Disparities in Short-Term Depression Among Prefrontal Cortex Synapses Sustain Persistent Activity in a Balanced Network.

Persistent activity of cue-representing neurons in the prefrontal cortex (PFC) is regarded as a neural basis for working memory. The contribution of short-term synaptic plasticity (STP) at different types of synapses comprising the cortical network to persistent activity, however, remains unclear. Characterizing STP at synapses of the rat PFC layer 5 network, we found that PFC synapses exhibit distinct STP patterns according to presynaptic and postsynaptic identities. Excitatory postsynaptic currents (EPSCs) from corticopontine (Cpn) neurons were well sustained throughout continued activity, with stronger depression at synapses onto fast-spiking interneurons than those onto pyramidal cells. Inhibitory postsynaptic currents (IPSCs) were sustained at a weaker level compared with EPSC from Cpn synapses. Computational modeling of a balanced network incorporating empirically observed STP revealed that little depression at recurrent excitatory synapses, combined with stronger depression at other synapses, could provide the PFC with a unique synaptic mechanism for the generation and maintenance of persistent activity.

Evidence for presynaptically silent synapses in the immature hippocampus.

Silent synapses show NMDA receptor (NMDAR)-mediated synaptic responses, but not AMPAR-mediated synaptic responses. A prevailing hypothesis states that silent synapses contain NMDARs, but not AMPARs. However, alternative presynaptic hypotheses, according to which AMPARs are present at silent synapses, have been proposed; silent synapses show slow glutamate release via a fusion pore, and glutamate spillover from the neighboring synaptic terminals. Consistent with these presynaptic hypotheses, the peak glutamate concentrations at silent synapses have been estimated to be ≪170 µM, much lower than those seen at functional synapses. Glutamate transients predicted based on the two presynaptic mechanisms have been shown to activate only high-affinity NMDARs, but not low-affinity AMPARs. Interestingly, a previous study has developed a new approach to distinguish between the two presynaptic mechanisms using dextran, an inert macromolecule that reduces the diffusivity of released glutamate: postsynaptic responses through the fusion pore mechanism, but not through the spillover mechanism, are potentiated by reduced glutamate diffusivity. Therefore, we reasoned that if the fusion pore mechanism underlies silent synapses, dextran application would reveal AMPAR-mediated synaptic responses at silent synapses. In the present study, we recorded AMPAR-mediated synaptic responses at the CA3-CA1 synapses in neonatal rats in the presence of blockers for NMDARs and GABAARs. Bath application of dextran revealed synaptic responses at silent synapses. GYKI53655, a selective AMPAR-antagonist, completely inhibited the unsilenced synaptic responses, indicating that the unsilenced synaptic responses are mediated by AMPARs. The dextran-mediated reduction in glutamate diffusivity would also lead to the activation of metabotropic glutamate receptors (mGluRs), which might induce unsilencing via the activation of unknown intracellular signaling. Hence, we determined whether mGluR-blockers alter the dextran-induced unsilencing. However, dextran application continued to produce significant synaptic unsilencing in the presence of a cocktail of the blockers for all subtypes of mGluRs. Our findings provide evidence that slowed glutamate diffusion produces synaptic unsilencing by enhancing the peak glutamate occupancy of pre-existing AMPARs, supporting the fusion pore mechanism of silent synapses.

Effect of an electronic alert on risk of contrast-induced acute kidney injury in hospitalized patients undergoing computed tomography.

BACKGROUND: Prophylaxis against contrast-induced acute kidney injury (AKI) in hospitalized patients is underused. We evaluated the impact of a computerized alert program for contrast-induced AKI for hospitalized patients undergoing contrast-enhanced computed tomography (CT). STUDY DESIGN: Quality improvement report. SETTING & PARTICIPANTS: 463 adult inpatients in a single center with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2). QUALITY IMPROVEMENT PLAN: We developed a computer alert program in which the responsible physician was alerted to a patient's risk of contrast-induced AKI in the form of a warning message box and was recommended to consider prophylactic measures for contrast-induced AKI when he or she ordered contrast-enhanced CT for patients with eGFR <60 mL/min/1.73 m(2). The intervention was applied simultaneously to all hospitalized patients from March 18, 2010. The hospital's contrast-induced AKI preventive guidelines included prehydration, posthydration, and oral N-acetylcysteine. OUTCOME & MEASUREMENTS: Use of prophylactic interventions, development of contrast-induced AKI. Contrast-induced AKI was defined as an increase in serum creatinine level (≥0.3 mg/dL or ≥50%) 24-72 hours after contrast medium exposure. RESULTS: 258 adult inpatients with eGFR <60 mL/min/1.73 m(2) were identified as undergoing contrast-enhanced CT before application of the computer alert program (from October 28, 2009, to March 17, 2010), and 205, after its application (from March 18, 2010, to August 5, 2010). Individuals in the postalert group received contrast-induced AKI prophylaxis more often than those in the prealert group (55% vs 25% for total prophylaxis; P < 0.001). The incidence of contrast-induced AKI was lower in the postalert group than in the prealert group (3% vs 10%; P = 0.02). LIMITATIONS: Observation bias; only 61.5% of participants were evaluated for contrast-induced AKI. CONCLUSIONS: Implementation of a computerized alert program in hospitalized patients was followed by increased use of prophylaxis and decreased risk of contrast-induced AKI.

