Evidence for reduced cerebellar volumes in trichotillomania.

BACKGROUND: Limited knowledge exists regarding the neurobiology of trichotillomania (TTM). Cerebellum (CBM) volumes were explored, given its role in complex, coordinated motor sequences. METHODS: Morphometric magnetic resonance imaging (MRI) scans were obtained for 14 female subjects with DSM-IV diagnoses of TTM and 12 age-, education-, and gender-matched normal control (NC) participants. Parcellation was performed utilizing a recently developed methodology to measure subterritory volumes of the CBM. Regions were defined based on knowledge of the structural and functional subunits of the CBM. RESULTS: As predicted, significant group differences were reported for CBM raw cortical volumes (p = .008) that survived correction for total brain volume (TBV; p = .037) and head circumference (HC; p = .011). A priori and post hoc group raw volume comparisons for CBM subterritories and functional clusters revealed many significant differences. However, most differences failed to withstand correction for total CBM volumes (TCV). Smaller volumes were consistently reported for the TTM versus NC cohorts. Total Massachusetts General Hospital Hair Pulling Scale (MGHHPS) scores were significantly inversely correlated with left primary sensorimotor cluster volumes (p = .008), with smaller volumes associated with more severe TTM symptoms. CONCLUSIONS: These findings implicate the CBM in the neurobiology of TTM, with reduced subterritory volumes reported for the TTM versus NC groups.     

Morphogenetic adaptation of the looping embryonic heart to altered mechanical loads.

The biophysical mechanisms that drive and regulate cardiac looping are not well understood, but mechanical forces likely play a central role. Previous studies have shown that cardiac torsion, which defines left-right directionality, is caused largely by forces exerted on the heart tube by a membrane called the splanchnopleure (SPL). Here we show that, when the SPL is removed from the embryonic chick heart, torsion is initially suppressed. Several hours later, however, normal torsion is restored. This delayed torsion coincides with increased myocardial stiffness, especially on the right side of the heart. Exposure to the myosin inhibitor Y-27632 suppressed both responses, suggesting that the delayed torsion is caused by an abnormal cytoskeletal contraction. This hypothesis is supported further by computational modeling. These results suggest that the looping embryonic heart has the ability to adapt to changes in the mechanical environment, which may play a regulatory role during morphogenesis.     

Chemoprevention of melanoma: an unexplored strategy.

The incidence and mortality of melanoma has continued to increase steeply-faster than most other preventable cancers in the United States. Current sun protection strategies have yet to reduce this increased incidence and mortality. Chemoprevention, defined as the use of natural or synthetic agents to delay, reverse, suppress, or prevent premalignant molecular or histologic lesions from progressing to invasive cancer, has become an important area in cancer research. Melanoma, with its associated risk factors and its known precursors or premalignant lesions, should lend itself well to chemoprevention. Prerequisites for this research should include determination of the molecular mechanisms of ultraviolet (UV) melanomagenesis; use of animal models to test candidate prevention agents; use of molecular and histologic markers as surrogate end point markers; collection of epidemiological, basic science, or in vitro data on potential chemoprevention candidate drugs; and selection of a high-risk patient population in which to carry out clinical chemoprevention trials. Preliminary data available in all these areas are reviewed. Possible mechanisms and molecular targets for the chemoprevention of UV-induced melanoma are discussed. This recent information should stimulate research in the chemoprevention of melanoma.     

Where's the Beef? The Promise and the Reality of Clinical Documentation

Physician-generated emergency department clinical documentation (information obtained from clinician observations and summarized decision processes inclusive of all manner of electronic systems capturing, storing, and presenting clinical documentation) serves four purposes: recording of medical care and communication among providers; payment for hospital and physician; legal defense from medical negligence allegations; and symptom/disease surveillance, public health, and research functions. In the consensus development process described by Handler, these objectives were balanced with the consideration of efficiency, often evaluated as physician time and clinical documentation system costs, in recording the information necessary for their accomplishment. The consensus panel session participants and authors recommend that 1) clinical documentation be electronically retrievable; 2) selection and implementation be evidence-based and grounded on valid metrics (research is needed to identify these metrics); 3) the user interface be crafted to promote clinical excellence through high-quality information collection and efficient charting techniques; 4) the priorities for integration of clinical information be standardized and implemented within enterprises and across health and information systems; 5) systems use accepted standards for bidirectional, real-time clinical data exchange, without limiting the location or number of simultaneous users; 6) systems fully utilize existing electronic sources of specific patient information and general medical knowledge; 7) systems automatically and reliably capture appropriate data that support electronic billing for emergency department services; and 8) systems promote bedside documentation and mobile access.     

Mapping the social and physical contexts of physical activity across adolescence using ecological momentary assessment

BACKGROUND: Research has sought to understand how environmental factors influence adolescent physical activity, yet little is known about where and with whom adolescents are physically active. PURPOSE: This study used electronic ecological momentary assessment (e.EMA) to map the social and physical contexts of exercise and walking across adolescence. Differences in physical activity contexts by gender, grade in school, day of the week, and season were examined. METHODS: Twice a year between 9th and 12th grade, 502 adolescents (51% female) of mixed ethnicity (55% White) participated in 4-day e.EMA intervals (Thursday-Sunday) where their primary activity (e.g., exercise, TV, homework), social company (e.g., friends, family, class), and physical location (e.g., home, school, outdoors) were assessed every 30 (+/-10) min during waking hours. RESULTS: Overall, greater proportions of exercise and walking were reported with friends, outdoors, and at school. However, boys were more likely to report exercising and walking in outdoor locations than girls. Exercising with classmates, family, and at school decreased across high school. Walking with family, friends, and outdoors also decreased. On weekdays compared to weekends, students reported a greater proportion of their exercise and walking at school. Students were more likely to report exercising and walking outdoors in the fall and the spring than in the winter. CONCLUSION: e.EMA showed that the social and physical contexts of adolescent exercise and walking vary as a function of gender, grade in school, day of the week, and season. Understanding the contexts of physical activity during the high school years can be helpful in designing interventions during adolescence.     

