Childhood family structure and women's adult overweight risk: A longitudinal study.

AIM: The aim of this study was to investigate whether women's adult overweight and obesity risk was associated with their childhood family structure, measured as their mothers' marital status history, during the women's first 18 years of life. METHODS: Using linked register data, we analyzed 30,584 primiparous women born in Sweden in 1975 who were between 19-35 years of age when their height and pre-pregnancy weight was recorded. The outcomes were women's overweight/obesity (body mass index (BMI) ≥ 25 kg/m2) and obesity (BMI ≥ 30 kg/m2) and the predictor was mothers' marital status history, which was summarized using sequence analysis. We carried out nested logistic regression models adjusting for women's age and maternal sociodemographic characteristics. RESULTS: Mothers' marital status history was summarized into six clusters: stable marriage, stable cohabitation, married then divorcing, cohabiting then separating, varied transitions, and not with father. In fully adjusted models and compared with women whose mothers belonged to the stable marriage cluster: (1) women whose mothers belonged to the other marital status clusters had higher odds of overweight/obesity (odds ratio (OR) ranging 1.15-1.19; p < 0.05); and (2) women whose mothers belonged to the stable cohabitation (OR = 1.31; 95% confidence interval (CI) = 1.14-1.52), cohabiting then separating (OR = 1.23; 95% CI = 1.01-1.49), varied transitions (OR = 1.24; 95% CI = 1.11-1.39), and not with father (OR = 1.24; 95% CI = 1.00-1.54) clusters had higher odds of obesity. CONCLUSIONS: Women whose mothers were not in stable marriage relationships had higher odds of being overweight or obese in adulthood. The finding that even women raised in the context of stable cohabitation had higher odds of being overweight or obese is intriguing as these relationships are socially accepted in Sweden.

Regional inequalities in pre-pregnancy overweight and obesity in Sweden, 1992, 2000, and 2010.

AIMS: To investigate regional differences and time trends in women's overweight and obesity in Sweden. METHODS: Using data from the Swedish Medical Birth Register (women aged ⩾18 years, first pregnancy only) and the Total Population Register accessed through the Umeå SIMSAM Lab, age-standardized prevalence of pre-pregnancy overweight/obesity (BMI ⩾ 25 kg/m(2)) and obesity (BMI ⩾ 30 kg/m(2)) were estimated by county for the years 1992, 2000, and 2010. Maps were created using ArcMap v10.2.2 to display regional variations over time and logistic regression analyses were used to assess if the observed trends were significant. RESULTS: The prevalence of pre-pregnancy overweight/obesity and obesity increased significantly in all Swedish counties between 1992, and 2010. In 2010, Södermanland and Gotland exhibited the highest age-standardized overweight/obesity (39.7%) and obesity (15.1%) prevalence, respectively. The sharpest increases between 1992 and 2010 were observed in Västerbotten for overweight/obesity (75% increase) and in Gotland for obesity (233% increase). Across the years, Stockholm had the lowest prevalence of overweight/obesity (26.3% in 2010) and obesity (7.3% in 2010) and one of the least steep increases in prevalence of both between 1992 and 2010. CONCLUSIONS: Substantial regional differences in pre-pregnancy overweight and obesity prevalence are apparent in Sweden. Further research should elucidate the mechanisms causing these differences.

Neighborhood conditions and celiac disease risk among children in Sweden.

AIM: To investigate celiac disease (CD) clustering at different geographical levels and to examine the association between neighborhood demographic and socioeconomic conditions and the risk of neighborhood CD. METHODS: We included 2080 children diagnosed with CD between 1998 and 2003, identified from 43 of the 47 reporting hospitals in Sweden. A total of 8036 small area market statistics (SAMS) areas were included; these were nested in 253 municipalities that were further nested into eight 'nomenclature of territorial units for statistics' (NUTS) 2 regions. We performed multilevel logistic regression analyses. RESULTS: We found the highest geographical variation in CD incidence at the municipality level, compared to the region level. The probability of having CD increased in the statistical areas of (SAMS) areas with higher average annual work income, with an odds ratio (OR) of 2.24 and 95% CI of 1.76-2.85. Reduced CD risk in neighborhoods was associated with higher average age (OR 0.96; 95% CI 0.95-0.97), higher proportion of residents with a university education (OR 0.98; 95% CI 0.97-0.99), and higher level of industrial and commercial activity (OR 0.59; 95% CI 0.44-0.82). We found no significant association between CD risk and population density, proportion of Nordic to non-Nordic inhabitants, nor share of the population with only a compulsory education. CONCLUSIONS: Neighborhood composition influences cd risk this is one of the first attempts to identify factors explaining geographical variation in CD.

