Neurocognitive impairment in relation to glutathione S-transferase enzyme polymorphisms among medulloblastoma patients

Background. Medulloblastoma is a type of brain cancer that accounts for approximately 7-8% of all intracranial tumors and 20-30% of pediatric brain tumors. It is the most common type of malignant brain tumor in childhood. It was reported that majority of survivors with medulloblastoma have social problems, endocrine deficits, and neurological complications. Furthermore, all had significant deficits in neurocognitive functioning. Glutathione S-transferases belong to a family of isoenzymes that catalyze the glutathione conjugation of a variety of electrophilic compounds. ^ Objective. We aimed to determine whether the development of neurocognitive impairment is associated with GST polymorphisms among children and adolescents diagnosed with medulloblastoma (MB) after radiation therapy. ^ Methods. A pilot study composing of 16 children and adolescents diagnosed with MB at Texas Children's Cancer Center was conducted. The t-test was used to determine if the GST polymorphisms were related to neurocognitive impairment and logistic regression was performed to explore association between GST polymorphisms and gender, age at diagnosis, race/ethnicity, and risk group. ^ Results. An association was observed between GSTT1 polymorphism and cognitive impairment one year after radiation and GSTM1 polymorphism two years after radiation. It was observed that patients with GSTT1 null genotype have lower performance IQ (p=0.03) and full scale IQ (p=0.02) one year after radiation and patients with GSTM1 null genotype have lower verbal IQ (p=0.02) two years after radiation. Patients under age 8 have a statistically non-significant higher risk of having not null genotypes compared to those older than age 8 (OR= 7.5, 95%CI: 0.62-90.65 and OR= 2.63, 95%CI: 0.30-23.00 for GSTT1 and GSTM1 respectively). ^ Conclusion. There was a significant association between GSTT1 polymorphism and cognitive impairment one year after radiation and between GSTM1 polymorphism and cognitive impairment two years after radiation. Further large scale studies may be needed to confirm this finding and to examine the underlying mechanism of neurocognitive impairments after treatment of medulloblastoma patients.^

Use of tabletop exercises for disaster preparedness training

Background. In public health preparedness, disaster preparedness refers to the strategic planning of responses to all types of disasters. Preparation and training for disaster response can be conducted using different teaching modalities, ranging from discussion-based programs such as seminars, drills and tabletop exercises to more complex operation-based programs such as functional exercises and full-scale exercises. Each method of instruction has its advantages and disadvantages. Tabletop exercises are facilitated discussions designed to evaluate programs, policies, and procedures; they are usually conducted in a classroom, often with tabletop props (e.g. models, maps or diagrams). ^ Objective. The overall goal of this project was to determine whether tabletop exercises are effective teaching modalities for disaster preparedness, with an emphasis on intentional chemical exposure. ^ Method. The target audience for the exercise was the Medical Reserve Brigade of the Texas State Guard, a group of volunteer healthcare providers and first responders who prepare for response to local disasters. A new tabletop exercise was designed to provide information on the complex, interrelated organizations within the national disaster preparedness program that this group would interact with in the event of a local disaster. This educational intervention consisted of a four hour multipart program that included a pretest of knowledge, lecture series, an interactive group discussion using a mock disaster scenario, a posttest of knowledge, and a course evaluation. ^ Results. Approximately 40 volunteers attended the intervention session; roughly half (n=21) had previously participated in a full scale drill. There was an 11% improvement in fund of knowledge between the pre- and post-test scores (p=0.002). Overall, the tabletop exercise was well received by those with and without prior training, with no significant differences found between these two groups in terms of relevance and appropriateness of content. However, the separate components of the tabletop exercise were variably effective, as gauged by written text comments on the questionnaire. ^ Conclusions. Tabletop exercises can be a useful training modality in disaster preparedness, as evidenced by improvement in knowledge and qualitative feedback on its value. Future offerings could incorporate recordings of participant responses during the drill, so that better feedback can be provided to them. Additional research should be conducted, using the same or similar design, in different populations that are stakeholders in disaster preparedness, so that the generalizability of these findings can be determined.^

