The Neuromodulatory and Hormonal Effects of Transcutaneous Vagus Nerve Stimulation as Evidenced by Salivary Alpha Amylase, Salivary Cortisol, Pupil Diameter, and the P3 Event-Related Potential

Background Transcutaneous vagus nerve stimulation (tVNS) is a new, non-invasive technique being investigated as an intervention for a variety of clinical disorders, including epilepsy and depression. It is thought to exert its therapeutic effect by increasing central norepinephrine (NE) activity, but the evidence supporting this notion is limited. Objective In order to test for an impact of tVNS on psychophysiological and hormonal indices of noradrenergic function, we applied tVNS in concert with assessment of salivary alpha amylase (SAA) and cortisol, pupil size, and electroencephalograph (EEG) recordings. Methods Across three experiments, we applied real and sham tVNS to 61 healthy participants while they performed a set of simple stimulus-discrimination tasks. Before and after the task, as well as during one break, participants provided saliva samples and had their pupil size recorded. EEG was recorded throughout the task. The target for tVNS was the cymba conchae, which is heavily innervated by the auricular branch of the vagus nerve. Sham stimulation was applied to the ear lobe. Results P3 amplitude was not affected by tVNS (Experiment 1A: N = 24; Experiment 1B: N = 20; Bayes factor supporting null model = 4.53), nor was pupil size (Experiment 2: N = 16; interaction of treatment and time: p = .79). However, tVNS increased SAA (Experiments 1A and 2: N = 25) and attenuated the decline of salivary cortisol compared to sham (Experiment 2: N = 17), as indicated by significant interactions involving treatment and time (p = .023 and p = .040, respectively). Conclusion These findings suggest that tVNS modulates hormonal indices but not psychophysiological indices of noradrenergic function

Repeated use of rich pictures to explore changes in subjective experiences over time of patients with advanced cancer

BACKGROUND: The combination of verbal and visual tools may help unravel the experiences of advanced cancer patients. However, most previous studies have focused on a specific symptom, at only one moment in time. We recently found that a specific visual tool, originating from systems thinking, that is, rich pictures (RPs), could provide a more comprehensive view of the experiences of patients with advanced cancer. AIMS: To examine whether the repeated use of RPs can make changes in subjective experiences of patients living with advanced cancer visible over time. METHODS AND RESULTS: We performed a prospective study with a generic qualitative approach that was mostly informed by the process of grounded theory. We invited patients to make an RP twice, at the start of the study, and again after 2 months. Both RP drawing sessions were directly followed by a semi‐structured interview. Patients with all types of solid tumors, above the age of 18, and with a diagnosis of advanced, incurable cancer, were eligible. Eighteen patients participated and 15 patients were able to draw an RP twice. In eight RP‐sets, considerable differences between the first and second RP were noticeable. Two patterns were distinguished: (1) a change (decline or improvement) in physical health (five patients), and/or (2) a change in the way patients related to cancer (three patients). CONCLUSION: RPs are a valuable qualitative research method that can be used to explore the experiences of patients with advanced cancer, not only at a single point in time but also over time

Relation between Red Cell Distribution Width and Fibroblast Growth Factor 23 Cleaving in Patients with Chronic Kidney Disease and Heart Failure

In chronic kidney disease (CKD), both anemia and deregulated phosphate metabolism are common and predictive of adverse outcome. Previous studies suggest that iron status influences phosphate metabolism by modulating proteolytic cleavage of FGF23 into C-terminal fragments. Red cell distribution width (RDW) was recently identified as a strong prognostic determinant for cardiovascular morbidity and mortality, independently of iron status. We assessed whether RDW is associated with FGF23 cleaving in CKD patients with heart failure.The associations between RDW and either intact FGF23 (iFGF23), C-terminal FGF23 (cFGF23, reflecting iFGF23 and C-terminal fragments together) and the iFGF23/cFGF23 ratio were analyzed in 52 patients with CKD (eGFR 34,9 ± 13.9 ml/min/1.73m2) and chronic heart failure (CHF). Associations between RDW and FGF23 forms were studied by linear regression analysis adjusted for parameters of renal function, iron metabolism, phosphate metabolism and inflammation.Median cFGF23 levels were 197.5 [110-408.5] RU/ml, median iFGF23 levels were 107.3 [65.1-162.2] pg/ml and median FGF23 ratio was 0.80 [0.37-0.86]. Mean RDW was 14.1 ± 1.2%. cFGF23 and RDW were associated (β = 1.63 x 10(-3), P < 0.001), whereas iFGF23 and RDW were not (β = -1.38 x 10(-3), P = 0.336). The iFGF23/cFGF23 ratio was inversely associated with RDW. The difference between cFGF23 and iFGF23 (cFGF23- iFGF23) was positively associated with RDW (β = 1.74 x 10(-3), P < 0.001). The association between cFGF23 and RDW persisted upon multivariable linear regression analysis, adjusted for parameters of renal function, phosphate metabolism, iron metabolism and inflammation (β = 0.97 x 10(-3), P = 0.047).RDW is associated with cFGF23 but not with iFGF23 levels in patients with CKD and CHF. This suggests a connection between RDW and FGF23 catabolism, independent of iron status and inflammation. Future studies are needed to unravel underlying mechanisms and whether these pertain to the link between RDW and outcome

