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Pseudoaneurysms of the lower limb are rare and frequently iatrogenics complications. Closed traumas are likely to generate lesions of the arterial wall, which generally become symptomatic at a later stage. The diagnosis of such vascular lesion is difficult because the symptomatology and the onset can be delayed. We herein report the case of a 15-year-old patient in whom the diagnosis of pseudoaneurysm of the anterior tibial artery was made 5 months after a non-displaced closed fracture of the tibial shaft. The radiographs were evocative of a malignant bone tumor. The study of vessels by a contrast-enhanced CT-scan enabled us to diagnose the pseudoaneurysm. Before the occurrence of late onset swelling, a history of trauma must be sought, even old.

Purpose: The purpose was to study intraoperative spinal cord monitoring (IOM) particularities and performances in children under 4 years old with congenital spinal deformities. IOM is characterized by specific difficulties due to the immaturity of sensory-motor pathways in such young patients. To the best of our knowledge, this study is the largest dedicated to IOM in this challenging population., Methods: This study was retrospective and monocentric. 78 IOM in children under 4 years old were analyzed. Somatosensory evoked potentials (SSEP), neurogenic mixed evoked potentials (NMEP) and D waves were performed. Patients were classified into one of four categories with respect to IOM data and clinical outcome: true positive, false positive, true negative and false negative. Sensitivity and specificity were then calculated accordingly., Results: There were 6 true positive, 3 false positive, 67 true negative and 1 false negative outcomes. One patient was characterized by unreliable baseline IOM data. IOM sensitivity was 86 %. IOM specificity was 96 %. The false negative case was monitored using SSEP alone. IOM was difficult in 10/77 cases, being unilateral because of a planned fibular graft harvest. NMEP were characterized by higher signal-to-noise ratio than SSEP., Conclusions: Immaturity of sensory-motor pathways predominates in the central rather than the peripheral nervous system in young children. MEP and D waves could thus be difficult to obtain. Although non-specific to motor pathways, it could be useful to "by-pass" the brain, using NMEP. In regard to maturational particularities, IOM in children under 4 years old should be performed by experienced neurophysiologists, avoiding in these cases surgeon-guided devices.

Aims/hypothesis: The crosstalk between skeletal muscle (SkM) and beta cells plays a role in diabetes aetiology. In this study, we have investigated whether SkM-released exosome-like vesicles (ELVs) can be taken up by pancreatic beta cells and can deliver functional cargoes., Methods: Mice were fed for 16 weeks with standard chow diet (SCD) or with standard diet enriched with 20% palmitate (HPD) and ELVs were purified from quadriceps muscle. Fluorescent ELVs from HPD or SCD quadriceps were injected i.v. or intramuscularly (i.m.) into mice to determine their biodistributions. Micro (mi)RNA quantification in ELVs was determined using quantitative real-time RT-PCR (qRT-PCR)-based TaqMan low-density arrays. Microarray analyses were performed to determine whether standard diet ELVs (SD-ELVs) and high palmitate diet ELVs (HPD-ELVs) induced specific transcriptional signatures in MIN6B1 cells., Results: In vivo, muscle ELVs were taken up by pancreas, 24 h post-injection. In vitro, both SD-ELVs and HPD-ELVs transferred proteins and miRNAs to MIN6B1 cells and modulated gene expressions whereas only HPD-ELVs induced proliferation of MIN6B1 cells and isolated islets. Bioinformatic analyses suggested that transferred HPD-ELV miRNAs may participate in these effects. To validate this, we demonstrated that miR-16, which is overexpressed in HPD-ELVs, was transferred to MIN6B1 cells and regulated Ptch1, involved in pancreas development. In vivo, islets from HPD mice showed increased size and altered expression of genes involved in development, including Ptch1, suggesting that the effect of palm oil on islet size in vivo was reproduced in vitro by treating beta cells with HPD-ELVs., Conclusions/interpretation: Our data suggest that muscle ELVs might have an endocrine effect and could participate in adaptations in beta cell mass during insulin resistance.

Hypokyphosis is currently observed in thoracic idiopathic scoliosis. The use of sublaminar bands allows a good restoration of sagittal balance of the spine. The aim of the study was to provide a middle-term radiographic analysis of patients with adolescent idiopathic scoliosis with preoperative hypokyphosis treated by posterior arthrodesis with sublaminar bands. This retrospective study included 34 patients with Lenke 1 scoliosis associated with hypokyphosis (TK < 20°). A radiographic evaluation was performed with a 2-year follow-up. Cobb angle, cervical lordosis, thoracic kyphosis, lumbar lordosis, and pelvic parameters were measured preoperatively, postoperatively, and at 6-month and 2-year follow-up. The mean preoperative thoracic kyphosis was 10.5° versus 24.1° postoperatively ( p < 0.001), representing a mean gain of 13°. Cobb angle ranged from 59.3° to 17.9° postoperatively (mean correction 69%, p < 0.001). Cobb angle increased between the immediate postoperative measurement and the 6-month follow-up (17.9 versus 19.9, p = 0.03). Cervical curvature changed from a 5.6° kyphosis to a 3.5° lordosis ( p = 0.001). Concerning lumbar lordosis, preoperative measurement was 39.7° versus 41.3° postoperatively ( p = 0.27). At 6-month follow-up, lumbar lordosis significantly increased to 43.6° ( p = 0.03). All parameters were stable at final follow-up. Correction performed by sublaminar bands is efficient for both fontal and sagittal planes. Moreover, the restoration of normal thoracic kyphosis is followed by an adaptation of the adjacent curvatures with improved cervical lordosis and lumbar lordosis., Competing Interests: The authors declare no conflict of interests.

