Inhibition of P53-related apoptosis had no effect on PrP(Sc) accumulation and prion disease incubation time

Results from several laboratories indicate that apoptosis via the P53 pathway is involved in prion disease pathogenesis. Prion diseases, among them scrapie and BSE, are a group of fatal neurodegenerative disorders associated with the conversion of PrP(C) to PrP(Sc), its conformational abnormal isoform. In this work, we tested whether an established anti-apoptotic reagent, PFT, which has been shown in different systems to inhibit P53 activity, can delay the outbreak of prion disease in infected animals. Our findings indicate that although PFT efficiently reduced caspase 3 expression in brains from scrapie sick hamsters, as well as inhibited PrP(Sc) accumulation in cell culture, it had no effect on disease incubation time or PrP(Sc) accumulation in vivo. We conclude that the P53 dependent apoptosis may not be an obligatory mechanism for prion disease-induced cell death.     

Adaptation without parameter change: Dynamic gain control in motion detection

Many sensory systems adapt their input-output relationship to changes in the statistics of the ambient stimulus. Such adaptive behavior has been measured in a motion detection sensitive neuron of the fly visual system, H1. The rapid adaptation of the velocity response gain has been interpreted as evidence of optimal matching of the H1 response to the dynamic range of the stimulus, thereby maximizing its information transmission. Here, we show that correlation-type motion detectors, which are commonly thought to underlie fly motion vision, intrinsically possess adaptive properties. Increasing the amplitude of the velocity fluctuations leads to a decrease of the effective gain and the time constant of the velocity response without any change in the parameters of these detectors. The seemingly complex property of this adaptation turns out to be a straightforward consequence of the multidimensionality of the stimulus and the nonlinear nature of the system.     

Distinguishing separable domains of cognition in human and animal studies: what separations are optimal for targeting interventions? A summary of recommendations from breakout group 2 at the measurement and treatment research to improve cognition in schizophrenia new approaches conference

At the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) New Approaches Conference, a discussion group focused on directions for future research that are critical to enhancing our understanding of the distinctions among key cognitive domains that have relevance for the development of cognition-enhancing interventions. One set of recommendations emphasizes the need for examining and optimizing the psychometric properties of relevant measurement paradigms from cognitive psychology and cognitive neuroscience. This step is critical to translating many notable advances in these basic fields into measures that would be appropriate for clinical trials. A second set of recommendations focuses on key directions for the development and application of animal models of cognitive processes that would greatly aid the discovery and preclinical testing of potential cognition-enhancing agents. As part of this process, the group noted several existing animal paradigms that have particular promise as measures in the key cognitive domains in schizophrenia identified by the MATRICS Neurocognition Committee.     

Video and CD-ROM as a training tool for performing neurologic examinations of 1-year-old children in a multicenter epidemiologic study

In lieu of traditional training of examiners to identify cerebral palsy on a neurologic examination at age 1 year, we proposed an alternative approach using a multimedia training video and CD-ROM we developed after a two-step validation process. We hypothesized that use of CD-ROM interactive training will lead to reliable and valid performance of the neurologic examination by both pediatric neurologists and nonpediatric neurologists. All examiners were asked to take one of six interobserver variability tests found on the CD-ROM on two occasions. In the first interobserver variability evaluation, 89% (531 of 594) of the responses agreed with the gold standard responses. Following annotated feedback to the examiners about the two items that had a 60% correct rate, the correct response rate rose to 93% (114 of 123). In the second interobserver variability evaluation, 88% (493 of 560) of the responses agreed with the gold standard responses. Following annotated feedback to the examiners about the four items that had a 70% correct rate, the correct response rate rose to 96% (104 of 108). Interactive CD-ROM examination training is an efficient and cost-effective means of training both neurologists and non-neurologists to perform structured neurologic examinations in 1-year-old children. It provides an effective means to evaluate interobserver variability, offers a route for feedback, and creates an opportunity to reevaluate variability, both immediately and at periodic intervals.     

Assessment of multiple sclerosis lesions with spherical harmonics: comparison of MR imaging and pathologic findings

Spherical harmonics (SH) were used to approximate the volume and three-dimensional geometry of multiple sclerosis (MS) lesions in deceased patients. The institutional ethical committee does not require its approval for studies involving pathologic specimens. Pathologic findings were used as the reference standard. In addition, lesion volume was measured with cylindrical approximation (CA). Volumetric comparisons of biases were based on summary statistics, Spearman correlation, Wilcoxon test, and two-way analysis of variance. Shape comparison metrics included mean distance and Dice similarity coefficient (DSC). Eight of 11 lesions had smaller biases with SH method (P < .001). Median biases with SH and CA did not differ significantly, as compared with pathologic findings (r = 1.00 vs 0.99, respectively). Variances of the biases were significantly smaller for SH (P = .04). Ranges of normalized distance and DSC were 0.1%-2.5% and 75%-96%, respectively. Mean DSC was significantly higher than 70% (P < .001). SH method provided unbiased lesion volume and added geometric information that may enable a better understanding of the pathogenesis and lesion evolution over time.     