Cerebellar mechanisms for motor learning: Testing predictions from a large-scale computer simulation

The cerebellum is the major brain structure that contributes to our ability to improve movements through learning and experience. We have combined computer simulations with behavioral and lesion studies to investigate how modification of synaptic strength at two different sites within the cerebellum contributes to a simple form of motor learning—Pavlovian conditioning of the eyelid response. These studies are based on the wealth of knowledge about the intrinsic circuitry and physiology of the cerebellum and the straightforward manner in which this circuitry is engaged during eyelid conditioning. Thus, our simulations are constrained by the well-characterized synaptic organization of the cerebellum and further, the activity of cerebellar inputs during simulated eyelid conditioning is based on existing recording data. These simulations have allowed us to make two important predictions regarding the mechanisms underlying cerebellar function, which we have tested and confirmed with behavioral studies. The first prediction describes the mechanisms by which one of the sites of synaptic modification, the granule to Purkinje cell synapses (gr → Pkj) of the cerebellar cortex, could generate two time-dependent properties of eyelid conditioning—response timing and the ISI function. An empirical test of this prediction using small, electrolytic lesions of the cerebellar cortex revealed the pattern of results predicted by the simulations. The second prediction made by the simulations is that modification of synaptic strength at the other site of plasticity, the mossy fiber to deep nuclei synapses (mf → nuc), is under the control of Purkinje cell activity. The analysis predicts that this property should confer mf → nuc synapses with resistance to extinction. Thus, while extinction processes erase plasticity at the first site, residual plasticity at mf → nuc synapses remains. The residual plasticity at the mf → nuc site confers the cerebellum with the capability for rapid relearning long after the learned behavior has been extinguished. We confirmed this prediction using a lesion technique that reversibly disconnected the cerebellar cortex at various stages during extinction and reacquisition of eyelid responses. The results of these studies represent significant progress toward a complete understanding of how the cerebellum contributes to motor learning. ^

Affect and cognition measures in preference-based decisions: Validity testing of the Ottawa Decisional Conflict Scale and a decision-specific anxiety measure with men eligible for prostate cancer screening

Background. At present, prostate cancer screening (PCS) guidelines require a discussion of risks, benefits, alternatives, and personal values, making decision aids an important tool to help convey information and to help clarify values. Objective: The overall goal of this study is to provide evidence of the reliability and validity of a PCS anxiety measure and the Decisional Conflict Scale (DCS). Methods. Using data from a randomized, controlled PCS decision aid trial that measured PCS anxiety at baseline and DCS at baseline (T0) and at two-weeks (T2), four psychometric properties were assessed: (1) internal consistency reliability, indicated by factor analysis intraclass correlations and Cronbach's α; (2) construct validity, indicated by patterns of Pearson correlations among subscales; (3) discriminant validity, indicated by the measure's ability to discriminate between undecided men and those with a definite screening intention; and (4) factor validity and invariance using confirmatory factor analyses (CFA). Results. The PCS anxiety measure had adequate internal consistency reliability and good construct and discriminant validity. CFAs indicated that the 3-factor model did not have adequate fit. CFAs for a general PCS anxiety measure and a PSA anxiety measure indicated adequate fit. The general PCS anxiety measure was invariant across clinics. The DCS had adequate internal consistency reliability except for the support subscale and had adequate discriminate validity. Good construct validity was found at the private clinic, but was only found for the feeling informed subscale at the public clinic. The traditional DCS did not have adequate fit at T0 or at T2. The alternative DCS had adequate fit at T0 but was not identified at T2. Factor loadings indicated that two subscales, feeling informed and feeling clear about values, were not distinct factors. Conclusions. Our general PCS anxiety measure can be used in PCS decision aid studies. The alternative DCS may be appropriate for men eligible for PCS. Implications: More emphasis needs to be placed on the development of PCS anxiety items relating to testing procedures. We recommend that the two DCS versions be validated in other samples of men eligible for PCS and in other health care decisions that involve uncertainty. ^