The objective of this investigation was to determine the outcome of spine fusion for neuromuscular (NM) scoliosis, using Unit Rod technique, with emphasis on complications related to preoperative general health. Between 1997 and 2007, 96 consecutive patients with neuromuscular scoliosis operated on with Unit Rod instrumentation were retrospectively reviewed. The inclusion criteria were diagnosis of NM scoliosis due to cerebral palsy (CP) and muscular dystrophy (DMD). Patient's preoperative general health, weight, and nutrition were collected. Different radiographic and clinical parameters were evaluated. There were 66 CP patients (59 nonwalking) and 30 DMD patients (24 nonwalking). Mean age at surgery was 16.5 years and 13.9 years, respectively. All radiographic measurements improved significantly. Wound infection rate was 16.7% (11% of reoperation rate in CP; 10% in DMD; 3 hardware removal cases). No pelvic fracture due to rod irritation was observed. Unit Rod technique provides good radiographic and clinical outcomes even if this surgery is associated with a high complication rate. It is a quick, simple, and reliable technique. Perioperative management strategy should decrease postoperative complications and increases outcome. A standardized preoperative patient evaluation and preparation including respiratory capacity and nutritional, digestive, and musculoskeletal status are mandatory prior to surgery., Competing Interests: The authors declare that there are no competing interests.

Context: Postprandial endotoxemia is a metabolic risk factor, which has been shown to originate from the intestinal absorption of gut lipopolysaccharides (LPS) using nonphysiological high-fat tests., Objective: This study aimed to determine whether different realistic fat amounts can modulate postprandial dynamics and handling of LPS by varying postprandial lipidemia in humans of different body mass indices., Design, Setting, and Participants: In a randomized, controlled, cross-over study in nutrition research center, eight normal-weight (NW) and eight obese age-matched men, without diabetes nor dyslipidemia, ingested breakfasts containing 10 vs 40 g fat. Blood samples, leukocytes, and chylomicron-rich fractions were obtained during 8 h. Plasma and chylomicron-endotoxemia, plasma LPS transporters (LBP, sCD14) and IL-6, nuclear factor κB (NF-κB) translocation, and IL-6 gene expression of immune cells were measured., Main Outcome: The postprandial fatty acid handling after ingesting 40 g fat was previously published as primary outcome. The secondary outcomes were inflammatory ones including postprandial endotoxemia, LPS handling, and plasma markers of inflammation after ingesting 10 or 40 g fat., Results: Chylomicronemia increased in all subjects according to ingested fat amount (P < .01), but only obese had higher postprandial endotoxemia after 40 g (P < .05). Obese subject chylomicrons were more enriched with LPS compared with NW (PBMI < .01). We observed neither NF-κB translocation, nor variation of IL-6 expression in leukocytes. In both groups, fat amount did not modify postprandial response of plasma IL-6. However, the area under the curve (AUC) of IL-6 in obese was higher than in NW (P < .05) parallel to higher fasting LPS-binding protein (LBP; P < .05). AUC of IL-6 was correlated with LBP (P < .01)., Conclusion: Postprandial endotoxemia is modulated by ingested fat amount in obese men. LPS handling in plasma through chylomicrons and LBP seems critical in driving the acute inflammatory response. The pathophysiological importance of repeated postprandial endotoxemia excursions and their contribution to a vicious cycle of LBP-driven low-grade inflammation deserve further investigation in the nutritional management of cardio-metabolic risk prevention.

A growing body of evidence suggests that exposure to traffic-related air pollution is a risk factor for type 2 diabetes. Ozone, a major photochemical pollutant in urban areas, is negatively associated with fasting glucose and insulin levels, but most aspects of this association remain to be elucidated. Using an environmentally realistic concentration (0.8 parts per million), we demonstrated that exposure of rats to ozone induced whole-body insulin resistance and oxidative stress, with associated endoplasmic reticulum (ER) stress, c-Jun N-terminal kinase (JNK) activation, and disruption of insulin signaling in skeletal muscle. Bronchoalveolar lavage fluids from ozone-treated rats reproduced this effect in C2C12 myotubes, suggesting that toxic lung mediators were responsible for the phenotype. Pretreatment with the chemical chaperone 4-phenylbutyric acid, the JNK inhibitor SP600125, or the antioxidant N-acetylcysteine alleviated insulin resistance, demonstrating that ozone sequentially triggered oxidative stress, ER stress, and JNK activation to impair insulin signaling in muscle. This study is the first to report that ozone plays a causative role in the development of insulin resistance, suggesting that it could boost the development of diabetes. We therefore provide a potential mechanism linking pollutant exposure and the increased incidence of metabolic diseases., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Introduction: While thoracolumbar fractures are common lesions, no strong consensus is available at the moment., Objectives: The aim of this study was to evaluate the results of a minimal invasive strategy using percutaneous instrumentation and anterior approach in the management of thoracolumbar unstable fractures., Methods: 39 patients were included in this retrospective study. Radiologic evaluation was based on vertebral and regional kyphosis, vertebral body height restoration, and fusion rate. Clinical evaluation was based on Visual Analogic Score (VAS). All evaluations were done preoperatively and at 1-year follow-up., Results: Both vertebral and regional kyphoses were significantly improved on postoperative evaluation (13° and 7° versus -1° and -9°  P < 0.05, resp.) as well as vertebral body height (0.92 versus 1.16, P < 0.05). At 1-year follow-up, mean loss of correction was 1°. A solid fusion was visible in all the cases, and mean VAS was significantly reduced form 8/10 preoperatively to 1/10 at the last follow-up., Conclusion: Management of thoracolumbar fractures using percutaneous osteosynthesis and minimal invasive anterior approach (telescopic vertebral body prosthesis) is a valuable strategy. Results of this strategy offer satisfactory and stable results in time.

