Loss of intranetwork and internetwork resting state functional connections with Alzheimer's disease progression

Alzheimer's disease (AD) is the most common cause of dementia. Much is known concerning AD pathophysiology but our understanding of the disease at the systems level remains incomplete. Previous AD research has used resting-state functional connectivity magnetic resonance imaging (rs-fcMRI) to assess the integrity of functional networks within the brain. Most studies have focused on the default-mode network (DMN), a primary locus of AD pathology. However, other brain regions are inevitably affected with disease progression. We studied rs-fcMRI in five functionally defined brain networks within a large cohort of human participants of either gender (n = 510) that ranged in AD severity from unaffected [clinical dementia rating (CDR) 0] to very mild (CDR 0.5) to mild (CDR 1). We observed loss of correlations within not only the DMN but other networks at CDR 0.5. Within the salience network (SAL), increases were seen between CDR 0 and CDR 0.5. However, at CDR 1, all networks, including SAL, exhibited reduced correlations. Specific networks were preferentially affected at certain CDR stages. In addition, cross-network relations were consistently lost with increasing AD severity. Our results demonstrate that AD is associated with widespread loss of both intranetwork and internetwork correlations. These results provide insight into AD pathophysiology and reinforce an integrative view of the brain's functional organization.     

HIV and Chronic Methamphetamine Dependence Affect Cerebral Blood Flow

Human immunodeficiency virus (HIV) and methamphetamine (METH) dependence are independently associated with neuronal dysfunction. The coupling between cerebral blood flow (CBF) and neuronal activity is the basis of many task-based functional neuroimaging techniques. We examined the interaction between HIV infection and a previous history of METH dependence on CBF within the lenticular nuclei (LN). Twenty-four HIV−/METH−, eight HIV−/METH+, 24 HIV+/METH−, and 15 HIV+/METH+ participants performed a finger tapping paradigm. A multiple regression analysis of covariance assessed associations and two-way interactions between CBF and HIV serostatus and/or previous history of METH dependence. HIV+ individuals had a trend towards a lower baseline CBF (−10%, p = 0.07) and greater CBF changes for the functional task (+32%, p = 0.01) than HIV− subjects. Individuals with a previous history of METH dependence had a lower baseline CBF (−16%, p = 0.007) and greater CBF changes for a functional task (+33%, p = 0.02). However, no interaction existed between HIV serostatus and previous history of METH dependence for either baseline CBF (p = 0.53) or CBF changes for a functional task (p = 0.10). In addition, CBF and volume in the LN were not correlated. A possible additive relationship could exist between HIV infection and a history of METH dependence on CBF with a previous history of METH dependence having a larger contribution. Abnormalities in CBF could serve as a surrogate measure for assessing the chronic effects of HIV and previous METH dependence on brain function.     

Young maternal age and parity. Influences on pregnancy outcome.

The influence of very young maternal age and parity on pregnancy outcome was examined in a cohort of nearly 900 adolescents and mature women from Camden, New Jersey. Young primigravid primiparas (aged 12 to 15 years) were compared with mature primigravid primiparas (18 to 29 years). Young multiparas (19 years or younger, with a first pregnancy at the age of 12 to 15 years) were compared with mature, multiparas (19 to 29 years old, with a first pregnancy at 18 years or older). After controlling for confounding factors, young primiparas were found to have a modest increase in preterm delivery, which was not statistically significant. However, low gynecologic age contributed disproportionately to the risk of preterm delivery in this group, with risk decreasing with each year from menarche (Cox's proportional hazard, 0.80; 95% confidence interval [CI], 0.68 to 0.94). Among multiparas, there were several statistical interactions associated with increased risk of small-for-gestational-age infants, including interactions between young age and low pre-pregnancy body mass (adjusted odds ratio [AOR], 5.74; 95% CI, 2.18 to 15.08), young age and a prior low-birth-weight infant (AOR, 10.58; 95% CI, 3.89 to 28.77), and young age and a prior preterm delivery (AOR, 5.52; 95% CI, 2.04 to 14.98). Thus, while chronologic age per se may not be a good predictor of pregnancy outcome, adolescents remain a high-risk group because of factors that are more common among them (e.g., biologic immaturity, inadequate prenatal care, poverty, minority status, low prepregnancy weight) and because factors associated with an early adolescent pregnancy, such as low gynecologic age, may continue to influence the outcome of subsequent pregnancies.     

