Numerous studies have documented the short-term impact of BRCA1/BRCA2 (BRCA1/2) testing; however, little research has examined the long-term impact of testing. We conducted the first long-term ...prospective study of psychosocial outcomes in a U.S. sample of women who had BRCA1/2 testing.
Participants were 464 women who underwent genetic testing for BRCA1/2 mutations. Prior to testing, we measured sociodemographics, clinical variables, and cancer specific and general distress. At long-term follow-up (Median = 5.0 years; Range = 3.4-9.1 years), we assessed cancer-specific and genetic testing distress, perceived stress, and perceived cancer risk. We evaluated the impact of BRCA1/2 test result and risk-reducing surgery on long-term psychosocial outcomes.
Among participants who had been affected with breast or ovarian cancer, BRCA1/2 carriers reported higher genetic testing distress (β = 0.41, P < 0.0001), uncertainty (β = 0.18, P < 0.0001), and perceived stress (β = 0.17, P = 0.005) compared with women who received negative (i.e., uninformative) results. Among women unaffected with breast/ovarian cancer, BRCA1/2 carriers reported higher genetic testing distress (β = 0.39, P < 0.0001) and lower positive testing experiences (β = 0.25, P = 0.008) than women with negative results. Receipt of risk-reducing surgery was associated with lower perceived cancer risk (P < 0.0001).
In this first prospective long-term study in a U.S. sample, we found modestly increased distress in BRCA1/2 carriers compared with women who received uninformative or negative test results. Despite this modest increase in distress, we found no evidence of clinically significant dysfunction.
Although a positive BRCA1/2 result remains salient among carriers years after testing, testing does not seem to impact long-term psychologic dysfunction.
Implementing an Expressive Writing Study in a Cancer Clinic Morgan, Nancy P.; Graves, Kristi D.; Poggi, Elizabeth A. ...
The oncologist (Dayton, Ohio),
February 2008, 2008-Feb, 2008-02-01, 20080201, Letnik:
13, Številka:
2
Journal Article
Recenzirano
Odprti dostop
The feasibility of engaging a clinical population in a structured expressive writing task while they waited for an appointment in a cancer clinic is explored. Results suggest that expressive writing ...can be successfully conducted within a busy oncology clinic and provide support for future efforts to move beyond efficacy studies of expressive writing into community‐ and clinic‐based effectiveness trials.
Patients at a comprehensive cancer center have participated in a weekly writing program for 7 years. Anecdotal evidence following writing in this clinical setting appeared congruent with the results of expressive writing studies conducted in laboratory settings. To move expressive writing research beyond the laboratory, we evaluated the feasibility of engaging a clinical population in a structured expressive writing task while they waited for an appointment in a cancer clinic. Adult leukemia and lymphoma patients (n = 71) completed a baseline assessment, 20‐minute writing task, postwriting assessment, and 3‐week follow‐up; 88% completed the writing task and 56% completed the follow‐up. Participants reported positive responses to the writing, and immediately postwriting about half (49.1%) reported that writing resulted in changes in their thoughts about their illness, while 53.8% reported changes in their thoughts at the 3‐week follow‐up. Reports of changes in thoughts about illness immediately postwriting were significantly associated with better physical quality of life at follow‐up, controlling for baseline quality of life. Initial qualitative analyses of the texts identified themes related to experiences of positive change/transformation following a cancer diagnosis. Findings support the feasibility of conducting expressive writing with a clinical population in a nonlaboratory setting. Cancer patients were receptive to expressive writing and reported changes in the way they thought about their illness following writing. These preliminary findings indicate that a single, brief writing exercise is related to cancer patients' reports of improved quality of life.
Most BRCA1-associated breast tumours are basal-like yet originate from luminal progenitors. BRCA1 is best known for its functions in double-strand break repair and resolution of DNA replication ...stress. However, it is unclear whether loss of these ubiquitously important functions fully explains the cell lineage-specific tumorigenesis. In vitro studies implicate BRCA1 in elimination of R-loops, DNA-RNA hybrid structures involved in transcription and genetic instability. Here we show that R-loops accumulate preferentially in breast luminal epithelial cells, not in basal epithelial or stromal cells, of BRCA1 mutation carriers. Furthermore, R-loops are enriched at the 5' end of those genes with promoter-proximal RNA polymerase II (Pol II) pausing. Genetic ablation of Cobra1, which encodes a Pol II-pausing and BRCA1-binding protein, ameliorates R-loop accumulation and reduces tumorigenesis in Brca1-knockout mouse mammary epithelium. Our studies show that Pol II pausing is an important contributor to BRCA1-associated R-loop accumulation and breast cancer development.
Imaging genetics provides an opportunity to discern associations between genetic variants and brain imaging phenotypes. Historically, the field has focused on adults and adolescents; very few imaging ...genetics studies have focused on brain development in infancy and early childhood (from birth to age 6 years). This is an important knowledge gap because developmental changes in the brain during the prenatal and early postnatal period are regulated by dynamic gene expression patterns that likely play an important role in establishing an individual’s risk for later psychiatric illness and neurodevelopmental disabilities. In this review, we summarize findings from imaging genetics studies spanning from early infancy to early childhood, with a focus on studies examining genetic risk for neuropsychiatric disorders. We also introduce the Organization for Imaging Genomics in Infancy (ORIGINs), a working group of the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) consortium, which was established to facilitate large-scale imaging genetics studies in infancy and early childhood.
Obeticholic acid (OCA) is the second-line treatment approved for patients with primary biliary cholangitis (PBC) and an inadequate response or intolerance to ursodeoxycholic acid. We aimed to ...evaluate the effectiveness and safety of OCA under real-world conditions.
