Birth weight and creatinine clearance in young adult twins: influence of genetic, prenatal, and maternal factors

Previous studies have shown that low birth weight (LBW) is a risk factor for renal impairment in adult life. The effects of LBW and renal function were studied by using twins, which allows distinguishing among fetoplacental, maternal, and genetic influences. Perinatal data were obtained at birth, and absolute creatinine clearance (not corrected for body surface area) was measured at a mean age of 25.6 yr in 653 individuals. Twins were considered both as individuals and as members of twin pairs. Statistical analyses were performed with and without adjusting for gestational age, zygosity, gender, age, body mass index, glucose level, BP, and smoking status. Creatinine clearance was 4 ml/min lower in twins with LBW (<2500 g) than in twins with a high birth weight (P < 0.04, adjusted). Intrapair birth weight difference correlated positively with the intrapair difference in creatinine clearance equally in monozygotic and dizygotic twins (r = 0.35, P < 0.0001; r = 0.43, P < 0.0001, respectively). This suggests that fetoplacental factors are related to renal function and that genetic factors are less important. There was no significant difference in creatinine clearance between twins who both had LBW as compared with twins who both had a high birth weight. This may suggest that maternal factors, which influence the relation between LBW and renal function, are less important. LBW is related to a lower creatinine clearance at adult age. This relationship is probably due to fetoplacental factors. Surprising, genetic and maternal factors seem less important.     

A randomized experimental study to test the effects of discussing uncertainty during cancer genetic counseling: different strategies,different outcomes?

Uncertainty is increasingly discussed during genetic counseling due to innovative techniques, e.g., multigene panel testing. Discussions about uncertainty may impact counselees variably, depending on counselors’ communication styles. Ideally, the discussion of uncertainty enables counselees to cope with uncertainty and make well-informed decisions about testing. We examined the impact of how counselors convey uncertainty and address counselees’ uncertainty, and explored the role of individual characteristics. Therefore, a randomized controlled experiment using videos was conducted. Former counselees (N = 224) viewed one video depicting a genetic consultation about multigene panel testing. The extent of counselors’ communication of uncertainty (comprehensive vs. the essence) and their response to counselees’ uncertainty expressions (providing information vs. providing space for emotions vs. normalizing and counterbalancing uncertainty) were systematically manipulated. Individual characteristics, e.g., uncertainty tolerance, were assessed, as well as outcome variables (primary outcomes: feelings of uncertainty and information recall). No effects were found on primary outcomes. Participants were most satisfied when the essence was communicated, combined with providing information or providing space responses (p = 0.002). Comprehensive information resulted in less perceived steering toward testing (p = 0.005). Participants with lower uncertainty tolerance or higher trait anxiety were less confident about their understanding when receiving comprehensive information (p = 0.025). Participants seeking information experienced less uncertainty (p = 0.003), and trusted their counselor more (p = 0.028), when the counselor used information providing responses. In sum, the impact of discussing uncertainty primarily depends on individual characteristics. Practical guidelines should address how to tailor the discussion of uncertainty.Subject terms: Human behaviour, Patient education     

Experiences of hospital-based multidisciplinary team meetings in oncology: An interview study among participating general practitioners

Background: Cancer care has become complex, requiring healthcare professionals to collaborate to provide high-quality care. Multidisciplinary oncological team (MDT) meetings in the hospital have been implemented to coordinate individual cancer patients’ care. General practitioners (GPs) are invited to join, but their participation is minimal.

Objectives: Aim of this study is to explore participating GPs’ perceptions of their current role and to understand their preferences towards effective role execution during MDT meetings.

Methods: In May to June 2014, semi-structured interviews (n?=?16) were conducted involving GPs with MDT experience in Belgium. The analysis was done according to qualitative content analysis principles.

Results: Attendance of an MDT meeting is perceived as part of the GP’s work, especially for complex patient care situations. Interprofessional collaborative relationships and the GP’s perceived benefit to the MDT meeting discussions are important motivators to participate. Enhanced continuity of information flow and optimized organizational time management were practical aspects triggering the GP’s intention to participate. GPs valued the communication with the patient before and after the meeting as an integral part of the MDT dynamics.

Conclusion: GPs perceive attendance of the MDT meeting as an integral part of their job. Suggestions are made to enhance the efficiency of the meetings.     

Triad of physical activity, aerobic fitness and obesity in adolescents and young adults with myelomeningocele.