Deposition of amyloid β in the walls of human leptomeningeal arteries in relation to perivascular drainage pathways in cerebral amyloid angiopathy

Deposition of amyloid beta (AB) in the walls of cerebral arteries as cerebral amyloid angiopathy (CAA) suggests an age-related failure of perivascular drainage of soluble A? from the brain. As CAA is associated with Alzheimer's disease and with intracerebral haemorrhage, the present study determines the unique sequence of changes that occur as A? accumulates in artery walls. Paraffin sections of post-mortem human occipital cortex were immunostained for collagen IV, fibronectin, nidogen 2, AB and smooth muscle actin and the immunostaining was analysed using Image J and confocal microscopy. Results showed that nidogen 2 (entactin) increases with age and decreases in CAA. Confocal microscopy revealed stages in the progression of CAA: AB initially deposits in basement membranes in the tunica media, replaces first the smooth muscle cells and then the connective tissue elements to leave artery walls completely or focally replaced by AB. The pattern of development of CAA in the human brain suggests expansion of AB from the basement membranes to progressively replace all tissue elements in the artery wall. Establishing this full picture of the development of CAA is pivotal in understanding the clinical presentation of CAA and for developing therapies to prevent accumulation of AB in artery walls. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock

Міські проекції в ранній ліриці Лесі Українки

У статті вивчаються особливості художнього осмислення міського простору в ранній ліриці Лесі Українки. Звертається увага на те, що в процесі свого літературного становлення поетеса використала досвід різних традицій. Сентиментально налаштована героїня її творів оцінює місто як меркантильне, нелюдяне, байдуже до природної краси. В окремих поезіях переважає романтичний погляд: міський простір розглядається як тісний і задушливий, такий, що нівелює неповторність окремої особистості. Низка творів авторки репрезентує погодження неокласичних і романтичних тенденцій. Ключові слова: сентименталізм, романтизм, неокласицизм, лірика.В предлагаемой статье исследуются особенности художественного осмысления городского пространства в ранней лирике Леси Украинки. Учитывается тот факт, что в процессе своего литературного становления поэтесса использовала опыт различных традиций. Сентиментально настроенная героиня ее произведений оценивает город как меркантильный, исполненный безразличия к естественной красоте. В отдельных поэзиях преобладает романтический взгляд: городское пространство рассматривается как тесное, нивелирующее неповторимость отдельной личности. Ряд произведений Леси Украинки представляет взаимодействие романтических и неоклассических тенденций. Ключевые слова: сентиментализм, романтизм, неоклассицизм, лирика.In the article the features of early lyric poetry of Lesya Ukrainka are explored. That is taken into account, that in the process of the literary becoming a poetess used experience of different traditions. The sentimentally adjusted heroine gives preference to natural beauty. A romantic look prevails in separate poetries: urbanism space appears as incompatible with the uniqueness of individual. Romantic and neoclassical tendencies co-operate in a number of works of Lesya Ukrainka. Keywords: sentimentalizm, romanticism, neoclassicism, lyric poetry

The Influence of Multi-morbidity on the Work Ability of Ageing Employees and the Role of Coping Style

Purpose With an ageing workforce, employees are increasingly confronted with multi-morbidity. Especially physical and mental health problems often occur together. This study aims to (i) explore the effect of multi-morbidity on work ability of ageing employees, more specifically the effects of the number of health problems and the combination of physical and mental health problems, and to (ii) explore to what extent the effects of physical and mental health problems on work ability are explained by applying differing coping styles. Methods A 1 year follow up study (2012–2013) was conducted among 7175 employees aged 45–64 years. Linear regression analyses were conducted to examine longitudinal relationships between multi-morbidity, coping styles and work ability. To determine whether coping styles mediate the effects of multi-morbidity on work ability, Sobel tests were conducted. Results A higher number of health problems was related to poorer work ability, but this negative effect stabilized from three health problems onwards. The combination of physical and mental health problem(s) was more strongly related to poorer work ability than only physical health problems. The negative relation between physical health problems and work ability was partly suppressed by active coping, while the negative relation between the combination of physical and mental health problem(s) on work ability was partly explained by avoidant coping. Conclusions Ageing employees with multi-morbidity have a reduced work ability, especially when mental health problems are present. The greater negative effects of the combination of physical and mental health problems on work ability are partially due to unfavorable coping styles

Language differences in qualitative research: is meaning lost in translation?

