Previous Sport Activity During Childhood and Adolescence Is Associated With Increased Cortical Bone Size in Young Adult Men

Physical activity during growth has been associated with altered cortical bone geometry, but it remains uncertain if the physical activity–induced increments in cortical bone size remain when the level of physical activity is diminished or ceased. The aim of this study was to investigate if physical activity during growth is associated with cortical bone geometry in currently inactive young men. In this study, 1068 men (18.9 ± 0.6 [SD] yr) were included. Cortical bone geometry at the tibia and radius were measured using pQCT. A standardized questionnaire was used to collect information about current and previous sport activity. Subjects who continued to be active (n = 678) and who had been previously active (n = 285) in sports had a wider cortical bone (periosteal circumference [PC], 4.5% and 3.2%, respectively) with increased cross‐sectional area (CSA; 12.5% and 6.9%) of the tibia than the always inactive subjects (n = 82). In the currently inactive men (n = 367), regression analysis (including covariates age, height, weight, calcium intake, smoking, and duration of inactivity) showed that previous sport activity was independently associated with cortical bone size of the tibia (CSA and PC). Amount of previous sport activity explained 7.3% of the total variation in cortical CSA. Subjects, who ceased their sport activity for up to 6.5 yr previously, still had greater cortical PC and CSA of the tibia than always inactive subjects. The results from this study indicate that sport activity during growth confers positive effects on bone geometry even though sport activity is ceased.     

Interpersonal problems and cognitive characteristics of interpersonal representations in alexithymia: a study using a self-report and interview-based measure of alexithymia

In this study, associations between alexithymia, interpersonal problems, and cognitive-structural aspects of internal interpersonal representations were examined. Alexithymia was measured using the Toronto Structured Interview for Alexithymia (TSIA) and the 20-item Toronto Alexithymia Scale (TAS-20). To measure interpersonal problems, the dominance and affiliation dimension scores of the Inventory of Interpersonal Problems were used, and cognitive-structural characteristics of interpersonal representations were measured using the Social Cognition and Object Relations Scale (SCORS). As hypothesized, alexithymia was related to cold and withdrawn, but not to dominant or submissive, interpersonal functioning. In terms of the SCORS, alexithymia was negatively related to complexity of interpersonal representations, both in TAT and in interview narratives, indicating a link between alexithymia and mentalization. However, alexithymia was related only to the dimension of social causality when this dimension was scored on TAT narratives. Overall, the TSIA provides the most consistent and stable results after controlling for negative affectivity.     

Decreased axonal transport rates in the Tg2576 APP transgenic mouse: improvement with the gamma‐secretase inhibitor MRK‐560 as detected by manganese‐enhanced MRI

Neuropil deposition of beta‐amyloid (Aβ) peptides is believed to be a key event in the neurodegenerative process of Alzheimer’s disease (AD). An early and consistent clinical finding in AD is olfactory dysfunction with associated pathology. Interestingly, transgenic amyloid precursor protein (Tg2576) mice also show early amyloid pathology in olfactory regions. Moreover, a recent study indicates that axonal transport is compromised in the olfactory system of Tg2576 mice, as measured by manganese‐enhanced magnetic resonance imaging (MEMRI). Here we tested whether the putative axonal transport deficit in the Tg2576 mouse model improves in response to a selective gamma‐secretase inhibitor, N‐[cis‐4‐[(4‐chlorophenyl)‐sulfonyl]‐4‐(2,5‐difluorophenyl)cyclohexyl]‐1,1,1‐trifluoromethanesulfonamide (MRK‐560). Tg2576 mice or wild‐type (WT) littermates were treated daily with MRK‐560 (30 μmol/kg) or vehicle for 4 (acute) or 29 days (chronic). The subsequent MEMRI analysis revealed a distinct axonal transport dysfunction in the Tg2576 mice compared with its littermate controls. Interestingly, the impairment of axonal transport could be fully reversed by chronic administration of MRK‐560, in line with the significantly lowered levels of both soluble and insoluble forms of Aβ found in the brain and olfactory bulbs (OBs) following treatment. However, no improvement of axonal transport was observed after acute treatment with MRK‐560, where soluble but not insoluble forms of Aβ were reduced in the brain and OBs. The present results show that axonal transport is impaired in Tg2576 mice compared with WT controls, as measured by MEMRI. Chronic treatment in vivo with a gamma‐secretase inhibitor, MRK‐560, significantly reduces soluble and insoluble forms of Aβ, and fully reverses the axonal transport dysfunction.     

High prevalence of autoantibodies to C-reactive protein in patients with chronic hepatitis C infection: association with liver fibrosis and portal inflammation

The presence of autoantibodies against C-reactive protein (anti-CRP) has been reported in association with autoimmunity and histopathology in chronic hepatitis C virus (HCV) infection. Resistin could play a role in the pathogenesis of hepatitis, although results on HCV infection are ambiguous. Here we retrospectively analyzed anti-CRP and resistin levels in the sera of 38 untreated and well-characterized HCV patients at the time of their first liver biopsy. HCV activity and general health were assessed by a physician at least yearly until follow-up ended. Anti-CRP and resistin were also measured in patients with autoimmune hepatitis (AIH) and nonalcoholic fatty liver disease (NAFLD). Anti-CRP antibodies were registered in all HCV patients, whereas only a few AIH (11%) and NAFLD (12%) sera were positive. Anti-CRP levels were related to histopathological severity and were highest in patients with cirrhosis at baseline. Resistin levels were similar in HCV, AIH, and NAFLD patients, but high levels of resistin were associated with early mortality in HCV patients. Neither anti-CRP nor resistin predicted a response to interferon-based therapy or cirrhosis development or was associated with liver-related mortality. We conclude that anti-CRP antibodies are frequently observed in chronic HCV infection and could be a useful marker of advanced fibrosis and portal inflammation.     

