Protein kinase A regulates caspase-1 via Ets-1 in bone stromal cell-derived lesions: a link between cyclic AMP and pro-inflammatory pathways in osteoblast progenitors

Patients with genetic defects of the cyclic (c) adenosine-monophosphate (AMP)-signaling pathway and those with neonatal-onset multisystem inflammatory disease (NOMID) develop tumor-like lesions of the long bones. The molecular basis of this similarity is unknown. NOMID is caused by inappropriate caspase-1 activity, which in turn activates the inflammasome. The present study demonstrates that NOMID bone lesions are derived from the same osteoblast progenitor cells that form fibroblastoid tumors in mice and humans with defects that lead to increased cAMP-dependent protein kinase A (PKA) signaling. NOMID tumor cells showed high PKA activity, and an increase in their cAMP signaling led to PKA-specific activation of caspase-1. Increased PKA led to inflammation-independent activation of caspase-1 via over-expression of the proto-oncogene (and early osteoblast factor) Ets-1. In NOMID tumor cells, as in cells with defective PKA regulation, increased prostaglandin E2 (PGE2) led to increased cAMP levels and activation of Wnt signaling, like in other states of inappropriate PKA activity. Caspase-1 and PGE2 inhibition led to a decrease in cell proliferation of both NOMID and cells with abnormal PKA. These data reveal a previously unsuspected link between abnormal cAMP signaling and defective regulation of the inflammasome and suggest that caspase-1 and PGE2 inhibition may be therapeutic targets in bone lesions associated with defects of these two pathways.     

Noninvasive quantification of ascorbate and glutathione concentration in the elderly human brain

In this study, ascorbate (Asc) and glutathione (GSH) concentrations were quantified noninvasively using double-edited (1)H MRS at 4 T in the occipital cortex of healthy young [age (mean ± standard deviation) = 20.4 ± 1.4 years] and elderly (age = 76.6 ± 6.1 years) human subjects. Elderly subjects had a lower GSH concentration than younger subjects (p < 0.05). The Asc concentration was not significantly associated with age. Furthermore, the lactate (Lac) concentration was higher in elderly than young subjects. Lower GSH and higher Lac concentrations are indications of defective protection against oxidative damage and impaired mitochondrial respiration. The extent to which the observed concentration differences could be associated with physiological differences and methodological artifacts is discussed. In conclusion, GSH and Asc concentrations were compared noninvasively for the first time in young vs elderly subjects.     

Disruption of hippocampal connectivity in children and adolescents with schizophrenia--a voxel-based diffusion tensor imaging study

INTRODUCTION: One hypothesis that unifies the diversity of symptoms associated with schizophrenia involves the disruption of connectivity between brain regions. As white matter provides rapid and efficient communication between brain regions, this study was initiated to assess the early disruption of white matter pathways in children and adolescent with schizophrenia. MATERIALS AND METHODS: Diffusion tensor images were acquired on 14 children and adolescents with schizophrenia, one subject with schizoaffective disorder, and 15 age and gender matched controls. The DTI images were acquired in twelve directions on a 3 T Siemens Trio scanner. The images were transformed into fractional anisotropy and mean diffusivity maps and a group analysis was performed using SPM2. RESULTS: Children and adolescent patients with schizophrenia demonstrated a significant decrease in FA and associated increase in AD in the left posterior hippocampus (p<0.001, Bonferroni corrected on the cluster-level). These diffusion differences were not statistically significant when IQ was used as a covariate in the analysis. DISCUSSION: These findings suggest hippocampal white matter abnormalities that present early in the development of schizophrenia. The lack of significant differences when IQ is used as a covariate suggests that this hippocampal region is associated with cognitive changes associated with schizophrenia.     

