Workplace Incivility and Employee Sleep: The Role of Rumination and Recovery Experiences

This study examines the role of negative work rumination and recovery experiences in explaining the association between workplace incivility and employee insomnia symptoms. Drawing on the perseverative cognition model of stress and the effort–recovery model, we hypothesize a moderated mediation model in which workplace incivility is associated with insomnia symptoms via negative work rumination. This indirect effect is proposed to be conditional on employees’ reported level of recovery experiences (i.e., psychological detachment from work and relaxation during nonwork time). In examining this model, we further establish a link between workplace incivility and sleep and identify one pathway to explain this relationship, as well as resources that may be used to halt the negative spillover of workplace incivility on sleep. Based on a sample of 699 U.S. Forest Service employees, we find support for a moderated mediation model in which the association between workplace incivility and increased insomnia symptoms via increased negative work rumination was weakest for employees reporting high levels of recovery experiences during nonwork time. Findings from the current study contribute to our understanding of why workplace incivility is associated with nonwork outcomes, as well as point to implications for interventions aimed at promoting employees’ recovery from work

Evaluation of a novel autoinjector for subcutaneous self-administration of belimumab in systemic lupus erythematosus

Objective: To study self-administration and pharmacokinetics (PK) of subcutaneous (SC) belimumab in patients with systemic lupus erythematosus (SLE). Methods: Patients previously treated with belimumab self-administered belimumab 200 mg SC weekly for 8 weeks using an autoinjector. The primary endpoint was the proportion of patients able to self-administer their first and second dose (weeks 1 and 2) in the clinic. The proportion able to self-administer at weeks 4 and 8 (clinic) and weeks 3, 5, 6, and 7 (home) were secondary endpoints. Belimumab PK, safety, and injection-site pain were assessed. Results: 91/95 patients completed the study (withdrawals: adverse events (AEs): 3; lost to follow-up: 1). 93% were female, and mean (SD) age was 44.8 (12.50) years. The majority (99%, 89/90; no attempt, n = 5) successfully self-administered belimumab SC at weeks 1 and 2 (5 had clinic staff assistance), and 98% (85/87) successfully self-administered at weeks 4 and 8. Home-administration success rates were high (93%, (81/87) at weeks 3, 5, 6, and 7). Week 8 median trough concentration was 113 µg/mL. For patients with a ≤ 1.5-week interval between IV SC administration, week-1 concentrations were higher vs. week 8 (+ 51% median) but within a range observed with IV dosing; those with a ≥ 2.5-week interval had median differences close to 0. AEs and serious AEs were low, with no deaths; pain levels were low and decreased with subsequent injections. Conclusion: Patients with SLE successfully self-administered belimumab SC using a novel autoinjector; the PK profile was stable following a switch from IV with acceptable AE and pain levels. The recommended dosing interval between IV to SC dosing is 1 – 4 weeks

Steady-state pharmacokinetics of lamotrigine when converting from a twice-daily immediate-release to a once-daily extended-release formulation in subjects with epilepsy (The COMPASS Study).

PURPOSE: To compare the pharmacokinetics (PK) of lamotrigine (LTG) when converting from twice-daily immediate-release (LTG-IR) to once-daily extended-release (LTG-XR) in subjects with epilepsy. METHODS: An open-label, conversion study was conducted, consisting of a 2-week LTG-IR Baseline Phase, followed by a 2-week LTG-XR Treatment Phase and a 1-week LTG-IR Phase. Forty-four subjects (> or =13 years of age) were enrolled and grouped as metabolically neutral (15), induced (15), or inhibited (14) based on the effects of the concomitant antiepileptic drugs (AEDs) on the clearance of LTG. The primary outcome was LTG PK parameters upon conversion. Secondary outcomes included seizure frequency, adverse events, and subject's preference. RESULTS: LTG-XR and LTG-IR regimens were similar with respect to area under curve from 0 to 24 h (AUC (0-24)), apart from the induced group, where the AUC (0-24) of LTG-XR was on average 21% lower than for LTG-IR. A reduction in the LTG Cmax was observed for LTG-XR compared to LTG-IR resulting in a decrease in the peak-to-trough fluctuation in serum LTG concentrations. The steady-state, dose-normalized, trough concentrations for LTG-XR were similar to those of LTG-IR. The median time to peak concentration (Tmax) following administration of LTG-XR ranged from 4 to 6 h, 6 to 10 h, and 9 to 11 h in the induced, neutral, and inhibited groups, respectively. In comparison, the median Tmax following administration of LTG-IR was between 1 and 1.5 h. CONCLUSIONS: Trough concentrations of LTG can be maintained on conversion from twice-daily LTG-IR to once-daily LTG-XR at the same total daily dose

Rates of New Human Papillomavirus Detection and Loss of Detection in Middle-aged Women by Recent and Past Sexual Behavior.

