ABSTRACT
Vascular remodeling is the process of structural alteration and cell rearrangement of blood vessels in response to injury and is the cause of many of the world's most afflicted cardiovascular conditions, including pulmonary arterial hypertension (PAH). Many studies have focused on the effects of vascular endothelial cells and smooth muscle cells (SMCs) during vascular remodeling, but pericytes, an indispensable cell population residing largely in capillaries, are ignored in this maladaptive process. Here, we report that hypoxia-inducible factor 2α (HIF2α) expression is increased in the lung tissues of PAH patients, and HIF2α overexpressed pericytes result in greater contractility and an impaired endothelial-pericyte interaction. Using single-cell RNAseq and hypoxia-induced pulmonary hypertension (PH) models, we show that HIF2α is a major molecular regulator for the transformation of pericytes into SMC-like cells. Pericyte-selective HIF2α overexpression in mice exacerbates PH and right ventricular hypertrophy. Temporal cellular lineage tracing shows that HIF2α overexpressing reporter NG2+ cells (pericyte-selective) relocate from capillaries to arterioles and co-express SMA. This novel insight into the crucial role of NG2+ pericytes in pulmonary vascular remodeling via HIF2α signaling suggests a potential drug target for PH.
Subject(s)
Hypertension, Pulmonary , Vascular Remodeling , Mice , Humans , Animals , Pericytes/metabolism , Endothelial Cells/metabolism , Hypertension, Pulmonary/genetics , Hypertension, Pulmonary/metabolism , Hypoxia/genetics , Hypoxia/metabolism , LungABSTRACT
INTRODUCTION: The study explored the failure pattern and clinical outcomes in patients with ependymoma undergoing radiotherapy. METHODS: Between January 2004 and June 2022, we included 32 patients with ependymoma who underwent radiotherapy as part of the multimodality treatment at our institution. Of these, 27 (84.4%) underwent adjuvant radiotherapy, four received radiotherapy after local recurrence, and one received definitive CyberKnife radiotherapy (21 Gy in three fractions). The median prescribed dose was 54 Gy in patients who received conventional radiotherapy. We analyzed the local progression-free survival (LPFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), overall survival (OS), and potential prognostic factors. RESULTS: The median age was 29.8 years. Approximately 28.1% were pediatric patients. Fifteen tumors (46.9%) were World Health Organization (WHO) grade II, 10 (31.3%) were WHO grade III, and seven (22.8%) were WHO grade I. Among them, 15 patients (46.9%) had posterior fossa tumors, 10 (31.3%) had supratentorial tumors, and seven (22.8%) had spinal tumors. Of the 31 patients who underwent upfront surgical resection, 19 (61.3%) underwent gross total resection or near total resection. Seventeen of 19 patients with first failures (89.5%) had isolated local recurrences. Of the 19 patients with disease progression, 11 (57.9%) were disease-free or had stable disease after salvage therapy, and five (26.3%) had disease-related mortality. Most of the first local recurrences after radiotherapy occurred in the infield (13 of 16, 81.3%). The 5-year LPFS, DMFS, PFS, and OS rates were 48.5%, 89.6%, 45.1%, and 88.4%, respectively, at a median follow-up of 6.25 years. Subtotal resection was associated with poorer LPFS and PFS in patients with intracranial ependymoma (hazard ratio = 3.69, p = 0.018 for LPFS; hazard ratio = 3.20, p = 0.029 for PFS). CONCLUSION: Incorporating radiotherapy into multimodal treatment has led to favorable outcomes in patients with ependymoma, and the extent of resection is a prognostic factor for the local control of intracranial ependymoma.
