Photocycloaddition of S,S-Dioxo-benzothiophene-2-methanol, Reactivity in the Solid State and in Solution: Mechanistic Studies and Diastereoselective Formation of Cyclobutyl Rings.

The formation of cyclobutane rings is a promising strategy in the development of potential drugs and/or synthetic intermediates, typically challenging to obtain due to their constrained nature. In this work, the [2 + 2] photocycloaddition reaction of S,S-dioxobenzothiophene-2-methanol was explored in microcrystalline powders and its outcome was compared to that observed in solution. It was found that the molecular constraints inherited within the crystal lattice provide an optimal environment that leads to photodimer 4 as the major product in ca. 9.6:0.4 diastereomeric ratios with conversions >95%. The photoreaction was analyzed via X-ray, displaying a crystalline-to-amorphous transformation and showing that units of monomer 2 align to generate the corresponding dimer with a syn-head-to-tail regio- and diastereoselectivity. This result contrasted with that obtained in solution, where the diastereomeric ratio varied as a function of the excited state that is generated, to yield mixtures of dimers 4 and 5 (anti-head-to-tail), or exclusively 5 in the triplet-sensitized photoreaction, in the presence of benzophenone. Density functional theory was used to elucidate a plausible detailed mechanism for the phototransformation, which aided in justifying the results that led to the corresponding dimers. X-ray crystallography allowed us to establish the stereochemical assignment of the obtained cyclobutyl rings. Thus, the use of solid-state or solution photochemistry can be used to gain control of diastereo- and regioselectivities in the formation of this important moiety.

Protocol for the Solid-phase Synthesis of Oligomers of RNA Containing a 2'-O-thiophenylmethyl Modification and Characterization via Circular Dichroism.

Solid-phase synthesis has been used to obtain canonical and modified polymers of nucleic acids, specifically of DNA or RNA, which has made it a popular methodology for applications in various fields and for different research purposes. The procedure described herein focuses on the synthesis, purification, and characterization of dodecamers of RNA 5'-[CUA CGG AAU CAU]-3' containing zero, one, or two modifications located at the C2'-O-position. The probes are based on 2-thiophenylmethyl groups, incorporated into RNA nucleotides via standard organic synthesis and introduced into the corresponding oligonucleotides via their respective phosphoramidites. This report makes use of phosphoramidite chemistry via the four canonical nucleobases (Uridine (U), Cytosine (C), Guanosine (G), Adenosine (A)), as well as 2-thiophenylmethyl functionalized nucleotides modified at the 2'-O-position; however, the methodology is amenable for a large variety of modifications that have been developed over the years. The oligonucleotides were synthesized on a controlled-pore glass (CPG) support followed by cleavage from the resin and deprotection under standard conditions, i.e., a mixture of ammonia and methylamine (AMA) followed by hydrogen fluoride/triethylamine/N-methylpyrrolidinone. The corresponding oligonucleotides were purified via polyacrylamide electrophoresis (20% denaturing) followed by elution, desalting, and isolation via reversed-phase chromatography (Sep-pak, C18-column). Quantification and structural parameters were assessed via ultraviolet-visible (UV-vis) and circular dichroism (CD) photometric analysis, respectively. This report aims to serve as a resource and guide for beginner and expert researchers interested in embarking in this field. It is expected to serve as a work-in-progress as new technologies and methodologies are developed. The description of the methodologies and techniques within this document correspond to a DNA/RNA synthesizer (refurbished and purchased in 2013) that uses phosphoramidite chemistry.

Testing the Bivalent Fear of Evaluation Model of Social Anxiety: The Relationship between Fear of Positive Evaluation, Social Anxiety, and Perfectionism.

The Bivalent Fear of Evaluation (BFOE) model of social anxiety proposes that fear of negative evaluation (FNE) and fear of positive evaluation (FPE) play distinct roles in social anxiety. Research is however lacking in terms of how FPE is related to perfectionism and how these constructs interact to predict social anxiety. Participants were 382 individuals from the general community and included an oversampling of individuals with social anxiety. Measures of FPE, FNE, perfectionism, and social anxiety were administered. Results were mostly consistent with the predictions made by the BFOE model and showed that accounting for confounding variables, FPE correlated negatively with high standards but positively with maladaptive perfectionism. FNE was also positively correlated with maladaptive perfectionism, but there was no significant relationship between FNE and high standards. Also consistent with BFOE model, both FNE and FPE significantly moderated the relationship between maladaptive perfectionism and social anxiety with the relationship strengthened at high levels of FPE and FNE. These findings provide additional support for the BFOE model and implications are discussed.