Nampt expression increases during osteogenic differentiation of multi- and omnipotent progenitors.

Despite emerging data showing that metabolic changes occur with stem cell differentiation, the cross-talk between factors governing energy metabolism and epigenetic modification is not understood. Nicotinamide adenine dinucleotide (NAD) participates in both energy metabolism and protein modification processes. Changes of the intracellular NAD concentration have been shown to correlate with differentiation of adult and embryonic stem cells. In the present study, we investigated the expression pattern of Nampt, the rate-limiting enzyme in NAD salvaging pathway, during osteogenic differentiation of the multipotent mouse fibroblast C3H10T1/2 and the omnipotent preosteoblast MC3T3-E1 cells. We found that Nampt was increasingly expressed during differentiation in both cell models. The increase of Nampt was associated with higher NAD concentration and Sirt1 activity. Knockdown of Nampt or addition of its specific inhibitor FK866 leads to lower intracellular NAD concentration and decline in osteogenesis. These findings indicate that osteogenic differentiation correlates with intracellular NAD metabolism in which Nampt plays a regulatory role.

FGF23 affects the lineage fate determination of mesenchymal stem cells.

FGF23 is a bone-derived hormone that regulates mineral metabolism by inhibiting renal tubular phosphate reabsorption and suppressing circulating 1,25(OH)2D and PTH levels. These effects are mediated by FGF-receptor binding and activation in the presence of its coreceptor Klotho, which is expressed in the distal tubules of the kidney. Recently, expression of Klotho in skeletal tissues has been reported, indicating a direct, yet unclear, extrarenal effect of FGF23 on cells involved with bone development and remodeling. In the present study, we found that bone marrow stromal cells harvested from Klotho null mice developed fewer osteoblastic but more adipocytic colonies than cells from wild-type mice. The underlying mechanism was explored by experiments on mouse C3H10T1/2 cells. We found that Klotho was weakly expressed and that FGF23 dose-dependently affected the lineage fate determination. The effects of FGF23 on cell differentiation can be diminished by SU 5402, a specific tyrosine kinase inhibitor for FGF receptors. Our results indicate that FGF23 directly affects the differentiation of bone marrow stromal cells.

Resveratrol prevents RANKL-induced osteoclast differentiation of murine osteoclast progenitor RAW 264.7 cells through inhibition of ROS production.

The bone protective effects of resveratrol have been demonstrated in several osteoporosis models while the underlying mechanism is largely unclear. In the present study, we evaluated the effects of resveratrol on differentiation and apoptosis of murine osteoclast progenitor RAW 264.7 cells. We found that resveratrol at non-toxic concentrations dose-dependently inhibited RANKL-induced osteoclast differentiation and induced apoptosis. Resveratrol has been shown to be an activator of Sirt1, a NAD(+) dependent protein deacetylase, and has been demonstrated to mimic estrogen. However, we found that although Sirt1 protein was abundantly expressed in RAW264.7 cells, the specific Sirt1 inhibitor EX-527 could not attenuate the inhibition of osteoclastogenesis mediated by resveratrol. Also, the effects of resveratrol could not be attenuated by ICI-182780, a high affinity estrogen receptor antagonist. The central role of reactive oxygen species (ROS) in RANKL-induced osteoclast differentiation has recently been clarified. We found that resveratrol suppressed RANKL-induced ROS generation in a concentration dependent manner. We postulate that the direct inhibitory effects of resveratrol on osteoclastogenesis are mediated via inhibition of ROS generation.

Activation of Sirt1 decreases adipocyte formation during osteoblast differentiation of mesenchymal stem cells.