ABSTRACT
Selection criteria for clinical trials for medication-resistant epilepsy are used to limit variability and to ensure safety. However, it has become more challenging to recruit subjects for trials. This study investigated the impact of each inclusion and exclusion criterion on medication-resistant epilepsy clinical trial recruitment at a large academic epilepsy center. We retrospectively identified all patients with medication-resistant focal or generalized onset epilepsy who attended an outpatient clinic over a consecutive 3-month period. We assessed each patient's eligibility for trials with commonly required inclusion and exclusion criteria to evaluate the proportion of eligible patients and the most common reasons for exclusion. Among 212 patients with medication-resistant epilepsy, 144 and 28 patients met the criteria for focal or generalized onset epilepsy, respectively. Overall, 9.4% (n = 20) patients were eligible for trials (19 focal onset and one generalized onset). Most patients were excluded from the study due to insufficient seizure frequency (58% of focal onset, 55% of generalized onset). A small proportion of patients with medication-resistant epilepsy were eligible for trials based on common selection criteria. These eligible patients may not be representative of the general population of patients with medication-resistant epilepsy. Insufficient seizure frequency was the most common reason for exclusion.
Subject(s)
Drug Resistant Epilepsy , Epilepsy, Generalized , Epilepsy , Humans , Anticonvulsants/therapeutic use , Retrospective Studies , Seizures/drug therapy , Epilepsy/drug therapy , Drug Resistant Epilepsy/drug therapy , Epilepsy, Generalized/drug therapyABSTRACT
OBJECTIVE: To estimate the impact of opting into the community eligibility provision (CEP) on school meal participation among students in Texas. DESIGN: A quasi-experimental design using a two-way fixed effects panel difference-in-difference model and the variation in adoption timing to estimate the impact of opting into CEP on student breakfast and lunch participation in eligible, ever-adopting schools. SETTING: All public and charter K-12 schools in Texas participating in national school meals (breakfast and/or lunch) from 2013 to 2019 who are eligible for the CEP program in at least 1 year and choose to opt into the program in at least 1 year (n 2797 unique schools and 16 103 school-years). PARTICIPANTS: School-level administrative data from the Texas Department of Agriculture on meal counts, enrollment and summary characteristics of students merged with district-level educational and socio-demographic data from the Texas Education Authority. RESULTS: We find opting into CEP increased school breakfast participation by 4·59 percentage points (P < 0·001) and lunch participation by 4·32 percentage points (P < 0·001), on average. The effect is slightly larger (4·64 and 4·61, respectively) and still statistically significant when excluding summer months. CONCLUSION: Our findings suggest that opting into CEP modestly increases school meal participation in Texas, with a similar impact on breakfast and lunch.
Subject(s)
Food Assistance , Food Services , Humans , Lunch , Meals , Schools , TexasABSTRACT
Few clades of plants have proven as difficult to classify as cacti. One explanation may be an unusually high level of convergent and parallel evolution (homoplasy). To evaluate support for this phylogenetic hypothesis at the molecular level, we sequenced the genomes of four cacti in the especially problematic tribe Pachycereeae, which contains most of the large columnar cacti of Mexico and adjacent areas, including the iconic saguaro cactus (Carnegiea gigantea) of the Sonoran Desert. We assembled a high-coverage draft genome for saguaro and lower coverage genomes for three other genera of tribe Pachycereeae (Pachycereus, Lophocereus, and Stenocereus) and a more distant outgroup cactus, Pereskia We used these to construct 4,436 orthologous gene alignments. Species tree inference consistently returned the same phylogeny, but gene tree discordance was high: 37% of gene trees having at least 90% bootstrap support conflicted with the species tree. Evidently, discordance is a product of long generation times and moderately large effective population sizes, leading to extensive incomplete lineage sorting (ILS). In the best supported gene trees, 58% of apparent homoplasy at amino sites in the species tree is due to gene tree-species tree discordance rather than parallel substitutions in the gene trees themselves, a phenomenon termed "hemiplasy." The high rate of genomic hemiplasy may contribute to apparent parallelisms in phenotypic traits, which could confound understanding of species relationships and character evolution in cacti.