BACKGROUND: Understanding the source of newly detected human papillomavirus (HPV) in middle-aged women is important to inform preventive strategies, such as screening and HPV vaccination. METHODS: We conducted a prospective cohort study in Baltimore, Maryland. Women aged 35-60 years underwent HPV testing and completed health and sexual behavior questionnaires every 6 months over a 2-year period. New detection/loss of detection rates were calculated and adjusted hazard ratios were used to identify risk factors for new detection. RESULTS: The new and loss of detection analyses included 731 women, and 104 positive for high-risk HPV. The rate of new high-risk HPV detection was 5.0 per 1000 woman-months. Reporting a new sex partner was associated with higher detection rates (adjusted hazard ratio, 8.1; 95% confidence interval, 3.5-18.6), but accounted only for 19.4% of all new detections. Among monogamous and sexually abstinent women, new detection was higher in women reporting ?5 lifetime sexual partners than in those reporting <5 (adjusted hazard ratio, 2.2; 95% confidence interval, 1.2-4.2). CONCLUSION: Although women remain at risk of HPV acquisition from new sex partners as they age, our results suggest that most new detections in middle-aged women reflect recurrence of previously acquired HPV

Stimulation of the cuneiform nucleus enables training and boosts recovery after spinal cord injury

Severe spinal cord injuries result in permanent paraparesis in spite of the frequent sparing of small portions of white matter. Spared fibre tracts are often incapable of maintaining and modulating the activity of lower spinal motor centres. Effects of rehabilitative training thus remain limited. Here, we activated spared descending brainstem fibres by electrical deep brain stimulation of the cuneiform nucleus of the mesencephalic locomotor region, the main control centre for locomotion in the brainstem, in adult female Lewis rats. We show that deep brain stimulation of the cuneiform nucleus enhances the weak remaining motor drive in highly paraparetic rats with severe, incomplete spinal cord injuries and enables high-intensity locomotor training. Stimulation of the cuneiform nucleus during rehabilitative aquatraining after subchronic (n = 8 stimulated versus n = 7 unstimulated versus n = 7 untrained rats) and chronic (n = 14 stimulated versus n = 9 unstimulated versus n = 9 untrained rats) spinal cord injury re-established substantial locomotion and improved long-term recovery of motor function. We additionally identified a safety window of stimulation parameters ensuring context-specific locomotor control in intact rats (n = 18) and illustrate the importance of timing of treatment initiation after spinal cord injury (n = 14). This study highlights stimulation of the cuneiform nucleus as a highly promising therapeutic strategy to enhance motor recovery after subchronic and chronic incomplete spinal cord injury with direct clinical applicability

Investigation of the presence of human or bovine respiratory syncytial virus in the lungs of mink (Neovison vison) with hemorrhagic pneumonia due to Pseudomonas aeruginosa

<p>Abstract</p> <p>Background</p> <p>Hemorrhagic pneumonia is a disease of farmed mink (<it>Neovison vison</it>) caused by <it>Pseudomonas aeruginosa</it>. The disease is highly seasonal in Danish mink with outbreaks occurring almost exclusively in the autumn. Human respiratory syncytial virus (RSV) has been shown to augment infection with <it>P. aeruginosa</it> in mice and to promote adhesion of <it>P. aeruginosa</it> to human respiratory cells.</p> <p>Findings</p> <p>We tested 50 lung specimens from mink with hemorrhagic pneumonia for bovine RSV by reverse transcriptase polymerase chain reaction (PCR) and for human RSV by a commercial real-time PCR. RSV was not found.</p> <p>Conclusions</p> <p>This study indicates that human and bovine RSV is not a major co-factor for development of hemorrhagic pneumonia in Danish mink.</p

Whole tissue cervical mapping of HPV infection: Molecular evidence for focal latent HPV infection in humans.

In this study, we aimed to provide molecular evidence of HPV latency in humans and discuss potential challenges of conducting studies on latency. We analyzed the entire cervix of two women who underwent hysterectomy unrelated to cervical abnormality. The cervices were sectioned into 242 and 186 sets respectively, and each set was tested separately for HPV using the SPF10-PCR-DEIA-LiPA25 system. To identify whether there was any evidence of transforming or productive infection, we used the biomarkers E4 and P16INK4a to stain slides immediately adjacent to HPV-positive sections. HPV was detected in both cervices. In patient 1, 1/242 sets was positive for HPV31. In patient 2, 13/186 sets were positive for HPV18 and 1/186 was positive for HPV53. The infection was very focal in both patients, and there was no sign of a transforming or productive infection, as evaluated by the markers E4 and P16INK4a. Had we only analyzed one set from each block, the probability of detecting the infection would have been 32.3% and 2%, respectively.Our findings support the idea that HPV may be able to establish latency in the human cervix; however, the risk associated with a latent HPV infection remains unclear