Differential generation of class I H-2D- versus H-2K-restricted cytotoxicity against a demyelinating virus following central nervous system infection

Despite the fact that both H-2K and D molecules are up-regulated in the central nervous system (CNS) following Theiler's murine encephalomyelitis virus (TMEV) infection, resistance in this virus model of multiple sclerosis maps exclusively to D. To address this paradox, we examined the ability of the K and D molecules to present viral antigens to cytotoxic T lymphocytes (CTL). Whereas no virus-specific CTL were detected in the CNS of susceptible B10.Q and B10.S mice 7 days post-infection, D-restricted CTL were identified readily in the CNS of resistant B10 animals. There was no evidence of K-restricted CTL in the CNS of B10 mice at day 7 post-infection. The presence of both K- and D-restricted virus-specific CTL in the spleen of immunized B10 mice demonstrates that the exclusive use of D molecules by CTL in the CNS of mice 7 days post-infection is not due to the inability of the K molecules to present viral peptides to lymphocytes. We conclude that the prominent role of the D locus in determining resistance or susceptibility to TMEV-induced demyelination is determined by factors governing the regulation of the immune response, and not by the presence or absence of CTL precursors capable of recognizing viral peptides presented by the K and D antigen-presenting molecules, or by differences in the ability of the K and D molecules to present viral peptides.     

Is there disproportionate impairment in semantic or phonemic fluency in schizophrenia?

Phonemic and semantic fluency involve the capacity to generate words beginning with particular letters or belonging to particular categories, respectively. The former has been associated with frontal lobe function and the latter with temporoparietal function, but neuroimaging studies indicate overlap of underlying neural networks. Schizophrenia patients may experience disproportionate semantic fluency impairment owing to abnormal semantic organization; however, executive dysfunction in schizophrenia suggests possible disproportionate phonemic fluency impairment. Moreover, little is known about the diagnostic specificity of either verbal fluency deficit to schizophrenia or their stability over time. We examined 83 schizophrenia patients, 15 bipolar disorder patients, and 83 normal controls. Both fluency types were impaired in schizophrenia patients. Schizophrenia patients as a whole manifested disproportionate semantic fluency impairment relative to bipolar disorder patients, but only a subset of schizophrenia patients manifested disproportionate semantic fluency impairment relative to controls. Few characteristics, except to some extent paranoid-nonparanoid subtype, meaningfully differentiated schizophrenia patients with and without this disproportionate impairment. Verbal fluency measures were moderately stable over a 4-year period in schizophrenia patients and controls (.48 < rs < .79). These results mirror a literature that overall suggests a small degree of disproportionate semantic fluency impairment in schizophrenia, but also some heterogeneity in fluency deficits.     

Advances in the evaluation and treatment of the infertile man

Numerous advances in technology have been made in the last several years in the diagnosis and treatment of the infertile man. Using case presentations, this article highlights these important new developments and reviews the basics of a comprehensive male infertility evaluation. The use of ultrasound as a critical, indispensable, yet noninvasive tool in the evaluation of possible male reproductive tract obstruction is discussed. Since assisted reproductive techniques (ARTs) have be come increasingly important in the management of the otherwise untreatable infertile man, specialized testing of sperm function, e.g., the sperm penetration assay (SPA), and strict morphology assessment are often useful prior to the initiation of some of these assisted reproductive procedures such as intrauterine insemination (IUI) or in vitro fertilization (IVF). Testicular touch preparation cytology and image analysis are also important additions to routine testicular biopsy for quantifying the extent of spermatogenesis. Finally, the revolutionary micromanipulation procedure of intracytoplasmic sperm injection (ICSI) has forever changed the practice of andrology by enabling men previously thought to be irreversibly infertile the chance to initiate their own biologic pregnancy.     

Relationship between refractive error and monochromatic aberrations of the eye.

PURPOSE: To examine the relationship between ametropia and optical aberrations in a population of 200 normal human eyes with refractive errors spanning the range from +5.00 to -10.00 D. METHODS: Using a reduced-eye model of ametropia, we tested the hypothesis that the optical system of the eye is uncorrelated with the degree of ametropia. These predictions were evaluated experimentally with a Shack-Hartmann aberrometer that measured the monochromatic aberrations across the central 6 mm of the dilated pupil in well-corrected, cyclopleged eyes. RESULTS: Optical theory predicted, and control experiments on a model eye verified, that Shack-Hartmann measurements of spherical aberration will vary with axial elongation of the eye even if the dioptric components of the eye are fixed. Contrary to these predictions, spherical aberration was not significantly different from emmetropic eyes. Root mean square of third-order aberrations, fourth-order aberrations, and total higher aberrations (third to 10th) in myopic and hyperopic eyes were also uncorrelated with refractive error. Astigmatic eyes tended to have larger total higher-order aberrations than nonastigmatic eyes. CONCLUSIONS: We conclude that a reduced-eye model of myopia assuming fixed optical parameters and variable axial length is not tenable.