Subject(s)
Cactaceae/genetics , Genome, Plant/genetics , Base Sequence , Evolution, Molecular , Genomics/methods , Mexico , Models, Genetic , North America , PhylogenyABSTRACT
BACKGROUND: Primary lymphedema is an anomaly of the regional lymphatic system with long symptom duration or severe lymphatic obstruction. Few microsurgical treatments for primary lymphedema have been reported. This aim of this study was to investigate the outcomes of microsurgical treatments in pediatric primary lymphedema patients. METHODS: Between 2013 and 2017, pediatric primary lymphedema patients who underwent either lymphovenous anastomosis (LVA) or vascularized lymph node transfer (VLNT) were retrospectively reviewed. Cheng's Lymphedema Grading, Taiwan Lymphoscintigraphy Staging and indocyanine green lymphography were used to select the procedures. No compression garments were used postoperatively. Outcome measurements included circumferential difference, episodes of cellulitis, and Lymphedema-specific Quality of life questionnaire (LYMQoL). RESULTS: Nine patients with mean age of 9.2 years (range, 2-19 years) with 11 lower and two upper lymphedematous limbs underwent 11 VLNT and two LVA. All VLNT flaps survived. At a mean 38.4-months (range, 16-63 months) of follow-up, the mean circumferential difference in nine unilateral lymphedematous limbs was improved by 6.7 ± 9.9% (p = .066). Two patients with bilateral lower limb lymphedema had mean limb circumference improvements of 1.3 and 6.5 cm, respectively. In nine limbs with cellulitis preoperatively, episodes of cellulitis decreased by 2.67 times/year (p = .007). At a mean 22.3-months of follow-up (range, 13-24 months), the LYMQoL overall score in 6 patients older than 7 years was improved by 3.2 ± 1.1 points (p = .007). CONCLUSIONS: Lymphedema microsurgery significantly improved the episodes of cellulitis and quality of life without utilizing compression garments in pediatric primary lymphedema patients.
Subject(s)
Lymphatic Vessels , Lymphedema , Adolescent , Adult , Anastomosis, Surgical , Child , Child, Preschool , Humans , Lower Extremity , Lymph Nodes , Lymphatic Vessels/surgery , Lymphedema/surgery , Microsurgery , Quality of Life , Retrospective Studies , Taiwan , Upper Extremity , Young AdultABSTRACT
Studying the relative impact of various measures of coping strategies can help determine which ones are most useful for patients with osteoarthritis (OA).This study prospectively enrolled 108 patients with hip or knee OA who were seeing an orthopedic surgeon before or after arthroplasty. Measures of coping strategies included the Patient Activation Measure (PAM), Pain Self-Efficacy Questionnaire (PSEQ-2), and the Brief Resilience Scale (BRS). The Hip Disability and Osteoarthritis Outcome Score, Junior (HOOS, JR), the Knee Injury and Osteoarthritis Outcome Score, Junior (KOOS, JR), and Numeric Rating Scale (NRS) were used to measure pain intensity. Pearson correlations measured the interrelationships of the outcome measures. The PSEQ-2 correlated significantly with the NRS, but the confidence intervals for the three instruments overlapped. The PAM and the PSEQ-2 correlated with the KOOS, JR. Only the PSEQ-2 was associated with variation in the NRS. The PAM, PSEQ-2, and BRS correlated with one another. While measures of self-efficacy, active involvement in care, and general resilience were correlated, the measure of pain self-efficacy had the strongest association with patient-reported outcomes. (Journal of Surgical Orthopaedic Advances 28(1):48-52, 2019).
Subject(s)
Osteoarthritis, Hip , Osteoarthritis, Knee , Pain , Self Efficacy , Disability Evaluation , Humans , Osteoarthritis, Hip/complications , Osteoarthritis, Hip/psychology , Osteoarthritis, Knee/complications , Osteoarthritis, Knee/psychology , Pain/psychology , Pain Measurement , Patient Participation , Surveys and QuestionnairesSubject(s)
Hypertension, Pulmonary , Animals , Humans , Pericytes , Disease Models, Animal , Endothelial CellsABSTRACT
BACKGROUND: We developed a classifier using RNA sequencing data that identifies the usual interstitial pneumonia (UIP) pattern for the diagnosis of idiopathic pulmonary fibrosis. We addressed significant challenges, including limited sample size, biological and technical sample heterogeneity, and reagent and assay batch effects. RESULTS: We identified inter- and intra-patient heterogeneity, particularly within the non-UIP group. The models classified UIP on transbronchial biopsy samples with a receiver-operating characteristic area under the curve of ~ 0.9 in cross-validation. Using in silico mixed samples in training, we prospectively defined a decision boundary to optimize specificity at ≥85%. The penalized logistic regression model showed greater reproducibility across technical replicates and was chosen as the final model. The final model showed sensitivity of 70% and specificity of 88% in the test set. CONCLUSIONS: We demonstrated that the suggested methodologies appropriately addressed challenges of the sample size, disease heterogeneity and technical batch effects and developed a highly accurate and robust classifier leveraging RNA sequencing for the classification of UIP.
