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Phosphodiesterase type 2A (PDE2A) has received considerable interest as a molecular target for treating central nervous system diseases that affect memory, learning, and cognition. In this paper, the authors present the discovery of small molecules that have a novel modality of PDE2A inhibition. PDE2A possesses GAF-A and GAF-B domains and is a dual-substrate enzyme capable of hydrolyzing both cGMP and cAMP, and activation occurs through cGMP binding to the GAF-B domain. Thus, positive feedback of the catalytic activity to hydrolyze cyclic nucleotides occurs in the presence of appropriate concentrations of cGMP, which binds to the GAF-B domain, resulting in a "brake" that attenuates downstream cyclic nucleotide signaling. Here, we studied the inhibitory effects of some previously reported PDE2A inhibitors, all of which showed impaired inhibitory effects at a lower concentration of cGMP (70 nM) than a concentration effective for the positive feedback (4 μM). This impairment depended on the presence of the GAF domains but was not attributed to binding of the inhibitors to these domains. Notably, we identified PDE2A inhibitors that did not exhibit this behavior; that is, the inhibitory effects of these inhibitors were as strong at the lower concentration of cGMP (70 nM) as they were at the higher concentration (4 μM). This suggests that such inhibitors are likely to be more effective than previously reported PDE2A inhibitors in tissues of patients with lower cGMP concentrations.Background The purpose of this study is to assess the basic nutritional status (body metabolic index, BMI) and its risk factors in the patients suffering from chronic obstructive emphysema.Methods We described their demographic characteristics and comorbidity distribution of 2812 obstructive emphysema participants. Comparative analyzes were conducted on BMI with different demographic characteristics and comorbidities status, and comprehensive analysis on risk factors of excess weight and underweight in patients with different characters.Results The prevalence of underweight and excess weight was 17.57% and 31.54% respectively. There were differences in the distribution of three types of body mass index among patients with different demographic characteristics and different comorbidities. The study found that age of 50 ~ 64 (odds ratio, OR 2.99), tuberculosis (OR 2.41), and low TG (OR 2.32) were the risk factors about underweight. Low HDL-C (OR 4.15), nonalcoholic fatter liver (NAFLD) (OR 3.96), and age of 50 ~ 64 (OR 2.72) were closely related to the excess weight of participants.Conclusions This study highlighted the prevalence of underweight and excess weight in patients among emphysema. Comorbidities were important risk factors of underweight or excess weight among chronic emphysema patients. These findings were important for the prevention and treatment of chronic obstructive emphysema in the future.Objective To evaluate the effect of intrusive thoughts at diagnosis on quality of life, depressed mood and waking up with anxiety up to two years after radical prostatectomy.Method The Laparoscopic Prostatectomy Robot Open (LAPPRO) trial was a prospective, longitudinal multicenter study of 4003 patients undergoing radical prostatectomy. Questionnaire data were collected preoperatively, at 3, 12 and 24 months after surgery.Results The group of patients with intrusive thoughts at diagnosis had a statistically significant higher postoperative prevalence of impaired quality of life, depressed mood and waking up with anxiety as compared with the group of patients with no or minor intrusive thoughts. The highest risk increase for impaired QoL, depressed mood and waking up with anxiety ≥1/week was at 12, 3 and 3 months, respectively, where the three outcomes increased by 38% (RR 1.38; 95%CI 1.27-1.49)), 136% (RR 2.36; 95%CI 1.74-3.19)) and 165% (RR 2.65; 95%CI 2.22-3.17)), respectively.Conclusions The demonstrated link between intrusive thoughts and quality of life, depressed mood and waking up with anxiety deliver is further evidence to the idea that intrusive thoughts has potential as an endpoint for assessing and predicting psychological distress among men with prostate cancer diagnosis.Trial registration number ISRCTN06393679 (www.isrctn.com). Date of registration 07/02/2008. Retrospectively registered.Aim To investigate the effects of severe preeclampsia on the retinal nerve fiber layer (RNFL), macula thickness and ganglion cell density in pregnancy and postpartum, using High Definition Optical Coherence Tomography (HD-OCT).Material and Method The study group included 28 stable pregnant patients diagnosed with severe preeclampsia and the control group, 28 age and gestational week-matched healthy pregnant women. HD-OCT measurements were taken by the same researcher using a Cirrus HD-OCT device and were repeated at 8 weeks postpartum.ResultsThe mean systolic pressure, diastolic pressure, and intraocular perfusion pressure (IPP) values measured in pregnacy were determined to be higher in the preeclampsia group than in the control group (158.4 ± 7.3 vs.113.6 ± 6.8, 97.0 ± 5.7vs.73.8 ± 5.9 and 68.1 ± 3.9 vs.48.8 ± 3.3 mm Hg, respectively) (p  0.05 for all). No significant difference was determined postpartum between the groups in respect of mean systolic pressure, diastolic pressure, RNFL, macula thickness, ganglion cell analysis, and IOP values (114.3 ± 5.0 vs 114.6 ± 5.9 mm Hg, 74.6 ± 5.1 vs.74.5 ± 5.5 mm Hg, 96.0 ± 7.3 vs. 95.9 ± 6.7 µm, 228.2 ± 18.9 vs.234.5 ± 15.4 µm, 81.8 ± 8.0 vs. selleck 84.2 ± 4.6 µm, 14.1 ± 2.4 vs.13.8 ± 2, respectively) (p  less then  0.05 for all). Mean IPP during pregnancy was higher than the mean postpartum IPP in the severe pre-eclampsia group (68.1 ± 3.9 vs 49.1 ± 3.1 mm Hg) (p  less then  0.001).Conclusion This is the first study to have evaluated ganglion cell density of the retina, macula thickness, and RNFL using HD-OCT in severe pre-eclampsia cases, both during pregnancy and postpartum.Introduction For several years now, medicine has been benefiting from the contribution of nanoparticles (NPs) technology for both diagnosis and therapy. They can be used as adjuvants, being capable per se of immune-modulating activity, or as carriers for molecules to be transported to a specific target, eventually loaded with specific ligands favoring specific uptake.Areas covered The review focuses on experimental use of NPs as adjuvants/carriers for allergen immunotherapy (AIT). Human clinical trials conducted so far are discussed.Expert opinion Results of experimental studies and recent clinical trials support the use of NPs as carrier/adjuvant in AIT. Comparisons between NP-based and classical AIT are needed, to show the usefulness of the NP-based approach. However, there are still unsolved problems the persistence of non-degradable NPs with possible toxicological consequences, and the formation of the protein corona around the NPs, which could alter their activity and fate. Virus-like particles seem the most promising NPs for allergy treatment, as for other vaccines.

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