Inhibition of human prolyl oligopeptidase activity by the Cyclotide Psysol 2 isolated from Psychotria solitudinum

Cyclotides are head-to-tail cyclized peptides comprising a stabilizing cystine-knot motif. To date, they are well known for their diverse bioactivities such as anti-HIV and immunosuppressive properties. Yet little is known about specific molecular mechanisms, in particular the interaction of cyclotides with cellular protein targets. Native and synthetic cyclotide-like peptides from Momordica plants are potent and selective inhibitors of different serine-type proteinases such as trypsin, chymotrypsin, matriptase, and tryptase-beta. This study describes the bioactivity-guided isolation of a cyclotide from Psychotria solitudinum as an inhibitor of another serine-type protease, namely, the human prolyl oligopeptidase (POP). Analysis of the inhibitory potency of Psychotria extracts and subsequent fractionation by liquid chromatography yielded the isolated peptide psysol 2 (1), which exhibited an IC50 of 25 μM. In addition the prototypical cyclotide kalata B1 inhibited POP activity with an IC50 of 5.6 μM. The inhibitory activity appeared to be selective for POP, since neither psysol 2 nor kalata B1 were able to inhibit the proteolytic activity of trypsin or chymotrypsin. The enzyme POP is well known for its role in memory and learning processes, and it is currently being considered as a promising therapeutic target for the cognitive deficits associated with several psychiatric and neurodegenerative diseases, such as schizophrenia and Parkinson's disease. In the context of discovery and development of POP inhibitors with beneficial ADME properties, cyclotides may be suitable starting points considering their stability in biological fluids and possible oral bioavailability

Paradoxical effects of Worrisome Thoughts Suppression: the influence of depressive mood

Thought suppression increases the persistence of unwanted idiosyncratic worries thoughts when individuals try to suppress them. The failure of suppression may contribute to the development and maintenance of emotional disorders. Depressive people seem particulary prone to engage in unsuccessful mental control strategies such as thought suppression. Worry has been reported to be elevated in depressed individuals and a dysphoric mood may also contribute for the failure of suppression. No studies examine, however, the suppression of worisome thoughts in individuals with depressive symptoms. To investigate the suppression effects of worrisome thoughts, 46 participants were selected according to the cut-off score of a depressive symptomatology scale and they were divided in two groups (subclinical and nonclinical group). All the individuals took part in an experimental paradigm of thought suppression. The results of the mixed factorial analysis of variance revealed an increased frequency of worrisome thoughts during the suppression phase on depending of the depressive symptoms. These findings confirm that depressive mood can reduce the success of suppression.info:eu-repo/semantics/publishedVersio

Preferred roles in treatment decision making among patients with cancer: A pooled analysis of studies using the control preferences scale

OBJECTIVES: To collect normative data, assess differences between demographic groups, and indirectly compare US and Canadian medical systems relative to patient expectations of involvement in cancer treatment decision making. STUDY DESIGN: Meta-analysis. METHODS: Individual patient data were compiled across 6 clinical studies among 3491 patients with cancer who completed the 2-item Control Preferences Scale indicating the roles they preferred versus actually experienced in treatment decision making. RESULTS: The roles in treatment decision making that patients preferred were 26% active, 49% collaborative, and 25% passive. The roles that patients reported actually experiencing were 30% active, 34% collaborative, and 36% passive. Roughly 61% of patients reported having their preferred role; only 6% experienced extreme discordance between their preferred versus actual roles. More men than women (66% vs 60%, P = .001) and more US patients than Canadian patients (84% vs 54%, P <.001) reported concordance between their preferred versus actual roles. More Canadian patients than US patients preferred and actually experienced (42% vs 18%, P <.001) passive roles. More women than men reported taking a passive role (40% vs 24%, P <.001). Older patients preferred and were more likely than younger patients to assume a passive role. CONCLUSIONS: Roughly half of the studied patients with cancer indicated that they preferred to have a collaborative relationship with physicians. Although most patients had the decision-making role they preferred, about 40% experienced discordance. This highlights the need for incorporation of individualized patient communication styles into treatment plans

Do bone mineral content and density determine fracture in children? A possible threshold for physical activity

BackgroundRelations between bone parameters, physical exertion, and childhood fractures are complex. We aimed to estimate the associations between fracture history and bone mineral content (BMC) and areal bone mineral density (aBMD) at 7 years of age, by levels of physical activity, as a proxy for trauma frequency.MethodsWe used data collected from 2,261 children of the Generation XXI birth cohort, assembled in 2005/6 in Porto, Portugal. At the age of 7 years (2012/4), fracture history, time spent per week in active play, and sports practice were reported by parents. Subtotal and lumbar spine (LS) BMC and aBMD were measured using whole-body dual-energy X-ray absorptiometry.ResultsBoys and girls in the highest categories of time spent in sports practice or active play generally had higher BMC and aBMD. Among girls, BMC and aBMD were protective of fracture only in the highest quarter of active play (>660 min/week)-odds ratios (OR; 95% confidence interval (95% CI)) for subtotal BMC=0.27 (0.11-0.67), subtotal aBMD=0.18 (0.06-0.49), and LS aBMD=0.41 (0.22-0.75). For boys in the highest quarter of sports practice (>240 min/week), subtotal and LS BMC were protective of fracture-OR=0.39 (0.16-0.98) and 0.51 (0.27-0.96), respectively.ConclusionIn prepubertal children, BMC and aBMD predicted fracture history only in the highest levels of physical activity.info:eu-repo/semantics/publishedVersio

How does gender influence the recognition of cardiovascular risk and adherence to self-care recommendations? : a study in polish primary care