Development and preliminary validation of the cancer family impact scale for colorectal cancer

This study aimed to develop and validate The Cancer Family Impact Scale (CFIS), an instrument for use in studies investigating relationships among family factors and colorectal cancer (CRC) screening when family history is a risk factor. We used existing data to develop the measure from 1,285 participants (637 families) across the United States who were in the Johns Hopkins Colon Cancer Genetic Testing study. Participants were 94% white with an average age of 50.1 years, and 60% were women. None had a personal CRC history, and eighty percent had 1 FDR with CRC and 20% had more than one FDR with CRC. The study had three aims: (1) to identify the latent factors underlying the CFIS via exploratory factor analysis (EFA); (2) to confirm the findings of the EFA via confirmatory factor analysis (CFA); and (3) to assess the reliability of the scale via Cronbach's alpha. Exploratory analyses were performed on a split half of the sample, and the final model was confirmed on the other half. The EFA suggested the CFIS was an 18-item measure with 5 latent constructs: (1) NEGATIVE: negative effects of cancer on the family; (2) POSITIVE: positive effects of cancer on the family; (3) COMMUNICATE: how families communicate about cancer; (4) FLOW: how information about cancer is conveyed in families; and (5) NORM: how individuals react to family norms about cancer. CFA on the holdout sample showed the CFIS to have a reasonably good fit (Chi-square = 389.977, df = 122, RMSEA= 0.058 (.052-.065), CFI=.902, TLI=.877, GF1=.939). The overall reliability of the scale was α=0.65. The reliability of the subscales was: (1) NEGATIVE α = 0.682; (2) POSITIVE α = 0.686; (3) COMMUNICATE α = 0.723; (4) FLOW α = 0.467; and (5) NORM α = 0.732. ^ We concluded the CFIS to be a good measure with most fit levels over 0.90. The CFIS could be used to compare theoretically driven hypotheses about the pathways through which family factors could influence health behavior among unaffected individuals at risk due to family history, and also aid in the development and evaluation of cancer prevention interventions including a family component. ^

Psychosocial predictors of HIV testing behaviors among high risk heterosexuals

Though a lot of progress has been made in the treatment, prevention, and in increasing the knowledge and awareness of HIV/AIDS, the CDC reports that over 21% of the people infected with HIV are unaware of their HIV serostatus. Thirty-one percent of people infected with HIV are diagnosed late in the disease progression, often too late to prevent the transmission or the progression of HIV to AIDS. CDC has set a goal to increase by the year 2010, the number of people aware of the HIV serostatus by 5%. ^ This study examined the association between decision-making and risk-taking (assessed using the decision-making confidence and risk-taking scales of the Texas Christian University Self Rating Form) and HIV testing behaviors within a population of heterosexuals at risk for HIV infections living in Harris County, Texas (N=923). Data used in the study was obtained during the first cycle of the National HIV Behavioral Surveillance among heterosexuals at risk for HIV infection (NHBS-HET1), conducted from October, 2006 to June, 2007. Eighty percent of the study population reported testing for HIV at some point in their lives. The results showed that individuals who scored high (>3.3) on the decision-making confidence scale of the TCU/SRF were more likely to be tested for HIV when compared to those who scored low on the scale (OR= 2.02, 95% CI= 1.44–2.84), and that individuals who score low on the risk-taking scale of the TCU/SRF were more likely to have been tested for HIV when compared to those who scored high on the scale (OR= 1.65, 95% CI= 1.2–2.31). Several demographic factors were also assessed for their association with HIV testing behaviors. Only sex was found to be associated with HIV testing. ^ The findings suggest that risk-taking and decision-making are predictors of HIV testing behaviors such as prior HIV testing within heterosexuals living in high-risk areas of Houston, Texas, and that intervention designed to improve the risk-taking and decision-making attributes of this population might improve HIV testing within this population.^