The prevalence of BRCA1 mutations in Chinese patients with early onset breast cancer and affected relatives

The purpose of this study was to determine the prevalence of BRCA1 mutations in Chinese breast cancer patients in Singapore. BRCA1 analysis was conducted in consecutive patients with breast cancer before the age of 40 years (76 women), or whose relatives had breast or ovarian cancer (16 women). Ten patients had both early onset breast cancer and affected relatives. Genomic DNA from peripheral mononuclear blood cells was studied by using the protein transcription–translation assay (exon 11) and single-strand conformational polymorphism, with subsequent DNA sequencing. All six disease-causing mutations occurred in women under 40 years (8.6%) with three occurring in patients under 35 years (three out of 22 patients, 13.6%). Mis-sense mutations of unknown significance were found in three patients. Two of the ten women with affected relatives under 40 years had BRCA1 mutations. The prevalence of BRCA1 mutations in Chinese patients with early onset breast cancer is similar to that observed in Caucasian women. Most Chinese patients with affected relatives were not carriers of BRCA1 mutations. © 2000 Cancer Research Campaig

Risk factors for pelvic girdle pain postpartum and pregnancy related low back pain postpartum:a systematic review and meta-analysis

Contains fulltext : 221001.pdf (Publisher’s version ) (Closed access)BACKGROUND: Although pelvic girdle pain postpartum and pregnancy related low back pain postpartum (combined and named PGPP in this study) have a natural favourable course, there is a subgroup of women who have persistent complaints. The objective of this study was to identify personal-, (pre)pregnancy-, obstetric-, and child related risk factors on PGPP by means of a systematic literature review and meta-analysis. METHODS: Literature searches of PubMed, EMBASE, CINAHL and Cochrane up to October 2018 were conducted. Prospective cohort studies in English or Dutch describing three or more risk factors for PGPP were included. We assessed articles for inclusion and risk of bias. Studies with high risk of bias were excluded from data extraction. Data was extracted and checked for accuracy confirming to the CHARMS-checklist. Homogeneous variables were pooled. RESULTS: Twelve full text studies were assessed. Seven studies were excluded due to high risk of bias. Data was extracted from five studies. Multivariate analysis was not possible due to heterogeneity in included risk factors as well as outcome measures on risk factor per study. Pooled univariate significant risk factors on PGPP were: a history of low back pain, pre-pregnancy body mass index >25, pelvic girdle pain in pregnancy, depression in pregnancy, and a heavy workload in pregnancy. No significant obstetric and child related risk factors were reported. CONCLUSIONS: Risk factors on PGPP have been identified. Since multivariate analysis was not possible the outcome should be treated with care, because interaction between risk factors could not be analysed

Is the Clinical Risk Score for Patients with Colorectal Liver Metastases Still Useable in the Era of Effective Neoadjuvant Chemotherapy?

Background: Several clinical risk scores (CRSs) for the outcome of patients with colorectal liver metastases have been validated, but not in patients undergoing neoadjuvant chemotherapy. Therefore, this study evaluates the predictive value of these CRSs in this specific group. Methods: Between January 2000 and December 2008, all patients undergoing a metastasectomy were analyzed and divided into two groups: 193 patients did not receive neoadjuvant chemotherapy (group A), and 159 patients received neoadjuvant chemotherapy (group B). In group B, the CRSs were calculated before and after administration of neoadjuvant chemotherapy. Results were evaluated by using the CRSs proposed by Nordlinger et al., Fong et al., Nagashima et al., and Konopke et al. Results: In groups A and B, the overall median survival was 43 and 47 months, respectively (P = 0.648). In group A, all CRSs used were of statistically significant predictive value. Before administration of neoadjuvant chemotherapy, only the Nordlinger score was of predictive value. After administration of neoadjuvant chemotherapy, all CRSs were of predictive value again, except for the Konopke score. Conclusions: Traditional CRSs are not a reliable prognostic tool when used in patients before treatment with neoadjuvant chemotherapy. However, CRSs assessed after the administration of neoadjuvant chemotherapy are useful to predict prognosis

Anatomical Versus Nonanatomical Resection of Colorectal Liver Metastases: Is There a Difference in Surgical and Oncological Outcome?

