The influence of hepatitis C infection and interferon-α therapy on thyrotropin blocking and stimulating autoantibodies in Graves' ophthalmopathy: a case report

<p>Abstract</p> <p>Background</p> <p>Hepatitis C virus is a highly immunogenic pathogen often inducing autoimmune activation changes and this can often be further exacerbated by Interferon therapy. As HCV is lymphocytotropic, it can modulate T cell and B cell antibody responses, affecting many endocrine organs, most commonly the thyroid.</p> <p>Case presentation</p> <p>We hereby describe a case of fluctuating and wavering thyrotropin autoantibodies of both stimulating and blocking nature in the setting of Graves's ophthalmopathy, hepatitis C infection and interferon-α, causing hypo- and subsequently hyper-thyroidism. The autoantibody profile was clearly modified during interferon therapy and settled into a new equilibrium at the completion of treatment.</p> <p>Conclusion</p> <p>The case highlights the possible existence of a dual thyroid autoantibody population associated with hepatitis C, and its modulation by interferon therapy, which further compounds the difficulties in the assessment thyroid disease in this setting.</p

The natural history of interferon-α induced thyroiditis in chronic hepatitis c patients: a long term study

<p>Abstract</p> <p>Background</p> <p>Autoimmune thyroid disease is a common complication of patients with chronic hepatitis C undergoing combination pegylated interferon-α and ribavirin treatment. A small proportion develops interferon-induced thyroiditis of which the long term natural history is unknown and how it compares with de novo thyroiditis. The aim of the study is to determine the natural history of thyroid disease including antibody profile in this particular setting 36 months from the completion of therapy.</p> <p>Methods</p> <p>A cohort of 18 hepatitis C patients (mean age 45 ± 8 years (standard deviation)) who developed exclusively thyroiditis in this setting was followed every 12 months after the completion of therapy for 36 months. Investigations included thyrotropin, free tetra-iodothyronine, free tri-iodothyronine levels and thyroid autoantibodies.</p> <p>Results</p> <p>None of the patients developed any long term thyroid disease. Two patients had a prolonged hypothyroid phase of the thyroiditis early after the completion of treatment but recovered fully. The remaining 16 patients remained euthyroid. Similarly, thyroid autoantibodies all declined and returned to reference range.</p> <p>Conclusions</p> <p>The long term natural history in this small series of interferon induced thyroiditis was benign. If a larger series confirms a similar outcome then there is no long term residual effect on thyroid function and follow-up testing would not be warranted.</p

An XMM-Newton observation of the extreme Narrow Line Seyfert 1 Galaxy, Mrk 359

We present XMM-Newton observations of Mrk 359, the first Narrow Line Seyfert 1 galaxy discovered. Even among NLS1s, Mrk 359 is an extreme case with extraordinarily narrow optical emission lines. The XMM-Newton data show that Mrk 359 has a significant soft X-ray excess which displays only weak absorption and emission features. The (2-10) keV continuum, including reflection, is flatter than the typical NLS1, with Gamma approximately 1.84. A strong emission line of equivalent width approximately 200 eV is also observed, centred near 6.4 keV. We fit this emission with two line components of approximately equal strength: a broad iron-line from an accretion disc and a narrow, unresolved core. The unresolved line core has an equivalent width of approximately 120 eV and is consistent with fluorescence from neutral iron in distant reprocessing gas, possibly in the form of a `molecular torus'. Comparison of the narrow-line strengths in Mrk 359 and other low-moderate luminosity Seyfert 1 galaxies with those in QSOs suggests that the solid angle subtended by the distant reprocessing gas decreases with increasing AGN luminosity.Comment: Accepted for publication in MNRA

Disrupted reward processing in Parkinson's disease and its relationship with dopamine state and neuropsychiatric syndromes: a systematic review and meta-analysis

Background: Neuropsychiatric symptoms are common in Parkinson’s disease (PD) and predict poorer outcomes. Reward processing dysfunction is a candidate mechanism for the development of psychiatric symptoms including depression and impulse control disorders (ICDs). We aimed to determine whether reward processing is impaired in PD and its relationship with neuropsychiatric syndromes and dopamine replacement therapy. // Methods: The Ovid MEDLINE/PubMed, Embase and PsycInfo databases were searched for articles published up to 5 November 2020. Studies reporting reward processing task performance by patients with PD and healthy controls were included. Summary statistics comparing reward processing between groups were converted to standardised mean difference (SMD) scores and meta-analysed using a random effects model. // Results: We identified 55 studies containing 2578 participants (1638 PD and 940 healthy controls). Studies assessing three subcomponent categories of reward processing tasks were included: option valuation (n=12), reinforcement learning (n=37) and reward response vigour (n=6). Across all studies, patients with PD on medication exhibited a small-to-medium impairment versus healthy controls (SMD=0.34; 95% CI 0.14 to 0.53), with greater impairments observed off dopaminergic medication in within-subjects designs (SMD=0.43, 95% CI 0.29 to 0.57). Within-subjects subcomponent analysis revealed impaired processing off medication on option valuation (SMD=0.57, 95% CI 0.39 to 0.75) and reward response vigour (SMD=0.36, 95% CI 0.13 to 0.59) tasks. However, the opposite applied for reinforcement learning, which relative to healthy controls was impaired on-medication (SMD=0.45, 95% CI 0.25 to 0.65) but not off-medication (SMD=0.28, 95% CI −0.03 to 0.59). ICD was the only neuropsychiatric syndrome with sufficient studies (n=13) for meta-analysis, but no significant impairment was identified compared tonon-ICD patients (SMD=−0.02, 95% CI −0.43 to 0.39). // Conclusion: Reward processing disruption in PD differs according to subcomponent and dopamine medication state, and warrants further study as a potential treatment target and mechanism underlying associated neuropsychiatric syndromes