Subject(s)
Idiopathic Interstitial Pneumonias/diagnosis , Idiopathic Interstitial Pneumonias/genetics , Idiopathic Pulmonary Fibrosis/diagnosis , Idiopathic Pulmonary Fibrosis/genetics , Sequence Analysis, RNA/methods , Area Under Curve , Biopsy , Computational Biology/methods , Computer Simulation , Diagnosis, Differential , Genetic Predisposition to Disease , Humans , Logistic Models , Machine Learning , Prospective Studies , ROC Curve , Sensitivity and SpecificityABSTRACT
BACKGROUND: Although patient-reported outcomes measures (PROMs) provide valuable health information and aid medical decision making for patients with hip and knee arthritis, survey completion rates remain low. The purpose of this study is to elucidate patient preferences regarding location of completion, delivery method, and barriers or facilitators to pre-visit completion. METHODS: Patients with hip and/or knee pain who were asked to complete pre-visit PROMs at 2 urban arthroplasty clinics were recruited. In-person, semi-structured, audio-recorded interviews were conducted, transcribed, and coded for thematic analysis. Codes were developed using a data-driven approach. RESULTS: We analyzed 51 interviews. The mean age was 57 years, 57% were women, and 45% had private or Medicare insurance. Prevalent themes regarding location preferences were convenience and communication preferences. Thirty-four patients stated a preference for completing pre-visit PROMs at home, 19 for in-office completion, and 10 stated no preference. Prevalent themes around delivery methods included technology access and familiarity. Of the 43 patients asked to select their preferred pre-visit PROM delivery method (phone call, email, text message, or postal mail), 31 (72%) preferred email or text messaging. Barriers to completing pre-visit PROMs were technological issues, recognizing the message was healthcare-related, and being too busy or forgetting. Twenty patients identified no barriers. CONCLUSION: Electronic PROM collection is favored by many patients, but alternative methods for patients without access to or familiarity with technology remain important. Clear recognition that the message is from a physician's office and physician communication of the utility of PROMs in clinical decision making may increase pre-visit completion.
Subject(s)
Data Collection/methods , Decision Making , Pain , Patient Participation , Patient Reported Outcome Measures , Adult , Aged , Aged, 80 and over , Arthroplasty , Female , Humans , Insurance, Health , Male , Medicare , Middle Aged , Osteoarthritis, Hip/therapy , Osteoarthritis, Knee/therapy , Patient Preference , Physicians , Pilot Projects , Surveys and Questionnaires , United StatesABSTRACT
BACKGROUND: Preoperative optimization of risk factors has been suggested as a strategy to improve the value of total joint arthroplasty (TJA) care. We assessed the implementation of a TJA preoperative optimization protocol and its impact on length of hospital stay, discharge destination, 90-day readmissions, and hospital direct variable costs. METHODS: This retrospective cohort study included adults undergoing primary elective TJA from 07/2015-09/2016 at an urban tertiary care hospital. Post-implementation patients were preoperatively screened for 19 risk factors; results and recommended interventions were reported to surgeons, who had the option to postpone or continue surgery as scheduled. Metrics from hospital administrative databases were compared between post-implementation (02/2016-09/2016) and pre-implementation cohorts (07/2015-11/2015). RESULTS: The 314 post-implementation patients were slightly younger compared to the 351 pre-implementation patients (64.2 years vs 65.8 years, P = .02) and a higher percentage of patients had diabetes (18% vs 5.1%, P < .001). Of the 98% of post-implementation patients screened, 74% had at least 1 risk factor identified. Obstructive sleep apnea was the most common risk factor (52%), followed by depression (22%) and obesity (body mass index > 40 kg/m2 or 35-40 kg/m2 with comorbidities) (13%). Forty-six patients (20%) did not follow through with the recommended optimization before undergoing elective surgery. The post-implementation cohort had shorter average length of hospital stay (1.9 days vs 2.2 days, P < .001) and lower average total direct variable costs excluding implants ($5409 vs $5852, P < .001). There was no difference in patients discharged home (90% vs 89%, P = .53) or 90-day readmissions (4.1% vs 4.3%, P = .93). CONCLUSION: In our experience, the majority of elective TJA patients have modifiable risk factors, indicating opportunity for preoperative intervention. Our evidence-based preoperative optimization program resulted in higher value care, demonstrated by similar outcomes with lower resource utilization.