Mesenchymal stem cells (MSC) can differentiate into osteoblasts, adipocytes, chondrocytes and myoblasts. It has been suggested that a reciprocal relationship exists between the differentiation of MSC into osteoblasts and adipocytes. Peroxisome proliferator-activated receptor gamma2 (PPARgamma2) is a key element for the differentiation into adipocytes. Activation of the nuclear protein deacetylase Sirt1 has recently been shown to decrease adipocyte development from preadipocytes via inhibition of PPARgamma2. In vitro, MSC differentiate to osteoblasts when exposed to bone-inducing medium. However, adipocytes are also developed. In the present study we have targeted Sirt1 to control adipocyte development during differentiation of MSC into osteoblasts. The finding that resveratrol and isonicotinamide markedly inhibited adipocyte and promoted osteoblast differentiation demonstrates an interesting alternative to PPARgamma antagonists. These results are important for the evolving field of cell-based tissue engineering, but may also be relevant in the search for new treatments of osteoporosis.

The effect of neighbourhood social capital on child injuries: A gender-stratified analysis.

We designed a longitudinal retrospective cohort study to analyse the associations between neighbourhood social capital and child injures. Register data from the Umeå Simsam Lab in Sweden was used to measure child injuries and demographic and socioeconomic factors at individual, household and neighbourhood level. A social capital score from a previous survey was used to measure neighbourhood social capital. We conducted a three-level multilevel negative binomial regression analysis, with children (level 1, N = 77,193) nested within households (level 2, N = 10,465), and households nested within neighbourhoods (level 3, N = 49). The incidence rate of child injuries was lower in high social capital neighbourhoods. When controlling for factors at individual, household and neighbourhood levels, living in a high social capital neighbourhood was protective of injuries among girls, but not among boys. Promoting social capital in local neighbourhoods could be seen as a prevention strategy for injuries among girls.

IL-6 receptor expression and IL-6 effects change during osteoblast differentiation.

Studies of the effects of interleukin-6 on osteoblasts have yielded conflicting results. In several earlier in vitro studies it has been stated that IL-6 has no effects on osteoblasts unless soluble IL-6 receptor is added. These results are contradictory to the fact that IL-6 receptors are expressed in osteoblasts in vivo. In this study, MC3T3 preosteoblast cells and rat bone marrow stromal cells were cultured in bone inducing medium containing ascorbic acid, beta-glycerophosphate or dexamethasone. We found that IL-6 receptor expression increased in both types of cells during in vitro differentiation. Furthermore in MC3T3 cells IL-6 decreased proliferation and enhanced expression of two osteoblast-specific differentiation markers, Runx2 and osteocalcin, in proper sequential order. Interestingly, in both cell types IL-6-induced apoptosis only in later culture stages. We also found in MC3T3 cells that IL-6 induced STAT3 activation was significantly higher in later culture stages, i.e. when IL-6 receptor expression was high. The present study shows that IL-6 receptor expression increases during in vitro osteoblast differentiation and that IL-6 functions as a differentiation regulator of preosteoblast cells and an apoptosis initiator in more mature cells.

Species difference exists in the effects of 1alpha,25(OH)(2)D(3) and its analogue 2-methylene-19-nor-(20S)-1,25-dihydroxyvitamin D(3) (2MD) on osteoblastic cells.

The direct effect of 1alpha,25(OH)(2)D(3) on osteoblasts remains unclear. In this study, we evaluated the in vitro effects of 1alpha,25(OH)(2)D(3) and its analogue, 2-methylene-19-nor-(20S)-1,25-dihydroxyvitamin D(3) (2MD), on osteoblasts from three different species, i.e. bone marrow stromal cells from the Sprague-Dawley (SD) rat, from the C57BL/6 mouse, as well as human osteoblast NHOst cells and human osteosarcoma derived MG-63 cells. We found that in rat cells, both compounds increased cell proliferation, inhibited cell apoptosis and increased alkaline phosphatase (ALP) activity. In mouse cells, however, both compounds initiated cell apoptosis and inhibited ALP activity. In human cells, although cell proliferation was inhibited by both compounds, cell apoptosis was inhibited and ALP activity was enhanced. In each species, 2MD was much more potent than 1alpha,25(OH)(2)D(3). To summarize, species differences should be taken into account in studies of vitamin D effects. However, in all tested species - rat, mouse and human - 2MD is considerably more potent in its effects on osteoblastic cells in vitro than 1alpha,25(OH)(2)D(3).

