Atherosclerotic lesions in the thoracic aorta: A South African anatomical and histological mortuary study

Background. Worldwide, the prevalence of cardiovascular diseases such as atherosclerosis is on the increase. Younger people may be especially vulnerable owing to their exposure to risk factors such as drug abuse and HIV. Methods. The thoracic aortas of 149 South Africans under the age of 50 years were collected at the Salt River Mortuary, Cape Town, and examined macroscopically and microscopically for evidence of anomalies. The sample comprised predominantly males, and included black, coloured and white individuals. Results. A significantly higher level of macroscopic pathology was found in coloured males, although overall prevalence of pathology in this sample was lower than expected. A positive association was also found between body mass index and vascular pathology in the black and coloured population groups. Microscopic anomalies were common and present at high levels, irrespective of age and racial grouping. Conclusions. The widespread prevalence of microscopic anomalies in all groups suggests that these are normal variations that result from haemodynamic forces. The higher prevalence of atherosclerotic lesions in coloured males, however, probably results from specific genetic conditions such as hypercholesterolaemia or lifestyle factors such as diet or tik abuse. The findings suggest that coloured individuals may be at increased risk of developing cardiovascular disease

Atherosclerotic lesions in the thoracic aorta: A South African anatomical and histological mortuary study

Background. Worldwide, the prevalence of cardiovascular diseases such as atherosclerosis is on the increase. Younger people may be especially vulnerable owing to their exposure to risk factors such as drug abuse and HIV. Methods. The thoracic aortas of 149 South Africans under the age of 50 years were collected at the Salt River Mortuary, Cape Town, and examined macroscopically and microscopically for evidence of anomalies. The sample comprised predominantly males, and included black, coloured and white individuals. Results. A significantly higher level of macroscopic pathology was found in coloured males, although overall prevalence of pathology in this sample was lower than expected. A positive association was also found between body mass index and vascular pathology in the black and coloured population groups. Microscopic anomalies were common and present at high levels, irrespective of age and racial grouping. Conclusions. The widespread prevalence of microscopic anomalies in all groups suggests that these are normal variations that result from haemodynamic forces. The higher prevalence of atherosclerotic lesions in coloured males, however, probably results from specific genetic conditions such as hypercholesterolaemia or lifestyle factors such as diet or tik abuse. The findings suggest that coloured individuals may be at increased risk of developing cardiovascular disease

Atherosclerotic lesions in the thoracic aorta: A South African anatomical and histological mortuary study

Background. Worldwide, the prevalence of cardiovascular diseases such as atherosclerosis is on the increase. Younger people may be especially vulnerable owing to their exposure to risk factors such as drug abuse and HIV. Methods. The thoracic aortas of 149 South Africans under the age of 50 years were collected at the Salt River Mortuary, Cape Town, and examined macroscopically and microscopically for evidence of anomalies. The sample comprised predominantly males, and included black, coloured and white individuals. Results. A significantly higher level of macroscopic pathology was found in coloured males, although overall prevalence of pathology in this sample was lower than expected. A positive association was also found between body mass index and vascular pathology in the black and coloured population groups. Microscopic anomalies were common and present at high levels, irrespective of age and racial grouping. Conclusions. The widespread prevalence of microscopic anomalies in all groups suggests that these are normal variations that result from haemodynamic forces. The higher prevalence of atherosclerotic lesions in coloured males, however, probably results from specific genetic conditions such as hypercholesterolaemia or lifestyle factors such as diet or tik abuse. The findings suggest that coloured individuals may be at increased risk of developing cardiovascular disease

TUBectomy with delayed oophorectomy as an alternative to risk-reducing salpingo-oophorectomy in high-risk women to assess the safety of prevention:the TUBA-WISP II study protocol