This article discusses challenges of language differences in qualitative research, when participants and the main researcher have the same non-English native language and the non-English data lead to an English publication. Challenges of translation are discussed from the perspective that interpretation of meaning is the core of qualitative research. As translation is also an interpretive act, meaning may get lost in the translation process. Recommendations are suggested, aiming to contribute to the best possible representation and understanding of the interpreted experiences of the participants and thereby to the validity of qualitative research

Clinical, methodology, and patient/carer expert advice in pediatric drug development by conect4children

Many medicines are used “off-label” in children outside the terms of the license. Feasible pediatric clinical trials are a challenge to design. Conect4children (c4c) is an Innovative Medicines Initiative project to set up a pan-European pediatric clinical trial network aiming to facilitate the development of new medicines for children. To optimize pediatric trial development by promoting innovative trial design, c4c set up a European multidisciplinary advice service, including the voice of young patients and families, tailored to industry and academia. A network of experts was established to provide multidisciplinary advice to trial sponsors. Experts were selected to join clinical and innovative methodology expert groups. A patient and public involvement (PPI) database, to include the expert opinion of patients and parents/carers was formed. A stepwise process was developed: (1) sponsors contact c4c, (2) scoping interview takes place, (3) ad hoc advice group formed, (5) advice meeting held, and (6) advice report provided. Feedback on the process was collected. Twenty-four clinical and innovative methodology expert groups (&gt;400 experts) and a PPI database of 135 registrants were established. As of September 30, 2022, 36 advice requests were received, with 25 requests completed. Clinical and methodology experts and PPI representatives participated in several advice requests. Sponsors appreciated the advice quality and the multidisciplinary experts from different countries, including experts not known before. Experts and PPI participants were generally satisfied with the process. The c4c project has shown successful proof of concept for a service that presents a new framework to plan innovative and feasible pediatric trials.</p

Mental health issues and illness and substance use disorder (non-)disclosure to a supervisor: a cross-sectional study on beliefs, attitudes and needs of military personnel

OBJECTIVES: Research suggests that military personnel frequently delay disclosing mental health issues and illness (MHI), including substance use disorder, to supervisors. This delay causes missed opportunities for support and workplace accommodations which may help to avoid adverse occupational outcomes. The current study aims to examine disclosure-related beliefs, attitudes and needs, to create a better understanding of personnel's disclosure decision making. DESIGN: A cross-sectional questionnaire study among military personnel with and without MHI. Beliefs, attitudes and needs regarding the (non-)disclosure decision to a supervisor were examined, including factors associated with (non-)disclosure intentions and decisions. Descriptive and regression (logistic and ordinal) analyses were performed. SETTING: The study took place within the Dutch military. PARTICIPANTS: Military personnel with MHI (n=324) and without MHI (n=554) were participated in this study. OUTCOME MEASURE: (Non-)disclosure intentions and decisions. RESULTS: Common beliefs and attitudes pro non-disclosure were the preference to solve one's own problems (68.3%), the preference for privacy (58.9%) and a variety of stigma-related concerns. Common beliefs and attitudes pro disclosure were that personnel wanted to be their true authentic selves (93.3%) and the desire to act responsibly towards work colleagues (84.5%). The most reported need for future disclosure (96.8%) was having a supervisor who shows an understanding for MHI. The following factors were associated both with non-disclosure intentions and decisions: higher preference for privacy (OR (95% CI))=(1.99 (1.50 to 2.65) intention, 2.05 (1.12 to 3.76) decision) and self-management (OR (95% CI))=(1.64 (1.20 to 2.23) intention, 1.79 (1.00 to 3.20) decision), higher stigma-related concerns (OR (95% CI))=(1.76 (1.12 to 2.77) intention, 2.21 (1.02 to 4.79) decision) and lower quality of supervisor-employee relationship (OR (95% CI))=(0.25 (0.15 to 0.42) intention, 0.47 (0.25 to 0.87) decision). CONCLUSION: To facilitate (early-)disclosure to a supervisor, creating opportunities for workplace support, interventions should focus on decreasing stigma and discrimination and align with personnels' preference for self-management. Furthermore, training is needed for supervisors on how to recognise, and effectively communicate with, personnel with MHI. Focus should also be on improving supervisor-employee relationships