Interprofessional communication with hospitalist and consultant physicians in general internal medicine : a qualitative study

This study helps to improve our understanding of the collaborative environment in GIM, comparing the communication styles and strategies of hospitalist and consultant physicians, as well as the experiences of providers working with them. The implications of this research are globally important for understanding how to create opportunities for physicians and their colleagues to meaningfully and consistently participate in interprofessional communication which has been shown to improve patient, provider, and organizational outcomes

The impact of gastrointestinal parasitism on the behaviour and welfare of weaned housed lambs

Gastrointestinal (GI) parasitism is a health and production concern in sheep, yet its impact on animal welfare remains unclear. The impact of subclinical infections is especially ambiguous as GI parasitism often remains undiagnosed until clinical signs such as diarrhoea are evident. This study applied quantitative and qualitative methods to examine the effects of subclinical Teladorsagia circumcincta infection on the behaviour and welfare of 96 Suffolk-cross lambs (24 pens of 4 lambs) weaned at 10 weeks old. The hypothesis that parasitism causes negative affective states was tested. Lambs were divided into three groups at the pen level: ad-lib fed control (AC), restricted-fed control (RC), and ad-lib fed parasitised (AP). Parasitised lambs (AP) were dosed three times weekly with 7000 third stage T. circumcincta larvae (L 3) from 16 weeks of age. Lambs in the RC group were pair fed to match AP feed intake to separate the effects of infection-induced anorexia from the potential direct impacts of infection. From 7 days pre-infection to 23 days post-infection, scan and behaviour samples were taken from video recordings to quantitatively monitor behaviour, and animal-based measures such as faecal soiling score (FSS) were recorded as welfare indicators. Lying, standing, eating, play and social behaviour were monitored. Qualitative behaviour assessment (QBA) was conducted weekly using the AWIN (2015) protocol to gain insight into the lambs’ affective states over the onset of infection. Parasitised lambs were more likely to stand inactive than AC lambs as the infection progressed (P=0.006). They were also less likely to display eating behaviour in the third daily scan sample than RC lambs (P&lt;0.001). Principal Component Analysis of the QBA data revealed that the first dimension (PC1) described arousal levels, the second (PC2) described the valence of the animals’ affective states, and the third (PC3) described fearfulness and aggression levels. Parasitised lambs (est=10.64,SE=0.33) scored higher than RC lambs (est=9.42, SE=0.33) on PC3, the fearfulness dimension (P=0.030). There were no differences between fearfulness scores of AC and AP lambs or RC lambs and treatment group had no significant impact on the distribution of scores on PC1 or PC2. These findings demonstrate that subclinical GI parasitism negatively impacts lamb welfare not only in the health domain but in the behaviour and mental domains as well. This has implications for welfare assessments and early disease detection in lambs. Future research could explore remote monitoring of the indicators of parasitism identified in this study.</p

The impact of gastrointestinal parasitism on the behaviour and welfare of weaned housed lambs

Gastrointestinal (GI) parasitism is a health and production concern in sheep, yet its impact on animal welfare remains unclear. The impact of subclinical infections is especially ambiguous as GI parasitism often remains undiagnosed until clinical signs such as diarrhoea are evident. This study applied quantitative and qualitative methods to examine the effects of subclinical Teladorsagia circumcincta infection on the behaviour and welfare of 96 Suffolk-cross lambs (24 pens of 4 lambs) weaned at 10 weeks old. The hypothesis that parasitism causes negative affective states was tested. Lambs were divided into three groups at the pen level: ad-lib fed control (AC), restricted-fed control (RC), and ad-lib fed parasitised (AP). Parasitised lambs (AP) were dosed three times weekly with 7000 third stage T. circumcincta larvae (L 3) from 16 weeks of age. Lambs in the RC group were pair fed to match AP feed intake to separate the effects of infection-induced anorexia from the potential direct impacts of infection. From 7 days pre-infection to 23 days post-infection, scan and behaviour samples were taken from video recordings to quantitatively monitor behaviour, and animal-based measures such as faecal soiling score (FSS) were recorded as welfare indicators. Lying, standing, eating, play and social behaviour were monitored. Qualitative behaviour assessment (QBA) was conducted weekly using the AWIN (2015) protocol to gain insight into the lambs’ affective states over the onset of infection. Parasitised lambs were more likely to stand inactive than AC lambs as the infection progressed (P=0.006). They were also less likely to display eating behaviour in the third daily scan sample than RC lambs (P&lt;0.001). Principal Component Analysis of the QBA data revealed that the first dimension (PC1) described arousal levels, the second (PC2) described the valence of the animals’ affective states, and the third (PC3) described fearfulness and aggression levels. Parasitised lambs (est=10.64,SE=0.33) scored higher than RC lambs (est=9.42, SE=0.33) on PC3, the fearfulness dimension (P=0.030). There were no differences between fearfulness scores of AC and AP lambs or RC lambs and treatment group had no significant impact on the distribution of scores on PC1 or PC2. These findings demonstrate that subclinical GI parasitism negatively impacts lamb welfare not only in the health domain but in the behaviour and mental domains as well. This has implications for welfare assessments and early disease detection in lambs. Future research could explore remote monitoring of the indicators of parasitism identified in this study.</p