BACKGROUND: Risk-reducing salpingectomy with delayed oophorectomy has gained interest for individuals at high risk for tubo-ovarian cancer as there is compelling evidence that especially high-grade serous carcinoma originates in the fallopian tubes. Two studies have demonstrated a positive effect of salpingectomy on menopause-related quality of life and sexual health compared with standard risk-reducing salpingo-oophorectomy.PRIMARY OBJECTIVE: To investigate whether salpingectomy with delayed oophorectomy is non-inferior to the current standard salpingo-oophorectomy for the prevention of tubo-ovarian cancer among individuals at high inherited risk.STUDY HYPOTHESIS: We hypothesize that postponement of oophorectomy after salpingectomy, to the age of 40-45 (BRCA1) or 45-50 (BRCA2) years, compared with the current standard salpingo-oophorectomy at age 35-40 (BRCA1) or 40-45 (BRCA2) years, is non-inferior in regard to tubo-ovarian cancer risk.TRIAL DESIGN: In this international prospective preference trial, participants will choose between the novel salpingectomy with delayed oophorectomy and the current standard salpingo-oophorectomy. Salpingectomy can be performed after the completion of childbearing and between the age of 25 and 40 (BRCA1), 25 and 45 (BRCA2), or 25 and 50 (BRIP1, RAD51C, and RAD51D pathogenic variant carriers) years. Subsequent oophorectomy is recommended at a maximum delay of 5 years beyond the upper limit of the current guideline age for salpingo-oophorectomy. The current National Comprehensive Cancer Network (NCCN) guideline age, which is also the recommended age for salpingo-oophorectomy within the study, is 35-40 years for BRCA1, 40-45 years for BRCA2, and 45-50 years for BRIP1, RAD51C, and RAD51D pathogenic variant carriers.MAJOR INCLUSION/EXCLUSION CRITERIA: Premenopausal individuals with a documented class IV or V germline pathogenic variant in the BRCA1, BRCA2, BRIP1, RAD51C, or RAD51D gene who have completed childbearing are eligible for participation. Participants may have a personal history of a non-ovarian malignancy.PRIMARY ENDPOINT: The primary outcome is the cumulative tubo-ovarian cancer incidence at the target age: 46 years for BRCA1 and 51 years for BRCA2 pathogenic variant carriers.SAMPLE SIZE: The sample size to ensure sufficient power to test non-inferiority of salpingectomy with delayed oophorectomy compared with salpingo-oophorectomy requires 1500 BRCA1 and 1500 BRCA2 pathogenic variant carriers.ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Participant recruitment is expected to be completed at the end of 2026 (total recruitment period of 5 years). The primary outcome is expected to be available in 2036 (minimal follow-up period of 10 years).TRIAL REGISTRATION NUMBER: NCT04294927.</p

Risk of urothelial bladder cancer in Lynch syndrome is increased, in particular among MSH2 mutation carriers

Contains fulltext : 89346.pdf (publisher's version ) (Open Access)BACKGROUND: Colorectal, endometrial and upper urinary tract tumours are characteristic for Lynch syndrome (hereditary non-polyposis colon carcinoma, HNPCC). The aim of the present study was to establish whether carriers of mutations in mismatch repair genes MLH1, MSH2 or MSH6 are at increased risk of urinary bladder cancer. METHODS: Carriers and first degree relatives of 95 families with a germline mutation in the MLH1 (n=26), MSH2 (n=43), or MSH6 (n=26) gene were systematically questioned about the occurrence of carcinoma. The cumulative risk of cancer occurring before the age of 70 years (CR70) was compared to the CR70 of the general Dutch population. Microsatellite instability (MSI) testing and/or immunohistochemistry (IHC) for mismatch repair proteins was performed on bladder tumour tissue. RESULTS: Bladder cancer was diagnosed in 21 patients (90% men) from 19 Lynch syndrome families (2 MLH1, 15 MSH2, and 4 MSH6). CR70 for bladder cancer was 7.5% (95% CI 3.1% to 11.9%) for men and 1.0% (95% CI 0% to 2.4%) for women, resulting in relative risks for mutation carriers and first degree relatives of 4.2 (95% CI 2.2 to 7.2) for men and 2.2 (95% CI 0.3 to 8.0) for women. Men carrying an MSH2 mutation and their first degree relatives were at highest risks: CR70 for bladder and upper urinary tract cancer being 12.3% (95% CI 4.3% to 20.3%) and 5.9% (95% CI 0.7% to 11.1%). Bladder cancer tissue was MSI positive in 6/7 tumours and loss of IHC staining was found in 14/17 tumours, indicating Lynch syndrome aetiology. CONCLUSION: Patients with Lynch syndrome carrying an MSH2 mutation are at increased risk of urinary tract cancer including bladder cancer. In these cases surveillance should be considered.01 juli 201

