Evidence of associations between feto-maternal vitamin D status, cord parathyroid hormone and bone-specific alkaline phosphatase, and newborn whole body bone mineral content

In spite of a high prevalence of vitamin D inadequacy in pregnant women and neonates, relationships among vitamin D status (25(OH)D), parathyroid hormone (PTH), bone specific alkaline phosphatase (BALP), and whole body bone mineral content (WBBMC) in the newborn are poorly characterized. The purpose of the present study was to investigate the relationships between maternal and cord 25(OH)D, PTH, BALP, and WBBMC in newborns in a multiethnic population in Oakland, California and to evaluate the predictive value of the biochemical indices as indicators of WBBMC. Maternal and cord blood were collected from 80 mother-infant pairs and infant WBBMC was measured by dual energy X-ray absorptiometry 8-21 days post-birth. Cord PTH and BALP were each inversely correlated with infant WBBMC (r = -0.28, p = 0.01 and r = -0.26, p = 0.02) and with cord 25(OH)D (r = -0.24, p = 0.03 and r = -0.34, p = 0.002), while cord 25(OH)D and unadjusted or weight-adjusted WBBMC were not significantly correlated with one other. In multivariate regression modeling, infant WBBMC was most strongly predicted by infant weight (p < 0.0001), while either PTH or BALP contributed modestly but significantly to the model (p = 0.006 and p = 0.03 respectively). Cord 25(OH)D was not a significant predictor of infant WBBMC. This study provides evidence of associations between feto-maternal 25(OH)D, cord PTH and BALP, and early infant WBBMC, though neither feto-maternal 25(OH)D nor the measured biochemical indices were suitable indicators of WBBMC.     

Smoking habits and obesity in young adults

AIMS: The aim of this work was to study the association between obesity and smoking habits in young adults. Specifically, we tested the hypothesis that obesity does not prevent young adults from smoking and conversely smoking does not protect against obesity. DESIGN AND SETTING: Trained nurses interviewed participants concerning demographic data and health behaviors such as smoking. At the time of the interview, weight and height were measured. Data were analyzed retrospectively. PARTICIPANTS: A representative sample of Israel Defense Force (IDF) personnel upon discharge from compulsory service, usually at the age of 20-21 years. FINDINGS: Overall, 29 745 participants were included during the 13-year study (16,363 males and 13,382 females). Smoking rates were higher among obese participants than among overweight and non-obese participants (34.9%, 37.1%, 43.6% for non-obese, overweight and obese, respectively; P < 0.001). Mean number of cigarettes smoked per day were also higher among smokers that were obese and overweight compared to the non-obese (15.2 +/- 9.2, 15.6 +/- 10.7, 18.0 +/- 9.8, respectively; P < 0.001). Overweight and obesity were associated with the father's lower academic educational level. In logistic regression analysis, obesity, year of study and parental academic education were correlated independently with smoking (P < 0.001). CONCLUSION: The positive association between obesity and smoking suggests that obesity is not a deterrent to smoking and also that smoking does not help to prevent obesity.     

Improved regional left ventricular function after successful satellite cell grafting in rabbits with myocardial infarction

OBJECTIVE: To evaluate whether satellite cells injected into infarct areas in rabbits remain viable during 6 weeks follow-up and can improve cardiac function as assessed by echocardiography. METHODS: Myocardial infarction was induced in 16 New Zealand white rabbits, by ligation of the marginalis sinistra artery. Tissue from gluteus muscle biopsies was dissected into small pieces and cultured. Within 2-3 weeks the cells were expanded by 2-3 orders of magnitude and were fluorescent labeled. Single cell pellets for resuspension at >10(6)/1 ml were directly injected into the infarct areas in 8 rabbits. In 8 additional rabbits, 1 ml saline was injected (control). Regional left ventricular function was assessed weekly by 2-D echocardiography until animals were sacrificed. Analysis was performed blind and independently by two experienced echocardiographers, based on the American Society of Echocardiography scheme. RESULTS AND DISCUSSION: Six treated and five control rabbits completed the study. One week after the artery occlusion, left ventricular function scoring did not differ between groups, mean 8.7+/-1.6 vs 8.3+/-1.9 (P=0.74). At 6 weeks post-injection, echocardiographic score was significantly better in the treated group, mean 2.6+/-0.9 vs 6.9+/-2.1 (P=0.002). The treated group showed significant gradual segmental improvement between the first week up to week 6. After sacrifice, macro and microscopic transmural areas showed typical changes of myocardial infarction. Histochemical staining identified viable grafted cells in high density 6 weeks post-transplantation in all grafted hearts. CONCLUSION: Autologous satellite cells (skeletal myofiber), can be successfully grafted into rabbit hearts following myocardial infarction and may induce improved regional left ventricular function.     