Background: The increased use of neoadjuvant chemotherapy and minimally invasive therapies for recurrence in patients with colorectal liver metastases (CLM) makes a surgical strategy

Occupational exposure to gases/fumes and mineral dust affect DNA methylation levels of genes regulating expression

Many workers are daily exposed to occupational agents like gases/fumes, mineral dust or biological dust, which could induce adverse health effects. Epigenetic mechanisms, such as DNA methylation, have been suggested to play a role. We therefore aimed to identify differentially methylated regions (DMRs) upon occupational exposures in never-smokers and investigated if these DMRs associated with gene expression levels. To determine the effects of occupational exposures independent of smoking, 903 never-smokers of the LifeLines cohort study were included. We performed three genome-wide methylation analyses (Illumina 450 K), one per occupational exposure being gases/fumes, mineral dust and biological dust, using robust linear regression adjusted for appropriate confounders. DMRs were identified using comb-p in Python. Results were validated in the Rotterdam Study (233 never-smokers) and methylation-expression associations were assessed using Biobank-based Integrative Omics Study data (n = 2802). Of the total 21 significant DMRs, 14 DMRs were associated with gases/fumes and 7 with mineral dust. Three of these DMRs were associated with both exposures (RPLP1 and LINC02169 (2x)) and 11 DMRs were located within transcript start sites of gene expression regulating genes. We replicated two DMRs with gases/fumes (VTRNA2-1 and GNAS) and one with mineral dust (CCDC144NL). In addition, nine gases/fumes DMRs and six mineral dust DMRs significantly associated with gene expression levels. Our data suggest that occupational exposures may induce differential methylation of gene expression regulating genes and thereby may induce adverse health effects. Given the millions of workers that are exposed daily to occupational exposures, further studies on this epigenetic mechanism and health outcomes are warranted

Acceptability and Use of the Diaphragm and Replens® Lubricant Gel for HIV Prevention in Southern Africa

The acceptability and use of the diaphragm and lubricant gel were assessed as part of a large randomized controlled trial to determine the effectiveness of the methods in women’s HIV acquisition. 2,452 intervention-arm women were enrolled at five Southern African clinics and followed quarterly for 12–24 months. Acceptability and use data were collected by face-to-face interviews at Month 3 and Exit. Participants were “very comfortable” with the physical mechanics of diaphragm use throughout the trial, and approval of the gel consistency, quantity and the applicator was high. At Exit, consistent disclosure of use (AOR 1.97, 95% CI: 1.10–3.55); an overall high diaphragm rating (AOR 1.84, 95% CI: 1.45–2.34) and perception of partner approval (AOR 1.75, 95% CI: 1.35–2.26) were the most significant acceptability factors independently associated with consistent use. Despite being female-initiated, disclosure of use to male partners and his perceived approval of the products were factors significantly associated with their consistent use

Peptide receptor radionuclide therapy (PRRT) with [177Lu-DOTA0,Tyr3]octreotate in combination with RAD001 treatment: further investigations on tumor metastasis and response in the rat pancreatic CA20948 tumor model