Subject(s)
Arthroplasty, Replacement, Hip , Arthroplasty, Replacement, Knee , Clinical Protocols , Preoperative Care , Adult , Aged , Aged, 80 and over , Body Mass Index , Cohort Studies , Databases, Factual , Elective Surgical Procedures , Female , Hospital Costs , Hospitals , Humans , Length of Stay , Male , Middle Aged , Multivariate Analysis , Obesity , Patient Discharge , Retrospective Studies , Risk Assessment , Risk Factors , Young AdultABSTRACT
BACKGROUND: Accurate structural annotation depends on well-trained gene prediction programs. Training data for gene prediction programs are often chosen randomly from a subset of high-quality genes that ideally represent the variation found within a genome. One aspect of gene variation is GC content, which differs across species and is bimodal in grass genomes. When gene prediction programs are trained on a subset of grass genes with random GC content, they are effectively being trained on two classes of genes at once, and this can be expected to result in poor results when genes are predicted in new genome sequences. RESULTS: We find that gene prediction programs trained on grass genes with random GC content do not completely predict all grass genes with extreme GC content. We show that gene prediction programs that are trained with grass genes with high or low GC content can make both better and unique gene predictions compared to gene prediction programs that are trained on genes with random GC content. By separately training gene prediction programs with genes from multiple GC ranges and using the programs within the MAKER genome annotation pipeline, we were able to improve the annotation of the Oryza sativa genome compared to using the standard MAKER annotation protocol. Gene structure was improved in over 13% of genes, and 651 novel genes were predicted by the GC-specific MAKER protocol. CONCLUSIONS: We present a new GC-specific MAKER annotation protocol to predict new and improved gene models and assess the biological significance of this method in Oryza sativa. We expect that this protocol will also be beneficial for gene prediction in any organism with bimodal or other unusual gene GC content.
Subject(s)
Genome, Plant , Molecular Sequence Annotation/methods , Oryza/genetics , Base Composition , Markov Chains , RNA, Plant/chemistry , RNA, Plant/isolation & purification , RNA, Plant/metabolism , Ribosomes/metabolism , Sequence Analysis, RNAABSTRACT
PSEUDO-RESPONSE REGULATORs (PRRs) play overlapping and distinct roles in maintaining circadian rhythms and regulating diverse biological processes, including the photoperiodic control of flowering, growth, and abiotic stress responses. PRRs act as transcriptional repressors and associate with chromatin via their conserved C-terminal CCT (CONSTANS, CONSTANS-like, and TIMING OF CAB EXPRESSION 1 [TOC1/PRR1]) domains by a still-poorly understood mechanism. Here, we identified genome-wide targets of PRR9 using chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) and compared them with PRR7, PRR5, and TOC1/PRR1 ChIP-seq data. We found that PRR binding sites are located within genomic regions of low nucleosome occupancy and high DNase I hypersensitivity. Moreover, conserved noncoding regions among Brassicaceae species are enriched around PRR binding sites, indicating that PRRs associate with functionally relevant cis-regulatory regions. The PRRs shared a significant number of binding regions, and our results indicate that they coordinately restrict the expression of target genes to around dawn. A G-box-like motif was overrepresented at PRR binding regions, and we showed that this motif is necessary for mediating transcriptional regulation of CIRCADIAN CLOCK ASSOCIATED 1 and PRR9 by the PRRs. Our results further our understanding of how PRRs target specific promoters and provide an extensive resource for studying circadian regulatory networks in plants.