Neurophysiological correlates of configural face processing in schizotypy.

BACKGROUND: Face processing impairment in schizophrenia appears to be underpinned by poor configural (as opposed to feature-based) processing; however, few studies have sought to characterize this impairment electrophysiologically. Given the sensitivity of event-related potentials to antipsychotic medications, and the potential for neurophysiological abnormalities to serve as vulnerability markers for schizophrenia, a handful of studies have investigated early visual P100 and face-selective N170 in "at risk" populations. However, this is the first known neurophysiological investigation of configural face processing in a non-clinical schizotypal sample. METHODS: Using stimuli designed to engage configural processing in face perception (upright and inverted Mooney and photographic faces), P100 and N170 components were recorded in healthy individuals characterized by high (N = 14) and low (N = 14) schizotypal traits according to the Oxford-Liverpool Inventory of Feelings and Experiences. RESULTS: High schizotypes showed significantly reduced N170 amplitudes to inverted photographic faces. Typical N170 latency and amplitude inversion effects (delayed and enhanced N170 to inverted relative to upright photographic faces, and enhanced amplitude to upright versus inverted Mooney faces), were demonstrated by low, but not high, schizotypes. No group differences were shown for P100 analyses. CONCLUSIONS: The findings suggest that neurophysiological deficits in processing facial configurations (N170) are apparent in schizotypy, while the early sensory processing (P100) of faces appears intact. This work adds to the mounting evidence for analogous neural processing anomalies at the healthy end of the psychosis continuum.

Self-efficacy, pain-related fear, and disability in a heterogeneous pain sample.

The fear avoidance model of chronic pain is well established for specific chronic pain groups and of considerable clinical utility, but it suffers from poor generalizability. Therefore, in this study we examined the role of self-efficacy (SE) in the relationship between pain-related fear (PRF) and three pain-related outcomes-pain severity, disability, and depression-in a more heterogeneous chronic pain sample. Sixty-eight participants between the ages of 18 and 75 years experiencing chronic pain were recruited from the general public. Participants completed a questionnaire that measured catastrophizing, SE, fear of movement, avoidance behavior, PRF, pain severity, disability, and depression. In support of our first hypotheses, higher SE was associated with: (1) less catastrophizing, fear of movement, avoidance of pain, and PRF; and (2) less pain severity, disability, and depression. And higher catastrophizing, fear of movement, avoidance of pain, and PRF were associated with higher pain severity, disability, and depression. Although complete mediation was not found, post hoc examination of partial correlations revealed that the relationship between PRF and disability was partially mediated by SE; however, SE had no mediatory effect on the relationship between PRF and either pain severity or depression. Within the constraints of a relatively small sample size, we concluded that within a heterogeneous pain population, PRF remains the most integral component of the fear avoidance model.

Insecure attachment and disordered eating in women: the mediating processes of social comparison and emotion dysregulation.

Few studies have examined potential intermediary processes linking insecure attachment with eating disorders. The purpose of this study was to compare the relative contributions of social comparison and emotion dysregulation on disordered eating symptoms within an attachment framework. Participants were 247 women living in Australia, aged between 18 and 35 years. All the study variables were moderately, positively correlated. Disordered eating was most highly correlated with emotion dysregulation, whilst correlation magnitudes with both attachment styles were comparable. Multiple mediation analysis was performed using bootstrapping procedures. Consistent with hypotheses, the mediating roles of social comparison and emotion dysregulation were supported, suggesting they may be processes through which insecure attachment influences disordered eating. Results highlight the need for intervention to focus not only on eating symptomatology, but also on the ways in which eating disorders are maintained through maladaptive self-regulatory and comparison processes.

Caring for the country: fatigue, sleep and mental health in Australian rural paramedic shiftworkers.