Neither the WAD-classification nor the Quebec Task Force follow-up regimen seems to be important for the outcome after a whiplash injury. A prospective study on 186 consecutive patients.

A classification of injury and a follow-up schedule were proposed by the Quebec Task Force (QTF) in 1995. No general agreement about the clinical usefulness of the WAD-classification or of the suggested follow-up regimen exists. A series of 186 consecutive cases seen in the emergency room during the acute phase after a whiplash injury was prospectively studied for 1 year. All findings including history and physical findings were recorded using standardized QTF protocols. In one group follow-up visits were done according to the QTF regimen: at 1, 3, 6, 12 weeks and 1 year after the accident; in a control group no visit was scheduled. The outcome variable was neck pain at 1 year after the accident. After 1 year, 18% of the total number of patients had significant neck pain. Risk factors for chronic neck pain at 1 year after whiplash injury were: neck pain before the accident and a high degree of emotional distress at the time of the accident; both factors independently associated with a tenfold increased risk of developing chronic neck pain. Neither the WAD classification nor the QTF follow-up regimen could be linked to a better outcome. In this study the outcome was associated with patient-specific characteristics and not with physical signs of injury, the depth of the initial evaluation or the follow-up regimen.

Surgical treatment of hallux valgus and forefoot deformities in Sweden: a population-based study.

BACKGROUND: Although surgical correction for hallux valgus and other toe deformities is one of the most common procedures in foot surgery, its incidence in the general population is not well-known. MATERIALS AND METHODS: The study population comprised patients living in Sweden of a varied age group and both sexes who underwent forefoot surgery. We identified all inpatient cases from 1997 to 2000 and all ambulatory cases in 2000 registered in the National Swedish Patient Register (NSPR). Further, clinical data for the surgical treatment of hallux valgus deformity were extracted from medical records in patients treated in a geographically defined region (Stockholm). RESULTS: In total, 6956 patients with surgically treated forefoot deformities were identified from the adult population, equivalent to a cumulative incidence of 0.8 procedures per 1000 inhabitants for the whole analyzed group. There were regional variations and significant sex differences. The age distribution in both sexes was characterized by a peak in the fifth decade. Forefoot surgery was statistically more frequently performed in private clinics than in public hospitals (p < 0.001). Hallux valgus surgery was by far the most common procedure regarding forefoot surgery. CONCLUSION: The prevalence of forefoot- and hallux valgus surgery was not evenly distributed in the six major regions in Sweden. It is more common in urban than in rural regions. Furthermore, forefoot surgery is performed more frequently in private clinics than in community hospitals despite common financial sources.

Activation of Sirt1 decreases adipocyte formation during osteoblast differentiation of mesenchymal stem cells.

UNLABELLED: In vitro, mesenchymal stem cells differentiate to osteoblasts when exposed to bone-inducing medium. However, adipocytes are also formed. We showed that activation of the nuclear protein deacetylase Sirt1 reduces adipocyte formation and promotes osteoblast differentiation. INTRODUCTION: Mesenchymal stem cells (MSCs) can differentiate into osteoblasts, adipocytes, chondrocytes, and myoblasts. It has been suggested that a reciprocal relationship exists between the differentiation of MSCs into osteoblasts and adipocytes. Peroxisome proliferator-activated receptor gamma2 (PPARgamma2) is a key element for the differentiation into adipocytes. Activation of Sirt1 has recently been shown to decrease adipocyte development from preadipocytes through inhibition of PPARgamma2. MATERIALS AND METHODS: We used the mouse mesenchymal cell line C3H10T1/2 and primary rat bone marrow cells cultured in osteoblast differentiation medium with or without reagents affecting Sirt1 activity. Adipocyte levels were analyzed by light microscopy and flow cytometry (FACS) after staining with Oil red O and Nile red, respectively. Osteoblast and adipocyte markers were studied with quantitative real-time PCR. Mineralization in cultures of primary rat bone marrow stromal cells was studied by von Kossa and alizarin red staining. RESULTS: We found that Sirt1 is expressed in the mesenchymal cell line C3H10T1/2. Treatment with the plant polyphenol resveratrol as well as isonicotinamide, both of which activate Sirt1, blocked adipocyte development and increased the expression of osteoblast markers. Nicotinamide, which inhibits Sirt1, increased adipocyte number and increased expression of adipocyte markers. Furthermore, activation of Sirt1 prevented the increase in adipocytes caused by the PPARgamma-agonist troglitazone. Finally, activation of Sirt1 in rat primary bone marrow stromal cells increased expression of osteoblast markers and also mineralization. CONCLUSIONS: In this study, we targeted Sirt1 to control adipocyte development during differentiation of MSCs into osteoblasts. The finding that resveratrol and isonicotinamide markedly inhibited adipocyte and promoted osteoblast differentiation may be relevant in the search for new treatment regimens of osteoporosis but also important for the evolving field of cell-based tissue engineering.

