Self-centered or other-directed: neural correlates of performance monitoring are dependent on psychopathic traits and social context

Stress and Psychopatholog

Enhanced error-related brain activations for mistakes that harm others: ERP evidence from a novel social performance-monitoring paradigm

Our mistakes often have negative consequences for ourselves, but may also harm the people around us. Continuous monitoring of our performance is therefore crucial for both our own and others’ well-being. Here, we investigated how modulations in responsibility for other’s harm affects electrophysiological correlates of performance-monitoring, viz. the error-related negativity (ERN) and error positivity (Pe). Healthy participants (N = 27) performed a novel social performance-monitoring paradigm in two responsibility contexts. Mistakes made in the harmful context resulted in a negative consequence for a co-actor, i.e., hearing a loud aversive sound, while errors in the non-harmful context were followed by a soft non-aversive sound. Although participants themselves did not receive auditory feedback in either context, they did experience harmful mistakes as more distressing and reported higher effort to perform well in the harmful context. ERN amplitudes were enhanced for harmful compared to non-harmful mistakes. Pe amplitudes were unaffected. The present study shows that performing in a potentially harmful social context amplifies early automatic performance-monitoring processes and increases the impact of the resulting harmful mistakes. These outcomes not only further our theoretical knowledge of social performance monitoring, but also demonstrate a novel and useful paradigm to investigate aberrant responsibility attitudes in various clinical populations.Stress and Psychopatholog

Absence of zoonotic Bartonella species in questing ticks: First detection of Bartonella clarridgeiae and Rickettsia felis in cat fleas in the Netherlands

<p>Abstract</p> <p>Background</p> <p>Awareness for flea- and tick-borne infections has grown in recent years and the range of microorganisms associated with these ectoparasites is rising. <it>Bartonella henselae</it>, the causative agent of Cat Scratch Disease, and other <it>Bartonella </it>species have been reported in fleas and ticks. The role of <it>Ixodes ricinus </it>ticks in the natural cycle of <it>Bartonella </it>spp. and the transmission of these bacteria to humans is unclear. <it>Rickettsia </it>spp. have also been reported from as well ticks as also from fleas. However, to date no flea-borne <it>Rickettsia </it>spp. were reported from the Netherlands. Here, the presence of <it>Bartonellaceae </it>and <it>Rickettsiae </it>in ectoparasites was investigated using molecular detection and identification on part of the gltA- and 16S rRNA-genes.</p> <p>Results</p> <p>The zoonotic <it>Bartonella clarridgeiae </it>and <it>Rickettsia felis </it>were detected for the first time in Dutch cat fleas. <it>B. henselae </it>was found in cat fleas and <it>B. schoenbuchensis </it>in ticks and keds feeding on deer. Two <it>Bartonella </it>species, previously identified in rodents, were found in wild mice and their fleas. However, none of these microorganisms were found in 1719 questing <it>Ixodes ricinus </it>ticks. Notably, the gltA gene amplified from DNA lysates of approximately 10% of the questing nymph and adult ticks was similar to that of an uncultured <it>Bartonella-</it>related species found in other hard tick species. The gltA gene of this <it>Bartonella-</it>related species was also detected in questing larvae for which a 16S rRNA gene PCR also tested positive for "<it>Candidatus </it>Midichloria mitochondrii"<it/>. The gltA-gene of the <it>Bartonella-</it>related species found in <it>I. ricinus </it>may therefore be from this endosymbiont.</p> <p>Conclusions</p> <p>We conclude that the risk of acquiring Cat Scratch Disease or a related bartonellosis from questing ticks in the Netherlands is negligible. On the other hand fleas and deer keds are probable vectors for associated <it>Bartonella </it>species between animals and might also transmit <it>Bartonella </it>spp. to humans.</p

Design of a randomized controlled trial to evaluate effectiveness of methotrexate versus prednisone as first-line treatment for pulmonary sarcoidosis: the PREDMETH study

Background: Treatment of pulmonary sarcoidosis is recommended in case of significant symptoms, impaired or deteriorating lung function. Evidence-based treatment recommendations are limited and largely based on expert opinion. Prednisone is currently the first-choice therapy and leads to short-term improvement of lung function. Unfortunately, prednisone often has side-effects and may be associated with impaired quality of life. Methotrexate is presently considered second-line therapy, and appears to have fewer side-effects. Objective: The primary objective of this trial is to investigate the effectiveness and tolerability of methotrexate as first-line therapy in patients with pulmonary sarcoidosis compared with prednisone. The primary endpoint of this study will be the change in hospital-measured Forced Vital Capacity (FVC) between baseline and 24 weeks. Secondary objectives are to gain more insights in response to therapy in individual patients by home spirometry and patient-reported outcomes. Blood biomarkers will be examined to find predictors of response to therapy, disease progression and chronicity, and to improve our understanding of the underlying disease mechanism. Methods/design: In this prospective, randomized, non-blinded, multi-center, non-inferiority trial, we plan to randomize 138 treatment-naïve patients with pulmonary sarcoidosis who are about to start treatment. Patients will be randomized in a 1:1 ratio to receive either prednisone or methotrexate in a predefined schedule for 24 weeks, after which they will be followed up in regular care for up to 2 years. Regular hospital visits will include pulmonary function assessment, completion of patient-reported outcomes, and blood withdrawal. Additionally, patients will be asked to perform weekly home spirometry, and record symptoms and side-effects via a home monitoring application for 24 weeks. Discussion: This study will be the first randomized controlled trial comparing first-line treatment of prednisone and methotrexate and provide valuable data on efficacy, safety, quality of life and biomarkers. If this study confirms the hypothesis that methotrexate is as effective as prednisone as first-line treatment for sarcoidosis but with fewer sideeffects, this will lead to improvement in care and initiate a change in practice. Furthermore, insights into the immunological mechanisms underlying sarcoidosis pathology might reveal new therapeutic targets