OBJECTIVE: Comprehensively and objectively assess physical activity, aerobic fitness and body fat in adolescents and young adults with myelomeningocele and to investigate their relationships. DESIGN: Cross-sectional study. SUBJECTS: Fifty-one persons (26 males) with myelomeningocele aged 21.1 (standard deviation) 4.5) years. METHODS: Physical activity was measured with an accelerometry-based activity monitor. Aerobic fitness was defined as the maximum oxygen uptake during the last minute of a maximal exercise test. Body fat was assessed using sum of 4 skin-folds and body mass index. Correlations were studied using multiple regression analyses. RESULTS: Thirty-nine percent of the participants were inactive and another 37% were extremely inactive. Aerobic fitness was 42% lower than normative values and 35% were obese. Ambulatory status was related to daily physical activity (beta = 0.541), aerobic fitness (beta = 0.397) and body fat (beta = -0.243). Gender was related to aerobic fitness (beta = -0.529) and body fat (beta = 0.610). Physical activity was related to aerobic fitness in non-ambulatory persons with myelomeningocele (beta = 0.398), but not in ambulatory persons. CONCLUSION: Adolescents and young adults with myelomeningocele were physically inactive, had poor aerobic fitness and high body fat. Differences exist between subgroups regarding gender and ambulatory status.     

Centromeric breakage as a major cause of cytogenetic abnormalities in oral squamous cell carcinoma

Cytogenetic analysis of short-term explant tumor cultures derived from 11 human oral squamous cell carcinomas (nine from primary tumors and two from nude mice xenograft cultures) revealed clonal chromosomal aberrations with multiple numerical and structural changes in all tumors. Recurrent breakpoints were located at chromosomal bands 1p13 (five tumors), 11q13 (four tumors), 3q27-29 (three tumors), and 12q13 (three tumors). Four tumors had a homogeneously staining region at band 11q13. Consistent chromosomal losses included 3p, 9p13-pter, and 18q22-qter, each occurring in eight tumors. Gain of material was observed for chromosome arms 3q, 5p, 7p, and 8q. As many as 134 of a total of 218 chromosomal breakpoints (61%) occurred in centromeric regions, often resulting in isochromosomes and unbalanced whole-arm translocations. Using fluorescence in situ hybridization with chromosome-specific centromeric alphoid repeat probes, two whole-arm translocations, der(Xq;11q) and a der(3q;11q), each from a different tumor, were shown to contain juxtaposed centromeric sequences of both participating chromosomes, strongly suggesting that the breakpoints were within the centromeres. We propose that centromeric breakage is an important mechanism for the generation of genetic imbalance in the development of oral squamous cell carcinoma. Genes Chrom Cancer 14:000-000 (1995). © 1996 Wiley-Liss, Inc.     

Interleukin-6/interleukin-6 receptor pathway as a new therapy target in epithelial ovarian cancer

Epithelial ovarian cancer is a major problem as about 75% of patients develop recurrence after initial primary treatment and tumors are often chemoresistant. This article reviews the role of the interleukin-6 (IL-6) in chemoresistance and suppression of tumor immunity in ovarian cancer and provides the rationale for modulating the IL-6/ IL-6 receptor (IL-6R) induced pathway as a potential new target for the treatment of ovarian cancer. IL-6 is elevated in serum and ascites of ovarian cancer patients and increased IL-6 levels correlate with chemoresistance and poor prognosis in these patients. IL-6 induced Jak/Stat3, Ras/MEK/ERK and PI3K/Ras signaling pathways lead to cell survival, proliferation, angiogenesis, and confers resistance to apoptosis induced by conventional therapies. Furthermore, IL-6 induces tumor-promoting macrophages which are known to foster tumor growth and suppress local immunity. However, direct proof of the clinical impact of IL-6 blocking on disease progression is missing necessiting further studies in which the IL-6(R) pathway is modulated and its clinical impact on (epithelial) ovarian cancer is tested.     

Energy cost and physical strain of daily activities in adolescents and young adults with myelomeningocele

The aim of this study was to assess the energy cost and physical strain of daily activities in adolescents and young adults with myelomeningocele (MMC) compared with peers without a disability. Eighteen participants with MMC aged between 16 and 30 years (13 males, five females; mean age 21y 4mo [SD 4y 8mo]) and 18 age- and sex-matched non-disabled participants performed several standardized activities. Energy cost was assessed by oxygen uptake expressed per unit time (all activities) and per metre (walking and wheelchair use at preferred speed). Physical strain was calculated by dividing energy cost by aerobic capacity. For all activities no difference was found in energy cost per unit time between ambulatory participants with MMC and comparison participants. Energy cost per metre walking at preferred speed in participants with MMC was 0.26ml/kg/m (SD 0.08), and in comparison participants was 0.20ml/kg/m (SD 0.03); p=0.08. Non-ambulatory participants with MMC had lower energy cost (per unit time and per metre) during wheelchair use than comparison participants during walking (p<0.05). For most activities, physical strain was 1.4 to 2 times higher in participants with MMC than in comparison participants (p<0.05). In conclusion, energy cost per unit time of daily activities was not increased in participants with MMC. However, energy cost per metre during walking at preferred speed and physical strain were higher than in peers without disability.