Tissue levels of leu-enkephalin in rats with adjuvant arthritis.

To study the level of leu-enkephalin in bone and joint tissues and in the spinal cord of rats with adjuvant arthritis, arthritis was induced in Lewis rats by the injection of Mycobacterium butyricum in Freund's incomplete adjuvant (FIA). Immunoelectron microscopy (IEM) was used to monitor the cellular distribution of leu-enkephalin in control and arthritis groups, and radioimmunoassay (RIA) was used to measure the concentration in the tissues. The results of IEM showed increased levels of leu-enkephalin in the matrix of the sciatic nerve, in nerve fibres in the synovial membrane and periosteum, as well as in fibroblasts and endothelial cells of the periosteum in arthritic groups. In macrophage-like cells of the synovial membrane as well as monocyte and polymorphonuclear lineage cells in the bone marrow, the level of leu-enkephalin was decreased in the arthritic group. The results of RIA showed that the concentration of leu-enkephalin was lower in the ankle and increased in the spinal cord of arthritic animals compared with controls. In conclusion, leu-enkephalin levels were decreased in joints and in bone marrow, but increased in nerve tissues in the group with arthritis. Further studies are needed to show whether leu-enkephalin is involved in a process that serves to limit the effect of immunisation.

Distribution of galanin in bone and joint tissues.

The article describes the distribution of galanin in normal bone and joint tissues. Periosteum, cortical bone, bone marrow, and synovial membrane of normal rats were analyzed. Immunoelectron microscopy (iEM) was used to analyze the distribution of galanin, and radioimmunoassay (RIA) was used to determine its concentration. Immunoelectron microscopy showed that galanin is abundant in nerve fibers and endothelial cells in the periosteum and also in macrophage-like-cells and nerve fibers of the synovial membrane. The concentration of galanin measured by RIA showed the highest concentration in bone marrow, followed by periosteum and cortical bone. This study demonstrates that galanin is present and can be quantified in different compartments of bone and joint tissues and illustrates the possible role of galanin under physiological conditions.

Environmental and economic impacts of decision-making at an arable farm: an integrative modeling approach.

This study examines the dependency between physical and anthropogenic systems in arable farming. The dynamic simulation model, which has its methodological origins in the modeling traditions of environmental systems analysis and microsimulation, reproduces the mutual links between the physical flows (e.g. energy, materials, emissions, and products), the farmer as a decision-making agent, and structural conditions influencing the farm. In running the model, the intention is to answer the question: What are the impacts on profitability and the environment (i.e. greenhouse gas effects, eutrophication, acidification, and energy use) of variations in prices, subsidies, the farmer's environmental values, and the farmer's skill in making production allocation choices? The results of the model simulations indicate, for example, that in terms of economic performance, a farmer can choose between two relatively sustainable strategies--either to specialize in organic production (thereby benefiting from higher subsidies and output prices), or to focus on conventional cultivation and use of pesticides and fertilizers (thereby benefiting from large yields). Regarding environmental impacts, there was no clear-cut divide between organic and conventional farming due to difficulties in allocating the use of manure. This finding is essentially related to the choice of system boundary, which is thoroughly discussed in the paper.

Effects of 1alpha,25-dihydroxyvitamin D3 and growth hormone on apoptosis and proliferation in UMR 106 osteoblast-like cells.

