Pilot Study of Psychopathology Among Roman Catholic Secular Clergy

This pilot study gathered information regarding overall levels of psychopathology in a nationally selected, random sample of U.S. Roman Catholic secular (i.e., diocesan) priests using the Symptom Checklist-90-Revised (SCL-90-R; Derogatis, 2004). The study yielded a response rate of 45%. One-half of the participants reported marked psychological problems, with interpersonal sensitivity, anxiety, and depression most strongly correlated with the instrument’s overall index of psychopathology. Four dimensional scales were elevated (i.e., obsessive-compulsive, interpersonal sensitivity, depression, psychoticism), as were two indices (i.e., GSI, PST). Implications and directions for future research are discussed

Depression and Anxiety in Roman Catholic Secular Clergy

A nationally selected random sample of Roman Catholic secular priests was investigated using the Center for Epidemiological Studies-Depression scale and the State-Trait Anxiety Inventory Form Y. Additionally, a Self-Report Inventory requested information regarding participants\u27 demographics as well as four categories of predictor variables (i.e., Vocational Satisfaction, Social Support, Spiritual Activities, Physical Environment) potentially associated with depression and anxiety. The study yielded a return rate of 64%. Secular clergy reported significantly greater depression and anxiety (both state and trait) than are reported in the general population. Low Vocational Satisfaction was found to be predictive of depression as well as both state and trait anxiety. Additionally, low Social Support was found to be predictive of state and trait anxiety. When the significant predictor variables were conceptually collapsed, it appeared that both people and place were significantly related to Roman Catholic secular priests\u27 experience of depression and anxiety

Depression and Contributors to Vocational Satisfaction in Roman Catholic Secular Clergy

A nationally selected, random sample of Roman Catholic secular (i.e., diocesan) priests was examined using the Center for Epidemiological Studies-Depression scale and an instrument developed for this study to assess contributors to priests’ vocational satisfaction. In addition, a self-report inventory gathered information regarding participants’ demographics as well as four categories of predictor variables (i.e., overall level of vocational satisfaction, social support, spiritual activities, physical environment). The study yielded a response rate of 45%. Secular clergy reported rates of depression approximately seven times greater than are found in the general population, and also indicated that the recent sexual abuse scandal in the Roman Catholic church had negatively affected their mood. Priests’ engagement in sacramental activities contributed greatly to their vocational satisfaction, and low levels of vocational satisfaction were found to be most predictive of depression. Factors comprising priests’ vocational satisfaction were External Manifestations (e.g., preaching, teaching), Internal Manifestations (e.g., prayer life, affirmation of God’s call), and Social Manifestations (e.g., relationships with parishioners, appreciation from others)

Increased TLR4 Expression and Downstream Cytokine Production in Immunosuppressed Adults Compared to Non-Immunosuppressed Adults

An increasing number of patients have medical conditions with altered host immunity or that require immunosuppressive medications. While immunosuppression is associated with increased risk of infection, the precise effect of immunosuppression on innate immunity is not well understood. We studied monocyte Toll-like receptor (TLR) expression and cytokine production in 137 patients with autoimmune diseases who were maintained on immunosuppressive medications and 419 non-immunosuppressed individuals.Human peripheral blood monocytes were assessed for surface expression of TLRs 1, 2, and 4. After incubation with TLR agonists, in vitro production of the cytokines IL-8, TNFalpha, and MIF were measured by ELISA as a measure of TLR signaling efficiency and downstream effector responsiveness. Immunosuppressed patients had significantly higher TLR4 surface expression when compared to non-immunosuppressed adults (TLR4 %-positive 70.12+/-2.28 vs. 61.72+/-2.05, p = 0.0008). IL-8 and TNF-alpha baseline levels did not differ, but were significantly higher in the autoimmune disease group following TLR stimulation. By contrast, baseline MIF levels were elevated in monocytes from immunosuppressed individuals. By multivariable analyses, IL-8 and TNFalpha, but not MIF levels, were associated with the diagnosis of an underlying autoimmune disease. However, only MIF levels were significantly associated with the use of immunosuppressive medications.Our results reveal that an enhanced innate immune response is a feature of patients with autoimmune diseases treated with immunosuppressive agents. The increased risk for infection evident in this patient group may reflect a dysregulation rather than a simple suppression of innate immunity

