Association of orexin receptor polymorphisms with antipsychotic-induced weight gain

Objectives: Antipsychotic-induced weight gain (AIWG) is a common side effect of treatment with antipsychotics such as clozapine and olanzapine. The orexin gene and its receptors are expressed in the hypothalamus and have been associated with maintenance of energy homeostasis. In this study, we have analysed tagging single nucleotide polymorphisms (SNPs) in orexin receptors 1 and 2 (HCRTR1 and HCRTR2) for association with AIWG. Methods: Schizophrenia or schizoaffective disorder subjects (n?=?218), treated mostly with clozapine and olanzapine for up to 14 weeks, were included. Replication was conducted in a subset of CATIE samples (n?=?122) treated with either olanzapine or risperidone for up to 190 days. Association between SNPs and AIWG was assessed using analysis of covariance (ANCOVA) with baseline weight and duration of treatment as covariates. Results: Several SNPs in HCRTR2 were nominally associated with AIWG in patients of European ancestry treated with either clozapine or olanzapine (P<0.05). In the replication analysis two SNPs rs3134701 (P?=?0.043) and rs12662510 (P?=?0.012) were nominally associated with AIWG. None of the SNPs in HCRTR1 were associated with AIWG. Conclusion: This study provides preliminary evidence supporting the role of HCRTR2 in AIWG. However, these results need to be confirmed in large study samples.     

The systemic inflammatory response after spinal cord injury in the rat is decreased by α4β1 integrin blockade

Abstract The systemic inflammatory response syndrome (SIRS) follows spinal cord injury (SCI) and causes damage to the lungs, kidney, and liver due to an influx of inflammatory cells from the circulation. After SCI in rats, the SIRS develops within 12?h and is sustained for at least 3 days. We have previously shown that blockade of CD11d/CD18 integrin reduces inflammation-driven secondary damage to the spinal cord. This treatment reduces the SIRS after SCI. In another study we found that blockade of α4β1 integrin limited secondary cord damage more effectively than blockade of CD11d/CD18. Therefore we considered it important to assess the effects of anti-α4β1 treatment on the SIRS in the lung, kidney, and liver after SCI. An anti-α4 antibody was given IV at 2 h after SCI at the fourth thoracic segment and the effects on the organs were evaluated at 24 h post-injury. The migration of neutrophils into the lungs and liver was markedly reduced and all three organs contained fewer macrophages. In the lungs and liver, the activation of the oxidative enzymes myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and gp91(phox), the production of free radicals, lipid peroxidation, and cell death were substantially and similarly reduced. Treatment effects were less robust in the kidney. Overall, the efficacy of the anti-α4β1 treatment did not differ greatly from that of the anti-CD11d antibody, although details of the results differed. The SIRS after SCI impedes recovery, and attenuation of the SIRS with an anti-integrin treatment is an important, clinically-relevant finding.     

Short-Term Jump Activity on Bone Metabolism in Female College-Aged Nonathletes

There have been few studies examining the short-term effect of high-impact activities on bone metabolism measured by bone serum marker concentrations. The purpose of this study was to examine the effect of short-term high-impact jump activity on bone turnover in female college-aged non-athletes. Twenty six healthy females were randomly assigned to a control or jump group. The subjects jumped 5 days per week for 2 weeks. The participants completed 10 jumps per session. A general health questionnaire and a bone-specific physical activity assessment instrument (BPAQ) were completed. BPAQ scores were calculated based on the past history of exercise. Blood draws were taken in both groups before and after the two-week experimental period. The vertical ground reaction force (VGRF) of all jumps and jump height were measured for each subject daily and the osteogenic index (OI) was measured. Concentrations of serum osteocalcin (OC), Bone Specific Alkaline Phosphatase (BAP), C-Terminal Telopeptides of Type I Collagen (CTX) and plasma Tartrate-Resistant Acid Phosphatase (TRAP5b) were assessed pre and post jump protocol to measure bone formation and resoprtion respectively. A significant interaction (time x group) was found in TRAP5b, and BAP values (p < 0.05). There was a significant decrease in CTX and BAP values in the jump group (p < 0.05) after the two week jump protocol. No significant interactions or changes were observed in OC values for either the jump or the control group. Two weeks of jump activity consisting of 10 jumps/day for 5 days/week with a weekly osteogenic index of 52.6 significantly decreased markers of bone resorption (TRAP5b and CTX) and bone formation (BAP) in young female non-athletes.