Subject(s)
Arabidopsis Proteins/genetics , Arabidopsis/genetics , Circadian Rhythm/genetics , Gene Expression Regulation, Plant , Arabidopsis Proteins/metabolism , Binding Sites , Chromatin Immunoprecipitation , Genome, Plant , Nucleotide Motifs , Plants, Genetically Modified , Promoter Regions, Genetic , Regulatory Sequences, Nucleic Acid , Repressor Proteins/genetics , Transcription Factors/genetics , Transcription Factors/metabolismABSTRACT
Brain tumor-initiating cells (BTICs) are self-renewing multipotent cells critical for tumor maintenance and growth. Using single-cell microfluidic profiling, we identified multiple subpopulations of BTICs coexisting in human glioblastoma, characterized by distinct surface marker expression and single-cell molecular profiles relating to divergent bulk tissue molecular subtypes. These data suggest BTIC subpopulation heterogeneity as an underlying source of intra-tumoral bulk tissue molecular heterogeneity, and will support future studies into BTIC subpopulation-specific therapies. Stem Cells 2016;34:1702-1707.
Subject(s)
Brain Neoplasms/pathology , Glioblastoma/pathology , Neoplastic Stem Cells/pathology , Biomarkers, Tumor/metabolism , Brain Neoplasms/genetics , Cell Line, Tumor , Glioblastoma/genetics , Humans , Phenotype , Single-Cell Analysis , Transcription, GeneticABSTRACT
BACKGROUND: Minor events that occur in the workplace sometimes are evaluated with MRI, which may reveal age-related changes in the symptomatic body part. These age-related changes are often ascribed to the event. However, evidence of similar or worse pathophysiology in the contralateral joint would suggest that the symptoms might be new, but the pathophysiology is not. QUESTIONS/PURPOSES: Using a convenience sample of occupational injury claimants with bilateral MRI to evaluate unilateral knee or shoulder symptoms ascribed to a single event at work, we sought to determine whether MRI findings of the shoulder and knee are more often congruent or incongruent with new unilateral symptoms. METHODS: Two hundred ninety-four occupational injury claimants employed at companies throughout Texas that do not subscribe to workers' compensation insurance, who were older than 40 years, and with unilateral shoulder or knee symptoms, were studied. Starting in 2012, all patients seen by OccMD Group PA who present with unilateral symptoms ascribed to work undergo bilateral MRI, based on several previous occasions where bilateral MRI proved to be a compelling demonstration that perceived injuries are more likely age-related, previously well-adapted pathophysiology. MRI findings (anything described as abnormal by the radiologist; eg, defect size or signal change) was considered congruent if the abnormality of one or more structures on the symptomatic side was greater than that of the corresponding structures in the asymptomatic joint. Bivariate analysis was used to compare the frequency of MRI findings congruent and incongruent with symptoms. Logistic regression was used to evaluate factors associated with MRI findings of the shoulder or knee. RESULTS: Less than half of the patients with shoulder (90 of 189; 48%; p = 0.36) or knee (45 of 105; 43%; p = 0.038) symptoms had worse pathologic features on the symptomatic side. Older age was associated with disorders in the infraspinatus tendon (59 ± 8 versus 56 ± 8 years; p = 0.012), glenoid labrum (60 ± 9 versus 57 ± 8 years; p = 0.025), and biceps tendon (60 ± 8 versus 57 ± 8 years; p = 0.0038). Eighty-seven percent of patients (91 of 105) had structural changes in the medial meniscus described by the radiologist. CONCLUSIONS: Occupational injury claimants 40 years of age and older with unilateral knee and shoulder symptoms ascribed to a work event tend to have bilateral age-related MRI changes. Age-related disorders should be distinguished from acute injury. LEVEL OF EVIDENCE: Level IV, diagnostic study.
