Axonal growth arrests after an increased accumulation of Schwann cells expressing senescence markers and stromal cells in acellular nerve allografts

Acellular nerve allografts (ANAs) and other nerve constructs do not reliably facilitate axonal regeneration across long defects (>3 cm). Causes for this deficiency are poorly understood. In this study, we determined what cells are present within ANAs before axonal growth arrest in nerve constructs and if these cells express markers of cellular stress and senescence. Using the Thy1-GFP rat and serial imaging, we identified the time and location of axonal growth arrest in long (6 cm) ANAs. Axonal growth halted within long ANAs by 4 weeks, while axons successfully regenerated across short (3 cm) ANAs. Cellular populations and markers of senescence were determined using immunohistochemistry, histology, and senescence-associated β-galactosidase staining. Both short and long ANAs were robustly repopulated with Schwann cells (SCs) and stromal cells by 2 weeks. Schwann cells (S100β(+)) represented the majority of cells repopulating both ANAs. Overall, both ANAs demonstrated similar cellular populations with the exception of increased stromal cells (fibronectin(+)/S100β(−)/CD68(−) cells) in long ANAs. Characterization of ANAs for markers of cellular senescence revealed that long ANAs accumulated much greater levels of senescence markers and a greater percentage of Schwann cells expressing the senescence marker p16 compared to short ANAs. To establish the impact of the long ANA environment on axonal regeneration, short ANAs (2 cm) that would normally support axonal regeneration were generated from long ANAs near the time of axonal growth arrest (“stressed” ANAs). These stressed ANAs contained mainly S100β(+)/p16(+) cells and markedly reduced axonal regeneration. In additional experiments, removal of the distal portion (4 cm) of long ANAs near the time of axonal growth arrest and replacement with long isografts (4 cm) rescued axonal regeneration across the defect. Neuronal culture derived from nerve following axonal growth arrest in long ANAs revealed no deficits in axonal extension. Overall, this evidence demonstrates that long ANAs are repopulated with increased p16(+) Schwann cells and stromal cells compared to short ANAs, suggesting a role for these cells in poor axonal regeneration across nerve constructs

The kinetics and mechanism of the organo-iridium catalysed racemisation of amines

The dimeric iodo-iridium complex [IrCp*I2 ]2 (Cp*=pentamethylcyclopentadiene) is an efficient catalyst for the racemisation of secondary and tertiary amines at ambient and higher temperatures with a low catalyst loading. The racemisation occurs with pseudo-first-order kinetics and the orresponding four rate constants were obtained by monitoring the time dependence of the concentrations of the (R) and (S) enantiomers starting with either pure (R) or (S) and show a first-order dependence on catalyst concentration. Low temperature 1H NMR data is consistent with the formation of a 1:1 complex with the amine coordinated to the iridium and with both iodide anions still bound to the metal-ion, but at the higher temperatures used for kinetic studies binding is weak and so no saturation zero-order kinetics are observed. A cross-over experiment with isotopically labelled amines demonstrates the intermediate formation of an imine which can dissociate from the iridium complex. Replacing the iodides in the catalyst by other ligands or having an amide substituent in Cp* results in a much less effective catalysts for the racemisation of amines. The rate constants for a deuterated amine yield a significant primary kinetic isotope effect kH/kD = 3.24 ndicating that hydride transfer is involved in the rate-limiting step

Dynamic assessment of word learning skills of preschool children with primary language impairment

Dynamic assessment has been shown to have considerable theoretical and clinical significance in the assessment of socially disadvantaged and culturally and linguistically diverse children. In this study it is used to enhance assessment of pre-school children with primary language impairment. The purpose of the study was to determine whether a dynamic assessment (DA) has the potential to enhance the predictive capacity of a static measure of receptive vocabulary in pre-school children. Forty pre-school children were assessed using the static British Picture Vocabulary Scale (BPVS), a DA of word learning potential and an assessment of non-verbal cognitive ability. Thirty-seven children were followed up 6 months later and re-assessed using the BPVS. Although the predictive capacity of the static measure was found to be substantial, the DA increased this significantly especially for children with static scores below the 25th centile. The DA of children's word learning has the potential to add value to the static assessment of the child with low language skills, to predict subsequent receptive vocabulary skills and to increase the chance of correctly identifying children in need of ongoing support

ROCK Inhibitor Is Not Required for Embryoid Body Formation from Singularized Human Embryonic Stem Cells

