Smoking before the birth of a first child is not associated with increased risk of breast cancer: findings from the British Women's Heart and Health Cohort Study and a meta-analysis

It has been suggested that the period between puberty and first birth is a time when the breast is particularly susceptible to carcinogenic effects. In a cohort of 3047 women aged 60-79 years (N=139 breast cancer cases), we found no association between smoking before the birth of a first child and breast cancer risk: fully adjusted (for age, number of children, age at birth of first child, age at menarche, age at menopausal, hysterectomy and/or oophorectomy, ever use of oral contraception, use of hormone replacement therapy, alcohol consumption, body mass index, childhood and adulthood social class) odds ratio 1.06 (95% confidence interval: 0.72, 1.56). The pooled estimate from a meta-analysis of our study and 11 previously published studies (N=6528 cases) was 1.07 (0.94, 1.22). We conclude that smoking prior to the birth of a first child is not associated with increased risk of breast cancer

Early motion and directed exercise (EMADE) versus usual care post ankle fracture fixation: study protocol for a pragmatic randomised controlled trial

Background: Following surgical fixation of ankle fractures, the traditional management has included immobilisation for 6 weeks in a below-knee cast. However, this can lead to disuse atrophy of the affected leg and joint stiffness. While early rehabilitation from 2 weeks post surgery is viewed as safe, controversy remains regarding its benefits. We will compare the effectiveness of early motion and directed exercise (EMADE) ankle rehabilitation, against usual care, i.e. 6 weeks’ immobilisation in a below-knee cast. Method/design: We have designed a pragmatic randomised controlled trial (p-RCT) to compare the EMADE intervention against usual care. We will recruit 144 independently living adult participants, absent of tissue-healing comorbidities, who have undergone surgical stabilisation of isolated Weber B ankle fractures. The EMADE intervention consists of a non-weight-bearing progressive home exercise programme, complemented with manual therapy and education. Usual care consists of immobilisation in a non-weight-bearing below-knee cast. The intervention period is between week 2 and week 6 post surgery. The primary outcome is the Olerud and Molander Ankle Score (OMAS) patient-reported outcome measure (PROM) at 12 weeks post surgery. Secondary PROMs include the EQ-5D-5 L questionnaire, return to work and return to driving, with objective outcomes including ankle range of motion. Analysis will be on an intention-to-treat basis. An economic evaluation will be included. Discussion: The EMADE intervention is a package of care designed to address the detrimental effects of disuse atrophy and joint stiffness. An advantage of the OMAS is the potential of meta-analysis with other designs. Within the economic evaluation, the cost-utility analysis, may be used by commissioners, while the use of patient-relevant outcomes, such as return to work and driving, will ensure that the study remains pertinent to patients and their families. As it is being conducted in the clinical environment, this p-RCT has high external validity. Accordingly, if significant clinical benefits and cost-effectiveness are demonstrated, EMADE should become a worthwhile treatment option. A larger-scale, multicentre trial may be required to influence national guidelines. Trial registration: ISRCTN, ID: ISRCTN11212729. Registered retrospectively on 20 March 2017

Prognosis of ovarian cancer subsequent to venous thromboembolism: a nationwide Danish cohort study

BACKGROUND: Venous thromboembolism (VTE) is associated with ovarian cancer and may impact the prognosis of ovarian cancer. Our aims were to examine the extent of disease at the time of the diagnosis of ovarian cancer and to estimate the impact of VTE on survival of ovarian cancer. METHODS: We identified 12,835 ovarian cancer patients diagnosed from 1980 to 2003 in the Danish Cancer Registry and obtained information on previous primary VTE diagnosis from the Danish National Hospital Discharge Registry. Ovarian cancer patients with previous VTE related to other cancers, surgery, or pregnancy were excluded. The vital status was determined by linking data to the Civil Registration System. RESULTS: We identified 50 ovarian cancer patients diagnosed less than 4 months after the VTE and 78 ovarian cancer patients diagnosed more than 4 months after the VTE diagnosis. Advanced stages tended to be more common among patients with VTE. One-year survivals were 44% and 54% among the two VTE groups, compared with 63% among patients without VTE. Adjusted (for age, calendar time, comorbidity, and FIGO-stage) mortality ratios were 1.7 (95% CI = 1.2–2.5) and 1.2 (95% CI = 0.8–1.7), respectively. CONCLUSION: Ovarian cancer diagnosed less than four months before VTE is associated with an advanced stage and a poorer prognosis

Early mortality experience in a large military cohort and a comparison of mortality data sources

<p>Abstract</p> <p>Background</p> <p>Complete and accurate ascertainment of mortality is critically important in any longitudinal study. Tracking of mortality is particularly essential among US military members because of unique occupational exposures (e.g., worldwide deployments as well as combat experiences). Our study objectives were to describe the early mortality experience of Panel 1 of the Millennium Cohort, consisting of participants in a 21-year prospective study of US military service members, and to assess data sources used to ascertain mortality.</p> <p>Methods</p> <p>A population-based random sample (n = 256,400) of all US military service members on service rosters as of October 1, 2000, was selected for study recruitment. Among this original sample, 214,388 had valid mailing addresses, were not in the pilot study, and comprised the group referred to in this study as the invited sample. Panel 1 participants were enrolled from 2001 to 2003, represented all armed service branches, and included active-duty, Reserve, and National Guard members. Crude death rates, as well as age- and sex-adjusted overall and age-adjusted, category-specific death rates were calculated and compared for participants (n = 77,047) and non-participants (n = 137,341) based on data from the Social Security Administration Death Master File, Department of Veterans Affairs (VA) files, and the Department of Defense Medical Mortality Registry, 2001-2006. Numbers of deaths identified by these three data sources, as well as the National Death Index, were compared for 2001-2004.</p> <p>Results</p> <p>There were 341 deaths among the participants for a crude death rate of 80.7 per 100,000 person-years (95% confidence interval [CI]: 72.2,89.3) compared to 820 deaths and a crude death rate of 113.2 per 100,000 person-years (95% CI: 105.4, 120.9) for non-participants. Age-adjusted, category-specific death rates highlighted consistently higher rates among study non-participants. Although there were advantages and disadvantages for each data source, the VA mortality files identified the largest number of deaths (97%).</p> <p>Conclusions</p> <p>The difference in crude and adjusted death rates between Panel 1 participants and non-participants may reflect healthier segments of the military having the opportunity and choosing to participate. In our study population, mortality information was best captured using multiple data sources.</p

