN had similar connectivity to the primary sensory cortex. CONCLUSIONS: On patient-specific imaging, structural connectivity differences existed between GPi and STN DBS, as measured with standardized electrical field modeling of the DBS targets. These connectivity differences may correlate with the differential clinical benefits obtained by targeting each of the two nuclei with DBS for PD. Prospective work is needed to relate these differences to clinical outcomes and to inform targeting and programming.
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Estimulación Encefálica Profunda , Enfermedad de Parkinson , Núcleo Subtalámico , Sustancia Blanca , Humanos , Núcleo Subtalámico/diagnóstico por imagen , Globo Pálido/diagnóstico por imagen , Globo Pálido/fisiología , Estimulación Encefálica Profunda/métodos , Estudios Prospectivos , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/terapiaRESUMEN
BACKGROUND: The Knosp criteria have been the historical standard for predicting cavernous sinus invasion, and therefore extent of surgical resection, of pituitary macroadenomas. Few studies have sought to reappraise the utility of this tool after recent advances in visualization and modeling of tumors in complex endoscopic surgery. OBJECTIVE: To evaluate our proposed alternative method, using 3-dimensional (3D) volumetric imaging, and whether it can better predict extent of resection in nonfunctional pituitary adenomas. METHODS: Patients who underwent endoscopic transsphenoidal resection of pituitary macroadenomas at our institution were reviewed. Information was collected on neurological, endocrine, and visual function. Volumetric segmentation was performed using 3D Slicer software. Relationship of tumor volume, clinical features, and Knosp grade on extent of resection was examined. RESULTS: One hundred forty patients were identified who had transsphenoidal resection of nonfunctional pituitary adenomas. Macroadenomas had a median volume of 6 cm 3 (IQR 3.4-8.7), and 17% had a unilateral Knosp grade of at least 3B. On multiple logistic regression, only smaller log-transformed preoperative tumor volume was independently associated with increased odds of gross total resection (GTR; odds ratio: 0.27, 95% CI: 0.07-0.89, P < .05) when controlling for tumor proliferative status, age, and sex (area under the curve 0.67). The Knosp criteria did not independently predict GTR in this cohort ( P > .05, area under the curve 0.46). CONCLUSION: Increasing use of volumetric 3D imaging may better anticipate extent of resection compared with the Knosp grade metric and may have a greater positive predictive value for GTR. More research is needed to validate these findings and implement them using automated methods.
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Adenoma , Neoplasias Hipofisarias , Humanos , Neoplasias Hipofisarias/diagnóstico por imagen , Neoplasias Hipofisarias/cirugía , Neoplasias Hipofisarias/patología , Adenoma/diagnóstico por imagen , Adenoma/cirugía , Adenoma/patología , Estudios Retrospectivos , Resultado del Tratamiento , Endoscopía/métodosRESUMEN
For accurate diagnosis of interstitial lung disease (ILD), a consensus of radiologic, pathological, and clinical findings is vital. Management of ILD also requires thorough follow-up with computed tomography (CT) studies and lung function tests to assess disease progression, severity, and response to treatment. However, accurate classification of ILD subtypes can be challenging, especially for those not accustomed to reading chest CTs regularly. Dynamic models to predict patient survival rates based on longitudinal data are challenging to create due to disease complexity, variation, and irregular visit intervals. Here, we utilize RadImageNet pretrained models to diagnose five types of ILD with multimodal data and a transformer model to determine a patient's 3-year survival rate. When clinical history and associated CT scans are available, the proposed deep learning system can help clinicians diagnose and classify ILD patients and, importantly, dynamically predict disease progression and prognosis.