Key points

• Please provide 3-5 bullet points of the study.
• Inductive qualitative methodologies can encourage the much-needed voice of female youth in sport and physical activity research.
• Vignettes serve, not only as a method to illustrate data, but also as a medium to teach contextually relevant information to participants and sport science service providers.
• The barriers and solutions to female youth engagement in physical activity are best understood through the perspectives of the intended participant.
• Female youth can serve as central informants in the development and analysis of research projects relating to female youth physical activity.

Key words: Jump exercise, vertical ground reaction force, bone serum markers, randomized controlled study     

A CD11d Monoclonal Antibody Treatment Reduces Tissue Injury and Improves Neurological Outcome after Fluid Percussion Brain Injury in Rats

Abstract Traumatic brain injury (TBI) is an international health concern often resulting in chronic neurological abnormalities, including cognitive deficits, emotional disturbances, and motor impairments. An anti-CD11d monoclonal antibody that blocks the CD11d/CD18 integrin and vascular cell adhesion molecule (VCAM)-1 interaction following experimental spinal cord injury improves functional recovery, while reducing the intraspinal number of neutrophils and macrophages, oxidative activity, and tissue damage. Since the mechanisms of secondary injury in the brain and spinal cord are similar, we designed a study to evaluate fully the effects of anti-CD11d treatment after a moderate lateral fluid percussion TBI in the rat. Rats were treated at 2?h after TBI with either the anti-CD11d antibody or an isotype-matched control antibody 1B7, and both short (24- to 72-h) and long (4-week) recovery periods were examined. The anti-CD11d integrin treatment reduced neutrophil and macrophage levels in the injured brain, with concomitant reductions in lipid peroxidation, astrocyte activation, amyloid precursor protein accumulation, and neuronal loss. The reduced neuroinflammation seen in anti-CD11d-treated rats correlated with improved performance on a number of behavioral tests. At 24?h, the anti-CD11d group performed significantly better than the 1B7 controls on several water maze measures of spatial cognition. At 4 weeks post-injury the anti-CD11d-treated rats had better sensorimotor function as assessed by the beam task, and reduced anxiety-like behaviors, as evidenced by elevated-plus maze testing, compared to 1B7 controls. These findings suggest that neuroinflammation is associated with behavioral deficits after TBI, and that anti-CD11d antibody treatment is a viable strategy to improve neurological outcomes after TBI.     

Multislice computed tomography angiography in pediatric liver transplantation

BACKGROUND: Preoperative delineation of any vascular anomalies offers planning for possible alteration of surgical procedures, especially in pediatric recipients undergoing living-related liver transplantation. PURPOSE: We assess the efficacy of three-dimensional (3D) multislice computed tomography (CT) angiography in the hope of replacing conventional angiography as the pretransplant evaluation of the hepatic vascular system for potential recipients of liver transplantation. METHODS: 3D CT angiography was performed in 38 children with biliary atresia. Conventional angiography was also performed in the first 15 patients. Twelve patients underwent living-related liver transplantation. The findings on 3D CT angiography were compared with conventional angiography and operative findings. RESULTS: 3D CT angiography was successfully performed in 37 pediatric patients. All findings of 3D CT angiography on hepatic artery, portal vein, and inferior vena cava paralleled those of catheter angiography and operative findings. Four patients were unsuitable to receive living grafts because of pathologic insults of the hepatic artery (one patient) and the portal vein (three patients). Three patients were advised to undergo a venous graft for portal anastomoses. Eight patients demonstrated portosystemic shunts that may require closure. CONCLUSION: 3D CT angiography proves to be a better tool in the demonstration of the vascular system and identification of pathologic insults in pediatric patients. It is superior to conventional angiography because it is less invasive, more convenient, and more efficient in providing thorough preoperative information that would have a major impact on patient selection and surgical planning.     