A Rapid and Simple Procedure for the Establishment of Human Normal and Cancer Renal Primary Cell Cultures from Surgical Specimens

The kidney is a target organ for the toxicity of several xenobiotics and is also highly susceptible to the development of malignant tumors. In both cases, in vitro studies provide insight to cellular damage, and represent adequate models to study either the mechanisms underlying the toxic effects of several nephrotoxicants or therapeutic approaches in renal cancer. The development of efficient methods for the establishment of human normal and tumor renal cell models is hence crucial. In this study, a technically simple and rapid protocol for the isolation and culture of human proximal tubular epithelial cells and human renal tumor cells from surgical specimens is presented. Tumor and normal tissues were processed by using the same methodology, based on mechanical disaggregation of tissue followed by enzymatic digestion and cell purification by sequential sieving. The overall procedure takes roughly one hour. The resulting cell preparations have excellent viabilities and yield. Establishment of primary cultures from all specimens was achieved successfully. The origin of primary cultured cells was established through morphological evaluation. Normal cells purity was confirmed by immunofluorescent staining and reverse transcription-polymerase chain reaction analysis for expression of specific markers

TWEAK Appears as a Modulator of Endometrial IL-18 Related Cytotoxic Activity of Uterine Natural Killers

BACKGROUND: TWEAK (Tumor necrosis factor like WEAK inducer of apoptosis) is highly expressed by different immune cells and triggers multiple cellular responses, including control of angiogenesis. Our objective was to investigate its role in the human endometrium during the implantation window, using an ex-vivo endometrial microhistoculture model. Indeed, previous results suggested that basic TWEAK expression influences the IL-18 related uNK recruitment and local cytotoxicity. METHODOLOGY/PRINCIPAL FINDINGS: Endometrial biopsies were performed 7 to 9 days after the ovulation surge of women in monitored natural cycles. Biopsies were cut in micro-pieces and cultured on collagen sponge with appropriate medium. Morphology, functionality and cell death were analysed at different time of the culture. We used this ex vivo model to study mRNA expressions of NKp46 (a uNK cytotoxic receptor) and TGF-beta1 (protein which regulates uNK cytokine production) after adjunction of excess of recombinant IL-18 and either recombinant TWEAK or its antibody. NKp46 protein expression was also detailed by immunohistochemistry in selected patients with high basic mRNA level of IL-18 and either low or high mRNA level of TWEAK. The NKp46 immunostaining was stronger in patients with an IL-18 over-expression and a low TWEAK expression, when compared with patients with both IL-18 and TWEAK high expressions. We did not observe any difference for TWEAK expression when recombinant protein IL-18 or its antibody was added, or conversely, for IL-18 expression when TWEAK or its antibody was added in the culture medium. In a pro-inflammatory environment (obtained by an excess of IL-18), inhibition of TWEAK was able to increase significantly NKp46 and TGF-beta1 mRNA expressions. CONCLUSIONS/SIGNIFICANCE: TWEAK doesn't act on IL-18 expression but seems to control IL-18 related cytotoxicity on uNK cells when IL-18 is over-expressed. Thus, TWEAK appears as a crucial physiological modulator to prevent endometrial uNK cytotoxicity in human

Doing masculinity, not doing health? a qualitative study among dutch male employees about health beliefs and workplace physical activity

<p>Abstract</p> <p>Background</p> <p>Being female is a strong predictor of health promoting behaviours. Workplaces show great potential for lifestyle interventions, but such interventions do not necessarily take the gendered background of lifestyle behaviours into account. A perspective analyzing how masculine gender norms affect health promoting behaviours is important. This study aims to explore men's health beliefs and attitudes towards health promotion; in particular, it explores workplace physical activity in relation to masculine ideals among male employees.</p> <p>Methods</p> <p>In the Fall of 2008, we interviewed 13 white Dutch male employees aged 23-56 years. The men worked in a wide range of professions and occupational sectors and all interviewees had been offered a workplace physical activity program. Interviews lasted approximately one to one-and-a-half hour and addressed beliefs about health and lifestyle behaviours including workplace physical activity, as well as normative beliefs about masculinity. Thematic analysis was used to analyze the data.</p> <p>Results</p> <p>Two normative themes were found: first, the ideal man is equated with being a winner and real men are prepared to compete, and second, real men are not whiners and ideally, not vulnerable. Workplace physical activity is associated with a particular type of masculinity - young, occupied with looks, and interested in muscle building. Masculine norms are related to challenging health while taking care of health is feminine and, hence, something to avoid. Workplace physical activity is not framed as a health measure, and not mentioned as of importance to the work role.</p> <p>Conclusions</p> <p>Competitiveness and nonchalant attitudes towards health shape masculine ideals. In regards to workplace physical activity, some men resist what they perceive to be an emphasis on muscled looks, whereas for others it contributes to looking self-confident. In order to establish a greater reach among vulnerable employees such as ageing men, worksite health promotion programs including workplace physical activity may benefit from greater insight in the tensions between health behaviours and masculinity.</p