Purpose: Thoracic adolescent idiopathic scoliosis (AIS) curves (Lenke 1-4) are often characterized by hypokyphosis. Sagittal alignment remains challenging to correct, even with recent posterior segmental instrumentation. Some authors recommend anterior endoscopic release (AER) to reduce anterior column height, and facilitate thoracic kyphosis correction. The aim of this study was to assess the contribution of AER to sagittal correction in hypokyphotic AIS., Methods: Fifty-six hypokyphotic (T4T12<20°) AIS patients were included. In group 1 (28 patients), patients first underwent AER, followed by posterior instrumentation and correction 5-7 days later. In group 2 (28 patients), patients underwent the same posterior procedure without AER. Posterior correction was performed in all cases using posteromedial translation and hybrid constructs consisting of lumbar pedicle screws and thoracic sublaminar bands. From radiological measurements performed using low-dose EOS radiographs, the correction of thoracic kyphosis was compared between the two groups., Results: Groups 1 and 2 were comparable regarding demographic data and preoperative thoracic kyphosis (group 1: 11.7° ± 6.9° vs group 2: 12.1° ± 6.3°, p = 0.89). Postoperative thoracic kyphosis increase averaged 18.3° ± 13.6° in group 1 and 15.2° ± 9.0° in group 2. The benefit of anterior release was not statistically significant (p = 0.35)., Conclusion: Although previous studies have suggested that thoracoscopic release improved correction compared to posterior surgery alone, the current study did not confirm this finding. Moreover, results of the current series showed that no significant benefit can be expected from AER in terms of sagittal plane improvement when the posteromedial translation technique is used, even in challenging hypokyphotic patients.

Aims/hypothesis: Exosomes released from cells can transfer both functional proteins and RNAs between cells. In this study we tested the hypothesis that muscle cells might transmit specific signals during lipid-induced insulin resistance through the exosomal route., Methods: Exosomes were collected from quadriceps muscles of C57Bl/6 mice fed for 16 weeks with either a standard chow diet (SD) or an SD enriched with 20% palm oil (HP) and from C2C12 cells exposed to 0.5 mmol/l palmitate (EXO-Post Palm), oleate (EXO-Post Oleate) or BSA (EXO-Post BSA)., Results: HP-fed mice were obese and insulin resistant and had altered insulin-induced Akt phosphorylation in skeletal muscle (SkM). They also had reduced expression of Myod1 and Myog and increased levels of Ccnd1 mRNA, indicating that palm oil had a deep impact on SkM homeostasis in addition to insulin resistance. HP-fed mouse SkM secreted more exosomes than SD-fed mouse SkM. This was reproduced in-vitro using C2C12 cells pre-treated with palmitate, the most abundant saturated fatty acid of palm oil. Exosomes from HP-fed mice, EXO-Post Palm and EXO-Post Oleate induced myoblast proliferation and modified the expressions of genes involved in the cell cycle and muscle differentiation but did not alter insulin-induced Akt phosphorylation. Lipidomic analyses showed that exosomes from palmitate-treated cells were enriched in palmitate, indicating that exosomes likely transfer the deleterious effect of palm oil between muscle cells by transferring lipids. Muscle exosomes were incorporated into various tissues in vivo, including the pancreas and liver, suggesting that SkM could transfer specific signals through the exosomal route to key metabolic tissues., Conclusions/interpretation: Exosomes act as 'paracrine-like' signals and modify muscle homeostasis during high-fat diets.

Our objective was to describe the management and prevention of thoracic aortic injuries caused by a malposition of pedicle screws in corrective surgery of major spine deformities. Positioning pedicle screws in thoracic vertebras by posterior approach exposes to the risk of injury of the elements placed ahead of the thoracic spine, as the descending thoracic aorta. This complication can result in a cataclysmic bleeding, needing urgent vascular care, but it can also be totally asymptomatic, resulting in the long run in a pseudoaneurysm, justifying the systematic removal of the hardware. We report the case of a 76-year-old woman who underwent spinal correction surgery for thoraco-lumbar degenerative kypho-scoliosis. Immediately after the surgery, a thoracic aortic injury caused by the left T7 pedicle screw was diagnosed. The patient underwent a two-step surgery. The first step was realized by vascular surgeons and aimed to secure the aortic wall by short endovascular aortic grafting. During the second step, spine surgeons removed the responsible screw by posterior approach. The patient was discharged in a rehabilitation center 7 days after the second surgery. When such a complication occurs, a co-management by vascular and spine surgeons is necessary to avoid major complications. Endovascular management of this kind of vascular injuries permits to avoid an open surgery that have a great rate of morbi-mortality in frail patients. Nowadays, technologies exist to prevent this kind of event and may improve the security when positioning pedicle screws., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Purpose: Management of high-grade spondylolisthesis is challenging and to date no therapeutic consensus is available. Various surgical procedures have been described using unique or double approach. The aim of the study is to describe an original technique using a posterior-only approach to achieve a circumferential lumbosacral fusion with a custom-made screw., Methods: In our experience, eight patients (mean age 15 years old) were treated for grade III or IV slipping without instrumental reduction. Surgical technique included a laminectomy from L5 to S2, then after mobilization of neural elements a guide wire was inserted from the posterior side of S2 to the antero-superior corner of L5. A specific drill was used and the 10-mm screw was then inserted under fluoroscopic guidance. Further steps included a discectomy, lumbosacral interbody graft and posterolateral graft to obtain a circumferential fusion. Clinical and radiological evaluations were obtained., Results: On the whole series, solid fusion was achieved after 6 months on average. Sagittal realignment was observed with a regression of pelvic retroversion and hip flessum, a lumbarization of the lumbar lordosis and an improvement of the thoracic kyphosis. For one patient, a postoperative S1 deficit was observed., Conclusion: This technique provides satisfactory results in the management of high-grade spondylolisthesis. This concept is based on a double spine instability considering viscoelastic properties of the disc and postoperative sagittal reciprocal changes as prerequisite. This posterior-only approach represents a valuable alternative to other procedures.