Bilateral infraorbital nerve blocks decrease postoperative pain but do not reduce time to discharge following outpatient nasal surgery

Purpose

While infraorbital nerve blocks have demonstrated analgesic benefits for pediatric nasal and facial plastic surgery, no studies to date have explored the effect of this regional anesthetic technique on adult postoperative recovery. We designed this study to test the hypothesis that infraorbital nerve blocks combined with a standardized general anesthetic decrease the duration of recovery following outpatient nasal surgery.

Methods

At a tertiary care university hospital, healthy adult subjects scheduled for outpatient nasal surgery were randomly assigned to receive bilateral infraorbital injections with either 0.5% bupivacaine (Group IOB) or normal saline (Group NS) using an intraoral technique immediately following induction of general anesthesia. All subjects underwent a standardized general anesthetic regimen and were transported to the recovery room following tracheal extubation. The primary outcome was the duration of recovery (minutes) from recovery room admission until actual discharge to home. Secondary outcomes included average and worst pain scores, nausea and vomiting, and supplemental opioid requirements.

Results

Forty patients were enrolled. A statistically significant difference in mean [SD] recovery room duration was not observed between Groups IOB and NS (131 [61] min vs 133 [58] min, respectively; P = 0.77). Subjects in Group IOB did experience a reduction in average pain on a 0–100 mm scale (mean [95% confidence interval]) compared to Group NS (?11 [?21 to 0], P = 0.047), but no other comparison of secondary outcomes was statistically significant.

Conclusions

When added to a standardized general anesthetic, bilateral IOB do not decrease actual time to discharge following outpatient nasal surgery despite a beneficial effect on postoperative pain.     

Medium-Term Anatomic and Functional Results of Laparoscopic Sacrocolpopexy Beyond the Learning Curve

Background

Limited prospective data on the anatomic and functional outcome after laparoscopic sacrocolpopexy (LSC) are available in the literature.

Objective

To describe the medium-term anatomic and functional outcome of LSC.

Design, setting, and participants

Prospective consecutive series of 132 women with vaginal vault prolapse undergoing LSC between 2001 and 2006, which was after our learning curve. Patients with urodynamically proven stress incontinence (SI) underwent a concomitant tension-free vaginal tape (TVT) procedure.

Intervention

Patients underwent LSC with a polypropylene implant.

Measurements

Principal outcome measures were anatomic cure (stage 1 or lower) assessed by the Pelvic Organ Prolapse Quantification (POPQ) system and subjective cure and impact on quality of life measured by a standardised interview and, since its introduction in 2004, by a prolapse-specific quality-of-life questionnaire (P-QOL).

Results and limitations

At a mean follow-up of 12.5 mo, the anatomic cure rate for the apex was 98%. Anatomic failures elsewhere were mainly at the posterior compartment (18%). Subjective prolapse cure rate was 91.7%, and no patients required reoperation for recurrent prolapse. Symptoms of preoperative SI, urge incontinence, or constipation were cured in 43%, 46%, and 42% of patients, respectively. The rate of de novo SI was 7.3%. De novo constipation developed in 5% and de novo dyspareunia developed in 19%. Patients’ quality of life improved significantly. Erosions occurred in 4.5%, all within 1 yr. A limitation of the study is that the quality-of-life assessment score became available halfway through the study, limiting the number of preoperative observations (n = 36).

Conclusions

We demonstrated that LSC results in good anatomic outcome and subjective cure of prolapse symptoms at medium term. The posterior compartment was most vulnerable for recurrence.