Working memory maintenance of grasp-target information in the human posterior parietal cortex

Event-related functional magnetic resonance imaging was applied to identify cortical areas involved in maintaining target information in working memory used for an upcoming grasping action. Participants had to grasp with their thumb and index finger of the dominant right hand three-dimensional objects of different size and orientation. Reaching-to-grasp movements were performed without visual feedback either immediately after object presentation or after a variable delay of 2-12 s. The right inferior parietal cortex demonstrated sustained neural activity throughout the delay, which overlapped with activity observed during encoding of the grasp target. Immediate and delayed grasping activated similar motor-related brain areas and showed no differential activity. The results suggest that the right inferior parietal cortex plays an important functional role in working memory maintenance of grasp-related information. Moreover, our findings confirm the assumption that brain areas engaged in maintaining information are also involved in encoding the same information, and thus extend previous findings on working memory function of the posterior parietal cortex in saccadic behavior to reach-to-grasp movements.     

Anticipation of reward in a nonaversive differential conditioning paradigm and the brain reward system: an event-related fMRI study

Findings from animal as well as human neuroimaging studies suggest that reward delivery is associated with the activation of subcortical limbic and prefrontal brain regions, including the thalamus, the striatum, the anterior cingulate and the prefrontal cortex. The aim of the present study was to explore if these reward-sensitive regions are also activated during the anticipation of reinforcers that vary with regard to their motivational value. A differential conditioning paradigm was performed, with the presentation of a rewarded reaction time task serving as the unconditioned stimulus (US). Depending on their reaction time, subjects were given (or not given) a monetary reward, or were presented with a verbal feedback consisting of being fast or slow. In a third control condition no task needed to be executed. Each of the three conditions was introduced by a different visual cue (CS). Brain activation of 27 subjects was recorded using event-related functional magnetic resonance imaging. The results showed significant activation of the substantia nigra, thalamic, striatal, and orbitofrontal brain regions as well as of the insula and the anterior cingulate during the presentation of a CS signalling a rewarded task. The anticipation of a monetary reward produced stronger activation in these regions than the anticipation of positive verbal feedback. The results are interpreted as reflecting the motivation-dependent reactivity of the brain reward system with highly motivating stimuli (monetary reward) leading to a stronger activation than those less motivating ones (verbal reward).     

Ketoprofen controlled release from composite microcapsules for cell encapsulation: effect on post-transplant acute inflammation.

Cell encapsulation technology raises hopes in medicine and biotechnology. Encapsulated pancreatic islets is a promising approach for the final solution of Type 1 diabetes. Unfortunately, evidence of long-term encapsulated islet graft survival and functional competence lies behind expectancy. Failure was often ascribed to the lack of biocompatibility generating inflammatory response, or limited immunobarrier competence or hypoxia or finally, low beta-cell replication. In order to prevent severe inflammation at early stages after implantation, composite microcapsules were designed. Biodegradable microspheres containing ketoprofen were enveloped into the well established alginate/poly-L-ornithine/alginate capsules. Polyester microspheres were prepared, by solvent evaporation, and characterized for encapsulation efficiency, particle size and in vitro release. Biocompatibility and efficacy to prevent the inflammatory response were studied in vivo. Good encapsulation efficiency and the desired particle size were achieved. In vitro release studies evidenced a high burst effect probably due to a plasticizing effect of both water and ketoprofen. The composite systems showed good biocompatibility and capacity to completely avoid the inflammatory response and the pericapsular cell overgrowth. In conclusion, the inflammatory response in the immediate post-transplant period can be circumvented using multicompartment microcapsules releasing non-steroidal anti inflammatory drugs.     

Consistency of efficacy, patient acceptability, and nasal tolerability of fentanyl pectin nasal spray compared with immediate-release morphine sulfate in breakthrough cancer pain

ContextWe recently reported that fentanyl pectin nasal spray (FPNS) provides superior pain relief from breakthrough cancer pain (BTCP) compared with immediate-release morphine sulfate (IRMS), with significant effects by five minutes and clinically meaningful pain relief from 10 minutes postdose.ObjectivesTo report the consistency of efficacy, tolerability, and patient acceptability of FPNS vs. IRMS.MethodsPatients (n = 110) experiencing one to four BTCP episodes/day while taking ≥60 mg/day oral morphine (or equivalent) for background pain entered a double-blind, double-dummy (DB/DD), multiple-crossover study. Those who completed an open-label titration phase (n = 84) continued to a DB/DD phase; 10 episodes were randomly treated with FPNS and overencapsulated placebo or IRMS and nasal spray placebo (five episodes each). Pain intensity (PI) and pain relief scores were assessed. Patient acceptability scores were assessed at 30 and 60 minutes. Safety and tolerability were assessed by adverse events (AEs) and nasal assessments.ResultsPer-episode analysis revealed that FPNS consistently provided relief from pain more rapidly than IRMS; by 10 minutes, there were significant differences in PI difference scores and in the percentages of episodes showing clinically meaningful pain relief (P < 0.05). Overall acceptability scores were significantly greater for FPNS than for IRMS at 30 (P < 0.01) and 60 (P < 0.05) minutes. Patients were “satisfied/very satisfied” with the convenience (79.8%) and ease of use (77.2%) of FPNS. Only 4.7% of patients withdrew from titration because of AEs; no significant nasal effects were reported.ConclusionThis study demonstrates that FPNS is efficacious, well accepted, and well tolerated by patients with BTCP.     

Identification of New Natural CphA Metallo-β-Lactamases CphA4 and CphA5 in Aeromonas veronii and Aeromonas hydrophila Isolates from Municipal Sewage in Central Italy

Two new natural CphA metallo-β-lactamases, the CphA4 and CphA5 enzymes, were identified in water samples from municipal sewage in central Italy. Compared to CphA, the CphA4 and CphA5 enzymes showed numerous point mutations. These enzymes have a narrow spectrum of substrates focused on carbapenems only. CphA5 showed k_cat values about 40-, 12-, and 97-fold higher than those observed for CphA4 versus imipenem, ertapenem, and biapenem, respectively.