Subject(s)
Disability Evaluation , Insurance, Disability , Knee Joint/diagnostic imaging , Magnetic Resonance Imaging , Musculoskeletal Diseases/diagnostic imaging , Occupational Diseases/diagnostic imaging , Occupational Health , Shoulder Joint/diagnostic imaging , Adult , Age Factors , Biomechanical Phenomena , Female , Humans , Insurance, Disability/economics , Knee Joint/physiopathology , Male , Middle Aged , Musculoskeletal Diseases/economics , Musculoskeletal Diseases/physiopathology , Occupational Diseases/economics , Occupational Diseases/physiopathology , Predictive Value of Tests , Risk Factors , Shoulder Joint/physiopathology , TexasABSTRACT
PURPOSE: It remains unclear which factors, patient- or disease-specific, are associated with electing to undergo operative management for de Quervain tendinopathy. Our null hypothesis was that no patient- or disease-specific factors would be associated with the choice of surgical treatment of de Quervain tendinopathy. METHODS: We performed a retrospective review of consecutive patients diagnosed with de Quervain tendinopathy over 3 years by 1 of 3 fellowship-trained hand surgeons at an urban academic institution. Descriptive statistics were calculated for patient baseline and disease-specific characteristics. Cohorts were compared using bivariate analysis for all collected variables. Binary logistic regression with backward stepwise term selection was performed including independent predictors identified by bivariate analysis. RESULTS: A total of 200 patients were identified for inclusion. Bivariate analysis revealed that surgically treated patients were significantly more likely to have Medicaid insurance, psychiatric illness history, and disabled work status. Regression analysis revealed an association between surgical treatment and 2 of the factors evaluated: Medicaid insurance status and psychiatric illness history. CONCLUSIONS: Psychiatric illness and Medicaid insurance status are associated with undergoing surgical release of the first dorsal compartment. These findings support the use of a biopsychosocial framework when treating patients with de Quervain tendinopathy. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.
Subject(s)
De Quervain Disease/surgery , Orthopedic Procedures/methods , Tendinopathy/surgery , Academic Medical Centers , Adrenal Cortex Hormones/therapeutic use , Adult , Cohort Studies , De Quervain Disease/diagnosis , De Quervain Disease/drug therapy , Disability Evaluation , Female , Follow-Up Studies , Humans , Injections, Intralesional , Logistic Models , Male , Middle Aged , Multivariate Analysis , Patient Selection , Retrospective Studies , Severity of Illness Index , Tendinopathy/diagnostic imaging , Tendinopathy/rehabilitation , Treatment OutcomeABSTRACT
Innovative strategies are needed to generate resources to replicate and sustain proven, community-based health promotion programs. Authors describe how civic-minded university students can conduct such programs while simultaneously gaining skills that make them competitive graduate school applicants.
Subject(s)
Asian/psychology , Breast Neoplasms/diagnosis , Breast Neoplasms/therapy , Early Detection of Cancer/psychology , Mammography/psychology , Mammography/statistics & numerical data , Patient Education as Topic/methods , Adult , Aged , Aged, 80 and over , Community Health Services/methods , Female , Health Promotion/methods , Humans , Middle Aged , Students, Medical , Vulnerable PopulationsABSTRACT
KEY MESSAGE: SrTA10187 was fine-mapped to a 1.1 cM interval, candidate genes were identified in the region of interest, and molecular markers were developed for marker-assisted selection and Sr gene pyramiding. Stem rust (Puccinia graminis f. sp. tritici, Pgt) races belonging to the Ug99 (TTKSK) race group pose a serious threat to global wheat (Triticum aestivum L.) production. To improve Pgt host resistance, the Ug99-effective resistance gene SrTA10187 previously identified in Aegilops tauschii Coss. was introgressed into wheat, and mapped to the short arm of wheat chromosome 6D. In this study, high-resolution mapping of SrTA10187 was done using a population of 1,060 plants. Pgt resistance was screened using race QFCSC. PCR-based SNP and STS markers were developed from genotyping-by-sequencing tags and SNP sequences available in online databases. SrTA10187 segregated as expected in a 3:1 ratio of resistant to susceptible individuals in three out of six BC3F2 families, and was fine-mapped to a 1.1 cM region on wheat chromosome 6DS. Marker context sequence was aligned to the reference Ae. tauschii genome to identify the physical region encompassing SrTA10187. Due to the size of the corresponding region, candidate disease resistance genes could not be identified with confidence. Comparisons with the Ae. tauschii genetic map developed by Luo et al. (PNAS 110(19):7940-7945, 2013) enabled identification of a discrete genetic locus and a BAC minimum tiling path of the region spanning SrTA10187. Annotation of pooled BAC library sequences led to the identification of candidate genes in the region of interest-including a single NB-ARC-LRR gene. The shorter genetic interval and flanking KASP™ and STS markers developed in this study will facilitate marker-assisted selection, gene pyramiding, and positional cloning of SrTA10187.