Impact of childhood experiences on the development of entrepreneurial intentions

Fostering entrepreneurship and an entrepreneurial culture has become a key policy priority for governments. To encourage entrepreneurship and an entrepreneurial culture, however, there is a need to understand the factors that influence and shape individuals' intentions to start a business. This study extends models of entrepreneurial intentions by investigating the influence of various childhood-experience factors on the perceived feasibility and desirability of starting a business. A structured questionnaire was completed by over 1,000 university students and analysed using regression analysis. Results indicated that perceptions of entrepreneurship were influenced not only by parental ownership of a business, but also by a difficult childhood and frequent relocation

Patients with an unexplained microsatellite instable tumour have a low risk of familial cancer

The cancer risk is unknown for those families in which a microsatellite instable tumour is neither explained by MLH1 promoter methylation nor by a germline mutation in a mismatch repair (MMR) gene. Such information is essential for genetic counselling. Families suspected of Lynch syndrome (n=614) were analysed for microsatellite instability, MLH1 promoter methylation and/or germline mutations in MLH1, MSH2, MSH6, and PMS2. Characteristics of the 76 families with a germline mutation (24 MLH1, 2 PMS2, 32 MSH2, and 18 MSH6) were compared with those of 18 families with an unexplained microsatellite instable tumour. The mean age at diagnosis of the index patients in both groups was comparable at 44 years. Immunohistochemistry confirmed the loss of an MMR protein. Together this suggests germline inactivation of a known gene. The Amsterdam II criteria were fulfilled in 50/75 families (66%) that carried a germline mutation in an MMR gene and in only 2/18 families (11%) with an unexplained microsatellite instable tumour (P<0.0001). Current diagnostic strategies can detect almost all highly penetrant MMR gene mutations. Patients with an as yet unexplained microsatellite instable tumour likely carry a different type of mutation that confers a lower risk of cancer for relatives

Feeder layer- and animal product-free culture of neonatal foreskin keratinocytes: improved performance, usability, quality and safety

Since 1987, keratinocytes have been cultured at the Queen Astrid Military Hospital. These keratinocytes have been used routinely as auto and allografts on more than 1,000 patients, primarily to accelerate the healing of burns and chronic wounds. Initially the method of Rheinwald and Green was used to prepare cultured epithelial autografts, starting from skin samples from burn patients and using animal-derived feeder layers and media containing animal-derived products. More recently we systematically optimised our production system to accommodate scientific advances and legal changes. An important step was the removal of the mouse fibroblast feeder layer from the cell culture system. Thereafter we introduced neonatal foreskin keratinocytes (NFK) as source of cultured epithelial allografts, which significantly increased the consistency and the reliability of our cell production. NFK master and working cell banks were established, which were extensively screened and characterised. An ISO 9001 certified Quality Management System (QMS) governs all aspects of testing, validation and traceability. Finally, as far as possible, animal components were systematically removed from the cell culture environment. Today, quality controlled allograft production batches are routine and, due to efficient cryopreservation, stocks are created for off-the-shelf use. These optimisations have significantly increased the performance, usability, quality and safety of our allografts. This paper describes, in detail, our current cryopreserved allograft production process

Lack of genotype-phenotype correlation in basal cell nevus syndrome:A Dutch multicenter retrospective cohort study

Contains fulltext : 225468.pdf (Publisher’s version ) (Closed access