BackgroundA shorter duration of untreated psychosis has been associated with better prognosis in schizophrenia. In this study, we measured the duration mismatch negativity (dMMN), an event-related potential, and cognitive performance in subjects with at-risk mental state (ARMS), patients with first-episode or chronic schizophrenia, and healthy volunteers. The main interest was to determine if these neurocognitive measures predict progression to overt schizophrenia in ARMS subjects.Methodology/Principal FindingsSeventeen ARMS subjects, meeting the criteria of the Comprehensive Assessment of At-Risk Mental State, 31 schizophrenia patients (20 first-episode and 11 chronic) and healthy controls (N = 20) participated in the study. dMMN was measured by an auditory odd-ball paradigm at baseline. Neuropsychological performance was evaluated by the Japanese version of the Brief assessment of cognitive function of schizophrenia (BACS-J). The first-episode schizophrenia group showed significantly smaller amplitudes at frontal electrodes than did control subjects whereas chronic patients elicited smaller amplitudes at frontal and central electrodes, consistent with previous reports. During the follow-up period, 4 out of the 17 ARMS subjects transitioned to schizophrenia (converters) while 13 did not (non-converters). Specifically, dMMN amplitudes of non-converters did not differ from those of healthy controls, while converters showed significantly smaller dMMN amplitudes at some electrodes compared to control subjects. Converters performed significantly worse on tests of working memory, verbal fluency, and attention/information processing than did non-converters. There was a significant positive correlation between dMMN amplitudes at the frontal electrodes and verbal fluency, as measured by the BACS, in the AMRS subjects as a whole.Conclusions/SignificanceARMS subjects who later developed schizophrenia elicited smaller dMMN amplitudes to begin with, compared to non-converters. Notably, we have provided the first evidence for the ability of verbal fluency to predict dMMN amplitudes in ARMS subjects. These findings are expected to add to the efforts for early diagnosis and intervention of schizophrenia.

Detergent-resistant membrane microdomains in the plasma membrane, known as lipid rafts, have been implicated in various cellular processes. We report here that a low-density Triton X-100-insoluble membrane (detergent-resistant membrane; DRM) fraction is present in bovine rod photoreceptor outer segments (ROS). In dark-adapted ROS, transducin and most of cGMPphosphodiesterase (PDE) were detergent-soluble. When ROS membranes were exposed to light, however, a large portion of transducin localized in the DRM fraction. Furthermore, on addition of guanosine 5-3-O-(thio)triphosphate (GTP␥S) to light-bleached ROS, transducin became detergent-soluble again. PDE was not recruited to the DRM fraction after light stimulus alone, but simultaneous stimulation by light and GTP␥S induced a massive translocation of all PDE subunits to the DRM. A cholesterol-removing reagent, methyl-␤-cyclodextrin, selectively but partially solubilized PDE from the DRM, suggesting that cholesterol contributes, at least in part, to the association of PDE with the DRM. By contrast, transducin was not extracted by the depletion of cholesterol. These data suggest that transducin and PDE are likely to perform their functions in phototransduction by changing their localization between two distinct lipid phases, rafts and surrounding fluid membrane, on disc membranes in an activation-dependent manner.The phototransduction system in the photoreceptor rod outer segments (ROS) 1 of vertebrates is a typical G protein-mediated signaling system. In the prevailing model of phototransduction (1), light-excited rhodopsin interacts with the GDP form of the heterotrimeric G protein transducin and stimulates GDP-GTP exchange on its ␣-subunit (T ␣ ). GTP-T ␣ separates from its counterpart, the ␤␥ subunit of transducin (T ␤␥ ), and binds the inhibitory subunit (P ␥ ) of cGMP-phosphodiesterase (PDE), thus releasing the constraint of P ␥ on the catalytic subunits (P ␣ and P ␤ ) of PDE. The resulting decrease in cytoplasmic cGMP leads to the closure of cGMP-gated channels and the hyperpolarization of photoreceptor plasma membranes. Although the signaling cascade of ROS has been intensively studied during the past two decades, the whole mechanism has not yet been elucidated (for review see Ref.2).

The aims of this study were to evaluate in vivo the biological responses to implants composed of biodegradable anodized WE43 (containing magnesium yttrium, rare earth elements and zirconium; Elektron SynerMag®) magnesium alloy, monolithic WE43 magnesium alloy and poly-l-lactic acid (PLLA), which are commonly used materials in clinic settings, and to evaluate the effectiveness of the materials as bone screws. The effectiveness of the magnesium alloy implants in osteosynthesis was evaluated using a bone fracture model involving the tibia of beagle dogs. For the monolithic WE43 implants, radiological, and histological evaluation revealed that bone trabeculae around the implanted monolithic WE43 decreased because of an inflammatory response. However, there was no damage due to hydrogen gas or inflammatory response in the bone tissue around the anodized WE43 implants. After 4 weeks, all the PLLA implants (n = 3) had broken but the WE43 implants had not (n = 6). These results suggest that the WE43 implants had sufficient strength to fix bone fractures at load-bearing sites in orthopedic and oral maxillofacial surgery. Therefore, these biodegradable magnesium alloys are good candidates for replacing biodegradable polymers. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1282-1289, 2016.

No abstract

Introduction: We measured duration mismatch negativity (dMMN), P3a, and reorienting negativity (RON) in subjects with at-risk mental state (ARMS), patients with first-episode or chronic schizophrenia, and healthy volunteers. The main interest was to determine if these event-related potentials provide a biomarker associated with progression to overt schizophrenia in ARMS subjects.Methods: Nineteen ARMS subjects meeting the criteria of the Comprehensive Assessment of ARMS, 38 patients with schizophrenia (19 first-episode and 19 chronic), and 19 healthy controls participated in the study. dMMN, P3a, and RON were measured with an auditory odd-ball paradigm at baseline.Results: During the follow-up period (2.2 years), 4 out of the 19 ARMS subjects transitioned to schizophrenia (Converters) while 15 did not (non-Converters). dMMN amplitudes of Converters were significantly smaller than those of non-Converters at frontal and central electrodes before onset of illness. dMMN amplitudes of non-Converters did not differ from those of healthy controls, while Converters showed significantly smaller dMMN amplitudes compared to control subjects. RON amplitudes were also reduced at frontal and central electrodes in subjects with schizophrenia, but not ARMS. Converter subjects tended to show smaller RON amplitudes compared to non-Converters.Conclusions: Our data confirm that diminished dMMN amplitudes provide a biomarker, which is present before and after the development of psychosis. In this respect, RON amplitudes may also be useful, as suggested for the first time based on longitudinal observations.