The integrity of genomes is constantly threatened by problems encountered by the replication fork. BRCA1, BRCA2 and a subset of Fanconi anaemia proteins protect stalled replication forks from ...degradation by nucleases, through pathways that involve RAD51. The contribution and regulation of BRCA1 in replication fork protection, and how this role relates to its role in homologous recombination, is unclear. Here we show that BRCA1 in complex with BARD1, and not the canonical BRCA1-PALB2 interaction, is required for fork protection. BRCA1-BARD1 is regulated by a conformational change mediated by the phosphorylation-directed prolyl isomerase PIN1. PIN1 activity enhances BRCA1-BARD1 interaction with RAD51, thereby increasing the presence of RAD51 at stalled replication structures. We identify genetic variants of BRCA1-BARD1 in patients with cancer that exhibit poor protection of nascent strands but retain homologous recombination proficiency, thus defining domains of BRCA1-BARD1 that are required for fork protection and associated with cancer development. Together, these findings reveal a BRCA1-mediated pathway that governs replication fork protection.
Medication nonadherence is common in patients with systemic lupus erythematosus (SLE) and negatively affects outcomes. To better recognize and address nonadherence in this population, there is a need ...for an easily implementable tool with interpretable scores. Domains of Subjective Extent of Nonadherence (DOSE-Nonadherence) is a measure that captures both extent of and reasons for nonadherence. We refined and evaluated DOSE-Nonadherence for patients with SLE.
We refined the reasons for the nonadherence domain of DOSE-Nonadherence through rheumatologist feedback and patient cognitive interviewing. We then administered the refined instrument to patients prescribed oral SLE medications and compared the results to the Beliefs About Medicines Questionnaire (BMQ), the Medication Adherence Self-Report Inventory (MASRI), medication possession ratios (MPRs), and hydroxychloroquine (HCQ) blood levels using Pearson correlations.
Five rheumatologists provided feedback; 16 patients (median age 43 yrs, 100% female, 50% Black) participated in cognitive interviews and 128 (median age 49 yrs, 95% female, 49% Black, 88% on antimalarials, and 59% on immunosuppressants) completed the refined instrument. Items assessing extent of nonadherence produced reliable scores (α 0.89) and identified 47% as nonadherent. They showed convergent validity with MASRI (r = -0.57), HCQ blood levels (r = -0.55), to a lesser extent MPRs (r = -0.34 to -0.40), and discriminant validity with BMQ domains (r = -0.27 to 0.32). Nonadherent patients reported on average 3.5 adherence barriers, the most common being busyness/forgetting (62%), physical fatigue (38%), and pill fatigue (33%).
Our results support the reliability and validity of DOSE-Nonadherence for SLE medications. This refined instrument, DOSE-Nonadherence-SLE, can be used to identify, rigorously study, and guide adherence intervention development in SLE.
Purpose
The purpose of this study is to evaluate potential gender-based differences in interpreting the Kansas City Cardiomyopathy Questionnaire (KCCQ-23) and to explore if there are aspects of ...health-related quality of life (HRQOL) not captured by the KCCQ-23 that are important to assess in men and/or women with heart failure (HF).
Methods
Patients ≥ 22 years of age with clinician-diagnosed HF and left ventricular ejection fraction ≤ 40% were recruited from two academic medical centers to participate in semi-structured concept elicitation and cognitive debriefing interviews. Enrollment was stratified by patient-identified gender (half women/half men). All interviews were conducted over the phone/web and audio recorded. Interviews were transcribed and descriptive qualitative content analysis was used to summarize findings overall and by gender.
Results
Twenty-five adults (56% women) diagnosed with HF participated. The average age was 67 years (range: 25–88). Women attributed a wider variety of symptoms to HF than men. Some participants had difficulty differentiating whether their experiences were due to HF, side effects of their medications, or age. We found very little evidence that participants interpreted KCCQ-23 items differently based on gender.
Conclusions
Overall, our findings indicate that interpretation of the KCCQ-23 items were similar in men and women. However, some modifications to items may improve clarity of interpretation for a wide range of patients.
Pro-inflammatory fibroblasts are critical for pathogenesis in rheumatoid arthritis, inflammatory bowel disease, interstitial lung disease, and Sjögren's syndrome and represent a novel therapeutic ...target for chronic inflammatory disease. However, the heterogeneity of fibroblast phenotypes, exacerbated by the lack of a common cross-tissue taxonomy, has limited our understanding of which pathways are shared by multiple diseases.
