Successful hematopoietic stem cell transplantation for Niemann-Pick disease type B

Histocompatible hematopoietic stem cell transplantation (HSCT) was conducted on a 4.5-year-old girl with Niemann-Pick disease type B. The donor was her unaffected brother. At the time of transplantation, she had severe pulmonary disease. After her first HSCT, she developed graft failure. Five years after her second HSCT, her sphingomyelinase levels are within normal levels, she has no pulmonary symptoms, and aside from persistent graft versus host disease, she is doing well.     

Neural coding of distinct statistical properties of reward information in humans

Brain processing of reward information is essential for complex functions such as learning and motivation. Recent primate electrophysiological studies using concepts from information, economic and learning theories indicate that the midbrain may code two statistical parameters of reward information: a transient reward error prediction signal that varies linearly with reward probability and a sustained signal that varies highly non-linearly with reward probability and that is highest with maximal reward uncertainty (reward probability = 0.5). Here, using event-related functional magnetic resonance imaging, we disentangled these two signals in humans using a novel paradigm that systematically varied monetary reward probability, magnitude and expected reward value. The midbrain was activated both transiently with the error prediction signal and in a sustained fashion with reward uncertainty. Moreover, distinct activity dynamics were observed in post-synaptic midbrain projection sites: the prefrontal cortex responded to the transient error prediction signal while the ventral striatum covaried with the sustained reward uncertainty signal. These data suggest that the prefrontal cortex may generate the reward prediction while the ventral striatum may be involved in motivational processes that are useful when an organism needs to obtain more information about its environment. Our results indicate that distinct functional brain networks code different aspects of the statistical properties of reward information in humans.     

Reading, hearing, and the planum temporale

Many neuroimaging studies of single-word reading have been carried out over the last 15 years, and a consensus as to the brain regions relevant to this task has emerged. Surprisingly, the planum temporale (PT) does not appear among the catalog of consistently active regions in these investigations. Recently, however, several studies have offered evidence suggesting that the left posteromedial PT plays a role in both speech production and speech perception. It is not clear, then, why so many neuroimaging studies of single-word reading--a task requiring speech production--have tended not to find evidence of PT involvement. In the present work, we employed a high-powered rapid event-related fMRI paradigm involving both single pseudoword reading and single pseudoword listening to assess activity related to reading and speech perception in the PT as a function of the degree of spatial smoothing applied to the functional images. We show that the speech area of the PT [Sylvian-parietal-temporal (Spt)] is best identified when only a moderate (5 mm) amount of spatial smoothing is applied to the data before statistical analysis. Moreover, increasing the smoothing window to 10 mm obliterates activation in the PT, suggesting that failure to find PT activation in past studies may relate to this factor.     

Training Latin American primary care physicians in the WPA module on depression: results of a multicenter trial

BACKGROUND: In order to improve care for people with depressive disorders and to reduce the increasing burden of depression, the American Regional Office of the World Health Organization has launched a major region-wide initiative. A central part of this effort was directed to the primary care system where the diagnosis and treatment of depression are deficient in many countries. This study evaluated the materials developed by the World Psychiatric Association in a training program on depression among primary care physicians by measuring changes in their knowledge, attitudes, and practice (KAP). METHOD: One hundred and seven physicians and 6174 patients from five Latin American countries participated in the trial. KAP were assessed 1 month before and 1 month following the training program. In addition, the presence of depressive symptoms was measured in patients who visited the clinic during a typical week at both times using the Zung Depression Scale and a DSM-IV/ ICD-10 major depression checklist. RESULTS: The program slightly improved knowledge about depression and modified some attitudes, but had limited impact on actual practice. There was no evidence that the diagnosis of depression was made more frequently, nor was there an improvement in psychopharmacological management. The post-training agreement between physician diagnosis and that based on patient self-report remained low. The physicians, however, seemed more confident in treating depressed patients after training, and referred fewer patients to psychiatrists. CONCLUSIONS: Traditional means of training primary care physicians in depression have little impact on clinical practice regardless of the quality of the teaching materials.     

The Inventory of College Students' Recent Life Experiences: A decontaminated hassles scale for a special population

The development and validation of a new decontaminated hassles measure, the Inventory of College Students' Recent Life Experiences, are described. An initial pool of 85 items was administered to 100 undergraduates along with the Perceived Stress Scale. Forty-nine items were selected based on significant correlations against the Perceived Stress Scale. The alpha reliability of the resultant final form of the Inventory of College Students' Recent Life Experiences and its correlation against the Perceived Stress Scale were both high. In a separate cross-replication sample of 108 undergraduates, the alpha reliability of the Inventory and its correlation against the Perceived Stress Scale showed little shrinkage. Furthermore, separate analyses for male and female subjects supported the reliability and validity of the Inventory of College Students' Recent Life Experiences across gender. Factor analysis of the Inventory yielded seven interpretable factors. Intercorrelations among subscales based on these factors were generally modest, though in all cases significant, suggesting that the Inventory is relatively free of contamination by psychological distress.The work reported was facilitated by a grant from the Social Sciences and Humanities Research Council of Canada's Small Grant Program, administered by the Office of Research Administration, York University. The authors gratefully acknowledge the helpful comments of Dr. Norman S. Endler.     

Fluorescence polarization of DPH-labeled cells adsorbing viruses and its diagnostic potential

Summary Mammalian or avian cells were laboled with a fluorescent probe DPH (1,6-diphenyl-1,3,5-hexatriene). Within a few minutes after adsorption of various naked and enveloped viruses, the degree of fluorescence polarization (P) of the DPH embedded in the adsorbing cells as measured at 37° C, was reduced, a finding indicating a decrease in the microviscosity of the lipids in the cell membrane. This change of fluidity was proportional to the concentration of the adsorbing virus and could be abolished or inhibited by homologous specific antiviral sera, but not by heterologous sera. Potential use of fluorescence polarization tests is described for titration of virus concentration, as well as for serological identification of a virus.With 5 Figures     

JC virus chromogenic in situ hybridization in brain biopsies from patients with and without PML.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by the JC polyoma virus. Electron microscopy and immunohistochemistry are the traditional methods of confirming the presence of the virus in brain biopsies from these patients. We studied the brain biopsies from 7 patients with PML and 6 patients without PML with chromogenic in situ hybridization (CISH) for the JC polyoma virus using a commercially available probe. The biopsies from the patients with the PML cases were proven to contain the JC polyoma virus by traditional and molecular methods. The CISH findings were compared with the known state of infection. All (7/7) of the biopsies from patients with PML were positive for the presence of polyoma virus by CISH, whereas the biopsies from patients without PML were uniformly negative. CISH seems to be a useful tool for the detection of the JC virus in brain biopsies from patients with PML, and is more accessible because a commercial probe is available.