In 2012, 32.3% of the French population over 18 years of age was considered overweight (25 ≤ BMI<30 kg/m(2)) and 15% obese (BMI ≥ 30 kg/m(2)). Worldwide, 2.8 million people die every year from the complications of obesity. In 2008, the prevalence of obesity was almost double that of 1980. Obesity is a genuine concern for the orthopedic surgeon, as it affects bones and soft tissues on the biomechanical and biochemical level. In traumatology, low-energy trauma is more frequent in obese patients and induces complex comminutive fractures of the extremities. In orthopedics, obesity is an independent risk factor for osteoarthritis, particularly for the knee joint. The goals of this review are to describe specific aspects of the care of obese patients in trauma and orthopedics surgery during the pre-, intra- and postoperative periods, as well as the risk-benefit ratio related to the treatment of the obese patients., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Introduction: Management of elderly patients with thoracolumbar fractures is still challenging due to frequent osteoporosis and risk of screws pull-out. The aim of this study was to evaluate results of a percutaneous-only procedure to treat these fragile patients using cement-augmented screws., Methods: 12 patients diagnosed with a thoracolumbar fracture associated with an important loss of bone stock were included in this prospective study. Surgical procedure included systematically a percutaneous osteosynthesis using cemented fenestrated screws. When necessary, additional anterior support was performed using a kyphoplasty procedure. Clinical and radiographic evaluations were performed using CT scan., Results: On the whole series, 15 fractures were diagnosed and 96 cemented screws were inserted. The difference between the pre- and postoperative vertebral kyphosis was statistically significant (12.9° versus 4.4°, P = 0.0006). No extrapedicular screw was reported and one patient was diagnosed with a cement-related pulmonary embolism. During follow-up period, no infectious complications, implant failures, or pull-out screws were noticed., Discussion: Aging spine is becoming an increasing public health issue. Management of these patients requires specific attention due to the augmented risk of complications. Using percutaneous-only screws fixation with cemented screw provides satisfactory results. A rigorous technique is mandatory in order to achieve best outcomes.

It has recently been established that exosomes can mediate intercellular cross-talk under normal and pathological conditions through the transfer of specific miRNAs. As muscle cells secrete exosomes, we addressed the question of whether skeletal muscle (SkM) exosomes contained specific miRNAs, and whether they could act as "endocrine signals" during myogenesis. We compared the miRNA repertoires found in exosomes released from C2C12 myoblasts and myotubes and found that 171 and 182 miRNAs were exported into exosomes from myoblasts and myotubes, respectively. Interestingly, some miRNAs were expressed at higher levels in exosomes than in their donor cells and vice versa, indicating a selectivity in the incorporation of miRNAs into exosomes. Moreover miRNAs from C2C12 exosomes were regulated during myogenesis. The predicted target genes of regulated exosomal miRNAs are mainly involved in the control of important signaling pathways for muscle cell differentiation (e.g., Wnt signaling pathway). We demonstrated that exosomes from myotubes can transfer small RNAs (C. elegans miRNAs and siRNA) into myoblasts. Moreover, we present evidence that exosome miRNAs secreted by myotubes are functionally able to silence Sirt1 in myoblasts. As Sirt1 regulates muscle gene expression and differentiation, our results show that myotube-exosome miRNAs could contribute to the commitment of myoblasts in the process of differentiation. Until now, myokines in muscle cell secretome provided a conceptual basis for communication between muscles. Here, we show that miRNA exosomal transfer would be a powerful means by which gene expression is orchestrated to regulate SkM metabolic homeostasis.

Traumatic patellar dislocation usually occurs in the lateral direction. In a few cases, however, the patella rotates around its horizontal axis and becomes wedged between the femoral condyles. We report two cases of traumatic inter-condylar patellar dislocation that required surgical management., (Copyright © 2013. Published by Elsevier Masson SAS.)

Animal studies using a high-fat diet (HFD) have studied the effects of lipid overconsumption by comparing a defined HFD either with a natural-ingredient chow diet or with a defined low-fat diet (LFD), despite the dramatic differences between these control diets. We hypothesized that these differences in the control diet could modify the conclusions regarding the effects that an increase of fat in the diet has on several metabolic parameters. For 11 weeks, C57bl6/J mice were fed a low-fat chow diet (8% energy from fat), a typical semisynthetic LFD (12%), or a semisynthetic HFD (sy-HF) (40%). Conclusions about the effect of sy-HF on body weight gain, subcutaneous adipose tissue, insulin sensitivity, and adipose tissue inflammation were modified according to the control LFD. Conversely, conclusions about epididymal and retroperitoneal adipose tissue; fat intake effects on liver and muscular lipids, cholesterol, free fatty acids, and markers of low-grade inflammation; and of adipose tissue macrophage infiltration were the same regardless of the use of low-fat chow diet or semisynthetic LFD. For some physiological outcomes, conflicting conclusions were even reached about the effects of increased fat intake according to the chosen low-fat control. Some deleterious effects of sy-HF may not be explained by lipid overconsumption but rather by the overall quality of ingredients in a semisynthetic diet. According to the control LFD chosen, conclusions on the lipid-related effects of HFDs must be formulated with great care because some end points are profoundly affected by the ingredient composition of the diet rather than by fat content., (© 2013.)

Objective: To assess the clinical efficacy of nutritional amounts of grape polyphenols (PPs) in counteracting the metabolic alterations of high-fructose diet, including oxidative stress and insulin resistance (IR), in healthy volunteers with high metabolic risk., Research Design and Methods: Thirty-eight healthy overweight/obese first-degree relatives of type 2 diabetic patients (18 men and 20 women) were randomized in a double-blind controlled trial between a grape PP (2 g/day) and a placebo (PCB) group. Subjects were investigated at baseline and after 8 and 9 weeks of supplementation, the last 6 days of which they all received 3 g/kg fat-free mass/day of fructose. The primary end point was the protective effect of grape PPs on fructose-induced IR., Results: In the PCB group, fructose induced 1) a 20% decrease in hepatic insulin sensitivity index (P < 0.05) and an 11% decrease in glucose infusion rate (P < 0.05) as evaluated during a two-step hyperinsulinemic-euglycemic clamp, 2) an increase in systemic (urinary F2-isoprostanes) and muscle (thiobarbituric acid-reactive substances and protein carbonylation) oxidative stress (P < 0.05), and 3) a downregulation of mitochondrial genes and decreased mitochondrial respiration (P < 0.05). All the deleterious effects of fructose were fully blunted by grape PP supplementation. Antioxidative defenses, inflammatory markers, and main adipokines were affected neither by fructose nor by grape PPs., Conclusions: A natural mixture of grape PPs at nutritional doses efficiently prevents fructose-induced oxidative stress and IR. The current interest in grape PP ingredients and products by the global food and nutrition industries could well make them a stepping-stone of preventive nutrition.