Subject(s)
Chromosome Mapping , Disease Resistance/genetics , Genes, Plant , Plant Diseases/genetics , Triticum/genetics , Basidiomycota , Chromosomes, Plant , Genetic Linkage , Phenotype , Physical Chromosome Mapping , Plant Diseases/microbiology , Poaceae/genetics , Polymorphism, Single Nucleotide , Sequence Tagged Sites , Triticum/microbiologyABSTRACT
Up to 30% of the plant transcriptome is circadian clock-regulated in different species; however, we still lack a good understanding of the mechanisms involved in these genome-wide oscillations in gene expression. Here, we show that PSEUDO-RESPONSE REGULATOR 7 (PRR7), a central component of the Arabidopsis clock, is directly involved in the repression of master regulators of plant growth, light signaling and stress responses. The expression levels of most PRR7 target genes peak around dawn, in an antiphasic manner to PRR7 protein levels, and were repressed by PRR7. These findings indicate that PRR7 is important for cyclic gene expression by repressing the transcription of morning-expressed genes. In particular we found an enrichment of the genes involved in abiotic stress responses, and in accordance we observed that PRR7 is involved in the oxidative stress response and the regulation of stomata conductance.
Subject(s)
Adaptation, Physiological , Arabidopsis Proteins/metabolism , Arabidopsis/genetics , Circadian Clocks , Gene Expression Regulation, Plant , Repressor Proteins/metabolism , Signal Transduction , Abscisic Acid/metabolism , Arabidopsis/drug effects , Arabidopsis/physiology , Arabidopsis/radiation effects , Arabidopsis Proteins/genetics , Binding Sites , Chromatin Immunoprecipitation , High-Throughput Nucleotide Sequencing , Iron/pharmacology , Light , Mutation , Oxidative Stress , Phenotype , Plant Leaves/drug effects , Plant Leaves/genetics , Plant Leaves/physiology , Plant Leaves/radiation effects , Plant Transpiration/physiology , Plants, Genetically Modified , Repressor Proteins/genetics , Seedlings/drug effects , Seedlings/genetics , Seedlings/physiology , Seedlings/radiation effects , Sequence Analysis, DNAABSTRACT
BACKGROUND: We initiate in silico rigidity-theoretical studies of biological assemblies and small crystals for protein structures. The goal is to determine if, and how, the interactions among neighboring cells and subchains affect the flexibility of a molecule in its crystallized state. We use experimental X-ray crystallography data from the Protein Data Bank (PDB). The analysis relies on an effcient graph-based algorithm. Computational experiments were performed using new protein rigidity analysis tools available in the new release of our KINARI-Web server http://kinari.cs.umass.edu. RESULTS: We provide two types of results: on biological assemblies and on crystals. We found that when only isolated subchains are considered, structural and functional information may be missed. Indeed, the rigidity of biological assemblies is sometimes dependent on the count and placement of hydrogen bonds and other interactions among the individual subchains of the biological unit. Similarly, the rigidity of small crystals may be affected by the interactions between atoms belonging to different unit cells. CONCLUSION: The rigidity analysis of a single asymmetric unit may not accurately reflect the protein's behavior in the tightly packed crystal environment. Using our KINARI software, we demonstrated that additional functional and rigidity information can be gained by analyzing a protein's biological assembly and/or crystal structure. However, performing a larger scale study would be computationally expensive (due to the size of the molecules involved). Overcoming this limitation will require novel mathematical and computational extensions to our software.