Potassium channel gene associations with joint processing speed and white matter impairments in schizophrenia.

Patients with schizophrenia show decreased processing speed on neuropsychological testing and decreased white matter integrity as measured by diffusion tensor imaging, two traits shown to be both heritable and genetically associated indicating that there may be genes that influence both traits as well as schizophrenia disease risk. The potassium channel gene family is a reasonable candidate to harbor such a gene given the prominent role potassium channels play in the central nervous system in signal transduction, particularly in myelinated axons. We genotyped members of the large potassium channel gene family focusing on putatively functional single nucleotide polymorphisms (SNPs) in a population of 363 controls, 194 patients with schizophrenia spectrum disorder (SSD) and 28 patients with affective disorders with psychotic features who completed imaging and neuropsychological testing. We then performed three association analyses using three phenotypes - processing speed, whole-brain white matter fractional anisotropy (FA) and schizophrenia spectrum diagnosis. We extracted SNPs showing an association at a nominal P value of <0.05 with all three phenotypes in the expected direction: decreased processing speed, decreased FA and increased risk of SSD. A single SNP, rs8234, in the 3' untranslated region of voltage-gated potassium channel subfamily Q member 1 (KCNQ1) was identified. Rs8234 has been shown to affect KCNQ1 expression levels, and KCNQ1 levels have been shown to affect neuronal action potentials. This exploratory analysis provides preliminary data suggesting that KCNQ1 may contribute to the shared risk for diminished processing speed, diminished white mater integrity and increased risk of schizophrenia.

Zinc: an underappreciated modulatory factor of brain function.

The divalent cation, zinc is the second most abundant metal in the human body and is indispensable for life. Zinc concentrations must however, be tightly regulated as deficiencies are associated with multiple pathological conditions while an excess can be toxic. Zinc plays an important role as a cofactor in protein folding and function, e.g. catalytic interactions, DNA recognition by zinc finger proteins and modulation ion channel activity. There are 24 mammalian proteins specific for zinc transport that are subdivided in two groups with opposing functions: ZnT proteins reduce cytosolic zinc concentration while ZIP proteins increase it. The mammalian brain contains a significant amount of zinc, with 5-15% concentrated in synaptic vesicles of glutamatergic neurons alone. Accumulated in these vesicles by the ZnT3 transporter, zinc is released into the synaptic cleft at concentrations from nanomolar at rest to high micromolar during active neurotransmission. Low concentrations of zinc modulate the activity of a multitude of voltage- or ligand-gated ion channels, indicating that this divalent cation must be taken into account in the analysis of the pathophysiology of CNS disorders including epilepsy, schizophrenia and Alzheimer's disease. In the context of the latest findings, we review the role of zinc in the central nervous system and discuss the relevance of the most recent association between the zinc transporter, ZIP8 and schizophrenia. An enhanced understanding of zinc transporters in the context of ion channel modulation may offer new avenues in identifying novel therapeutic entities that target neurological disorders.

Measuring taste impairment in epidemiologic studies: the Beaver Dam Offspring Study.

Taste or gustatory function may play an important role in determining diet and nutritional status and therefore indirectly impact health. Yet there have been few attempts to study the spectrum of taste function and dysfunction in human populations. Epidemiologic studies are needed to understand the impact of taste function and dysfunction on public health, to identify modifiable risk factors, and to develop and test strategies to prevent clinically significant dysfunction. However, measuring taste function in epidemiologic studies is challenging and requires repeatable, efficient methods that can measure change over time. Insights gained from translating laboratory-based methods to a population-based study, the Beaver Dam Offspring Study (BOSS) will be shared. In this study, a generalized labeled magnitude scale (gLMS) method was used to measure taste intensity of filter paper disks saturated with salt, sucrose, citric acid, quinine, or 6-n-propylthiouracil, and a gLMS measure of taste preferences was administered. In addition, a portable, inexpensive camera system to capture digital images of fungiform papillae and a masked grading system to measure the density of fungiform papillae were developed. Adult children of participants in the population-based Epidemiology of Hearing Loss Study in Beaver Dam, Wisconsin, are eligible for this ongoing study. The parents were residents of Beaver Dam and 43-84 years of age in 1987-1988; offspring ranged in age from 21-84 years in 2005-2008. Methods will be described in detail and preliminary results about the distributions of taste function in the BOSS cohort will be presented.