Objective: The beneficial effects of ω-3 polyunsaturated fatty acids (PUFAs) in cardiovascular disease are partly attributed to their anti-inflammatory properties. Their potential effect on the adipose tissue of chronic kidney disease (CKD) patients has never been explored., Methods: To determine the metabolic effect of supplementation with two different doses of fish oil (FO), 12 non-dialyzed patients with stage IV/V CKD were randomly allocated to receive 1.8 g or 3.6 g/d of ω-3 PUFA for 10 wk. Metabolic parameters, adipose tissue function, and gene expression were evaluated at baseline and 10 wk., Results: Body weight, fat mass, energy intake, fasting glucose, and insulin were unchanged. The daily intake of 3.6 g of ω-3 PUFA resulted in decreased serum triacylglycerol and increased high-density lipoprotein cholesterol, whereas low-density lipoprotein cholesterol increased with 1.8 g of ω-3 PUFA. Serum adiponectin, leptin, C-reactive protein, and tumor necrosis factor-α were not modified in either group. Interleukin-6 levels tended to decrease with 1.8 g of ω-3 PUFA. Additionally, a subset of inflammation-related genes (CD68 and MMP9) was reduced in subcutaneous adipose tissue in this group. Adiponectin, leptin, and adipoR2 gene expression were upregulated with 3.6 g of ω-3 PUFA., Conclusions: A moderate dose of FO alters the gene expression profile of adipose tissue to a more antiinflammatory status. Higher doses of FO have a favorable effect on lipid profile and lead to the upregulation of adipokines gene expression suggesting a different dose response to ω-3 PUFA administration in patients with CKD., (Copyright © 2013 Elsevier Inc. All rights reserved.)

There is a growing interest in the optimization of dietary emulsions for monitoring postprandial lipid metabolism in the frame of preventing metabolic diseases. Using various emulsions, we investigated in a systematic scheme the combination of (i) in vitro gastrointestinal lipolysis and (ii) absorption and metabolism of lipolysis media in Caco-2 cells. Four emulsions based on either milk fat olein (OL) or rapeseed oil (RA) as the dispersed phase and either lecithin (LE) or sodium caseinate (CA) as the emulsifier were tested. After a sequential incubation of these emulsions with gastric and pancreatic enzymes, lipolysis media were incubated with Caco-2 cells, after dilution (1 : 20) to maintain the barrier integrity. Both gastric and duodenal lipolysis levels were similar to values reported in vivo and the rates of lipolysis were higher with LE-stabilized emulsions than with CA-stabilized emulsions (P < 0.05). TAG secretion by Caco-2 cells was found to be higher using (i) duodenal vs. gastric media (P < 0.001) and (ii) emulsions stabilized with CA vs. LE (P < 0.01). Consistently, gene expression of both FABP2 and FATP4 induced by the duodenal media was (i) higher than that with gastric media (P < 0.001) and (ii) faster than that with model mixed micelles. Using gastric media, TAG secretion of Caco-2 cells after 12 h was higher with RA than with OL (P < 0.001). Moreover, the RA-CA emulsion increased the size of secreted lipoprotein particles (514 nm vs. 61 to 130 nm; P < 0.01). In conclusion, it was possible to observe distinct responses in the lipid metabolism of Caco-2 cells incubated with lipolysis media obtained from different dietary emulsions digested by gastrointestinal lipases in vitro.

Objective: A strong association between genetic variants and obesity was found for the fat mass and obesity-associated gene (FTO). However, few details are known concerning the expression and function of FTO in skeletal muscle of patients with metabolic diseases., Research Design and Methods: We investigated basal FTO expression in skeletal muscle from obese nondiabetic subjects and type 1 and type 2 diabetic patients, compared with age-matched control subjects, and its regulation in vivo by insulin, glucose, or rosiglitazone. The function of FTO was further studied in myotubes by overexpression experiments., Results: We found a significant increase of FTO mRNA and protein levels in muscle from type 2 diabetic patients, whereas its expression was unchanged in obese or type 1 diabetic patients. Moreover, insulin or glucose infusion during specific clamps did not regulate FTO expression in skeletal muscle from control or type 2 diabetic patients. Interestingly, rosiglitazone treatment improved insulin sensitivity and reduced FTO expression in muscle from type 2 diabetic patients. In myotubes, adenoviral FTO overexpression increased basal protein kinase B phosphorylation, enhanced lipogenesis and oxidative stress, and reduced mitochondrial oxidative function, a cluster of metabolic defects associated with type 2 diabetes., Conclusions: This study demonstrates increased FTO expression in skeletal muscle from type 2 diabetic patients, which can be normalized by thiazolidinedione treatment. Furthermore, in vitro data support a potential implication of FTO in oxidative metabolism, lipogenesis and oxidative stress in muscle, suggesting that it could be involved in the muscle defects that characterize type 2 diabetes.

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and dioxin-like compounds are widely encountered toxic substances suspected of interfering with the endocrine systems of humans and wildlife, and of contributing to the loss of fertility. In this study, we determined the changes in testicular gene expression caused by in utero exposure to TCDD along with the intra-testicular testosterone levels, epididymal sperm reserves, daily sperm production (DSP) and testis histology. To this purpose, female pregnant Sprague-Dawley rats orally received TCDD (10, 100 or 200 ng/kg body weight) or vehicle at embryonic day 15, and the offspring was killed throughout development. Hepatic Cyp1a1 gene expression was measured in the offspring to confirm the exposure to TCDD. The gross histology of the testes and intra-testicular testosterone levels were normal among the studied groups. Sperm reserves were altered in 67-day-old rats of the TCDD-200 group, but not in 145-day-old animals or in the other TCDD-exposed groups. Nonetheless, fertility was not altered in males of the TCDD-200 group, and the F2 males generated had normal sperm reserves and DSP. Microarray analysis permitted the identification of eight differentially expressed genes in the 4-week-old testes of the TCDD-200 compared with that of the control group (cut-off value +/- 1.40), including the down-regulated chemokine Ccl5/Rantes. Inhibition of Ccl5/Rantes gene expression was observed throughout development in the TCDD-200 group, and at 67 and 145 days in the TCDD-100 group (animals of younger ages were not examined). Ccl5/Rantes gene expression was mostly confined in Leydig cells. F2 males generated from males of the TCDD-200 group had normal levels of Ccl5/Rantes in testis and Cyp1a1 in liver, which might indicate that Ccl5/Rantes is a marker of TCDD exposure in testis such as Cyp1a1 in liver. In conclusion, we demonstrated a decrease in Ccl5/Rantes RNA levels and a transitory decline in sperm reserves in the testes of rats of TCDD-dosed dams.