Background: Studies have shown a correlation between gender and an ability to change lifestyle to reduce the risk of disease. However, the results of these studies are ambiguous, especially where a healthy lifestyle is concerned. Additionally, health behaviors are strongly modified by culture and the environment. Psychological factors also substantially affect engagement with disease-related lifestyle interventions. This study aimed to examine whether there are differences between men and women in the frequency of health care behavior for the purpose of reducing cardiovascular risk (CVR), as well as cognitive appraisal of this type of risk. We also aimed to identify the psychological predictors of engaging in recommended behavior for reducing the risk of cardiovascular disease after providing information about this risk in men and women. Methods: A total of 134 consecutive eligible patients in a family practice entered a longitudinal study. At initial consultation, the individual’s CVR and associated health burden was examined, and preventive measures were recommended by the physician. Self-care behavior, cognitive appraisal of risk, and coping styles were then assessed using psychological questionnaires. Six months after the initial data collection, the frequency of subjects’ self-care behavior was examined. Results: We found an increase in health care behavior after providing information regarding the rate of CVR in both sexes; this increase was greater for women than for men. Women followed self-care guidelines more often than men, particularly for preventive measures and dietary advice. Women were more inclined to recognize their CVR as a challenge. Coping style, cognitive appraisal, age, level of health behaviors at baseline and CVR values accounted for 48% of the variance in adherence to self-care guidelines in women and it was 52% in men. In women, total risk of CVD values were most important, while in men, cognitive appraisal of harm/loss was most important. Conclusions: Different predictors of acquisition of health behavior are encountered in men and women. Our results suggest that gender-adjusted motivation models influencing the recognition process need to be considered to optimize compliance in patients with CVR

Continuing medical education challenges in chronic fatigue syndrome

<p>Abstract</p> <p>Background</p> <p>Chronic fatigue syndrome (CFS) affects at least 4 million people in the United States, yet only 16% of people with CFS have received a diagnosis or medical care for their illness. Educating health care professionals about the diagnosis and management of CFS may help to reduce population morbidity associated with CFS.</p> <p>Methods</p> <p>This report presents findings over a 5-year period from May 2000 to June 2006 during which we developed and implemented a health care professional educational program. The objective of the program was to distribute CFS continuing education materials to providers at professional conferences, offer online continuing education credits in different formats (e.g., print, video, and online), and evaluate the number of accreditation certificates awarded.</p> <p>Results</p> <p>We found that smaller conference size (OR = 80.17; 95% CI 8.80, 730.25), CFS illness related target audiences (OR = 36.0; 95% CI 2.94, 436.34), and conferences in which CFS research was highlighted (OR = 4.15; 95% CI 1.16, 14.83) significantly contributed to higher dissemination levels, as measured by visit rates to the education booth. While print and online courses were equally requested for continuing education credit opportunities, the online course resulted in 84% of the overall award certificates, compared to 14% for the print course. This remained consistent across all provider occupations: physicians, nurses, physician assistants, and allied health professionals.</p> <p>Conclusion</p> <p>These findings suggest that educational programs promoting materials at conferences may increase dissemination efforts by targeting audiences, examining conference characteristics, and promoting online continuing education forums.</p

Paraherquamide and 2-Deoxy-paraherquamide Distinguish Cholinergic Receptor Subtypes in Ascaris Muscle

Paraherquamide is a novel natural anthelmintic product with a mode of action that is incompletely characterized. Nicotine and cholinergic-anthelmintic agonists of different chemical classes were used to produce contraction in Ascaris muscle strips. Paraherquamide and a semisynthetic derivative, 2-deoxy-paraherquamide, antagonized these responses. Analysis of the actions of the antagonists was made using the simple competitive model and nonlinear regression to estimate the pKB values of the antagonists. The analysis was tested using Clark plots. The pKB values for paraherquamide were: nicotine, 5.86 0.14; levamisole, 6.61 0.19; pyrantel, 6.50 0.11; and bephenium, 6.75 0.15. The pKB of nicotine was significantly different from the pKB values for levamisole, pyrantel, and bephenium, showing that paraherquamide can distinguish a subtype of cholinergic receptors sensitive to nicotine and a subtype of cholinergic receptors sensitive to levamisole, pyrantel, and bephenium. The pKB values for 2-deoxy-paraherquamide were: levamisole, 5.31 0.13; pyrantel, 5.63 0.10; and bephenium, 6.07 0.13. The Clark plots of the antagonism illustrated the degree of fit to the competitive model for 2-deoxy-paraherquamide. 2-Deoxy-paraherquamide selectively antagonized the effects of bephenium; the pKB values of levamisole and pyrantel were significantly different from the pKB of bephenium. Paraherquamide and 2-deoxy-paraherquamide are selective competitive cholinergic antagonists that distinguish subtypes of cholinergic receptor in Ascaris muscle corresponding to nicotine-, levamisole-, and bephenium-sensitive receptors

Spintronics: Fundamentals and applications

Spintronics, or spin electronics, involves the study of active control and manipulation of spin degrees of freedom in solid-state systems. This article reviews the current status of this subject, including both recent advances and well-established results. The primary focus is on the basic physical principles underlying the generation of carrier spin polarization, spin dynamics, and spin-polarized transport in semiconductors and metals. Spin transport differs from charge transport in that spin is a nonconserved quantity in solids due to spin-orbit and hyperfine coupling. The authors discuss in detail spin decoherence mechanisms in metals and semiconductors. Various theories of spin injection and spin-polarized transport are applied to hybrid structures relevant to spin-based devices and fundamental studies of materials properties. Experimental work is reviewed with the emphasis on projected applications, in which external electric and magnetic fields and illumination by light will be used to control spin and charge dynamics to create new functionalities not feasible or ineffective with conventional electronics.Comment: invited review, 36 figures, 900+ references; minor stylistic changes from the published versio