Fibronectin attenuates process outgrowth in oligodendrocytes by mislocalizing MMP-9 activity

The extension of multiple oligodendroglial branched processes towards axons is an important event during the early stages of myelination that likely requires remodeling of the extracellular matrix (ECM) microenvironment via matrix metalloproteinases (MMPs). Here we investigated whether fibronectin-mediated inhibition of myelin sheet formation in oligodendrocytes correlated with an altered MMP activity. Our data reveal that fibronectin enhanced, in a PKC-dependent manner, the net activity of MMP-9, but not its expression, in conditioned medium of oligodendrocytes. Residual cellular MMP-9 activity on fibronectin was confined to the cell body, whereas MMP-9 activity on laminin-2 was localized along extending processes of oligodendrocytes. The mislocalization of MMP-9 activity on fibronectin correlated with a perturbed outgrowth of oligodendroglial processes. In conclusion, our findings suggest that ECM molecules influence both the net activity of secreted MMP and the spatial distribution of cell-associated MMP activity, and thereby morphological oligodendrocyte differentiation.     

Can structural MRI indices of cerebral integrity track cognitive trends in executive control function during normal maturation and adulthood?

We explored the relationship between structural neuroimaging‐based indices of cerebral integrity and executive control function (ECF) in two groups of healthy subjects: A maturing group (33 subjects; 19–29 years) and a senescing group (38 adults; 30–90 years). ECF was assessed using the Executive Interview (EXIT) battery. Cortical indices of cerebral integrity included GM thickness, intergyral span, and sulcal span, each measured for five cortical regions per hemisphere. Subcortical indices included fractional anisotropy (FA), measured using track‐based‐spatial‐statistics (TBSS), and the volume of T2‐hyperintense WM (HWM). In the maturing group, no significant relationships between neuroanatomical changes and ECF were found; however, there were hints that late‐term maturation of cerebral WM influenced variability in ECF. In the senescing group, the decline in ECF corresponded to atrophic changes in cerebral WM (sulcal and intergyral span) primarily in the superior frontal and anterior cingulate regions. A large fraction of the variability in ECF (62%) can be explained by variability in the structural indices from these two regions. Hum Brain Mapp 2009. © 2008 Wiley‐Liss, Inc.     

Psychological and behavioral correlates of entering care for HIV infection: the Antiretroviral Treatment Access Study (ARTAS)

The present study sought to examine psychological and behavioral variables as predictors of attending an HIV medical care provider among person's recently diagnosed with HIV. The study, carried out between 2001 and 2003, was a two-arm randomized intervention trial with participants recruited from public HIV testing centers, sexually transmitted disease (STD) clinics, hospitals, and community-based organizations in Atlanta, Georgia; Baltimore, Maryland; Miami, Florida; and Los Angeles, California. Eighty-six percent of those enrolled (273) had complete baseline and 12-month follow-up data. Measures of number of months since HIV diagnosis, readiness to enter care (based on stages of change), barriers and facilitators to entering care, drug use, and intervention arm (case managed versus simple referral) were examined as predictors of attending an HIV care provider, defined as being in care at least once in each of two consecutive 6-month follow-up periods. In logistic regression, seeing a care provider was significantly more likely among participants diagnosed with HIV within 6 months of enrollment (odds ratio [OR] = 2.52, 95% confidence interval [CI], 1.25, 5.06), those in the preparation versus precontemplation stages at baseline (OR = 2.87, 95% CI, 1.21, 6.81), those who reported at baseline that someone (friend, family member, social worker, other) was helping them get into care (OR = 2.13, 95% CI, 1.02, 4.44), and those who received a case manager intervention (OR = 2.16, 95% CI, 1.23, 3.78). The findings indicate a need to reach HIV-positive person's soon after diagnosis and assist them in getting into medical care. Knowing a person's stages of readiness to enter care and their support networks can help case managers formulate optimal client plans.     

Prevalence of HIV,Hepatitis B,Syphilis, and Chlamydia Among Adults Seeking Treatment for a Mental Disorder in Southern India

This study estimated the prevalence, and identified the correlates, of HIV, chlamydia, syphilis, and Hepatitis B among patients seeking treatment for a mental disorder in India. Patients (n = 948) submitted a blood sample for serologic testing and participated in a brief interview. Lifetime prevalence rates were nearly 2% for HIV, 10% for chlamydia, 3% for Hepatitis B, and 3% for syphilis; 15% of patients had evidence of at least one infection. Bivariate associations between infection status and patient characteristics, including age, gender, psychiatric diagnosis, did not reveal any consistent risk profile. Instead, behavioral characteristics (i.e., multiple partners, exchanging sex for money, and engagement in anal sex) were associated with infection status. Recommendations for the sexual health care of psychiatric patients in India are provided. SUPPORT: R01-MH54929 and K02-MH01582 from the National Institute of Mental Health.     

Clinical assessment of chronic cough severity

The assessment of cough severity solely through consultation with the patient is limited by its subjective nature and variability of physician judgement. The assessment of cough has been hampered by a paucity of objective tools, those available have been poorly validated, non-standardized and are impractical for clinical use. Recent developments have overcome some of these problems and a variety of tools can now be used to assess cough that include visual analogue scales (VAS), quality-of-life questionnaires, cough reflex sensitivity measurement and automated cough frequency monitors. These tools can be used to validate the presence of cough and assess response to therapy. They will also have an important role in clinical trials.     

Exploring the relationship between genetic and environmental influences on initiation and progression of substance use

AIMS: To examine the genetic and environmental contributions to the initiation of use and progression to more serious use of alcohol, cigarettes and marijuana during adolescence, and to examine the relationship between initiation and progression of substance use. DESIGN: The study used a twin-based design and a new theoretical model, the causal-common-contingent (CCC) model. This allows modelling of the relationship between initiation of use and progression to heavier use as a two-stage model and the examination of genetic and environmental influences on both stages, while taking into account their relationship. PARTICIPANTS: The participants consisted of 1214 twin pairs (69% response rate) aged 11-19 years sampled from the UK population-based Cardiff Study of All Wales and North-west of England Twins (CaStANET). MEASUREMENTS: Data on adolescent initiation and progression to more serious use of alcohol, cigarettes and marijuana were obtained using self-report questionnaires. FINDINGS: Initiation of alcohol and progression to heavier alcohol use had separate but related underlying aetiologies. For cigarette and marijuana use the relation between initiation and progression to heavier use was stronger, suggesting greater overlap in aetiologies. For all three substances, environmental influences that make twins more similar (common environment) tended to be greater for initiation, while genetic influences were stronger for heavier use. CONCLUSIONS: These findings have implications for policy decisions aimed at an adolescent and early adult age group. Specifically, these findings suggest that it may be more efficacious to focus alcohol interventions on risk factors for the development of heavier use rather than initiation of use. In contrast, interventions aimed at reducing the initiation of cigarettes and marijuana use may be more appropriate.