Daniel Berglind

Restriction of cisplatin induction of acute apoptosis to a subpopulation of cells in a three-dimensional carcinoma culture model

Cisplatin is a clinically important chemotherapeutical agent used to treat epithelial malignancies. High concentrations (20–100 μM) of cisplatin have been used in numerous studies to induce apoptosis of carcinoma cells grown in monolayer culture over 24–48 hr. These conditions may not be relevant to 3‐D tumor tissue in vivo and the importance of apoptosis for tumor response is controversial. We here studied the effects of cisplatin on a 3‐D colon carcinoma in vitro model (multicellular spheroids). Cisplatin at a dose of 40 μM induced active caspase‐3 preferentially in the peripheral 30 μm cell layer of spheroids, mainly during late stages (72–96 hr). The p53 response to cisplatin was also largely confined to peripheral cell layers. Despite the use of a high cisplatin concentration, a significant fraction of the cells in the spheroids survived treatment. A high proportion of surviving cells stained positive for β‐galactosidase, a marker of premature senescence. Cells growth‐arrested by cisplatin treatment showed a higher spontaneous cell death rate than untreated proliferating cells. We propose that acute apoptosis is of minor significance for the overall response of carcinoma cells to cisplatin treatment.

Motivational Interviewing to Prevent Childhood Obesity : A Cluster RCT

OBJECTIVE: The objective was to evaluate a manualized theory-driven primary preventive intervention aimed at early childhood obesity. The intervention was embedded in Swedish child health services, starting when eligible children were 9 to 10 months of age and continuing until the children reached age 4. METHODS: Child health care centers in 8 Swedish counties were randomized into intervention and control units and included 1355 families with 1369 infants. Over ∼39 months, families in the intervention group participated in 1 group session and 8 individual sessions with a nurse trained in motivational interviewing, focusing on healthy food habits and physical activity. Families in the control group received care as usual. Primary outcomes were children’s BMI, overweight prevalence, and waist circumference at age 4. Secondary outcomes were children’s and mothers’ food and physical activity habits and mothers’ anthropometrics. Effects were assessed in linear and log-binominal regression models using generalized estimating equations. RESULTS: There were no statistically significant differences in children’s BMI (β = –0.11, 95% confidence interval [CI]: –0.31 to 0.08), waist circumference (β = –0.48, 95% CI: –0.99 to 0.04), and prevalence of overweight (relative risk = 0.95, 95% CI: 0.69 to 1.32). No significant intervention effects were observed in mothers’ anthropometric data or regarding mothers’ and children’s physical activity habits. There was a small intervention effect in terms of healthier food habits among children and mothers. CONCLUSIONS: There were no significant group differences in children’s and mothers’ anthropometric data and physical activity habits. There was, however, some evidence suggesting healthier food habits, but this should be interpreted with caution.

Differential methylation in inflammation and type 2 diabetes genes in siblings born before and after maternal bariatric surgery.

Siblings born before (BMS) and after (AMS) maternal biliopancreatic diversion (BPD) show differences in the methylome. The objective was to use a sibling‐pair design to examine the effects from interpregnancy weight loss as a consequence of maternal bariatric surgery, other than BPD, on the methylome comparing BMS and AMS.

Differences in gestational weight gain between pregnancies before and after maternal bariatric surgery correlate with differences in birth weight but not with scores on the body mass index in early childhood

Large maternal gestational weight gain (GWG) is associated with increased birth weight and increased risk of obesity in offspring, but these associations may be confounded by genetic and environmental factors. The aim was to investigate the effects of differences in GWG in all three trimesters on differences in birth weight and in body mass index (BMI) scores at 4 and 6 years of age, within siblings born before and after bariatric surgery.

Changes in eating behaviour and food choices in families where the mother undergoes gastric bypass surgery for obesity

Background/Objectives:There is a lack of research exploring the effects of Roux-en-Y gastric bypass (RYGB) surgery on the patient’s family’s eating behaviour and food choices. The aim of the current study was to investigate changes in partners’ and children’s eating behaviour and food choices following maternal RYGB.Subjects/Methods:Sixty-nine women and their families were recruited from RYGB waiting lists at five Swedish surgical clinics. Data were collected during home visits 3 months before and 9 months after RYGB. Anthropometrical measures were taken, the adults completed the Three-Factor Eating Questionnaire and the children completed the Children’s Eating Attitudes Test (ChEAT). All participants also completed a short food frequency questionnaire.Results:Changes in scores were analysed using paired t-tests for unadjusted estimates or linear regression models with robust variance (General Estimating Equations) in order to enable age- and sex-adjusted estimates for the children. There were no meaningful differences in the partners’ eating behaviour or food choices. The boys, but not the girls, improved their ChEAT scores, as did the overweight/obese children in comparison with the normal-weight children. The boys, unlike the girls, also decreased their intake of soft drinks, as did the normal-weight children when compared with the overweight/obese children.Conclusions:No clear-cut changes were found in partners’ eating behaviour and food choices. Eating attitudes and soft drinks intake were improved among boys but not among girls. Differing modelling behaviour may partially explain these findings, but available data did not allow us to understand the underlying mechanisms.

Birth order and hospitalization for alcohol and narcotics use in Sweden

BACKGROUND Previous studies have shown that birth order is an important predictor of later life health as well as socioeconomic attainment. In this study, we examine the relationship between birth order and hospitalization for alcohol and narcotics use in Sweden. METHODS We study the relationship between birth order and hospitalization related to alcohol and narcotics use before and after the age of 20 using Swedish register data for cohorts born 1987-1994. We apply Cox proportional hazard models and use sibling fixed effects, eliminating confounding by factors shared by the siblings. RESULTS Before age 20 we find that later born siblings are hospitalized for alcohol use at a higher rate than first-borns, and there is a monotonic increase in the hazard of hospitalization with increasing birth order. Second-borns are hospitalized at a rate 47% higher than first-borns, and third-borns at a rate 65% higher. Similar patterns are observed for hospitalization for narcotics use. After age 20 the pattern is similar, but the association is weaker. These patterns are consistent across various sibling group sizes. CONCLUSIONS Later born siblings are more likely to be hospitalized for both alcohol and narcotics use in Sweden. These birth order effects are substantial in size, and larger than the estimated sex differences for the risk of hospitalization related to alcohol and drug use before age 20, and previous estimates for socioeconomic status differences in alcohol and drug abuse.

Levels and Patterns of Objectively Measured Physical Activity and Sedentary Time in 4-Year-Old Swedish Children

BACKGROUND Levels of physical activity (PA) affect health already at 4 years of age. The aims of this study were to describe levels and patterns of PA and sedentary time (ST) in a sample of 4-year-old Swedish children and to assess the number of children achieving PA guidelines throughout the week. METHODS Data from 540 4-year-old children enrolled in the population-based PRIMROSE trial was used. PA was measured for a period of 1 week by the Actigraph GT3X+ accelerometer. Average PA, time spent in light PA, moderate-to-vigorous PA (MVPA) and ST were assessed. RESULTS On average children spent 6.7% of the day in MVPA and 45% of the day being sedentary and 33% (n = 178) of the children met the PA guidelines of 60 minutes of MVPA per day. Boys spent 56.8 (SD 21.8) minutes/day in MVPA, while girls spent 43.0 (SD 18.1) minutes/day in MVPA (P < .001). CONCLUSIONS Four-year-old children spent almost half of the day being sedentary and only one-third meet the recommended PA guidelines. This finding is alarming as higher levels of PA, already at 4 years of age, seem to reduce the risk of childhood obesity and provides long-term health benefits.