Proof of concept of faecal egg nematode counting as a practical means of veterinary engagement with planned livestock health management in a lower income country

Abstract Background The wellbeing and livelihood of farmers in impoverished regions of the world is intrinsically linked to the health and welfare of their livestock; hence improved animal health is a pragmatic component of poverty alleviation. Prerequisite knowledge and understanding of the animal health challenges facing cattle keepers in Malawi is constrained by the lack of veterinary infrastructure, which inevitably accompanies under-resourced rural development in a poor country. Methods We collaborated with public and private paraveterinary services to locate 62 village Zebu calves and 60 dairy co-operative calves dispersed over a wide geographical area. All calves were visited twice about 2 to 3 weeks apart, when they were clinically examined and faecal samples were collected. The calves were treated with 7.5 mg/kg of a locally-available albendazole drench on the first visit, and pre- and post- treatment trichostrongyle and Toxocara faecal egg counts were performed using a modified McMaster method. Results Our clinical findings point towards a generally poor level of animal health, implying a role of ticks and tick-transmitted diseases in village calves and need for improvement in neonatal calf husbandry in the dairy co-operative holdings. High faecal trichostrongyle egg counts were not intuitive, based on our interpretation of the animal management information that was provided. This shows the need for better understanding of nematode parasite epidemiology within the context of local husbandry and environmental conditions. The albendazole anthelmintic was effective against Toxocara, while efficacy against trichostrongyle nematodes was poor in both village and dairy co-operative calves, demonstrating the need for further research to inform sustainable drug use. Conclusions Here we describe the potential value of faecal nematode egg counting as a platform for communicating with and gaining access to cattle keepers and their animals, respectively, in southern Malawi, with the aim of providing informative background knowledge and understanding that may aid in the establishment of effective veterinary services in an under-resourced community

The PRO-RCC study:a long-term PROspective Renal Cell Carcinoma cohort in the Netherlands, providing an infrastructure for ‘Trial within Cohorts’ study designs

BACKGROUND: Ongoing research in the field of both localized, locally advanced and metastatic renal cell carcinoma has resulted in the availability of multiple treatment options. Hence, many questions are still unanswered and await further research. A nationwide collaborative registry allows to collect corresponding data. For this purpose, the Dutch PROspective Renal Cell Carcinoma cohort (PRO-RCC) has been founded, for the prospective collection of long-term clinical data, patient reported outcome measures (PROMs) and patient reported experience measures (PREMs).METHODS: PRO-RCC is designed as a multicenter cohort for all Dutch patients with renal cell carcinoma (RCC). Recruitment will start in the Netherlands in 2023. Importantly, participants may also consent to participation in a 'Trial within cohorts' studies (TwiCs). The TwiCs design provides a method to perform (randomized) interventional studies within the registry. The clinical data collection is embedded in the Netherlands Cancer Registry (NCR). Next to the standardly available data on RCC, additional clinical data will be collected. PROMS entail Health-Related Quality of Life (HRQoL), symptom monitoring with optional ecological momentary assessment (EMA) of pain and fatigue, and optional return to work- and/or nutrition questionnaires. PREMS entail satisfaction with care. Both PROMS and PREMS are collected through the PROFILES registry and are accessible for the patient and the treating physician.TRIAL REGISTRATION: Ethical board approval has been obtained (2021_218) and the study has been registered at ClinicalTrials.gov (NCT05326620).DISCUSSION: PRO-RCC is a nationwide long-term cohort for the collection of real-world clinical data, PROMS and PREMS. By facilitating an infrastructure for the collection of prospective data on RCC, PRO-RCC will contribute to observational research in a real-world study population and prove effectiveness in daily clinical practice. The infrastructure of this cohort also enables that interventional studies can be conducted with the TwiCs design, without the disadvantages of classic RCTs such as slow patient accrual and risk of dropping out after randomization.</p

The Mitochondrial Genome of Toxocara canis

Toxocara canis (Ascaridida: Nematoda), which parasitizes (at the adult stage) the small intestine of canids, can be transmitted to a range of other mammals, including humans, and can cause the disease toxocariasis. Despite its significance as a pathogen, the genetics, epidemiology and biology of this parasite remain poorly understood. In addition, the zoonotic potential of related species of Toxocara, such as T. cati and T. malaysiensis, is not well known. Mitochondrial DNA is known to provide genetic markers for investigations in these areas, but complete mitochondrial genomic data have been lacking for T. canis and its congeners. In the present study, the mitochondrial genome of T. canis was amplified by long-range polymerase chain reaction (long PCR) and sequenced using a primer-walking strategy. This circular mitochondrial genome was 14162 bp and contained 12 protein-coding, 22 transfer RNA, and 2 ribosomal RNA genes consistent for secernentean nematodes, including Ascaris suum and Anisakis simplex (Ascaridida). The mitochondrial genome of T. canis provides genetic markers for studies into the systematics, population genetics and epidemiology of this zoonotic parasite and its congeners. Such markers can now be used in prospecting for cryptic species and for exploring host specificity and zoonotic potential, thus underpinning the prevention and control of toxocariasis in humans and other hosts