Mechanisms maintaining a correct balance between bone-forming osteoblasts and bone-resorbing osteoclasts are essential for bone formation. Apoptosis has been proposed to play a key role in controlling osteoblast homeostasis. 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and GH, which are important regulators of bone growth and bone metabolism, also play pivotal roles in regulation of mitogenesis, differentiation, and apoptosis. We have recently shown that 1,25(OH)2D3 prolongs GH signaling via the Janus kinase 2 (JAK2)/STAT5 (signal transducer and activator of transcription 5) pathway in UMR 106 osteoblast-like cells. In the present study, we have investigated the effects of GH and 1,25(OH)2D3 on proliferation and apoptosis in UMR 106 cells. We found that 1,25(OH)2D3 and GH, separate or in combination, inhibited apoptosis. GH also had profound effects on cell cycle distribution and proliferation. In addition, pretreatment of cells with 1,25(OH)2D3 was necessary to detect GH-induced MAPK activation. We hypothesize that these hormones separately regulate the processes of apoptosis and proliferation, which may be important for maintaining osteoblast cell number.

Ovariectomy and gonadal hormone treatment: effects on insulin-like growth factor-1 receptors in the rat brain.

Various studies demonstrate that estradiol regulates structure and function of adult neurons. Long-term effect of estradiol in terms of neuroprotection is less documented compared to short-term one. It is well documented that estradiol interacts with insulin-like growth factor-1 (IGF-I) in the brain. The present study examines the effect of ovariectomy and two doses of ovarian hormone treatment on IGF-I receptor density in the adult rat by receptor autoradiography using (125)I-IGF-I as a ligand. Our result showed that ovariectomy decreased IGF-I receptor density in hippocampus, hypothalamus and parietal cortex compared to that of the sham-operated group. Treatment with low or high dose estrogen restored IGF-I receptor density to the control levels in nearly all areas studied in this investigation. It seems that low dose estrogen has more pronounced effect than the high dose in restoring IGF-I receptor density. On the other hand, progesterone treatment in high but not in low dose restored IGF-I receptor density to that of the control. These results demonstrate that both estrogen and progesterone significantly affects IGF-I receptor density in different areas of the brain. These effects indicate a dose-dependent modulator effect of ovarian hormones on IGF-I activity in the brain.

Validity and reliability of a modified version of the neck disability index.

The Neck Disability Index was tested for validity and reliability. Fifty-nine Swedish patients (28 men, 31 women) were included. Twenty patients were in the acute phase after a neck sprain, 19 had chronic neck pain and 20 had no neck pain but had other musculoskeletal symptoms. On 5 occasions, the patients completed the Neck Disability Index, the Disability Rating Index, the MOS 36-item short-form health survey, 2 visual analogue scales, for pain and overall activity and some complementary questions. Levels of sensitivity, test-retest reliability and validity were acceptable. In order to increase specificity, we modified the Neck Disability Index by clarifying that the items only referred to the pain in the neck in 9 of 10 items. Thirty-eight patients (16 men, 22 women) were included in a study of the modified version. Twenty patients with acute neck sprain and 18 with other musculoskeletal symptoms filled out the modified version of the Neck Disability Index, which provided a more specific measure of disability due to neck pain.

Factors shaping workplace segregation between natives and immigrants.

Research on segregation of immigrant groups is increasingly turning its attention from residential areas toward other important places, such as the workplace, where immigrants can meet and interact with members of the native population. This article examines workplace segregation of immigrants. We use longitudinal, georeferenced Swedish population register data, which enables us to observe all immigrants in Sweden for the period 1990-2005 on an annual basis. We compare estimates from ordinary least squares with fixed-effects regressions to quantify the extent of immigrants' self-selection into specific workplaces, neighborhoods, and partnerships, which may bias more naïve ordinary least squares results. In line with previous research, we find lower levels of workplace segregation than residential segregation. The main finding is that low levels of residential segregation reduce workplace segregation, even after we take into account intermarriage with natives as well as unobserved characteristics of immigrants' such as willingness and ability to integrate into the host society. Being intermarried with a native reduces workplace segregation for immigrant men but not for immigrant women.