A Unified Functional Network Target for Deep Brain Stimulation in Obsessive-Compulsive Disorder

BACKGROUND: Multiple deep brain stimulation (DBS) targets have been proposed for treating intractable obsessive-compulsive disorder (OCD). Here, we investigated whether stimulation effects of different target sites would be mediated by one common or several segregated functional brain networks. METHODS: First, seeding from active electrodes of 4 OCD patient cohorts (N = 50) receiving DBS to anterior limb of the internal capsule or subthalamic nucleus zones, optimal functional connectivity profiles for maximal Yale-Brown Obsessive Compulsive Scale improvements were calculated and cross-validated in leave-one-cohort-out and leave-one-patient-out designs. Second, we derived optimal target-specific connectivity patterns to determine brain regions mutually predictive of clinical outcome for both targets and others predictive for either target alone. Functional connectivity was defined using resting-state functional magnetic resonance imaging data acquired in 1000 healthy participants. RESULTS: While optimal functional connectivity profiles showed both commonalities and differences between target sites, robust cross-predictions of clinical improvements across OCD cohorts and targets suggested a shared network. Connectivity to the anterior cingulate cortex, insula, and precuneus, among other regions, was predictive regardless of stimulation target. Regions with maximal connectivity to these commonly predictive areas included the insula, superior frontal gyrus, anterior cingulate cortex, and anterior thalamus, as well as the original stereotactic targets. CONCLUSIONS: Pinpointing the network modulated by DBS for OCD from different target sites identified a set of brain regions to which DBS electrodes associated with optimal outcomes were functionally connected-regardless of target choice. On these grounds, we establish potential brain areas that could prospectively inform additional or alternative neuromodulation targets for obsessive-compulsive disorder

A comparison of sunlight exposure in men with prostate cancer and basal cell carcinoma

Ultraviolet radiation exposure increases basal cell carcinoma (BCC) risk, but may be protective against prostate cancer. We attempted to identify exposure patterns that confer reduced prostate cancer risk without increasing that of BCC. We used a questionnaire to assess exposure in 528 prostate cancer patients and 442 men with basal cell carcinoma, using 365 benign prostatic hypertrophy patients as controls. Skin type 1 (odds ratio (OR)=0.47, 95% CI=0.26–0.86), childhood sunburning (OR=0.38, 95% CI=0.26–0.57), occasional/frequent sunbathing (OR=0.21, 95% CI=0.14–0.31), lifetime weekday (OR=0.85, 95% CI=0.80–0.91) and weekend exposure (OR=0.79, 95% CI=0.73–0.86) were associated with reduced prostate cancer risk. Skin type 1 (OR=4.00, 95% CI=2.16–7.41), childhood sunburning (OR=1.91, 95% CI=1.36–2.68), regular foreign holidays (OR=6.91, 95% CI=5.00-9.55) and weekend (OR=1.17, 95% CI=1.08–1.27) but not weekday exposure were linked with increased BCC risk. Combinations of one or two parameters were associated with a progressive decrease in the ORs for prostate cancer risk (OR=0.54–0.25) with correspondingly increased BCC risk (OR=1.60–2.54). Our data do not define exposure patterns that reduce prostate cancer risk without increasing BCC risk

A case-control study of GST polymorphisms and arsenic related skin lesions

BACKGROUND: Polymorphisms in GSTT1, GSTM1 and GSTP1 impact detoxification of carcinogens by GSTs and have been reported to increase susceptibility to environmentally related health outcomes. Individual factors in arsenic biotransformation may influence disease susceptibility. GST activity is involved in the metabolism of endogenous and exogenous compounds, including catalyzing the formation of arsenic-GSH conjugates. METHODS: We investigated whether polymorphisms in GSTT1, GSTP1 and GSTM1 were associated with risk of skin lesions and whether these polymorphisms modify the relationship between drinking water arsenic exposure and skin lesions in a case control study of 1200 subjects frequency matched on age and gender in community clinics in Pabna, Bangladesh in 2001–2002. RESULTS AND DISCUSSION: GSTT1 homozygous wildtype status was associated with increased odds of skin lesions compared to the null status (OR1.56 95% CI 1.10–2.19). The GSTP1 GG polymorphism was associated with greater odds of skin lesions compared to GSTP1 AA, (OR 1.86 (95%CI 1.15–3.00). No evidence of effect modification by GSTT1, GSTM1 or GSTP1 polymorphisms on the association between arsenic exposure and skin lesions was detected. CONCLUSION: GSTT1 wildtype and GSTP1 GG are associated with increased risk of skin lesions

Vitamin D and oestrogen receptor polymorphisms in developmental dysplasia of the hip and primary protrusio acetabuli – A preliminary study