We report a technology to form human embryoid bodies (hEBs) from singularized human embryonic stem cells (hESCs) without the use of the p160 rho-associated coiled-coil kinase inhibitor (ROCKi) or centrifugation (spin). hEB formation was tested under four conditions: +ROCKi/+spin, +ROCKi/-spin, -ROCKi/+spin, and -ROCKi/-spin. Cell suspensions of BG01V/hOG and H9 hESC lines were pipetted into non-adherent hydrogel substrates containing defined microwell arrays. hEBs of consistent size and spherical geometry can be formed in each of the four conditions, including the -ROCKi/-spin condition. The hEBs formed under the -ROCKi/-spin condition differentiated to develop the three embryonic germ layers and tissues derived from each of the germ layers. This simplified hEB production technique offers homogeneity in hEB size and shape to support synchronous differentiation, elimination of the ROCKi xeno-factor and rate-limiting centrifugation treatment, and low-cost scalability, which will directly support automated, large-scale production of hEBs and hESC-derived cells needed for clinical, research, or therapeutic applications

Development and validation of the Overall Fidelity Enactment Scale for Complex Interventions (OFES-CI)

Background In many quality improvement (QI) and other complex interventions, assessing the fidelity with which participants ‘enact’ intervention activities (ie, implement them as intended) is underexplored. Adapting the evaluative approach used in objective structured clinical examinations, we aimed to develop and validate a practical approach to assessing fidelity enactment—the Overall Fidelity Enactment Scale for Complex Interventions (OFES-CI). Methods We developed the OFES-CI to evaluate enactment of the SCOPE QI intervention, which teaches nursing home teams to use plan-do-study-act (PDSA) cycles. The OFES-CI was piloted and revised early in SCOPE with good inter-rater reliability, so we proceeded with a single rater. An intraclass correlation coefficient (ICC) was used to assess inter-rater reliability. For 27 SCOPE teams, we used ICC to compare two methods for assessing fidelity enactment: (1) OFES-CI ratings provided by one of five trained experts who observed structured 6 min PDSA progress presentations made at the end of SCOPE, (2) average rating of two coders’ deductive content analysis of qualitative process evaluation data collected during the final 3 months of SCOPE (our gold standard). Results Using Cicchetti’s classification, inter-rater reliability between two coders who derived the gold standard enactment score was ‘excellent’ (ICC=0.93, 95% CI=0.85 to 0.97). Inter-rater reliability between the OFES-CI and the gold standard was good (ICC=0.71, 95% CI=0.46 to 0.86), after removing one team where open-text comments were discrepant with the rating. Rater feedback suggests the OFES-CI has strong face validity and positive implementation qualities (acceptability, easy to use, low training requirements). Conclusions The OFES-CI provides a promising novel approach for assessing fidelity enactment in QI and other complex interventions. It demonstrates good reliability against our gold standard assessment approach and addresses the practicality problem in fidelity assessment by virtue of its suitable implementation qualities. Steps for adapting the OFES-CI to other complex interventions are offered.publishedVersio

Burnout among nursing home care aides and the effects on resident outcomes

While burnout among health care workers has been well studied, little is known about the extent to which burnout among health care workers impacts the outcomes of their care recipients. To test this, we used a multi-year (2014-2020) survey of care aides working in approximately 90 nursing homes (NHs); the survey focused on work-life measures, including the Maslach Burnout Inventory (MBI) and work-unit identifier. Resident Assessment Instrument Minimum Data Set (RAI-MDS 2.0) data were obtained on all residents in the sampled NHs during this time and included a unit identifier for each resident. We used multi-level models to test associations between the MBI emotional exhaustion and cynicism sub-scales reported by care aides and the resident outcomes of antipsychotics without indication, depressive symptoms, and responsive behaviors among residents on units. In 2019/2020, our sample included 3,547 care aides and 10,117 residents in 282 units. The mean frequency of emotional exhaustion and cynicism across units was 43% and 50%, respectively. While residents frequently experienced antipsychotics without indication 1,852 (18.3%), depressive symptoms 2,089 (20.7%), and responsive behaviors 3,891 (38.5%), none were found to be associated with either emotional exhaustion or cynicism among care aides.</p

European Nature and Health Network Initiatives

Attention to the importance of nature and human health linkages has increased in the past years, both in science and in policy. While knowledge about and recognition of the importance of nature and human health linkages are increasing rapidly, challenges still remain. Among them are building bridges between relevant but often still somewhat disconnected sectors and topics. There is a need to bring together researchers in the fields of health sciences, ecology, social sciences, sustainability sciences and other interdisciplinary sciences, as well as for cooperation between governments, companies and citizens. In this chapter, we introduce European networking initiatives aimed at building such bridges

Measurement invariance and differential item functioning of a care staff proxy measure of nursing home resident dementia-specific quality of life (DEMQOL-CH): do care aides' first language, and care aides' and residents’ ethno-cultural background matter?