We profiled fibroblasts derived from inflamed and non-inflamed synovium, intestine, lungs, and salivary glands from affected individuals with single-cell RNA sequencing. We integrated all fibroblasts into a multi-tissue atlas to characterize shared and tissue-specific phenotypes.
Two shared clusters, CXCL10
CCL19
immune-interacting and SPARC
COL3A1
vascular-interacting fibroblasts, were expanded in all inflamed tissues and mapped to dermal analogs in a public atopic dermatitis atlas. We confirmed these human pro-inflammatory fibroblasts in animal models of lung, joint, and intestinal inflammation.
This work represents a thorough investigation into fibroblasts across organ systems, individual donors, and disease states that reveals shared pathogenic activation states across four chronic inflammatory diseases.
Grant from F. Hoffmann-La Roche (Roche) AG.
ObjectiveManifestations of SLE can be categorised as type 1 (classic signs and symptoms of SLE) or type 2 (fatigue, widespread pain and brain fog with an unclear relationship to inflammation). While ...measures of type 1 SLE activity exist, most current physician-reported measures do not encompass type 2 SLE manifestations. To better evaluate type 2 SLE symptoms, we developed and psychometrically evaluated a physician-reported measure of type 2 symptoms, the Type 2 Physician Global Assessment (‘Type 2 PGA’).Methods and analysisThe Type 2 PGA was developed and evaluated by six rheumatologists practising in the same academic lupus clinic. The study began with a roundtable discussion to establish consensus guidelines for scoring the Type 2 PGA. Following the roundtable, the Type 2 PGA was psychometrically evaluated using data prospectively collected from 263 patients with SLE enrolled in the Duke Lupus Registry.ResultsThere was strong intra-rater and inter-rater reliability (intraclass correlation coefficient=0.83), indicating the Type 2 PGA scores were consistent within a rheumatologist and across rheumatologists. The Type 2 PGA was correlated with patient-reported symptoms of polysymptomatic distress (r=0.76), fatigue (r=0.68), cognitive dysfunction (r=0.63), waking unrefreshed (r=0.62) and forgetfulness (r=0.60), and weakly correlated with the Type 1 PGA and the Systemic Lupus Erythematosus Disease Activity Index.ConclusionThe Type 2 PGA performed well as a physician-reported measure of type 2 SLE symptoms. The incorporation of the Type 2 PGA into a routine rheumatology visit may improve patient care by bringing the provider’s attention to certain symptoms not well represented in conventional measures of disease activity.
The purpose of this study is to determine the incidence, risk factors, and outcomes for chylothorax in children undergoing cardiothoracic surgery.
Hospital databases were used to identify chylothorax ...cases. Surgical databases were used to identify all patients undergoing cardiothoracic surgery. Medical records were reviewed, including daily records of drainage volumes and management.
From September 2000 to December 2002, there were 48 cases of chylothorax in 1,257 surgeries—an incidence of 3.8% (95% confidence interval: 2.8% to 4.8%). Overall mortality rate was similar, but cases had longer postoperative hospital stays (median, 22 versus 8 days; p < 0.001). Incidence of chylothorax was significantly higher with heart transplantation and Fontan procedures. Diagnosis was made at a median of 6 days after surgery. Duration of drainage was a median of 15 days, with 11 patients draining more than 30 days. Longer duration of drainage was associated with cavopulmonary anastomosis procedures and longer time to diagnosis of chylothorax. Nutritional management included low fat diet, enteral feeds enriched with medium-chain triglycerides, and parenteral nutrition. Five patients were treated with octreotide, 4 with thoracic duct ligation, and 1 with pleurodesis. Octreotide was associated with a variable effect on drainage. Thoracic duct ligation reduced, but did not stop drainage.
Chylothorax increases duration of hospitalization after cardiovascular surgery in children. Early diagnosis may reduce the duration of chylothorax. Nutritional strategies remain the cornerstone for management of postoperative chylothorax. The impact of octreotide and surgical intervention is limited when reserved for patients with severe or prolonged drainage.