We investigated the association of developmental dysplasia of the hip (DDH) and primary protrusion acetabuli (PPA) with Vitamin D receptor polymorphisms Taq I and Fok I and oestrogen receptor polymorphisms Pvu II and Xba I. 45 patients with DDH and 20 patients with PPA were included in the study. Healthy controls (n = 101) aged 18–60 years were recruited from the same geographical area. The control subjects had a normal acetabular morphology based on a recent pelvic radiograph performed for an unrelated cause. DNA was obtained from all the subjects from peripheral blood. Genotype frequencies were compared in the three groups. The relationship between the genotype and morphology of the hip joint, severity of the disease, age at onset of disease and gender were examined. The oestrogen receptor Xba I wild-type genotype (XX, compared with Xx and xx combined) was more common in the DDH group (55.8%) than controls (37.9%), though this just failed to achieve statistical significance (p = 0.053, odds ratio = 2.1, 95% CI = 0.9–4.6). In the DDH group, homozygosity for the mutant Taq I Vitamin D receptor t allele was associated with higher acetabular index (Mann-Whitney U-test, p = 0.03). Pvu II pp oestrogen receptor genotype was associated with low centre edge angle (p = 0.07). This study suggests a possible correlation between gene polymorphism in the oestrogen and vitamin D receptors and susceptibility to, and severity of DDH. The Taq I vitamin D receptor polymorphisms may be associated with abnormal acetabular morphology leading to DDH while the Xba I oestrogen receptor XX genotype may be associated with increased risk of developing DDH. No such correlations were found in the group with PPA

Isolation and Culture of Larval Cells from C. elegans

Cell culture is an essential tool to study cell function. In C. elegans the ability to isolate and culture cells has been limited to embryonically derived cells. However, cells or blastomeres isolated from mixed stage embryos terminally differentiate within 24 hours of culture, thus precluding post-embryonic stage cell culture. We have developed an efficient and technically simple method for large-scale isolation and primary culture of larval-stage cells. We have optimized the treatment to maximize cell number and minimize cell death for each of the four larval stages. We obtained up to 7.8×104 cells per microliter of packed larvae, and up to 97% of adherent cells isolated by this method were viable for at least 16 hours. Cultured larval cells showed stage-specific increases in both cell size and multinuclearity and expressed lineage- and cell type-specific reporters. The majority (81%) of larval cells isolated by our method were muscle cells that exhibited stage-specific phenotypes. L1 muscle cells developed 1 to 2 wide cytoplasmic processes, while L4 muscle cells developed 4 to 14 processes of various thicknesses. L4 muscle cells developed bands of myosin heavy chain A thick filaments at the cell center and spontaneously contracted ex vivo. Neurons constituted less than 10% of the isolated cells and the majority of neurons developed one or more long, microtubule-rich protrusions that terminated in actin-rich growth cones. In addition to cells such as muscle and neuron that are high abundance in vivo, we were also able to isolate M-lineage cells that constitute less than 0.2% of cells in vivo. Our novel method of cell isolation extends C. elegans cell culture to larval developmental stages, and allows use of the wealth of cell culture tools, such as cell sorting, electrophysiology, co-culture, and high-resolution imaging of subcellular dynamics, in investigation of post-embryonic development and physiology

Evaluation of a school-based HIV prevention intervention among Yemeni adolescents

<p>Abstract</p> <p>Background</p> <p>This article describes an evaluation of a school-based peer education intervention for HIV prevention among students in twenty seven high schools in Aden, Yemen. The intervention was developed after a survey among the same population in 2005, which revealed a high level of stigma towards people living with HIV (PLWH) and a low level of HIV knowledge.</p> <p>Methods</p> <p>In a quasi-experimental design students who received the peer education intervention (78.6%) were compared with students who did not receive the intervention (21.4%). No systematic procedure was applied in selecting students for the intervention condition. Data were collected using a self-administered questionnaire from a sample of 2510 students from all 27 high-schools in Aden governorate. To increase internal validity, students were also compared with a cohort control sample surveyed in 2005, which was a random sample of 2274 students from the same schools.</p> <p>Results</p> <p>Sixty eight percent of students targeted by peer education had good knowledge scores, compared with 43.3% of students not targeted by peer education (χ²= (df = 1) = 111.15, p < .01). Multi-level regression analysis revealed that, although there was a significant difference among schools, the intervention effect of peer education at the individual level was significant; students who received peer education had a statistically higher knowledge score(9.24 out of 12.0) compared with those not targeted (7.89 out of 12.0), OR = 2.11, 95% CI = 1.04-4.27, p < .05). Compared with the 2005 cohort control sample, students targeted by peer education had better knowledge on the modes of transmission and prevention and fewer misconceptions; and knowledge on the use of condoms increased from 49.4% to 67.8%. In addition, students who received the peer education interventions suggested significantly more actions to provide care and support for PLWH. Also, the levels of stigma and discrimination were much higher among the 2005 cohort control group, compared with those who received the peer education intervention.</p> <p>Conclusion</p> <p>The school-based peer education intervention has succeeded in improving levels of knowledge on modes of transmission and prevention, and in decreasing levels of stigma and discrimination in a culturally conservative setting.</p

Imaging Lung Disease in Systemic Sclerosis

Interstitial lung disease and pulmonary hypertension (PH) are the most common cardiopulmonary findings in patients with systemic sclerosis (SSc). About two thirds of patients suffering from SSc develop scleroderma interstitial lung disease. PH is present in about 20% of SSc patients and is typically associated with severe lung disease, although it may be an isolated manifestation of SSc. High-resolution CT scanning is a key method for evaluating chest involvement. There are four roles of imaging in scleroderma interstitial lung disease: 1) detection of lung involvement, 2) identification of patients likely to respond to treatment, 3) assessment of treatment efficacy, and 4) exclusion of other significant diseases to include PH and cardiac and esophageal abnormalities