Patients were recruited into the Italian PBC Registry, a multicentre, observational cohort study that monitors patients with PBC at national level. The primary endpoint was the biochemical response according to Poise criteria; the secondary endpoint was the biochemical response according to normal range criteria, defined as normal levels of bilirubin, alkaline phosphatase (ALP), and alanine aminotransferase (ALT) at 12 months. Safety and tolerability were also assessed.
We analysed 191 patients until at least 12 months of follow-up. Median age was 57 years, 94% female, 61 (32%) had cirrhosis, 28 (15%) had histologically proven overlap with autoimmune hepatitis (PBC-AIH). At 12 months, significant median reductions of ALP (-32.3%), ALT (-31.4%), and bilirubin (-11.2%) were observed. Response rates were 42.9% according to Poise criteria, and 11% by normal range criteria. Patients with cirrhosis had lower response than patients without cirrhosis (29.5% vs. 49.2%, p = 0.01), owing to a higher rate of OCA discontinuation (30% vs. 12%, p = 0.004), although with similar ALP reduction (29.4% vs. 34%, p = 0.53). Overlap PBC-AIH had a similar response to pure PBC (46.4% vs. 42.3%, p = 0.68), with higher ALT reduction at 6 months (-38% vs. -29%, p = 0.04). Thirty-three patients (17%) prematurely discontinued OCA because of adverse events, of whom 11 experienced serious adverse events. Treatment-induced pruritus was the leading cause of OCA discontinuation (67%).
Effectiveness and safety of OCA under real-world conditions mirror those in the Poise trial. Patients with cirrhosis had lower tolerability. Overlap PBC-AIH showed higher ALT reduction at 6 months compared with patients with pure PBC.
Obeticholic acid (OCA) was shown to be effective in more than one-third of patients not responding to ursodeoxycholic acid in a real-world context in Italy. Patients with cirrhosis had more side effects with OCA, and this led to suspension of the drug in one-third of patients. OCA was also effective in patients who had overlap between autoimmune hepatitis and primary biliary cholangitis.
Display omitted
•Under real-world conditions, OCA was effective in ~43% of patients who were non-responders to UDCA, according to Poise criteria.•Patients with cirrhosis showed lower efficacy (29.5%), mainly attributed to reduced tolerability and higher discontinuation rate.•Patients with overlap AIH-PBC showed a comparable efficacy to pure PBC, with a higher ALT reduction at 6 months.•Most patients with PBC are still in need of additional therapy if aiming to normalise liver biochemistry.
Nature Communications 8: Article number: 15908 (2017); Published 26 June 2017; Updated 30 March 2018 The original version of this Article omitted the following from the Acknowledgements: ‘The work ...was also supported by a grant to Y.H. from the Cancer Prevention Research Institute of Texas CPRIT RP170126.
Purpose
Recent trends indicate increased use of contralateral prophylactic mastectomy (CPM) among newly diagnosed breast cancer patients, particularly those who test positive for a pathogenic variant ...in the
BRCA1/2
genes. However, the rate of CPM among patients who test negative or choose not to be tested is surprisingly high. We aimed to identify patient predictors of CPM following breast cancer diagnosis among such patients.
Methods
As part of a randomized controlled trial of rapid genetic counseling and testing vs. usual care, breast cancer patients completed a baseline survey within 6 weeks of diagnosis and before definitive surgery. Analyses focused on patients who opted against testing (
n
= 136) or who received negative
BRCA
1/2 test results (
n
= 149). We used multivariable logistic regression to assess the associations between sociodemographic, clinical- and patient-reported factors with use of CPM.
Results
Among patients who were untested or who received negative test results, having discussed CPM with one’s surgeon at the time of diagnosis predicted subsequent CPM. Patients who were not candidates for breast-conserving surgery and those with higher levels of cancer-specific intrusive thoughts were also more likely to obtain a CPM.
Conclusion
The strongest predictors of CPM in this population were objective clinical factors and discussion with providers. However, baseline psychosocial factors were also independently related to the receipt of CPM. Thus, although CPM decisions are largely guided by relevant clinical factors, it is important to attend to psychosocial factors when counseling newly diagnosed breast cancer patients about treatment options.
Scanning Probe Microscopy Poggi, Mark A; Gadsby, Elizabeth D; Bottomley, Lawrence A ...
Analytical chemistry (Washington),
06/2004, Letnik:
76, Številka:
12
Journal Article
Recenzirano
Scanning probe microscopy comprises a family of techniques that measure surface topography and properties on the atomic scale. There are an ever increasing number of papers devoted to technical ...advances and applications of SPM.
A pesar de la ubicuidad de Cucullanus spp. en los ecosistemas acuáticos de todo el mundo, su desarrollo embionario y post-embrionario, así como los patrones de transmisión, siguen siendo poco ...conocidos y, en algunos casos, controvertidos. En el presente estudio se proporcionan datos comparativos y embriológicos de Cucullanus pinnai pinnai (Travassos, Artigas & Pereira, 1928). Los nematodes adultos provenientes de Rhamdia quelen (Quoy & Gaimard, 1824) (Heptapteridae) se describen e ilustran mediante microfotografía electrónica de barrido. Se obtuvieron huevos de hembras grávidas y se siguió el desarrollo embrionario y larvario in vitro. Las etapas L y L se describen e ilustran por primera vez. El 2 3 desarrollo embrionario de C. pinnai pinnai es muy rápido a 20-22°C. En cinco días tiene lugar la eclosión y las L libres permanecen vivas menos de dos semanas. Se plantea la hipótesis de un patrón de transmisión 2 heteroxeno que involucra a R. quelen como hospedador definitivo y Bryconamericus iheringii (Boulenger, 1887) (Characidae) como hospedador intermediario.
PDF