The Use of Intravenous Zoledronate May Reduce Retear Rate after Rotator Cuff Repair in Older Female Patients with Osteoporosis: A First In-Human Prospective Study.

The objective of this study was to demonstrate the effect of intravenous (IV) zoledronate administration on rotator cuff healing, retear rate, and clinical outcomes in osteoporotic patients who underwent arthroscopic rotator cuff repair (ARCR) compared with patients with normal bone densities. In this prospective nonrandomized comparative study with propensity score matching, 30 patients who were postoperatively administered IV zoledronate (5 mg) were enrolled as the study group. The control group was matched using 1-to-2 propensity score matching. Radiologic and functional outcomes were evaluated 6 months after surgery. The functional scores in both groups exhibited significant improvement 6 months after surgery. Compared with Group 1 (osteoporosis with IV zoledronate injection) Group 2 (normal bone density) showed significant improvement in their University of California, Los Angeles (UCLA) shoulder score and Constant Shoulder Score (CSS) at 6 months postoperatively. The range of motion improved in both groups at 6 months after surgery. The retear rates according to Sugaya's classification (IV and V) were 13.3% (4 of 30 patients) and 25% (15 of 60 patients) in Groups 1 and 2, respectively, which established a non-inferiority of Group 1 to the control group. The retear pattern according to Rhee's classification in Group 1 was type I in all cases, whereas eight cases of type I and seven cases of type II patterns were observed in Group 2, which was statistically insignificant between the groups. In conclusion, anti-osteoporotic drug use is beneficial for patients with osteoporosis to reduce the failure rate after an ARCR of length > 2 cm, especially in older female patients. Moreover, thorough scrutiny is required to detect osteoporosis in patients with rotator cuff tears, especially in female patients.

[A case of allopurinol-induced granulomatous hepatitis with ductopenia and cholestasis].

Allopurinol-induced hypersensitivity syndrome is characterized by an idiosyncratic reaction involving multiple-organs, which usually begins 2 to 6 weeks after starting allopurinol. In rare cases, the adverse reactions to allopurinol are accompanied by a variety of liver injury, such as reactive hepatitis, granulomatous hepatitis, vanishing bile duct syndrome, or fulminant hepatic failure. Here we report a case with granulomatous hepatitis and ductopenia. A 69-year-old man with chronic renal failure, hyperuricemia, and previously normal liver function presented with jaundice, skin rash, and fever 2 weeks after taking allopurinol (200 mg/day). In histopathology, a liver biopsy specimen showed mild spotty necrosis of hepatocytes, marked cholestasis in parenchyma, and some granulomas in the portal area. There were vacuolar degeneration in the interlobular bile ducts and ductopenia in the portal tracts. Pathologic criteria strongly suggested the presence of allopurinol-induced granulomatous hepatitis with ductopenia and cholestasis. The patient fully recovered following the early administration of systemic corticosteroid therapy.

Factors affecting employment among people with mobility disabilities in South Korea.

Employment provides not only income but also opportunities for social participation. This is especially important for people with disabilities, but the employment of disabled people in many countries is subject to significant barriers. This study examines the actual state of employment of people with mobility disabilities in Korea and which characteristics affect employment among people with mobility disabilities. Analysis of responses to the Community Integration Questionnaire and independent variables among the study participants showed that the rate of employment among people with mobility disabilities (34.2%) is much lower than that of the general population (60.3%), with only 13.2% in full-time positions. Gender appeared to be a statistically significant factor influencing employment. Other demographic characteristics such as age, level of education and cohabitation did not influence employment in this study, but people with less severe disability had a higher probability of being employed. Disability acceptance appeared to be a vital factor in the process of vocational rehabilitation. The use of vocational rehabilitation services did not have a significant effect on employment. These results suggest that the role of the formal services system in the employment process of disabled people is insufficient.

[A case of recurrent pneumatosis cystoides intestinalis associated with recurrent pneumoperitoneum].

Pneumatosis cystoides intestinalis is an uncommon condition of unknown etiology, characterized by the presence of multiple gas filled cysts in the gastrointestinal tract. Many different causes of pneumatosis cystoides intestinalis have been proposed, including mechanical, pulmonary, and bacterial causes. Approximately 85% of cases are thought to be secondary to coexisting disorders of the gastrointestinal tract or the respiratory system. The condition has been associated with the therapeutic uses of lactulose, steroids, and various cancer chemotherapeutic regimens. Lactitol is a disaccharide analogue of lactulose which is available as a pure crystalline powder. There are three previous case reports suggestive of lactulose causing pneumatosis intestinalis. We report a case of recurrent pneumatosis cystoides intestinalis associated with benign recurrent pneumoperitoneum developed probably secondary to lactitol therapy.