Elevated Cocaine-and Amphetamine-Regulated Transcript Immunoreactivity in the Circulation of Patients with Neuroendocrine Malignancy

Context: Cocaine-and amphetamine-regulated transcript (CART) codes for a peptide widely distributed in nervous and endocrine tissues. CART immunoreactivity (CART-LI) has been detected in human insulinomas. Objective: The objective of the study was to investigate the measurement of plasma CART-LI as a tumor marker of neuroendocrine malignancy. Design and Subjects: Plasma CART-LI levels were measured in 401 patients with a range of diagnoses: neuroendocrine malignancy (n ϭ 131), after removal of neuroendocrine malignancy (n ϭ 27), without any form of tumor or renal impairment (n ϭ 192), with renal impairment (n ϭ 17) and with nonneuroendocrine tumors (n ϭ 34). Chromatography methods were used to investigate CART-LI circulating in human plasma. Results: The upper limit of normal calculated for CART-LI was 150 pmol/liter. Mean circulating plasma CART-LI among neuroendocrine tumor patients was 440 pmol/liter, 56% of subjects having levels greater than 150 pmol/liter. Measuring CART-LI in addition to chromogranin (Cg)-A improved the sensitivity for neuroendocrine malignancy from 85 to 91%, whereas combined use of CgA and CgB had a joint sensitivity of 89%. Of 38 patients with pancreatic neuroendocrine tumors, 71% had plasma CART-LI levels greater than 150 pmol/liter, increasing to 95% in those classified with progressive disease (n ϭ 20, mean CART-LI 625 pmol/liter), compared with 80% for CgA. Chromatographic analysis suggests that circulating CART-LI is present as one major form, which may correspond to CART (62-102) or another unknown form. Conclusions: We demonstrate CART-LI as a specific tumor marker in patients with a range of neuroendocrine tumors. Used in combination with CgA, CART-LI measurement has the potential to improve sensitivity in diagnosis and follow-up of neuroendocrine tumors, in particular progressive pancreatic neuroendocrine tumors

Effects of Experimental Sarcocystis neurona

Sarcocystis neurona is the most common cause of Equine Protozoal Myeloencephalitis (EPM), affecting 0.5–1% horses in the United States during their lifetimes. The objective of this study was to evaluate the equine immune responses in an experimentally induced Sarcocystis neurona infection model. Neurologic parameters were recorded prior to and throughout the 70-day study by blinded investigators. Recombinant SnSAG1 ELISA for serum and CSF were used to confirm and track disease progression. All experimentally infected horses displayed neurologic signs after infection. Neutrophils, monocytes, and lymphocytes from infected horses displayed significantly delayed apoptosis at some time points. Cell proliferation was significantly increased in S. neurona-infected horses when stimulated nonspecifically with PMA/I but significantly decreased when stimulated with S. neurona compared to controls. Collectively, our results suggest that horses experimentally infected with S. neurona manifest impaired antigen specific response to S. neurona, which could be a function of altered antigen presentation, lack of antigen recognition, or both

Gravitational waves: search results, data analysis and parameter estimation

The Amaldi 10 Parallel Session C2 on gravitational wave (GW) search results, data analysis and parameter estimation included three lively sessions of lectures by 13 presenters, and 34 posters. The talks and posters covered a huge range of material, including results and analysis techniques for ground-based GW detectors, targeting anticipated signals from different astrophysical sources: compact binary inspiral, merger and ringdown; GW bursts from intermediate mass binary black hole mergers, cosmic string cusps, core-collapse supernovae, and other unmodeled sources; continuous waves from spinning neutron stars; and a stochastic GW background. There was considerable emphasis on Bayesian techniques for estimating the parameters of coalescing compact binary systems from the gravitational waveforms extracted from the data from the advanced detector network. This included methods to distinguish deviations of the signals from what is expected in the context of General Relativity

Therapist Adherence in the Strong Without Anorexia Nervosa (SWAN) Study: A Randomized Controlled Trial of Three Treatments for Adults with Anorexia Nervosa