Partial purification of a novel mitogen for oligodendroglia

A protein with a MW_app of 50–70 kDa isolated from the salt extract of crude membranes from neonatal rat brain increases the numbers of oligodendroglia in mixed glial cultures prepared from neonatal rat cerebral white matter. After partial purification by ion exchange and gel exclusion chromatography, and elution from an SDS-polyacrylamide gel, this protein ( “oligodendroglial trophic factor,” OTF) elicited half-maximal oligodendroglial recruitment at a concentration of 5 ng/mL. OTF is a mitogen for oligodendroglia, and to a lesser extent, for oligodendroglial progenitor (O2A) cells, but does not stimulate proliferation of astroglia, Schwann cells, or endoneurial fibroblasts. OTF, unlike platelet-derived growth factor (PDGF), is not an oligodendroglial survival factor. Antibodies against PDGF and basic fibroblast growth factor (bFGF) do not interfere with the accumulation of oligodendroglia induced by OTF. When OTF is given simultaneously with either PDGF or bFGF, there is an additive increase in the numbers of cells of the oligodendroglial lineage. © 1995 Wiley-Liss, Inc.     

46, XY gonadal dysgenesis with secondary amenorrhea, virilization, and bilateral gonadoblastomas

A phenotypic girl with secondary amenorrhea, enlargement of the clitoris, XY gonadal dysgenesis, and bilateral gonadoblastomas is described. The presence of secondary amenorrhea does not obviate the existence of a Y chromosome. The presence of the Y chromosome should be a warning that a gonadal tumor may be present and, therefore, gonadectomy must be done as soon as possible and preferably before puberty.     

Serum concentrations of beta-melanocyte-stimulating hormone in human pregnancy

β-Melanocyte-stimulating hormone (β-MSH) has been measured in pregnant women with the use of a sensitive tube radioimmunoassay technique which does not require prior extraction. This peptide rises progressivley throughout pregnancy with its highest concentration at term. Measurable quantities exceeding maternal levels were observed in both cord blood and amniotic fluid and elevated levels of β-MSH were found in lactating women. The role and possible chorionic origin of β-MSH remain to be determined, as well as the possible clinical use.     

Role of psychiatric medications as adjunct therapy in the treatment of HIV associated neurocognitive disorders

Effective combination antiretroviral therapies (ART) have markedly lengthened survival among HIV infected individuals. In this long-surviving cohort, both psychiatric comorbidities and HIV-associated neurocognitive disorders (HAND) remain common. Even mild neurocognitive impairment can significantly disrupt of activities of daily living and reduce quality of life. Persistence of HAND might reflect incomplete containment of HIV within the central nervous system (CNS) due to the limited penetration of most antiretrovirals (ARVs) across the blood-brain barrier. Recent data support that certain medications used to treat psychiatric comorbidities in HIV-infected individuals may also protect the brain from toxic byproducts of HIV replication and neuroinflammation. Two drug classes in particular, glycogen synthase kinase-3 beta (GSK-3b) inhibitors and serotonin reuptake inhibitors (SRIs), may benefit individuals with HAND. Valproic acid (VPA) and lithium are potentially beneficial GSK-3b inhibitors. While the mechanism of benefit of SRIs in HAND remains unknown, evidence supports some benefit of citalopram and paroxetine. The present brief review focuses on these drugs and assesses their possible adjunct roles in the treatment of HIV-infected individuals.