This study investigated sleep quality, fatigue, mental health and physical activity in rural paramedic shiftworkers. Although limited, previous studies have associated high fatigue levels and poorer health in this sector with shiftwork rostering and occupational demands. A modified version of the Standard Shiftwork Index was completed by 150 paramedics (117 male and 31 females) from rural Victoria. Single sample t tests found significantly higher levels of fatigue, depression, anxiety, and stress, and significantly poorer sleep quality than reference samples. Paramedics also reported less physical activity than community samples. By regression analysis, sleep quality explained the greatest amount of variance in fatigue scores, followed by depression and age. No gender differences in levels of depression or fatigue were found. Consistent with an earlier study of metropolitan paramedics based on the same methodology, findings suggest rural ambulance paramedic shiftworkers are at particular risk for increased levels of fatigue and depression (regardless of age or gender) and poor quality sleep. Organisational intervention was suggested.

Locus of control beliefs mediate the relationship between religious functioning and psychological health.

Theistic and spiritually based beliefs and behaviors have been demonstrated to consistently predict physical and mental health, although the psychological processes underlying these relationships are unclear. This study investigated associative relationships and pathways of mediation between religious functioning, locus of control (LOC) and health. The sample consisted of 122 Christians (79 women, 43 men) who were predominately Catholic, ranging in age from 18 to 80 (M = 45.47, SD = 15.0). Participants were recruited from churches in the Western suburbs of Melbourne, Australia, and completed a questionnaire package measuring (1) psychological and physical health, (2) the religious variables of awareness of God, instability and impression management, and (3) God, internal and external LOC domains. Results indicated that awareness of God and internal LOC were associated with better health, whereas external LOC and instability were associated with poorer health. God LOC and impression management were not significantly associated with health. Sobel tests were used to analyse mediation hypotheses. Internal LOC was found to mediate the relationship between awareness of God and better psychological health, and external LOC was found to mediate the relationship between instability and poorer psychological health. These findings are of considerable clinical significance.

Reward sensitivity and outcome expectancies as predictors of ecstasy use in young adults.

Extending recent studies showing that sensitivity to reward and outcome expectancies are associated with problematic alcohol and cannabis use, we undertook to determine if similar relationships would hold for ecstasy. One hundred and twenty five males and females aged between 18 and 35years were recruited from RMIT University and through snowball sampling. Participants completed a questionnaire package measuring frequency, amount and first age of ecstasy use, sensitivity to reward and punishment as well as outcome expectancies relating to ecstasy use. Frequency of ecstasy use was significantly related to reward sensitivity (p<.05) and positive outcome expectancies (p<.01). Regression analysis revealed significant prediction of ecstasy use by study variables, with expectations of increased confidence making the largest individual contribution. Multiple intervention points are suggested by the results of this study, within a largely cognitive-based framework.

Expression of urocortin peptides in canine myocardium and plasma.

Urocortin (Ucn) peptides are the endogenous ligands for the corticotropin-releasing factor type 2 receptor (CRFR2). They have potentially important roles in cardiovascular physiology in health and disease, and show promise as therapeutics for congestive heart failure. Analysis of canine heart tissue showed mRNA expression of Ucn 1, Ucn 3 and CRFR2 in all heart chambers. Immunohistochemistry also demonstrated Ucns 1 and 3 expression in cardiomyocytes. To assess the potential usefulness of circulating Ucns as markers of heart disease, plasma samples from 45 dogs with cardiac disease and 15 controls were analysed by radioimmunoassay. Both Ucns 1 and 3 were measurable but the presence of cardiac disease did not alter their concentrations. Therefore, whilst Ucns are expressed in canine myocardium (where they may play a role in the endogenous neurohumoral response to cardiac disease or failure) they do not appear to be sensitive biomarkers of cardiac disease in our canine patient population.

Relaxation and imagery for chronic, nonmalignant pain: effects on pain symptoms, quality of life, and mental health.

Nonpharmacologic treatments are being increasingly adopted as alternative or primary approaches to chronic pain management. We present results of a pilot study examining the effect of a 6-week combined abbreviated progressive relaxation technique (APRT) and guided imagery (GI) intervention for the management of chronic pain (N=19) and, using power analysis, explore recommended sample sizes for future clinical trials. Results indicated consistent and clinically significant trends of improvement on pain (McGill Pain Questionnaire, visual analog scale), mental health (Depression Anxiety and Stress Scale), all domains of quality of life (RAND-36 Health Survey), and sleep for the treatment group only. Owing to inadequate power in this study, these results were not statistically significant. Methodologic concerns, along with suggestions for an improved intervention protocol, are discussed. It is concluded that there is strong preliminary evidence for the efficacy of APRT and GI as an adjunct to conventional treatment options for chronic pain.