The Authors. International Journal of Eating Disorders Published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Objective: To develop a psychotherapy rating scale to measure therapist adherence in the Strong Without Anorexia Nervosa (SWAN) study, a multi-center randomized controlled trial comparing three different psychological treatments for adults with anorexia nervosa. The three treatments under investigation were Enhanced Cognitive Behavioural Therapy (CBT-E), the Maudsley Anorexia Nervosa Treatment for Adults (MANTRA), and Specialist Supportive Clinical Management (SSCM). Method: The SWAN Psychotherapy Rating Scale (SWAN-PRS) was developed, after consultation with the developers of the treatments, and refined. Using the SWANPRS, two independent raters initially rated 48 audiotapes of treatment sessions to yield inter-rater reliability data. One rater proceeded to rate a total of 98 audiotapes from 64 trial participants. Results: The SWAN-PRS demonstrated sound psychometric properties, and was considered a reliable measure of therapist adherence. The three treatments were highly distinguishable by independent raters, with therapists demonstrating significantly more behaviors consistent with the actual allocated treatment compared to the other two treatment modalities. There were no significant site differences in therapist adherence observed. Discussion: The findings provide support for the internal validity of the SWAN study. The SWAN-PRS was deemed suitable for use in other trials involving CBT-E, MANTRA, or SSCM. VC 2015 The Authors. International Journal of Eating Disorders Published by Wiley Periodicals, Inc

C-reactive protein and risk of cognitive decline: The REGARDS study

Markers of systemic inflammation are associated with increased risk of cognitive impairment, but it is unclear if they are associated with a faster rate of cognitive decline and whether this relationship differs by race. Our objective was to examine the association of baseline C-reaction protein (CRP) with cognitive decline among a large racially diverse cohort of older adults. Participants included 21,782 adults aged 45 and older (36% were Black, Mean age at baseline 64) from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. CRP was measured at baseline and used as a continuous variable or a dichotomous grouping based on race-specific 90th percentile cutoffs. Cognitive measures of memory and verbal fluency were administered every 2 years for up to 12 years. Latent growth curve models evaluated the association of CRP on cognitive trajectories, adjusting for relevant demographic and health factors. We found that higher CRP was associated with worse memory (B = -.039, 95% CI [-.065,-.014]) and verbal fluency at baseline (B = -.195, 95% CI [-.219,-.170]), but not with rate of cognitive decline. After covariate adjustment, the association of CRP on memory was attenuated (B = -.005, 95% CI [-.031,-.021]). The association with verbal fluency at baseline, but not over time, remained (B = -.042, 95% CI [-.067,-.017]). Race did not modify the association between CRP and cognition. Findings suggest that levels of CRP at age 45+, are a marker of cognitive impairment but may not be suitable for risk prediction for cognitive decline

Biochemical characterization of protease activity of Nsp3 from SARS-CoV-2 and its inhibition by nanobodies

Of the 16 non-structural proteins (Nsps) encoded by SARS CoV-2, Nsp3 is the largest and plays important roles in the viral life cycle. Being a large, multidomain, transmembrane protein, Nsp3 has been the most challenging Nsp to characterize. Encoded within Nsp3 is the papain-like protease domain (PLpro) that cleaves not only the viral polypeptide but also K48-linked polyubiquitin and the ubiquitin-like modifier, ISG15, from host cell proteins. We here compare the interactors of PLpro and Nsp3 and find a largely overlapping interactome. Intriguingly, we find that near full length Nsp3 is a more active protease compared to the minimal catalytic domain of PLpro. Using a MALDI-TOF based assay, we screen 1971 approved clinical compounds and identify five compounds that inhibit PLpro with IC50s in the low micromolar range but showed cross reactivity with other human deubiquitinases and had no significant antiviral activity in cellular SARS-CoV-2 infection assays. We therefore looked for alternative methods to block PLpro activity and engineered competitive nanobodies that bind to PLpro at the substrate binding site with nanomolar affinity thus inhibiting the enzyme. Our work highlights the importance of studying Nsp3 and provides tools and valuable insights to investigate Nsp3 biology during the viral infection cycle