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Enfermedades Pulmonares Intersticiales , Humanos , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Progresión de la Enfermedad , Tórax , Tomografía Computarizada por Rayos X/métodos , Estudios Retrospectivos , Pulmón/diagnóstico por imagenRESUMEN
INTRODUCTION: Interpretation of high-resolution CT images plays an important role in the diagnosis and management of interstitial lung diseases. However, interreader variation may exist due to varying levels of training and expertise. This study aims to evaluate interreader variation and the role of thoracic radiology training in classifying interstitial lung disease (ILD). METHODS: This is a retrospective study where seven physicians (radiologists, thoracic radiologists, and a pulmonologist) classified the subtypes of ILD of 128 patients from a tertiary referral center, all selected from the Interstitial Lung Disease Registry which consists of patients from November 2014 to January 2021. Each patient was diagnosed with a subtype of interstitial lung disease by a consensus diagnosis from pathology, radiology, and pulmonology. Each reader was provided with only clinical history, only CT images, or both. Reader sensitivity and specificity and interreader agreements using Cohen's κ were calculated. RESULTS: Interreader agreement based only on clinical history, only on radiologic information, or combination of both was most consistent amongst readers with thoracic radiology training, ranging from fair (Cohen's κ: 0.2-0.46), moderate to almost perfect (Cohen's κ: 0.55-0.92), and moderate to almost perfect (Cohen's κ: 0.53-0.91) respectively. Radiologists with any thoracic training showed both increased sensitivity and specificity for NSIP as compared to other radiologists and the pulmonologist when using only clinical history, only CT information, or combination of both (p < 0.05). CONCLUSIONS: Readers with thoracic radiology training showed the least interreader variation and were more sensitive and specific at classifying certain subtypes of ILD. SUMMARY SENTENCE: Thoracic radiology training may improve sensitivity and specificity in classifying ILD based on HRCT images and clinical history.
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Enfermedades Pulmonares Intersticiales , Radiología , Humanos , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/patología , Radiografía Torácica , Radiología/educación , Pulmón/patologíaRESUMEN
OBJECTIVE: BI-RADS 0 screening mammograms require follow-up diagnostic imaging, optimally within 60 days. Our study aims to identify risk factors for delayed follow-up. METHODS: We conducted a retrospective case-control study of individuals who had a nondiagnostic BI-RADS 0 screening mammogram between March 19, 2018, and March 19, 2020. Sociodemographic information was collected from a self-reported questionnaire. We aimed to identify factors associated with <60-day follow-up, >60-day follow-up, or no follow-up outcomes. The χ2 test and univariate logistic regressions were performed. Significant variables were included in multinomial logistic regression. We also aimed to identify risk factors that lead to delayed follow-up times among individuals with follow-up. Spearman's correlation and Mann-Whitney Wilcoxon tests and Kruskal-Wallis tests were performed. RESULTS: Review returned 5,034 screening mammograms. Of 4,552 individuals included, 904 (19.9%) had no follow-up. Of the 3,648 (80.1%) with follow-up, 2,797 (76.7%) had a follow-up <60 days (median 20 days) and 851 (23.3%) had follow-up >60 days (median 176 days). Multinomial regression found that Asian (P = .022), Black (P < .0001), and individuals who identified their race as other (P < .0001) were independently more likely to have no or >60-day follow-up. Individuals who did not report their race (P = .001) or completed the questionnaire in Spanish (P = .025) were more likely to have no or >60-day follow-up. Among individuals with follow-up, Black individuals (P < .0001), those who identified their race as other (P < .0001), Hispanic individuals (P = .04), and those who completed the questionnaire in Spanish (P < .0001) had follow-up delays. BRCA-positive individuals had shorter follow-up times (P = .021). DISCUSSION: Follow-up time is affected by cancer risk factors such as BRCA status in addition to race, preferred language, and Hispanic ethnicity.
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Neoplasias de la Mama , Mamografía , Humanos , Femenino , Detección Precoz del Cáncer , Estudios Retrospectivos , Estudios de Casos y Controles , Neoplasias de la Mama/diagnóstico por imagen , Factores de Riesgo , Tamizaje Masivo/métodosRESUMEN
STUDY DESIGN: A retrospective analysis of data from the Healthcare Cost and Utilization Project Nationwide Readmissions Database (HCUP-NRD). PURPOSE: To identify the perioperative characteristics associated with 30-day and 90-day readmission due to intestinal bowel obstructions (IBOs) following posterior lumbar fusion (PLF) procedure. OVERVIEW OF LITERATURE: PLF procedures are used to repair spinal injuries and curvature deformities. IBO is a common surgical complication and its repair often necessitates surgery that increases the readmission rates and healthcare costs. Previous studies have identified the preoperative risk factors for 30-day readmissions in PLF; however, no study has specifically investigated IBO or identified risk factors for 90-day readmissions. METHODS: Data on demographic characteristics and medical comorbidities of patients who underwent PLF with subsequent readmission were obtained from the HCUP-NRD. The perioperative characteristics that were significantly different between patients readmitted with and without an active diagnosis of IBO were identified with bivariate analysis for both 30-day and 90-day readmissions. The significant characteristics were then included in a multivariate analysis to identify those that were independently associated with 30- day and 90-day readmissions. RESULTS: Drug abuse (odds ratio [OR], 4.00), uncomplicated diabetes (OR, 2.06), having Medicare insurance (OR, 1.65), age 55-64 years (OR, 2.42), age 65-79 years (OR, 2.77), and age >80 years (OR, 3.87) were significant risk factors for 30-day readmission attributable to IBO after a PLF procedure. CONCLUSIONS: Of the several preoperative risk factors identified for readmission with IBO after PLF surgery, drug abuse had the strongest association and was likely to be the most clinically relevant factor. Physicians and care teams should understand the risks of opioid-based pain management regimens, attempt to manage pain with a multimodal approach, and minimize the opioid use.