Background: The incidence of the insulin resistance syndrome has increased at an alarming rate worldwide, creating a serious challenge to public health care in the 21st century. Recently, epidemiological studies have associated the prevalence of type 2 diabetes with elevated body burdens of persistent organic pollutants (POPs). However, experimental evidence demonstrating a causal link between POPs and the development of insulin resistance is lacking., Objective: We investigated whether exposure to POPs contributes to insulin resistance and metabolic disorders., Methods: Sprague-Dawley rats were exposed for 28 days to lipophilic POPs through the consumption of a high-fat diet containing either refined or crude fish oil obtained from farmed Atlantic salmon. In addition, differentiated adipocytes were exposed to several POP mixtures that mimicked the relative abundance of organic pollutants present in crude salmon oil. We measured body weight, whole-body insulin sensitivity, POP accumulation, lipid and glucose homeostasis, and gene expression and we performed microarray analysis., Results: Adult male rats exposed to crude, but not refined, salmon oil developed insulin resistance, abdominal obesity, and hepatosteatosis. The contribution of POPs to insulin resistance was confirmed in cultured adipocytes where POPs, especially organochlorine pesticides, led to robust inhibition of insulin action. Moreover, POPs induced down-regulation of insulin-induced gene-1 (Insig-1) and Lpin1, two master regulators of lipid homeostasis., Conclusion: Our findings provide evidence that exposure to POPs commonly present in food chains leads to insulin resistance and associated metabolic disorders.

Tissue integrity relies on barriers formed between epithelial cells. In the testis, the barrier is formed at the initiation of puberty by a tight junction complex between adjacent Sertoli cells, thereby defining an adluminal compartment where meiosis and spermiogenesis occur. Claudin 11 is an obligatory protein for tight junction formation and barrier integrity in the testis. It is expressed by Sertoli cells, and spermatogenesis does not proceed beyond meiosis in its absence, resulting in male sterility. Sertoli cell maturation--arrest of proliferation and expression of proteins to support germ cell development--parallels tight junction assembly; however, the pathophysiology underlying the loss of tight junctions in the mature testis remains largely undefined. Here, using immunohistochemistry and microarrays we demonstrate that adult Cldn11(-/-) mouse Sertoli cells can proliferate while maintaining expression of mature markers. Sertoli cells detach from the basement membrane, acquire a fibroblast cell shape, are eliminated through the lumen together with apoptotic germ cells, and are found in epididymis. These changes are associated with tight junction regulation as well as actin-related and cell cycle gene expression. Thus, Cldn11(-/-) Sertoli cells exhibit a unique phenotype whereby loss of tight junction integrity results in loss of the epithelial phenotype.

Aims/hypothesis: One of the major processes by which insulin exerts its multiple biological actions is through gene expression regulation. Thus, the identification of transcription factors affected by insulin in target tissues represents an important challenge. The aim of the present study was to gain a greater insight into this issue through the identification of transcription factor genes with insulin-regulated expression in human skeletal muscle., Methods: Using microarray analysis, we defined the sets of genes modulated during a 3 h hyperinsulinaemic-euglycaemic clamp (2 mU min(-1) kg(-1)) in the skeletal muscle of insulin-sensitive control volunteers and in moderately obese insulin-resistant type 2 diabetic patients., Results: Of the 1,529 and 1,499 genes regulated during the clamp in control and diabetic volunteers, respectively, we identified 30 transcription factors with impaired insulin-regulation in type 2 diabetic patients. Analysis of the promoters of the genes encoding these factors revealed a possible contribution of the transcriptional repressor basic helix-loop-helix domain-containing, class B, 2 protein (BHLHB2), insulin regulation of which is strongly altered in the muscle of diabetic patients. Gene ontology analysis of BHLHB2 target genes, identified after BHLHB2 overexpression in human primary myotubes, demonstrated that about 10% of the genes regulated in vivo during hyperinsulinaemia are potentially under the control of this repressor. The data also suggested that BHLHB2 is situated at the crossroads of a complex transcriptional network that is able to modulate major metabolic and biological pathways in skeletal muscle, including the regulation of a cluster of genes involved in muscle development and contraction., Conclusions/interpretation: We have identified BHLHB2 as a potential novel mediator of insulin transcriptional action in human skeletal muscle.

Objectives: It has been hypothesized that cerebral neurotransmitters such as dopamine and serotonin could play a role in human romantic bonding. However, no data on the genetic basis of human romantic love are currently available. To address this issue, we looked for associations between markers in neurotransmitter genes (the serotonin transporter gene, 5-HTT; the serotonin receptor 2A, 5HT2A; the dopamine D2 receptor gene, DRD2; and the dopamine D4 receptor gene, DRD4) and the six styles of love as conceptualized by Lee (Eros, Ludus, Storge, Pragma, Mania and Agape)., Design: A total of 350 healthy young adults (165 males and 185 females, mean age: 24.1+/-3.9 years, range 18-32 years) filled the 24-item Love Attitudes Scale (LAS) and were genotyped for the following six polymorphic markers: the serotonin transporter-linked polymorphic region (5-HTTLPR), the 5HT2A T102C and C516T polymorphisms, the DRD2 TaqI A and TaqI B variants, and the DRD4 exon 3 VNTR polymorphism., Results: Statistical analysis revealed a significant association between the DRD2 TaqI A genotypes and "Eros" (a loving style characterized by a tendency to develop intense emotional experiences based on the physical attraction to the partner), as well as between the C516T 5HT2A polymorphism and "Mania" (a possessive and dependent romantic attachment, characterized by self-defeating emotions). These associations were present in both sexes and remained significant even after adjustment for potential confounders., Conclusions: Our data provide the first evidence of a possible genetic loading on human loving styles.