Background Previously, we reported on the unexpected development of distant metastases in the subcutaneous rat pancreas CA20948 tumor model after 4.5 weeks of treatment with RAD001-only or in combination with [177Lu-DOTA0,Tyr3]octreotate (177Lu-DOTATATE) (Cancer Res. 73:12-8, 2013). Moreover, the combination therapy was less effective compared to 177Lu-DOTATATE-only. In the current study, we address the following questions: (1) Why was the combination therapy less effective? Is 177Lu-DOTATATE tumor uptake affected by pretreatment with RAD001? (2) Could sudden cessation of RAD001 therapy cause the development of distant metastases? (3) Is 177Lu-DOTATATE an effective treatment option for these metastases? Methods Lewis rats (HanHsd or SsNHsd substrain with a slight difference in immune response) bearing subcutaneous CA20948 tumors were treated with either 125 or 275 MBq 177Lu-DOTATATE, RAD001, or their combination. RAD001 was given twice a week for 4.5 or 12 weeks, whereas 177Lu-DOTATATE was given as a single injection. When combined, RAD001 was started either 3 days prior to or 3 days post administration of 177Lu-DOTATATE. SPECT/CT was performed to quantify 177Lu-DOTATATE tumor uptake. Where indicated, primary tumors were surgically removed when tumor size is >6,000 mm3 to enable monitoring for possible metastasis. If metastases were suspected, an 111In-DTPA-octreotide SPECT/CT scan was performed. Seven rats with metastases were treated with 400 MBq 177Lu-DOTATATE. Results Lu-DOTATATE tumor uptake was not significantly affected by RAD001 pretreatment. The occurrence of metastases after RAD001 treatment was not dose dependent in the dose range tested, nor was it related to the duration of RAD001 treatment. In the experiment in which the LEW/SsNsd substrain was used, only 12.5% of RAD001-treated rats showed complete response (CR), compared to 50% tumor regression in the control group. Re-treatment with a high dose of 177Lu-DOTATATE resulted in CR in only two out of seven animals. Conclusion Less effective anti-tumor effects after the combination of RAD001 + 177Lu-DOTATATE could not be explained by reduced 177Lu-DOTATATE tumor uptake after RAD001. Our current data support RAD001-induced immune suppression as the reason for this observation. No evidence was found that cessation of RAD001 treatment caused development of metastases. Metastases appeared to be less sensitive to 177Lu-DOTATATE treatment than primary tumors

Metabolomics Profile in Depression:A Pooled Analysis of 230 Metabolic Markers in 5283 Cases With Depression and 10,145 Controls

Background: Depression has been associated with metabolic alterations, which adversely impact cardiometabolic health. Here, a comprehensive set of metabolic markers, predominantly lipids, was compared between depressed and nondepressed persons. Methods: Nine Dutch cohorts were included, comprising 10,145 control subjects and 5283 persons with depression, established with diagnostic interviews or questionnaires. A proton nuclear magnetic resonance metabolomics platform provided 230 metabolite measures: 51 lipids, fatty acids, and low-molecular-weight metabolites; 98 lipid composition and particle concentration measures of lipoprotein subclasses; and 81 lipid and fatty acids ratios. For each metabolite measure, logistic regression analyses adjusted for gender, age, smoking, fasting status, and lipid-modifying medication were performed within cohort, followed by random-effects meta-analyses. Results: Of the 51 lipids, fatty acids, and low-molecular-weight metabolites, 21 were significantly related to depression (false discovery rate q <.05). Higher levels of apolipoprotein B, very-low-density lipoprotein cholesterol, triglycerides, diglycerides, total and monounsaturated fatty acids, fatty acid chain length, glycoprotein acetyls, tyrosine, and isoleucine and lower levels of high-density lipoprotein cholesterol, acetate, and apolipoprotein A1 were associated with increased odds of depression. Analyses of lipid composition indicators confirmed a shift toward less high-density lipoprotein and more very-low-density lipoprotein and triglyceride particles in depression. Associations appeared generally consistent across gender, age, and body mass index strata and across cohorts with depressive diagnoses versus symptoms. Conclusions: This large-scale meta-analysis indicates a clear distinctive profile of circulating lipid metabolites associated with depression, potentially opening new prevention or treatment avenues for depression and its associated cardiometabolic comorbidity

Stability and change the role of keepsakes and family homes in the lives of parentally bereaved young adults in the Netherlands 1

This paper examines the loss of a parent in young adulthood, showing how this emergent and distinctive life stage shapes Dutch young people’s experience of bereavement. Youth material cultures have commonly been analysed in terms of the construction and expression of youth identities, for example, through style, music and leisure. In this research, we highlight three themes in young people’s relationship to material culture as part of their everyday lived experience of parental loss: first, the parental home as a space of departure, memory and return, and the potential for conflict, destabilisation and misunderstanding when the remaining parent transforms the home or embarks on a new relationship; second, the different strategies young adults use to commemorate their parent in their own temporary or shared accommodation and online space; and third, the role of small, portable but effective keepsakes and adornment, such as jewellery or tattoos, that meet their need for the emotional experience of closeness with the memory of their parent. A focus on the material trajectories of grief grants insights into how young adults cope with loss in their everyday life, generating understanding of the ways young people may support themselves and be supported by others in the context of parental bereavement