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BACKGROUND AND PURPOSE: Despite increasing demand for fluoroscopy-guided lumbar puncture (FG-LP), there is limited quantitative and epidemiological data on patients undergoing this procedure. Additionally, data are scarce on the correlation of iliac crest landmarks to the actual anatomical lumbar level (intercristal line). The aim of this study is to determine if (1) body mass index (BMI) correlates with skin to spinal canal distance (SCD) and (2) the iliac crest landmark correlates with the presumed anatomical landmark on cross-sectional imaging. METHODS: In this retrospective, single-center IRB-approved study, we assessed 495 patients who underwent FG-LP and had lumbar computed tomography/magnetic resonance imaging within 6 months of presentation. SCD was measured on the sagittal view at the L3-L4, L4-L5, and L5-S1 intervertebral levels. RESULTS: In our cohort of 495 adults (mean age ± standard deviation [SD], 53.2 ± 16.4 years), there was a statistically significant linear correlation between BMI and SCD at each intervertebral level. Mean ± SD (R2 ) SCD at L3-4, L4-5, and L5-S1 was 6.7 ± 1.6 cm (.5486), 7.4 ± 1.9 cm (.5894), and 7.8 ± 1.9 cm (.5968), respectively. The intercristal line aligned with L3-L4, L4-L5, and L5-S1 in 2.1%, 72.4%, and 6.2% of patients, respectively. CONCLUSIONS: There was direct, positive linear correlation between BMI and SCD at clinically relevant lumbar disc levels. Furthermore, there is considerable anatomical variance in the intervertebral space that aligns with the superior aspect of the iliac crest.
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Índice de Masa Corporal , Región Lumbosacra/diagnóstico por imagen , Canal Medular/diagnóstico por imagen , Adulto , Anciano , Antropometría , Estudios de Cohortes , Femenino , Fluoroscopía , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Punción Espinal , Tomografía Computarizada por Rayos XRESUMEN
Outpatient-based sharp debridement is considered an important element for the care of a chronic ulcer. OBJECTIVE: The aim of this study is to evaluate the change in bacterial amounts with sharp debridement in a clinical setting. MATERIALS AND METHODS: Bacterial autofluorescence, quantitative cultures, semiquantitative cultures, and qualitative speciation were performed predebridement and postdebridement during a single clinic visit. RESULTS: Thirty-six wounds were included in the analysis. The mean patient age was 62 years (range, 27-83 years), and there were 13 (36.11%) women and 23 (63.89%) men with an average body mass index of 33.8 kg/m² (range, 16.7-55.9 kg/m²). Of the 36 patients, 24 (66.67%) had type 2 diabetes and 19 (52.78%) had a prior history of lower extremity amputation. Majority of the ulcers were diabetic neuropathic (27, 75%); the most common location was on the plantar aspect of the foot (14, 41.67%) with a mean ulcer duration of 10 months (range, 1-36), mean ulcer area of 6.3 ± 12.8 cm² (range, 0.18-62.06 cm²), and mean volume of 2.2 ± 4.4 cm³ (range, 0.05-9.66 cm³). There was no statistically significant difference in bacterial autofluorescence between the predebridement (4.15 ± 8.82) and the postdebridement (4.65 ± 9.48) images (P = .32). There was a statistically significant difference in quantitative culture results between the predebridement (6.7 x 104 ± 1.4 x 106 CFU/cm²) and the postdebridement (1.7 x 104 ± 3.1 x 106 CFU/cm²) cultures (P = .04), although this is not a log reduction. CONCLUSIONS: There is no statistically significant difference between the predebridement versus postdebridement semiquantitative culture results or a detectable pattern of change for the most common bacterial species encountered. These results suggest little impact of clinic-based sharp debridement on bacteria.