The forkhead/winged helix box (FOX) gene family comprises at least 43 different genes encoding transcriptional factors with a highly conserved DNA-binding domain. To date, mutations in members of the FOX gene family have been causally linked to a variety of different human diseases. We describe a three-generation Albanian pedigree in which a complex phenotype consisting of dilated cardiomyopathy, obsessive-compulsive disorder, and suicidality is segregated with a missense mutation (W148R) in the human FOXD4 gene. This mutation disrupts an extremely highly conserved tryptophan residue in the forkhead domain of FOXD4, possibly resulting in reduced DNA binding capacity and altered transcriptional activity. Our present findings widen the spectrum of diseases associated with genetic aberrations in the forkhead gene family.

Dipeptidyl peptidase IV (DPPIV or CD26) is an ubiquitously expressed protease that could play a role in the pathogenesis of anxiety in view of its capacity to cleave several behaviourally active neuropeptides. Hereto we sought to determine the relationship between phobic anxiety, as measured by the Crown-Crisp index, and circulating levels of soluble CD26 (sCD26) in a large cohort of 1017 Italian women participating in a general health survey. The association between sCD26 levels and phobic anxiety was tested using simple correlation analysis, linear regression and multivariate logistic regression analysis. A highly significant inverse association was found between sCD26 concentrations and anxiety scores both in simple correlation and linear regression analysis. Compared with subjects in the first tertile of sCD26 levels, the age-adjusted odds ratio for scoring >/=6 compared to scoring 0 or 1 was 0.31 (95% CI: 0.18-0.74) for the second and 0.47 (95% CI: 0.34-0.63) for the third tertile. Altogether, our data suggest that reduced plasma sCD26 concentrations could be a marker of high levels of phobic anxiety in women.

Italian children (n = 125) were classified into dyslexics, poor readers and ordinary readers. The dyslexics were further classified into the Boder and Bakker subtypes. The children were tested with the form-resolving field (FRF), which measures central and peripheral visual recognition. Dyslexics show higher correct identification of letters in the periphery, supporting the notion of a different distribution of lateral masking. A numerical characterization of individual FRFs--C2R--reliably distinguishes between dyslexics and ordinary readers. The wider distribution of recognition, similar across the various subtypes of dyslexia, suggests a general characteristic of visual perception, and possibly a different visual-attentional mode.

A small subgroup of children, whose parents have suffered a heart attack in their late thirties and early forties, may be at particularly high cardiovascular risk. University Hospital "Split" gives tertiary health care to some 700,000 people in southern Croatia and treats about 300 acute myocardial infarctions per year, with a 3-5% share in the age under 45 years. This cross-sectional, clinical and laboratory study included all the patients below the age limit of 45 years, treated for acute myocardial infarction between 1990 and 1995, complexively 55 of them, and their natural children, 97 all in all. The results were compared to those of a stratified children's sample taken from the population of the same region. The relative weight, blood pressure, and plasma cholesterol were significantly higher in these children than in the control group (p < 0.05). In 50 of these offspring (51.5%), in addition to the obviously positive family history, detected were further cardiovascular risk factors, defined as values above the 95th distribution percentile for age and gender. The average blood pressure, relative weight and cholesterol levels were even higher in these, "risky" children than in the studied sample (p < 0.05), and much more elevated than in the matching control pupils (p < 0.001). The most often detected risk factors were elevated cholesterol (in 44%), arterial hypertension (in 40%), obesity (in 32%), and smoking (in 24%). Most of the children (64%) had only one additional risk factor, while in the remaining 36% the most prevalent risk factors were overweight (in 14 out of 18) and arterial hypertension (in 11 out of 18). It is concluded that cardiovascular risk factor screening among children with a positive family history of premature atherosclerotic complications is appropriate and cost-effective.

We present two patients who developed subacute diffuse infiltrative lung disease while receiving flecainide for supraventricular arrhythmia. They had bilateral subpleural lung opacities on computed tomography. Bronchoalveolar lavage revealed increased numbers of lymphocytes and eosinophils, and a low CD4/CD8 ratio. Nonspecific interstitial pneumonia was documented by open lung biopsy in patient 1. The outcome was favorable after flecainide withdrawal and prednisone treatment. Drug-induced pneumonitis should be suspected in patients treated with flecainide presenting with subacute diffuse infiltrative lung disease., (Copyright 2002 S. Karger AG, Basel)

Sixteen controls (age 6-13) and 20 native Italian children with developmental dyslexia (age 7-15) received a test of callosal transfer of tactile information. Among the dyslexic children, 7 had a diagnosis of L-type, 7 of P-type and 6 of M-type dyslexia according to Bakker's classification. Both control children and children with dyslexia made a significantly larger number of errors in the crossed localization condition (implying callosal transfer of tactile information) vs. the uncrossed condition. In the same condition, children with dyslexia made a significantly larger number of errors than controls. In the crossed localization condition L-types and M-types made a significantly larger number of errors than P-types and controls, while there was no significant difference in performance between P-types and controls. These findings are discussed in terms of defective callosal transfer or deficient somatosensory representation in children with L- and M-dyslexia.