Potential involvement of the bone marrow in experimental Graves’ disease and thyroid eye disease

IntroductionGraves’ disease is an autoimmune disorder caused by auto-antibodies against the thyroid stimulating hormone receptor (TSHR). Overstimulation of the TSHR induces hyperthyroidism and thyroid eye disease (TED) as the most common extra thyroidal manifestation of Graves’ disease. In TED, the TSHR cross talks with the insulin-like growth factor 1 receptor (IGF-1R) in orbital fibroblasts leading to inflammation, deposition of hyaluronan and adipogenesis. The bone marrow may play an important role in autoimmune diseases, but its role in Graves’ disease and TED is unknown. Here, we investigated whether induction of experimental Graves’ disease and accompanying TED involves bone marrow activation and whether interference with IGF-1R signaling prevents this activation.ResultsImmunization of mice with TSHR resulted in an increase the numbers of CD4-positive T-lymphocytes (p ≤0.0001), which was normalized by linsitinib (p = 0.0029), an increase of CD19-positive B-lymphocytes (p= 0.0018), which was unaffected by linsitinib and a decrease of GR1-positive cells (p= 0.0038), which was prevented by linsitinib (p= 0.0027). In addition, we observed an increase of Sca-1 positive hematopietic stem cells (p= 0.0007) and of stromal cell-derived factor 1 (SDF-1) (p ≤0.0001) after immunization with TSHR which was prevented by linsitinib (Sca-1: p= 0.0008, SDF-1: p ≤0.0001). TSHR-immunization also resulted in upregulation of CCL-5, IL-6 and osteopontin (all p ≤0.0001) and a concomitant decrease of the immune-inhibitory cytokines IL-10 (p= 0.0064) and PGE2 (p ≤0.0001) in the bone marrow (all p≤ 0.0001). Treatment with the IGF-1R antagonist linsitinib blocked these events (all p ≤0.0001). We further demonstrate a down-regulation of arginase-1 expression (p= 0.0005) in the bone marrow in TSHR immunized mice, with a concomitant increase of local arginine (p ≤0.0001). Linsitinib induces an upregulation of arginase-1 resulting in low arginase levels in the bone marrow. Reconstitution of arginine in bone marrow cells in vitro prevented immune-inhibition by linsitinib.ConclusionCollectively, these data indicate that the bone marrow is activated in experimental Graves’ disease and TED, which is prevented by linsitinib. Linsitinib-mediated immune-inhibition is mediated, at least in part, by arginase-1 up-regulation, consumption of arginine and thereby immune inhibition

Linsitinib, an IGF-1R inhibitor, attenuates disease development and progression in a model of thyroid eye disease

IntroductionGraves’ disease (GD) is an autoimmune disorder caused by autoantibodies against the thyroid stimulating hormone receptor (TSHR) leading to overstimulation of the thyroid gland. Thyroid eye disease (TED) is the most common extra thyroidal manifestation of GD. Therapeutic options to treat TED are very limited and novel treatments need to be developed. In the present study we investigated the effect of linsitinib, a dual small-molecule kinase inhibitor of the insulin-like growth factor 1 receptor (IGF-1R) and the Insulin receptor (IR) on the disease outcome of GD and TED.MethodsLinsitinib was administered orally for four weeks with therapy initiating in either the early (“active”) or the late (“chronic”) phases of the disease. In the thyroid and the orbit, autoimmune hyperthyroidism and orbitopathy were analyzed serologically (total anti-TSHR binding antibodies, stimulating anti TSHR antibodies, total T4 levels), immunohistochemically (H&amp;E-, CD3-, TNFa- and Sirius red staining) and with immunofluorescence (F4/80 staining). An MRI was performed to quantify in vivo tissue remodeling inside the orbit.ResultsLinsitinib prevented autoimmune hyperthyroidism in the early state of the disease, by reducing morphological changes indicative for hyperthyroidism and blocking T-cell infiltration, visualized by CD3 staining. In the late state of the disease linsitinib had its main effect in the orbit. Linsitinib reduced immune infiltration of T-cells (CD3 staining) and macrophages (F4/80 and TNFa staining) in the orbita in experimental GD suggesting an additional, direct effect of linsitinib on the autoimmune response. In addition, treatment with linsitinib normalized the amount of brown adipose tissue in both the early and late group. An in vivo MRI of the late group was performed and revealed a marked decrease of inflammation, visualized by 19F MR imaging, significant reduction of existing muscle edema and formation of brown adipose tissue.ConclusionHere, we demonstrate that linsitinib effectively prevents development and progression of thyroid eye disease in an experimental murine model for Graves’ disease. Linsitinib improved the total disease outcome, indicating the clinical significance of the findings and providing a path to therapeutic intervention of Graves’ Disease. Our data support the use of linsitinib as a novel treatment for thyroid eye disease