The present research extends the theory of planned behavior (TPB) to investigate how communication-related variables influence condom use intention and behavior among African American women. ...According to the TPB, attitudes, subjective norms, and self-efficacy are associated with behavioral intent, which predicts behavior. For women, it was argued that condom negotiation self-efficacy was more important than condom use self-efficacy in predicting consistent condom use. Moreover, an important environmental factor that affects condom use for African American women is fear or worry when negotiating condom use because the sex partners might leave, threaten, or abuse them. Fears associated with negotiating condom use were predicted to be negatively associated with attitudes, subjective norms, and self-efficacy. African American women (N = 560; M age = 20.58) completed assessments of TPB variables at baseline and condom use 3 months later. Condom negotiation self-efficacy was a significant indicator of behavioral intent, while condom use self-efficacy was not. Fear of condom negotiation was negatively associated with all TPB components, which was in turn significantly associated with behavioral intent and condom use. Implications for the TPB, safer sex literature, and sexually transmitted infection prevention intervention design are discussed.
Objective
We developed a model that categorizes systemic lupus erythematosus (SLE) activity into two dimensions: Type 1 SLE consists of inflammatory activity, including arthritis, nephritis, and ...rashes; Type 2 SLE includes fatigue, myalgia, mood disturbance, and cognitive dysfunction. Patient-reported outcome (PRO) measures have received attention as a way to capture symptomatology of SLE. The objective of this study was to explore the use of existing PRO measures to classify Type 1 and 2 SLE activity.
Methods
Systemic lupus erythematosus patients completed three questionnaires: Systemic Lupus Activity Questionnaire (SLAQ), Polysymptomatic Distress Scale (PSD), and Patient Health Questionnaire (PHQ-2). SLE Disease Activity Index (SLEDAI) and physician global assessments (PGA; 0–3) for Type 1 and Type 2 activity were also recorded. High Type 1 SLE activity was defined as cSLEDAI ≥4 (scored without labs), SLEDAI ≥6, active nephritis, or Type 1 PGA ≥1.0. High Type 2 SLE activity was defined as Type 2 PGA ≥1.0. Patients with both high Type 1 and 2 activity were defined as Mixed SLE, and patients with low Type 1 and 2 activity were defined as Minimal SLE. Data were reduced with a factor analysis. Using a reduced set of 13 variables, multinomial logistic regression models estimated the probability of Minimal, Type 1, Type 2, and Mixed SLE classification.
Results
The study included 208 patients with SLE. The model accurately predicted the clinician-based Type 1 and 2 SLE classification in 63% of patients; 73% of patients had their Type 1 SLE activity accurately predicted; and 83% had their Type 2 SLE activity accurately predicted. Performance varied by group: 87% of Minimal patients were correctly predicted to be in the Minimal SLE group, yet only about one-third of patients in the Type 1 group were correctly predicted to be in the Type 1 group.
Conclusions
Our findings indicate Type 2 SLE activity can be identified by patient-reported data. The use of PROs was not as accurate at predicting Type 1 activity. These findings highlight the challenges of using PROs to categorize and classify SLE symptoms since some manifestations of Type 1 activity (e.g., nephritis) may be essentially clinically silent while other Type 1 manifestations may cause severe symptoms.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
10.
Do As I Say Kollar, Laura M. Mercer; Davis, Teaniese L.; Monahan, Jennifer L. ...
Health education & behavior,
12/2016, Letnik:
43, Številka:
6
Journal Article
Recenzirano
Sexual risk reduction interventions are often ineffective for women who drink alcohol. The present study examines whether an alcohol-related sexual risk reduction intervention successfully trains ...women to increase assertive communication behaviors and decrease aggressive communication behaviors. Women demonstrated their communication skills during interactive role-plays with male role-play partners. Young, unmarried, and nonpregnant African American women (N = 228, ages 18-24) reporting unprotected vaginal or anal sex and greater than three alcoholic drinks in the past 90 days were randomly assigned to a control, a sexual risk reduction, or a sexual and alcohol risk reduction (NLITEN) condition. Women in the NLITEN condition significantly increased assertive communication behavior compared to women in the control condition, yet use of aggressive communicative behaviors was unchanged. These data suggest assertive communication training is an efficacious component of a sexual and alcohol risk reduction intervention. Public health practitioners and health educators may benefit from group motivational enhancement therapy (GMET) training and adding a GMET module to existing sexual health risk reduction interventions. Future research should examine GMET’s efficacy in combination with other evidencebased interventions within other populations and examine talking over and interrupting one’s sexual partner as an assertive communication behavior within sexual health contexts.
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