Psychometric properties of the CDC Symptom Inventory for assessment of Chronic Fatigue Syndrome

OBJECTIVES: Validated or standardized self-report questionnaires used in research studies and clinical evaluation of chronic fatigue syndrome (CFS) generally focus on the assessment of fatigue. There are relatively few published questionnaires that evaluate case defining and other accompanying symptoms in CFS. This paper introduces the self-report CDC CFS Symptom Inventory and analyzes its psychometric properties. METHODS: One hundred sixty-four subjects (with CFS, other fatiguing illnesses and non fatigued controls) identified from the general population of Wichita, Kansas were enrolled. Evaluation included a physical examination, a standardized psychiatric interview, three previously validated self-report questionnaires measuring fatigue and illness impact (Medical Outcomes Survey Short-Form-36 [MOS SF-36], Multidimensional Fatigue Inventory [MFI], Chalder Fatigue Scale), and the CDC CFS Symptom Inventory. Based on theoretical assumptions and statistical analyses, we developed several different Symptom Inventory scores and evaluated them on their ability to differentiate between participants with CFS and non-fatigued controls. RESULTS: The Symptom Inventory had good internal consistency and excellent convergent validity. A Total score (all symptoms), Case Definition score (CFS case defining symptoms) and Short Form score (6 symptoms with minimal correlation) differentiated CFS cases from controls. Furthermore, both the Case Definition and Short Form scores distinguished people with CFS from fatigued subjects who did not meet criteria for CFS. CONCLUSION: The Symptom Inventory appears to be a reliable and valid instrument to assess symptoms that accompany CFS. It is a positive addition to existing instruments measuring fatigue because it allows other dimensions of the illness to be assessed. Further research is needed to confirm and replicate the current findings in a normative population

Cognitive and social activities and long-term dementia risk: the prospective UK Million Women Study

BACKGROUND: Although dementia is associated with non-participation in cognitive and social activities, this association might merely reflect the consequences of dementia, rather than any direct effect of non-participation on the subsequent incidence of dementia. Because of the slowness with which dementia can develop, unbiased assessment of any such direct effects must relate non-participation in such activities to dementia detection rates many years later. Prospective studies with long-term follow-up can help achieve this by analysing separately the first and second decade of follow-up. We report such analyses of a large, 20-year study. METHODS: The UK Million Women Study is a population-based prospective study of 1·3 million women invited for National Health Service (NHS) breast cancer screening in median year 1998 (IQR 1997-1999). In median year 2001 (IQR 2001-2003), women were asked about participation in adult education, groups for art, craft, or music, and voluntary work, and in median year 2006 (IQR 2006-2006), they were asked about reading. All participants were followed up through electronic linkage to NHS records of hospital admission with mention of dementia, the first mention of which was the main outcome. Comparing non-participation with participation in a particular activity, we used Cox regression to assess fully adjusted dementia risk ratios (RRs) during 0-4, 5-9, and 10 or more years, after information on that activity was obtained. FINDINGS: In 2001, 851 307 women with a mean age of 60 years (SD 5) provided information on participation in adult education, groups for art, craft, or music, and voluntary work. After 10 years, only 9591 (1%) had been lost to follow-up and 789 339 (93%) remained alive with no recorded dementia. Follow-up was for a mean of 16 years (SD 3), during which 31 187 (4%) had at least one hospital admission with mention of dementia, including 25 636 (3%) with a hospital admission with dementia mentioned for the first time 10 years or more after follow-up began. Non-participation in cognitive or social activities was associated with higher relative risks of dementia detection only during the first decade after participation was recorded. During the second decade, there was little association. This was true for non-participation in adult education (RR 1·04, 99% CI 0·98-1·09), in groups for art, craft, or music (RR 1·04, 0·99-1·09), in voluntary work (RR 0·96, 0·92-1·00), or in any of these three (RR 0·99, 0·95-1·03). In 2006, 655 118 women provided information on reading. For non-reading versus any reading, there were similar associations with dementia, again with strong attenuation over time since reading was recorded, but longer follow-up is needed to assess this reliably. INTERPRETATION: Life has to be lived forwards, but can be understood only backwards. Long before dementia is diagnosed, there is a progressive reduction in various mental and physical activities, but this is chiefly because its gradual onset causes inactivity and not because inactivity causes dementia. FUNDING: UK Medical Research Council, Cancer Research UK