Effect of GB virus C co-infection on response to generic HAART in African patients with HIV-1 clade C infection

In 38 African AIDS patients initiating generic HAART, GB virus C (GBV-C) RNA-positive patients retained GBV-C viraemia during 52 weeks of HAART, had a faster decline in HIV viral load (P = 0.03), fewer opportunistic infections (14.3 versus 50%, P = 0.18), and suffered no serious adverse events (none versus 61%, P = 0.008) compared with patients without GBV-C. GBV-C co-infection may be associated with a beneficial effect on African AIDS patients treated with generic HAART.     

Part-time faculty and gerontology programs:dilemmas and solutions

This article presents an overview of the use of adjunct faculty generally and within gerontology programs and discusses the benefits, drawbacks and possible solutions for both adjunct faculty and gerontology programs to utilize part-time teaching staff. The benefits reported for being a part-time faculty member include wanting to be in academia and supplementing an income. The reasons gerontology programs hire adjunct faculty members include their being less costly and bringing new skills to the programs. There are also practical and substantive drawbacks faced by part-time faculty. Practical issues include confusion with the pay schedule and last-minute class cancellations. Substantive issues include a lack of both respect and opportunities for professional development. The solutions to these issues include assigned space and support to part-time faculty members, maintaining peer and student evaluations, and affirming diversity in gerontology by recruiting adjunct faculty with knowledge and research capabilities for tenure-track positions as a strategy for successful gerontology program development.     

Adaptation and adjustment in children of transsexual parents

It is a relatively uncommon event that children find themselves in a situation with a parent who undergoes a transition from one sex to another. Unlike situations of divorce or a parent with a medical or major psychiatric disorder, it is unlikely that the children will know of other children who encounter similar situations. There is very little literature that describes the adjustment of these children and the nature of their relationships with their parents and peers. Such information would be beneficial for clinicians assisting children and families in this situation. To better delineate the adjustment of these children, we interviewed 27 parents of 55 children. The interview took place on average 6 years after the gender transition. The measures obtained included the parent and child relationships at present and also at the time of the transition. We also inquired about academic function, peer relationships and social stigma. The results found that children who were younger at the time of the parent’s transition tended to have better relationships and less adjustment difficulties. In addition, parental conflict that continues after the transition period tends to reflect greater family conflict between the transitioned parent and their child.     

Using videoconferencing to support teachers to conduct preference assessments with students with autism and developmental disabilities

We used widely available videoconferencing equipment to support teachers to conduct preference assessments for three students with autism and developmental disabilities. Supervisors located at a university used videoconferencing equipment to collect data on students’ choice of items, the fidelity of teacher implementation of the assessment protocol, and to provide feedback to the teachers. Preference assessment results suggested a number of potentially reinforcing items for each student. In a second phase of the study, the students were given a routine classroom task to complete (i.e., clean up). The students could choose to complete the clean up task and gain access to a neutral item or one of the highly preferred items identified in the prior preference assessment. All students predominantly chose to complete the task in order to access a preferred item identified in the preference assessment. The results of this classroom intervention validated the results of the preference assessments. The findings of this study provide preliminary support for the use of videoconferencing equipment when supporting teaching personnel during common educational assessments.     

Using a cultural framework to assess the nutrition influences in relation to birth outcomes among African American women of childbearing age: application of the PEN-3 theoretical model

The purpose is to present the process and results of focus groups conducted to access information for the design of a healthy eating curriculum to reduce maternal nutritional risks and enhance protective factors among African American women in relation to birth outcomes. Sixteen younger (19 to 25 years) and 20 older African American women (45 to 60 years), respectively, participated. The PEN-3 model, (Airhihenbuwa, 1995, 1999) guided the focus groups. Most women stated that culture and family relationships impacted their food choices. Younger women expressed creativity with recipes and presented a desire to be more involved with preparing foods. Older women expressed eagerness to teach family-centered culinary skill-building classes. Both groups of women acknowledged time and budget barriers, identified the prevalence of lactose intolerance, and recognized that large grocery stores that offered food variety were not located in their community. Health professionals are encouraged to consider these findings while designing interventions targeting young African American women's nutrition in relation to birth outcomes.