The aim of this study was to evaluate some Children's Depression Inventory (CDI) psychometric properties and the prevalence of depressive symptoms in an unselected Italian sample of two hundred and eighty-four children aged 8 years. The CDI internal consistency was adequate (Cronbach's alpha:.80). The mean and standard deviation of CDI and the percentage of children at risk of depression (10.6%) in this sample are consistent with the figures reported by other studies carried out in northern Europe and North America. There were differences in gender and socioeconomic level in that boys scored higher than girls, and in the lower socioeconomic level there were more children at risk of depression. Ten items best discriminated children at risk for depression with 94% of correct classification. Most of these items consisted of observable signs. It is suggested that the CDI has noteworthy consistency across samples of relatively different cultures, that it can reliably be employed in the assessment of young children, and that observable signs outnumber internalizing symptoms of depression among children at risk

We present behavioral and anatomical evidence for a multi-component reading system in which different components are differentially weighted depending on culture-specific demands of orthography. Italian orthography is consistent, enabling reliable conversion of graphemes to phonemes to yield correct pronunciation of the word. English orthography is inconsistent, complicating mapping of letters to word sounds. In behavioral studies, Italian students showed faster word and non-word reading than English students. In two PET studies, Italians showed greater activation in left superior temporal regions associated with phoneme processing. In contrast, English readers showed greater activations, particularly for non-words, in left posterior inferior temporal gyrus and anterior inferior frontal gyrus, areas associated with word retrieval during both reading and naming tasks.

In a 5-year period analyzed were cardiovascular risk factors in 55 patients suffering from premature coronary accidents (below the age of 45) and in their 97 offsprings, aged 3-26 years. In 50 of these children (51.6%), 22 girls and 28 boys, in addition to the obvious positive family history, detected were other cardiovascular risk factors. The most common among them was hypercholesterolemia (in 45.0%), followed by arterial hypertension (40.0%), obesity (32.0%) and smoking (24.0%). Majority of these offsprings (64.0%) had only one additional risk factor. The average blood pressure, relative weight and cholesterol levels were significantly higher in these very children than in all the coronary offsprings (p < 0.05), and even more so (p < 0.01) than in the matching control sample.

The aim of this study was to assess whether acute myocardial infarction (AMI) in younger patients (< 45 years) differs from that in the older individuals (> 45 years). We have studied the records of all patients admitted to the Department of Medicine, Clinical Hospital of Split, Croatia, because of AMI from January 1st, 1987 to December 31st, 1991. The study group consisted of 1406 patients, 130 (9.2%) below, and 1276 (90.8%) above the age of 45. In the ¿young¿ subgroup there were only 9 females (6.9%), significantly less than in the ¿old¿ one (399 out of 1276 or 31.3%, p < 0.001). There were many more smokers among the younger (100 out of 130 or 76.9%) than among the older patients (524 out of 1276 or 41.1%, p < 0.001). The location of myocardial necrosis was also different: inferior infarction occurred in 65 out of 130 or 50% young patients and in 442 out of 1276 or 34.6% old patients; p < 0.001). Finally, the hospital mortality rate among the younger AMI patients was quite low (8 out of 130 or 6.2%) when compared to that of the older patients (282 out of 1276 or 22.1%, p < 0.001). In conclusion, AMI in younger individuals shows relevant peculiarities: the background of such patients almost invariably includes cigarette smoking; the female gender is about five times less affected, the diaphragmatic location is nearly two times more frequent, and the hospital mortality rate of these patients is almost four times lower than that of older patients.

In order to assess the influence of war calamities on the pupils' growth rate, the height, weight, and relative weight of children from Split at the time of entering two major elementary schools (age about 6.5 years) and some 10 months later, during the two pre-war years (i.e. 1988/1989 and 1989/1990) and the two years of the war against Croatia (i.e. 1990/1991 and 1991/1992) were compared. A notable increase in body weight, ranging from 12.24 to 14.50% (compared with 8.57-11.93%; t = 1.23, P > 0.05), but not in height was observed in the first, and a significant acceleration in the longitudinal growth (4.53-4.73% as compared with 3.38-4.24%; t = 4.01, P < 0.01) but not in weight gain was noted in the second war year. These unexpected findings lead to a conclusion that the war atrocities may affect the children's growth rate differently, depending on the amount and quality of the consumed food, on the level of energy expenditure, and possibly on the variable impact of emotional stress.

Three thousand three hundred and fifty-two patients (70% males and 28% females) were hospitalized and treated in Split for acute myocardial infarction (hospital mortality 20%) between 1982-1992. The number of these admissions has been constantly rising from 226 in 1982 to 397 in 1992. Over 45 years of age were 3043 (90.8%) of the patients (70% males and 30% females), while 309 of them (9.2%) were under 45 (93% males, 7% females). The lethality rate was 21% in the first and 8% in the second subgroup. In patients over 45 inferior myocardial infarction was found in 35%, and in patients under 45 in 49%. In the older group there were 40% smokers, 42% hypertensives and 39% hypercholesterolemics, while there were 75% smokers, 35% hypertensives and 33% hypercholesterolemic patients in the younger age group. The results show that the number of patients treated for acute myocardial infarction in the Split region is constantly increasing (p < 0.001). In patients under 45 years of age there is significantly higher inferior infarction prevalence (p < 0.001); a larger percentage of males (p < 0.001) and smokers (p < 0.001), and lower percentage of hypertensives (p < 0.001) and hypercholesterolemic patients (p < 0.05) was observed, as well as lower hospital mortality rate (p < 0.001).

In a 16 per cent systematic sample of the fifth grade elementary school pupils from Split, Yugoslavia (198 boys and 250 girls, aged 11.3 +/- 0.4 years; mean +/- SD), 116 children (25,9% of the sample; 61 girls and 55 boys) were found at risk for cardiovascular diseases, having the values of one or more of the recognized risk factors above the 90th percentile of distribution for age and sex, e.g. serum cholesterol greater than 5.6 mmol/l. After the 3-year follow-up period the parents and the available relatives of these children were checked for the same risk factors in order to evaluate the magnitude of family aggregation. The prevalence of cardiovascular risk factors was 3-5 times higher for the parents of the children at risk than for the control parents (e.g. 57.1 vs 11.8 per cent in boys; p less than 0.001). The observed parent-child agreement was highest for serum cholesterol and triglycerides (range 30.0-37.5%; p less than 0.01). The family clustering of risk factors was prominent in the second generation (e.g. grandparents, p less than 0.01) as well, and even among the other relatives (p less than 0.05). It is concluded that the probability of adverse cardiovascular outcome increases not only with the individual level of aberration and with the mutual enhancement of risk factors, but with positive history and family aggregation as well: these phenomena have important influence on the process of physicians' decision making, with obvious practical implications.