Test-retest reliability of the San Diego Odor Identification Test and comparison with the brief smell identification test.

This study described the San Diego Odor Identification Test (SDOIT) reliability and compared the SDOIT and the Brief Smell Identification Test (B-SIT). Ninety participants aged 50-70 years completed this 2-visit olfaction study. During visit 1, the SDOIT and B-SIT were administered according to standard protocols. Three weeks later, participants returned to retake the SDOIT. The SDOIT score was the total number of odorants correctly identified out of 8 odorants presented, and olfactory impairment was defined as correctly identifying less than 6 odorants. The B-SIT score was the total number of odorants correctly identified out of 12 odorants presented, and participants correctly identifying less than 9 odorants were categorized as abnormal. The SDOIT reliability was high (concordance correlation coefficient = 0.85, 95% confidence interval [CI] = 0.79-0.91). The same score was obtained on retest for 73% of participants, whereas 18% improved, and 9% declined. Test-retest agreement was 96% for the SDOIT; 4% improved from impaired at visit 1 to unimpaired at visit 2. Overall, SDOIT impairment classification and B-SIT abnormal classification agreed in 96% of participants (kappa = 0.81, 95% CI = 0.63-0.99). In conclusion, the SDOIT showed good test-retest reliability. Agreement for impaired/abnormal olfaction was demonstrated for the SDOIT and the B-SIT.

Diphtheria and hearing loss.

OBJECTIVE: To determine if infectious diseases usually experienced in childhood have an effect on hearing ability later in life. METHODS: The Epidemiology of Hearing Loss Study (N = 3,753) is a population-based study of age-related hearing loss in adults aged 48 to 92 years in Beaver Dam, Wisconsin. As part of this study, infectious disease history was obtained and hearing was tested using pure-tone audiometry. Hearing loss was defined as a pure-tone average of thresholds at 500 Hz, 1,000 Hz, 2,000 Hz, and 4,000 Hz greater than 25 decibels hearing level in either ear. RESULTS: After adjusting for confounders, only a history of diphtheria (n = 37) was associated with hearing loss (odds ratio [OR] 2.79; 95% confidence interval [CI] 1.05, 7.36). There was no relationship between hearing loss and history of chickenpox, measles, mumps, pertussis, polio, rheumatic fever, rubella, or scarlet fever. Only two participants with a history of diphtheria and hearing loss reported having a hearing loss before age 20. CONCLUSIONS: Diphtheria in childhood may have consequences for hearing that do not become apparent until later in life. A possible biological mechanism for a diphtheria effect on hearing ability exists: The toxin produced by the Corynebacterium diphtheriae bacteria can cause damage to cranial nerves and therefore may affect the auditory neural pathway. These data may have important implications for areas facing a resurgence of diphtheria cases.

Faculty practice: how it enhances teaching.

This article is a presentation of the two authors' views on faculty practice and how both have operationalized the practice option. Both describe how the practice option has positively affected their teaching and their students' learning in a university baccalaureate nursing program located in the midwestern United States. The authors are full-time, master's prepared faculty members who have been in the faculty practice track for 2 years. Both teach in the junior year of a 4-year baccalaureate program. The first author (D.M.G.) is a staff nurse who works in a community hospital and serves on the hospital's clinical nursing research committee. The second author (C.R.S.) is a clinical research nurse coordinator who performs and manages pharmaceutical trials at multiple inpatient and outpatient locations. In this article, the authors examine faculty practice in general and the various models currently used. In addition, they explain their individual academic positions, the duties and responsibilities accompanying each of their practice roles, and the integration of those practice experiences into their clinical and classroom learning.