Early maladaptive schemas and personality disorder symptoms: An examination in a non-clinical sample.

OBJECTIVE: This study aimed to examine the overall and specific relationship between early maladaptive schemas (EMSs) and personality disorder (PD) symptoms in a non-clinical sample. DESIGN: While a notable previous study has examined the relationship between EMSs and PD symptoms after statistically controlling for gender and within-cluster PD symptoms, they did not control for comorbid axis I and inter-cluster PD symptoms. Hence, we redressed this methodological problem by statistically controlling for these conditions in a series of multiple regressions. METHODS: In a sample of 178 non-clinical participants, we obtained self-reports of PD symptoms, depression, anxiety, eating disorder, and EMSs. RESULTS: Results of a series of multiple regressions found that EMSs significantly predicted all PD symptoms apart from borderline and antisocial PDs and our hypotheses were largely consistent with hypotheses for cluster A and C PDs. We also found that specific EMSs differentially predicted PD subtypes even after controlling for other PD symptoms, depression, anxiety, and eating disorder symptoms. CONCLUSION: This study supports the contention that PDs are related to EMSs and there are specific relationships between particular EMSs and particular PDs.

Pathology processes and emergency department length of stay: the impact of change.

OBJECTIVES: To determine whether redesign of pathology processes, including indicators of sample priority, could reduce patient length of stay (LOS) in an emergency department (ED), and assess the long-term impact of two indicators of sample priority on pathology clinical performance indicators for ED samples. DESIGN, SETTING AND PARTICIPANTS: Two observational studies of de-identified data from standard databases were conducted--a single-site pilot trial of patients attending the ED of one hospital compared with historical controls, and a multisite study of 132,521 full blood count (FBC) requests for patients attending seven EDs that utilised either of two pathology process changes (coloured specimen transport bags alone, or coloured specimen bags plus blood tubes with a priority indicator). MAIN OUTCOME MEASURES: LOS in the ED was measured for the pilot trial, and collected-to-validated times for FBCs that fulfilled computer algorithm validation rules were measured for the multisite study. RESULTS: In the pilot trial, the redesigned pathology process resulted in a 29-minute reduction (15.6%) in the median ED LOS for all patients (P < 0.001) compared with historical controls. In the multisite study, use of coloured specimen bags plus blood tubes with a priority indicator resulted in an 8-minute reduction (20.1%) in mean collected-to-validated times for FBC requests compared with FBC requests that used coloured specimen bags alone (P < 0.001). CONCLUSIONS: Our pilot trial revealed a direct relationship between pathology process design and LOS in the ED, suggesting that redesigned pathology processes can significantly reduce LOS in the ED. Our multisite study showed that collecting samples directly into blood tubes with an incorporated priority indicator reduces pathology test turnaround times. These data suggest that LOS in the ED can be significantly reduced by simple changes to pathology processes, such as collecting samples directly into specimen containers with an incorporated priority indicator.

Effects of Silybum marianum on serum hepatitis C virus RNA, alanine aminotransferase levels and well-being in patients with chronic hepatitis C.

BACKGROUND/AIMS: Silybum marianum is a herbal preparation commonly used by subjects with chronic hepatitis C (CHC). The aims of this pilot study were to assess the efficacy and safety of S. marianum on serum hepatitis C virus (HCV) RNA, alanine aminotransferase levels and well-being in patients with CHC. METHODS: Twenty-four subjects with CHC were enrolled into a randomized, double-blind, placebo-controlled, crossover study. Subjects received 12 weeks of S. marianum (either 600 mg or 1200 mg/day) and placebo separated by a 4-week washout interval. Baseline biochemical, virological, psychological and quality-of-life tests were performed, with biochemical tests repeated monthly, and HCV RNA titer and quality-of-life and psychological assessments repeated at the end of both treatment periods. RESULTS: Seventeen patients completed the trial. Mean changes in HCV RNA titers, serum ALT levels and Short Form-36 scores were not significantly different for subjects on S. marianum compared to those on placebo. There was no significant change in mean State-Trait Anxiety Inventory State-Anxiety scores on S. marianum from baseline. Adverse events were similar with S. marianum and placebo. CONCLUSIONS: S. marianum is well tolerated in subjects with CHC, but does significantly affect serum HCV RNA, alanine aminotransferase levels, quality of life or psychological well-being in subjects with this condition.