Involvement of BRCA1 and BRCA2 in breast cancer in a western Finnish sub-population

To date, two major familial breast cancer predisposition genes, BRCA1 and BRCA2, have been identified with hundreds of germ-line mutations, accounting for 5--10% of all breast cancer and 40--60% of all inherited breast cancer. Unexpectedly elevated incidence of breast cancer, especially in the older age classes, was observed in a Western Finnish region representing a relatively homogeneous population. This study was designed to test the hypothesis that there are inherited BRCA1 or BRCA2 mutations, which confer variable and/or age-dependent penetrance on carriers. Expecting a founder effect, we searched for geographical clustering of breast cancer cases and searched for associations between the affected phenotype and shared genomic segments in the BRCA1 and BRCA2 genomic regions. Our haplotype association study did not reveal any founder effects for either BRCA1 or BRCA2. However, there were two mutations prevalent in this geographical area with minor founder effects, BRCA2 T8555G and 999del5. This is one of the few geographically ascertained, population-based studies that indicate an overall frequency of BRCA1 and BRCA2 mutations at about 2--3% in all breast cancer cases. The geographical clustering of breast cancer cases was not explained by BRCA1 or BRCA2 genes.     

Radiological pulmonary findings after breast cancer irradiation: A prospective study

The aim of this study was to evaluate radiation-induced pulmonary abnormalities of breast cancer patients. Altogether 202 consecutive patients receiving postoperative radiotherapy entered the study. Plain chest radiographs taken at entry and 3, 6 and 12 months after radiotherapy were evaluated according to modified Arriagada classification. In addition, pulmonary symptoms were recorded. Supplementary high-resolution computed tomography (HRCT) was employed in a subgroup of patients (n = 15). Plain radiographs were interpreted by a radiologist, and uncertain findings were re-evaluated by a radiologist together with a radiation oncologist. Grade 2 pneumonitis was the most common abnormality. The proportion of patients yielding a grade 2 finding was 22.5%, 28.1%, and 16.0% at three, six, and twelve months, respectively. There were 2 normal findings in HRCTscans, and 8 in plain radiographs of the same patients. Radiological lung abnormalities are common after radiotherapy, but they are usually reversible, and their significance for the patient's well-being is minor. No correlation between symptoms and lung or pleural reactions was seen.     

Characterization of tet(32) genes from the oral metagenome

tet(32) was identified in three bacterial isolates and in metagenomic DNA from the human oral cavity. The regions immediately flanking the gene were found to have similarities to the mobile elements TnB1230 from Butyrivibrio fibrisolvens, ATE-3 from Arcanobacterium pyogenes, and CTn5 from Clostridium difficile.     

Communicating acute coronary syndrome risk to women in primary care: A scoping review of the literature

ObjectivesDelay from symptom onset to hospital arrival drives poor outcomes in acute coronary syndrome (ACS), particularly for women. Primary care clinicians can discuss ACS with high-risk women, potentially reducing delay. We conducted a scoping review to assess what is known about ACS risk communication to women in primary care.MethodsWe used Arksey and O'Malley's framework. The PubMed, CINAHL, PsycINFO, and Embase databases were searched for relevant articles from inception through September, 2018. No restrictions on study methodology were applied. At least two reviewers assessed each article. Articles addressing risk communication, coronary heart disease, and ACS, related to primary care settings, and including women were retained.ResultsEleven articles met inclusion criteria. Cardiovascular disease (CVD) risk communication is common in primary care; however, ACS symptoms are rarely discussed. Structured risk calculators are used to frame discussions. Communication styles include patient-centered discussions, paternalistic orders, and “scare tactics;” no single style is more effective. Analysis of gender differences in risk communication is extremely limited.ConclusionThere is scant evidence that primary care clinicians communicate effectively about ACS risk, symptoms, and appropriate symptom response.Practice implicationsInterventions are needed to improve communication about ACS to at-risk women in the primary care setting.     

Insomnia as a Moderator of Response to Time in Bed Restriction for Augmenting Antidepressant Treatment: A Preliminary Investigation

Background: There are complex, bidirectional associations between major depressive disorder and insomnia. In the present study, we evaluated insomnia as a moderator of response to antidepressant therapy in the context of a sleep manipulation (time in bed restriction) for major depressive disorder. Methods: Fifty-eight adults with major depressive disorder received 8 weeks of fluoxetine 20–40 mgs and were randomized to 8 hr time in bed (8h TIB) or 6 hr time in bed (6h TIB) for the first 2 weeks (participants in the 6h TIB condition were further randomized to a delayed bedtime (Late Bedtime) or advanced rise time (Early Rise Time) group). Insomnia was assessed at baseline using the Insomnia Severity Index. Depression symptom severity was determined by the clinician-rated 17-item Hamilton Rating Scale for Depression (HAMD-17), completed weekly. Results: A group by time interaction was observed whereby HAMD-17 scores were higher for participants assigned to the 6h TIB group (without insomnia, weeks 3 through 7; with insomnia from week 3 through 6, ps < .05) relative to participants without insomnia assigned to the 8h TIB group. There were no differences in HAMD-17 scores for participants with insomnia in the 6h TIB group relative to the 8h TIB group. Conclusion: These preliminary findings suggest that response to fluoxetine may be hindered by TIB restriction in individuals without insomnia. Individuals with insomnia respond similarly to fluoxetine regardless of whether their TIB is restricted. Limitations include exclusive use of self-report measures to categorize insomnia, and small sample sizes in several of the subgroups.