Quality of life (QoL) is a priority goal of dementia care, but measuring QoL becomes increasingly difficult as a person's ability to self-report declines. QoL measurement is particularly challenging among Nursing home (NH) residents, due to their often advanced cognitive impairment. The DEMQOL-CH is a validated tool to assess NH residents' QoL, using care staff proxy reports. Care staff and residents often have diverse ethno-cultural backgrounds, which may affect the measurement of QoL. Our objective was to assess measurement invariance and differential item functioning (DIF) of the DEMQOL-CH based on care staff ethno-cultural background, language, and resident ethno-cultural background. In a convenience sample of 9 NHs in the Canadian province of Alberta, research assistants conducted structured interviews with 119 care staff between July and September 2021 to complete DEMQOL-CH assessments of 612 residents. We performed confirmatory factor analyses, multiple group item response theory analyses, and DIF analyses. Measurement of the overall DEMQOL-CH score was affected by care staff ethno-cultural background and language (lack of scalar measurement invariance), but not by resident ethno-cultural background. Six of the 31 DEMQOL-CH items had DIF based on both, care staff ethno-cultural background and language, 2 items had DIF based on care staff ethno-cultural background, 4 items had DIF based on care staff language. Resident ethno-cultural background did not lead to DIF. The lack of measurement invariance and the presence of DIF affects the comparability of DEMQOL-CH assessments collected from care staff with diverse ethno-cultural and/or language backgrounds. However, the extent of the issues identified is small and the tool's other psychometric properties are robust. Therefore, we suggest that it is reasonable to continue to use the DEMQOL-CH in its current form, with careful consideration of methods to deal with and adjust for measurement invariance

Job Satisfaction among Care Aides in Residential Long-Term Care: A Systematic Review of Contributing Factors, Both Individual and Organizational

Despite an increasing literature on professional nurses’ job satisfaction, job satisfaction by nonprofessional nursing care providers and, in particular, in residential long-term care facilities, is sparsely described. The purpose of this study was to systematically review the evidence on which factors (individual and organizational) are associated with job satisfaction among care aides, nurse aides, and nursing assistants, who provide the majority of direct resident care, in residential long-term care facilities. Nine online databases were searched. Two authors independently screened, and extracted data and assessed the included publications for methodological quality. Decision rules were developed a priori to draw conclusions on which factors are important to care aide job satisfaction. Forty-two publications were included. Individual factors found to be important were empowerment and autonomy. Six additional individual factors were found to be not important: age, ethnicity, gender, education level, attending specialized training, and years of experience. Organizational factors found to be important were facility resources and workload. Two additional factors were found to be not important: satisfaction with salary/benefits and job performance. Factors important to care aide job satisfaction differ from those reported among hospital nurses, supporting the need for different strategies to improve care aide job satisfaction in residential long-term care

Social determinants of health inequalities in early phase clinical trials in Northern England

\ua9 The Author(s) 2024.Background: Early phase clinical trials in Oncology represent a subspecialised area where UK patient selection is influenced by access to Experimental Cancer Medicine Centres (ECMCs). Equity of access with respect to social determinants of health (SDoH) were explored for two major ECMCs. Methods: A retrospective cohort study including all referrals to Newcastle and Manchester ECMCs in 2021 was completed. Consent to screening or pre-screening was stratified against SDoH characteristics, including: Index of Multiple Deprivation (IMD) decile, ethnicity and distance to centre. Results: 1243 patients were referred for trials. IMD quintile 1 (most deprived) patients had reduced likelihood of referral compared to expected population models (OR, 0.67; 95% CI: 0.55 to 0.80, p = &lt;0.0001). IMD quintile 5 (least deprived) had increased likelihood of referral (OR, 1.46; 95% CI: 1.17 to 1.82, p = 0.0007). Living beyond median distance from Manchester reduced the likelihood of consenting to trials (OR, 0.72; 95% CI: 0.55 to 0.94, p = 0.015). Ethnicity data represented a White British propensity. Conclusions: Inequalities in socioeconomic and geographic factors influence referral and enrolment to early phase clinical trials in Northern England. This has implications for equity of access and generalisability of trial results internationally and warrants further study