Comparison of health care services for career soldiers throughout the world

Health care systems operate differently in every country and are products of historical and political factors. We compared health care systems for career soldiers in various countries with those of the Israel Defense Forces. Questionnaires requesting data regarding military health care services provided in their countries were sent to military attaches serving in Israel. The countries for which data were gathered include Argentina, Brazil, Chile, China, England, France, Finland, Germany, Hungary, Israel, Poland, Romania, Spain, and the United States. In most countries, career soldiers receive better health care services than civilians, especially in countries with military rule or under military threat.     

Sleep patterns in children and adolescents with functional recurrent abdominal pain: objective versus subjective assessment

Aim: To document objective sleep patterns of children and adolescents with functional recurrent abdominal pain (RAP), and to compare them with subjective sleep assessments and sleep patterns of healthy controls. Methods: Subjective sleep reports and sleep habit assessments were obtained from 25 adolescents with functional RAP and from 15 age- and gender-matched healthy volunteers, and were compared with continuous movement monitoring using the Actigraph for 7 consecutive days. Results: Abdominal pain before falling asleep was a unanimous complaint in the RAP group, with 29% reporting awakening from sleep by the pain. Only 25% of RAP patients assessed their sleep quality as good, compared with 87% of the control group. Objective sleep patterns measurements of the RAP patients were similar to those of the control group as well as to measurements observed in a large population of school-aged children and adolescents.

Conclusion: This study of a small group of children and adolescents with functional RAP provides objective evidence that their sleep patterns do not differ from those of normal peers, despite their subjective complaints.     

A new power Doppler ultrasound guiding technique for improved testicular sperm extraction

OBJECTIVE: To develop a noninvasive procedure that employs image processing of power Doppler ultrasound (PDUS) images of several orthogonal cross-sections of the testis to construct a three-dimensional (3D) mapping of preferential testicular regions in which spermatozoa are most likely to be found in nonobstructive azoospermic testes. DESIGN: Clinical study. SETTING: Ultrasound and andrology units in a large university-affiliated municipal hospital. PATIENT(S): Twenty-four nonobstructive azoospermic men. INTERVENTION(S): Before testicular sperm extraction was performed, PDUS images were acquired at seven cross-sections to reconstruct a 3D testicular vascularity index (TVI) matrix for spatial mapping of testicular regions in which spermatozoa are most likely to be found. The predictions based on TVI values of 107 regions were compared with the biopsy results. MAIN OUTCOME MEASURE(S): Prediction of presence or absence of spermatozoa by TVI values. RESULT(S): The prediction rate of the TVI matrix for the presence or absence of spermatozoa was 74.8%. The positive predicted value was 72%, negative predicted value was 75.6%, and specificity was 89.8%, but sensitivity was 47.3%. CONCLUSION(S): Our technique may obviate the need for arbitrary multiple biopsies that inflict some degree of damage upon testicular tissue and may increase the success rate of identifying viable spermatozoa in testicular tissue.     

Sertoli cell inactivation by cytotoxic damage to the human testis after cancer chemotherapy

OBJECTIVE: To assess Sertoli cell involvement in postchemotherapy azoospermia. DESIGN: Case report. SETTING: Teaching hospital. PATIENT(S): A 31-year-old azoospermic man who underwent cancer cytotoxic chemotherapy for non-Hodgkin's lymphoma at 13 years of age. INTERVENTION(S): Testicular biopsy specimens were obtained for sperm recovery in preparation for intracytoplasmic sperm injection. The biopsy specimens were evaluated by quantitative immunohistochemistry for the immature Sertoli cell markers cytokeratin 18 (CK-18) and D2-40. MAIN OUTCOME MEASURE(S): Extent of immature Sertoli cells. RESULT(S): A fraction of Sertoli cells (13%) in the atrophic tubules of this patient reexpressed the intermediate filament protein CK-18, which is normally absent after puberty, but not the D2-40 antigen, an Mr 40,000 a-linked membrane glycoprotein, whose loss of expression at puberty marks an irreversible step in Sertoli cell maturation. Tubules with normal spermatogenic progression lined by Sertoli cells negative for CK-18 were also observed. CONCLUSION(S): A fraction of Sertoli cells of this patient initially progressed to full maturation at puberty and reverted to a dedifferentiated state marked by reexpression of CK-18 as a consequence of chemotherapy. This inactivation of Sertoli cells caused by the cytotoxicity of the chemotherapeutic drugs may have contributed to the spermatogenic impairment and resulting infertility.