Recombinant PfEMP1 peptide inhibits and reverses cytoadherence of clinical Plasmodium falciparum isolates in vivo

The parasite ligand Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) and host endothelial receptors represent potential targets for antiadhesive therapy for cytoadherence. In the present study, the major host receptor CD36 was targeted in vitro and in vivo with a recombinant peptide, PpMC-179, corresponding to the minimal CD36-binding domain from the cysteine-rich interdomain region 1 (CIDR1) within the MCvar1 PfEMP1. The in vitro inhibitory effect of PpMC-179 on human dermal microvascular endothelial cells (HDMECs) expressing multiple relevant adhesion molecules was investigated using a parallel-plate flow chamber. Pretreatment of endothelial monolayers with PpMC-179 (2 microM) inhibited the adhesion of infected erythrocytes (IRBCs) from all clinical isolates tested by 84.4% on resting and 62.8% on tumor necrosis factor alpha (TNF-alpha)-stimulated monolayers. Adhesion to stimulated cells was further inhibited (90.4%) when PpMC-179 was administered with an inhibitory anti-intercellular adhesion molecule 1 (ICAM-1) monoclonal antibody 84H10 (5 microg/mL). To determine the in vivo effectiveness of PpMC-179, we used a human/severe combined immunodeficiency (SCID) mouse chimeric model that allowed direct visualization of cytoadherence on intact human microvasculature. In unstimulated skin grafts, PpMC-179 inhibited adhesion by 86.3% and by 84.6% in TNF-alpha-stimulated skin grafts. More importantly, PpMC-179 administration resulted in the detachment of already adherent IRBCs by 80.7% and 83.3% on resting and stimulated skin grafts, respectively. The antiadhesive effect of PpMC-179 was rapid and sustained in vivo for at least 30 minutes. Our data indicate that targeting cytoadhesion in vivo is feasible and may offer a rapid antimalarial therapy.     

Suppression of early atherosclerosis in LDL-receptor deficient mice by oral tolerance with beta 2-glycoprotein I

BACKGROUND: Atherosclerosis is considered analogous to chronic inflammatory diseases. Beta 2-glycoprotein I (beta 2GPI) is a phospholipid binding protein shown to serve as a target for prothrombotic antiphospholipid antibodies. It has recently been demonstrated to drive an immune mediated reaction and enhance murine atherosclerosis. Oral tolerance is a method in which feeding a given antigen, downregulates the respective immune responses towards it, and attenuates concomitant organ specific disorders. Herein, we tested the hypothesis, that inhibiting cellular immunity to beta 2GPI would result in suppression of fatty streak formation in mice. METHODS AND RESULTS: LDL receptor deficient mice were fed different doses of human or bovine beta 2GPI or BSA and than switched to an atherogenic diet. To determine the effect of feeding on lymph node proliferative indices, separate groups of mice were fed beta 2GPI and then immunized with the respective antigen. Feeding either human or bovine beta 2GPI was effective in attenuating atherosclerosis as compared to control fed animals. Oral feeding with of beta 2GPI inhibited lymph node cell reactivity to beta 2GPI in mice immunized against the human protein. Oral tolerance was also capable of reducing reactivity to oxidized LDL in mice immunized against oxLDL. IL-4 and IL-10 production was upregulated in lymph node cells of beta 2GPI-tolerant mice immunized against beta 2GPI, upon priming with the respective protein. CONCLUSION: Thus, oral administration of beta 2GPI is an effective means of suppressing atherogenesis in mice and should further be investigated.     

