Reduced caudate gray matter volume in women with major depressive disorder

Previous brain-imaging studies have reported that major depressive disorder (MDD) is characterized by decreased volumes of several cortical and subcortical structures, including the hippocampus, amygdala, anterior cingulate cortex, and caudate nucleus. The purpose of the present study was to identify structural volumetric differences between MDD and healthy participants using a method that allows a comparison of gray and white matter volume across the whole brain. In addition, we explored the relation between symptom severity and brain regions with decreased volumes in MDD participants. The study group comprised 22 women diagnosed with MDD and 25 healthy women with no history of major psychiatric disorders. Magnetic resonance brain images were analyzed using optimized voxel-based morphometry to examine group differences in regional gray and white matter volume. Compared with healthy controls, MDD participants were found to have decreased gray matter volume in the bilateral caudate nucleus and the thalamus. No group differences were found for white matter volume, nor were there significant correlations between gray matter volumes and symptom severity within the MDD group. The present results suggest that smaller volume of the caudate nucleus may be related to the pathophysiology of MDD and may account for abnormalities of the cortico-striatal-pallido-thalamic loop in MDD.     

Mapping the relationship between cortical convolution and intelligence: effects of gender

The pronounced convolution of the human cortex may be a morphological substrate that supports some of our species' most distinctive cognitive abilities. Therefore, individual intelligence within humans might be modulated by the degree of folding in certain cortical regions. We applied advanced methods to analyze cortical convolution at high spatial resolution and correlated those measurements with intelligence quotients. Within a large sample of healthy adult subjects (n = 65), we detected the most prominent correlations in the left medial hemisphere. More specifically, intelligence scores were positively associated with the degree of folding in the temporo-occipital lobe, particularly in the outermost section of the posterior cingulate gyrus (retrosplenial areas). Thus, this region might be an important contributor toward individual intelligence, either via modulating pathways to (pre)frontal regions or by serving as a location for the convergence of information. Prominent gender differences within the right frontal cortex were observed; females showed uncorrected significant positive correlations and males showed a nonsignificant trend toward negative correlations. It is possible that formerly described gender differences in regional convolution are associated with differences in the underlying architecture. This might lead to the development of sexually dimorphic information processing strategies and affect the relationship between intelligence and cortical convolution.     

Comparison of Two School-Based Smoking Prevention Programs among South African High School Students: Results of a Randomized Trial

Background  Smoking rates are projected to increase substantially in developing countries such as South Africa. Purpose  The aim of this study was to test the efficacy of two contrasting approaches to school-based smoking prevention in South African youth compared to the standard health education program. One experimental program was based on a skills training/peer resistance model and the other on a harm minimization model. Method  Thirty-six public schools from two South African provinces, KwaZulu-Natal and the Western Cape, were stratified by socioeconomic status and randomized to one of three groups. Group 1 (comparison) schools (n = 12) received usual tobacco use education. Group 2 schools (n = 12) received a harm minimization curriculum in grades 8 and 9. Group 3 schools (n = 12) received a life skills training curriculum in grades 8 and 9. The primary outcome was past month use of cigarettes based on a self-reported questionnaire. Result  Five thousand two hundred sixty-six students completed the baseline survey. Of these, 4,684 (89%) completed at least one follow-up assessment. The net change in 30-day smoking from baseline to 2-year follow-up in the control group was 6% compared to 3% in both harm minimization (HM) and life skills training (LST) schools. These differences were not statistically significant. Intervention response was significantly moderated by both gender and race. The HM intervention was more effective for males, whereas the life skills intervention was more effective for females. For black African students, the strongest effect was evident for the HM intervention, whereas the strongest intervention effect for “colored” students was evident for the LST group. Conclusion  The two experimental curricula both produced similar overall reductions in smoking prevalence that were not significantly different from each other or the control group. However, the impact differed by gender and race, suggesting a need to tailor tobacco and drug use prevention programs. More intensive intervention, in the classroom and beyond, may be needed to further impact smoking behavior.

Deep infection in total hip arthroplasty

Objective

To report on a 30-year prospective study of deep infection in 1993 consecutive total hip arthroplasties performed by a single surgeon.

Methods

The relations of numerous variables to the incidence of deep infection were studied.

Results

The cumulative infection rate after the index total hip arthroplasties rose from 0.8% at 2 years to 1.4% at 20 years; 9.6% of the index operations required further surgery. When infections attributed to these secondary procedures were included, the infection rate rose from 0.9% at 2 years to 2% at 20 years. Although the usual variables increased the incidence of infection, the significant and most precise predictors of infection were radiologic diagnoses of upper pole grade III and protrusio acetabuli, an elevated erythrocyte sedimentation rate, alcoholism and units of blood transfused.