The chromosome 2p21 region harbors a complex genetic architecture for association with risk for renal cell carcinoma

In follow-up of a recent genome-wide association study (GWAS) that identified a locus in chromosome 2p21 associated with risk for renal cell carcinoma (RCC), we conducted a fine mapping analysis of a 120 kb region that includes EPAS1. We genotyped 59 tagged common single-nucleotide polymorphisms (SNPs) in 2278 RCC and 3719 controls of European background and observed a novel signal for rs9679290 [P = 5.75 × 10(-8), per-allele odds ratio (OR) = 1.27, 95% confidence interval (CI): 1.17-1.39]. Imputation of common SNPs surrounding rs9679290 using HapMap 3 and 1000 Genomes data yielded two additional signals, rs4953346 (P = 4.09 × 10(-14)) and rs12617313 (P = 7.48 × 10(-12)), both highly correlated with rs9679290 (r(2) > 0.95), but interestingly not correlated with the two SNPs reported in the GWAS: rs11894252 and rs7579899 (r(2) < 0.1 with rs9679290). Genotype analysis of rs12617313 confirmed an association with RCC risk (P = 1.72 × 10(-9), per-allele OR = 1.28, 95% CI: 1.18-1.39) In conclusion, we report that chromosome 2p21 harbors a complex genetic architecture for common RCC risk variants.     

Prostheses Removal for Suture Removal after Immediate Load: Success of Implants

Purpose: The aim of this cohort study was to evaluate the success of implants after immediate loading in cases when the prostheses were removed for suture removal on the tenth day following implant placement. We describe a technique for fabricating effective definitive prostheses passively fitted to facilitate immediate load in edentulous patients. Materials and Methods: Seventy‐one patients with resin‐metal prostheses installed within less than 48 hours after implant placement were recalled. Patients for whom various amounts of time had elapsed since implant placement returned for follow‐up. Time elapsed ranged from 6 months to 7 years. Stability of the implants was tested after prosthesis removal by horizontal and vertical percussion tests. Implant success was determined as the number of functional implants displaying no mobility. Results: Follow‐up revealed that all implants from each period evaluated were stable, with no mobility (100% of implants success), except for the 1‐year time point (99.5%) and the 2‐year time point (98.9%). No signs of inflammation and/or bleeding were observed. Conclusion: Prosthesis removal for suture removal on the tenth day after implant placement represents a reliable and predictable procedure that did not jeopardize implant stability during bone remodeling.     

Fractionated irradiation of five human lung cancer cell lines and prediction of survival according to a radiobiology model

BACKGROUND: This study evaluates a predictive radiobiology model by measurements of surviving fraction (SF) by the clonogenic assay or the extrapolation method and the proliferation rate in vitro. It is hypothesized that incorporating proliferation to intrinsic radiosensitivity, measured by SF, to predict radiation responsiveness after fractionated irradiation adds to the model's accuracy. Materials and Methods. Five lung cancer cell lines with known SF after 1 Gy (SF1), and also SF2 and SF5, were irradiated with three different fractionation regimes; 10 × 1 Gy, 5 × 2 Gy or 2 × 5 Gy during the same total time to achieve empirical SF. In addition, the SF1, SF2 and SF5 after fractionated irradiation was calculated for each cell line based on the already known single fraction SF and with or without a proliferation factor. The results were compared to the empirical data. Results and Discussion: By using the clonogenic assay to measure radiosensitivity, prediction of radiosensitivity was improved after fractionated radiotherapy when proliferation was used in the radiobiology model. However, this was not the case in the cell lines where the extrapolation method was used to calculate SF. Thus, a radiobiology model including intrinsic radiosensitivity, measured by the clonogenic assay, as well as proliferation, is better at predicting survival after fractionated radiotherapy, compared to the use of intrinsic radiosensitivity alone.     

Uninephrectomy in young age or chronic salt loading causes salt-sensitive hypertension in adult rats

The importance of nephron endowment and salt intake for the development of hypertension is under debate. The present study was designed to investigate whether reduced nephron number, after completion of nephrogenesis, or chronic salt loading causes renal injury and salt-sensitive hypertension in adulthood. Rats were operated at 3 weeks of age (after completed nephrogenesis) and then subjected to either normal or high-salt diets for 6 to 8 weeks. Four different experimental groups were used: sham-operated animals raised with normal-salt diet (controls) or high-salt diet (HS) and uninephrectomized animals raised with normal-salt diet (UNX) or high-salt diet (UNX+HS). In the adult animals, renal and cardiovascular functions were evaluated and blood pressure recorded telemetrically under different sodium conditions (normal, high, and low). Hypertension was present in UNX+HS (122+/-9 mm Hg), UNX (101+/-3 mm Hg), and HS (96+/-1 mm Hg) groups on normal-salt diets compared with the controls (84+/-2 mm Hg), and the blood pressure was salt sensitive (high- versus normal-salt diet; 23+/-3, 9+/-2, 7+/-2, and 1+/-1 mm Hg, respectively). The hypertensive groups (UNX+HS, UNX, and HS) had increased diuresis and reduced ability to concentrate urine. The glomerular filtration rate (milliliters per minute) in anesthetized rats was reduced in the UNX+HS (2.36+/-0.30) and UNX animals (2.00+/-0.31) compared with both HS animals (3.55+/-0.45) and controls (3.01+/-0.35). Hypertensive groups displayed reduced plasma renin concentrations during high sodium conditions and hypertrophic kidneys and hearts with various degrees of histopathologic changes. In conclusion, at a young age after completed nephrogenesis, uninephrectomy or chronic salt loading causes renal and cardiovascular injury with salt-sensitive hypertension.