Physical activity is inversely associated with total homocysteine levels, independent of C677T MTHFR genotype and plasma B vitamins

The homocysteine level is considered to be a product of genetic and lifestyle interactions, mainly mutated methylenetetrahydrofolate reductase (MTHFR) and the intake of folate, vitamin B12 and pyridoxine, and their blood levels. Physical activity has been associated with lower homocysteine levels in some population studies, especially among elderly subjects. To further elucidate the observed association between homocysteine and physical activity, while accounting for the effect of the MTHFR C677T genotype, and of plasma levels of folate and B12 vitamins, a cross-sectional study of 620 males and females, aged 70.5 ± 6.8 years, was carried out. Information on lifestyle habits was collected and laboratory examinations of 12-h fasting total plasma homocysteine, folate, and vitamin B12, as well as DNA analysis for MTHFR C677T variant, were performed. Median total homocysteine values were 11.4 μmol/l for males and 9.4 for females; p < 0.001. Smoking and ethnic origin were not found to be associated with homocysteine levels. Physically active subjects had significantly lower total homocysteine levels when adjusted for sex (p = 0.01). Significant inverse correlations were found between body mass index, plasma folate, B12 and homocysteine levels. Homocysteine levels of the CC, CT and TT genotypes were 9.7, 10.6 and 10.2 μmol/l, respectively (p = 0.002, controlling for sex). In a multiple linear regression model, a sedentary lifestyle increased homocysteine levels by 7% as compared to an active one (p = 0.03) controlling for sex, age, body mass index, folate, vitamin B12, and C677T genotype, all of which were also found to be significantly associated with homocysteine levels. Any level of physical activity was found to be independently associated with lower homocysteine levels in an elderly population, controlling for MTHFR genotype, plasma B-vitamins, age, sex, smoking and BMI. This study emphasizes the importance of maintaining a physically active lifestyle in the elderly.     

Regenerative medicine as applied to general surgery

The present review illustrates the state of the art of regenerative medicine (RM) as applied to surgical diseases and demonstrates that this field has the potential to address some of the unmet needs in surgery. RM is a multidisciplinary field whose purpose is to regenerate in vivo or ex vivo human cells, tissues, or organs to restore or establish normal function through exploitation of the potential to regenerate, which is intrinsic to human cells, tissues, and organs. RM uses cells and/or specially designed biomaterials to reach its goals and RM-based therapies are already in use in several clinical trials in most fields of surgery. The main challenges for investigators are threefold: Creation of an appropriate microenvironment ex vivo that is able to sustain cell physiology and function in order to generate the desired cells or body parts; identification and appropriate manipulation of cells that have the potential to generate parenchymal, stromal and vascular components on demand, both in vivo and ex vivo; and production of smart materials that are able to drive cell fate.     

Factors associated with the success of the Rigo System Chêneau brace in treating mild to moderate adolescent idiopathic scoliosis

Background

Adolescent idiopathic scoliosis (AIS) is the most prevalent spine deformity within the pediatric population. Orthosis is the mainstay of conservative treatment for mild to moderate AIS. The Rigo System Chêneau (RSC) brace is a custom-made thoracolumbar sacral orthosis (TLSO) based on a three-dimensional correction concept. The purpose of this study was to identify factors that could predict the therapeutic success/failure of the RSC brace.

Materials and methods

A retrospective cohort study was performed on all consecutive patients according to the Scoliosis Research Society (SRS) criteria for the success of conservative treatment. Participants had a 2-year follow-up beyond the termination of brace treatment. All patients were treated with the RSC orthotic device.

Results

Ninety-three patients met the inclusion criteria. At treatment onset, their average age was 12.9 years, average Cobb angle 31.97°, Risser score 1.07, and the mean angle of thoracic rotation (ATR) was 10.2°. The mean brace treatment period was 36 months. Treatment was successful in 83.8 % of these patients (n = 79). The average final Cobb angle was 28.97°, Risser score 4.88, and ATR 8.09°. The pre-treatment factors associated with the success of applying the RSC brace were a high Risser score [odds ratio (OR) = 2.97, 95 % confidence interval [CI] 1.18–7.44; p = 0.02), a low Cobb angle (OR = 0.92, 95 % CI 0.85–0.99; p = 0.02), and low ATR (OR = 0.86, 95 % CI 0.75–0.99; p = 0.04).

Conclusions

The treatment of mild to moderate AIS with the RSC brace provides excellent clinical results. Its added benefit is enabling a three-dimensional correction of a three-dimensional deformity. Pre-treatment high Risser score, low Cobb angles, and low ATRs are associated with treatment success.

Level of evidence

Retrospective analysis, Level III.