Conclusion

From 2–20 years, the incidence of deep infection doubled. Preoperative recognition of the first 4 risk factors permits the use of additional prophylactic measures. Spinal or epidural anesthesia reduced the units of blood transfused (the fifth risk factor) and, hence, the risk of infection. Although most deep infections are seeded while the wound is open, there are many possible postoperative causes. In this study, fewer than one-third of the infections that presented after 2 years were related to hematogenous spread. The efficacy of clean air technology was supported, and it is recommended that all measures that may reduce the incidence of deep infection be employed.     

Creatine supplements in patients with idiopathic inflammatory myopathies who are clinically weak after conventional pharmacologic treatment: Six-month, double-blind, randomized, placebo-controlled trial

OBJECTIVE: To test the hypothesis that oral creatine supplements with exercise are more effective than exercise alone in improving muscle function in patients with established dermatomyositis or polymyositis receiving chronic medical therapies who are clinically weak yet stable. METHODS: In a 6-month, 2-center, double-blind, randomized controlled trial, patients were randomized to receive oral creatine supplements (8 days, 20 gm/day then 3 gm/day) or placebo. All patients followed a home exercise program. The primary outcome was aggregate functional performance time (AFPT), reflecting the ability to undertake high-intensity exercise. Secondary outcomes included a functional index measuring endurance and muscle bioenergetics on (31)P magnetic resonance spectroscopy ((31)P MRS). Patients were receiving stable immunosuppressive treatment and/or corticosteroids. RESULTS: A total of 37 patients with polymyositis or dermatomyositis were randomized (19 to creatine, 18 to placebo); 29 completed 6 months. Intent-to-treat analyses demonstrated that AFPT improved significantly at 6 months with creatine (median decrease 13%, range -32-8%) compared with placebo (median decrease 3%, range -13-16%; P = 0.029 by Mann-Whitney U test). A completer analysis also showed significant benefits from creatine (P = 0.014). The functional index improved significantly with both creatine and placebo (P < 0.05 by paired Wilcoxon's rank sum test), with a significant benefit between groups in the completer analysis only. Phosphocreatine/beta-nucleoside triphosphate ratios using MRS increased significantly in the creatine group (P < 0.05) but not in the control group. No clinically relevant adverse events were associated with creatine. CONCLUSION: Oral creatine supplements combined with home exercises improve functional performance without significant adverse effects in patients with polymyositis or dermatomyositis. They appear safe, effective, and inexpensive.     

The immune thrombocytopenic purpura (ITP) bleeding score: assessment of bleeding in patients with ITP

A method for objective quantification of bleeding symptoms in immune thrombocytopenic purpura (ITP) has not been established. The ITP Bleeding Scale (IBLS) is a novel bleeding assessment system comprising 11 site-specific grades. Implementation of the IBLS on 100 patient visits revealed that although platelet count and large platelet count correlated well with bleeding symptoms overall, this relationship disappeared in marked thrombocytopenia. The IBLS is a useful clinical tool for monitoring bleeding and may be used to aid the development of laboratory parameters that correlate with underlying bleeding propensity in thrombocytopenia.     

Activation of polyamine catabolism by N1, N11-diethylnorspermine alters the cellular localization of mTOR and downregulates mTOR protein level in glioblastoma cells

N(1), N(11)-Diethylnorspermine (DENSPM) is a spermine analog and prototype anti-cancer drug that depletes cellular polyamine, increases cellular oxidative stress through the generation of H(2)O(2) and induces the death of multiple types of cancer cells. However, the survival pathways perturbed by DENSPM are uncertain. To identify these pathways, we examined a series of proteins in the phosphoinositide 3-kinase /AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) pathways in glioblastoma cell lines before and after treatment with DENSPM. We found that DENSPM did not change the protein levels of PI3K but did reduce the levels of AKT, phosphorylated AKT, mTOR, phosphorylated mTOR, p70(S6K), phosphorylated p70(S6K), 4E-BP1, phosphorylated 4E-BP1 and eIF-4B proteins. From this it appears that DENSPM directly targets the mTOR protein level in these glioblastoma cells by inhibiting mTOR-mediated protein synthesis. Immunofluorescence analysis of mTOR showed that DENSPM sequestered mTOR in the perinuclear region of the cells. We also detected a marked collapse of microtubules in U87 cells and a detachment of cells in a process resembling anoikis. We further showed that the levels of many proteins regulating cell growth and cell adhesion were downregulated, suggesting a broad effect of DENSPM on mTOR-mediated protein synthesis. We conclude that the activation of polyamine catabolism alters the cellular location of mTOR, thus negatively affecting mTOR-mediated protein synthesis and leading to the death of glioblastoma cells.