Search

Abstract Precise, fast, and reliable identification and quantification of microplastic contamination are essential for determining their environmental concentrations for risk assessments. This study investigates the use of nuclear magnetic resonance (NMR) spectroscopy to quantify microplastics by analysing dilution series of polystyrene (PS), polyisoprene-cis (PI), polybutadiene-cis (PB), polylactic acid (PLA), polyvinyl chloride (PVC) and polyurethane (PU). Each polymer type was dissolved in a suitable solvent and an internal standard was utilized for quantification. Detection and quantification limits for each polymer type were established in two ways: (1) by using an equation based on proton signals and an internal standard with known concentration and (2) by using the LOQ based on the signal-to-noise ratio. Both data sets were compared and showed that using the internal standard (method 1) results in more accurate and lower concentration limits in the range of 0.2–8 µg mL−1 for all six polymer types, while the LOQ based on the SNR (method 2) gives consistently higher concentration limits (1–10 µg mL−1). The research shows the accuracy, efficacy, and reliability of quantitative NMR spectroscopy for polymer analysis in these concentration ranges compared to established quantifying methods, such as, PyGC/MS, FTIR, or Raman spectroscopy.

Abstract Background People with acquired brain injury (ABI) may experience concurrent conditions such as, mental health and substance use concerns, that require specialized care. There are services that aim to support people with ABI and these conditions separately; however, little is known about the facilitators and barriers of these services. Therefore, the purpose of this study was to engage stakeholders to investigate the facilitators and barriers of healthcare services for ABI and concurrent issues. Methods Semi-structured focus groups were conducted in-person and virtually with people with ABI, caregivers, healthcare professionals, and policy makers during a one-day event in British Columbia, Canada. Manifest content analysis was used with a constructivist perspective to analyze data. Results 90 participants (including 34 people with ABI) provided insights during 15 simultaneous focus groups. Three categories were identified: (1) complexity of ABI, (2) supports, (3) structure of care. Complexity of ABI outlined the ongoing basic needs after ABI and highlighted the need for public awareness of ABI. Supports outlined healthcare professional and community-based supports. Structure of care described people with ABI needing to meet criteria for support, experiences of navigating through the system and necessity of integrated services. Conclusions These findings highlight the facilitators and barriers of healthcare services for ABI and concurrent conditions and provide insights into the changes that may be needed. Doing so can improve the accessibility and quality of ABI healthcare services.

Background Functional cognitive disorder (FCD) may be common after a concussion, and no evidence-based treatment options are available. The current study evaluated the feasibility of a novel cognitive–behavioural therapy (CBT) protocol tailored to FCD after concussion.Methods Participants were randomised to CBT (n=11) or the current standard of care, cognitive rehabilitation (n=13). Both interventions consisted of eleven 50 min manualised videoconference sessions. CBT involved cognitive reappraisal and exposure-based strategies. Cognitive rehabilitation involved traditional memory compensation strategy training. Prespecified feasibility criteria were set for recruitment, perceived credibility, patient adherence, therapist protocol compliance and retention. The primary efficacy outcome was the Multifactorial Memory Questionnaire-Satisfaction (MMQ-S). The first five CBT completers completed a semistructured interview about their experience with the intervention.Results Most feasibility benchmarks were met, as 86% of invited patients consented, 96% of participants rated their intervention as credible, participants attended 96% of sessions, therapists covered all essential content in 94% of sessions and 100% of participants completed the post-treatment evaluation. Both groups improved on the MMQ-S. Post-treatment MMQ-S scores were similar between groups (Cohen’s d=−0.05 (95% CI [−0.86, 0.75])). Two themes resulted from the qualitative data analysis, which highlighted aspects of the CBT interventions that participants valued.Implications This pilot trial supports the feasibility of CBT tailored to FCD after concussion and suggests that patients with FCD may benefit from either CBT or standard cognitive rehabilitation. A larger trial is needed to evaluate the efficacy of these interventions for FCD after concussion and potentially FCD in other clinical contexts.Trial registration number NCT05581810.

ABSTRACT Objectives The purpose of this study was to engage key stakeholders in a health research priority‐setting process to identify, prioritize and produce a community‐driven list of research questions addressing intersectional issues on mental health and addictions (MHA) in acquired brain injury (ABI). Methods A multiphasic health research priority‐setting process was co‐designed and executed with community‐based stakeholders, including researchers, health professionals, clinicians, service providers, representatives from brain injury associations, policy makers and people with lived experience of ABI and MHA, including patients and their family members. Stakeholders' ideas led to the generation of research questions, which were prioritized at a 1‐day workshop. Results Fifty‐nine stakeholders participated in the priority‐setting activity during the workshop, which resulted in a rank‐ordered list of the top 10 questions for research addressing the intersections of ABI and MHA. Questions identified touched on several pressing issues (e.g., opioid crisis, homelessness), encompassed multiple subtypes of ABI (e.g., hypoxic‐ischaemic, mild traumatic), and involved different domains (e.g., identification, intervention) of health research. Conclusions This community‐driven health research priority‐setting study identified and prioritized research questions addressing the intersections of ABI and MHA. Researchers and funding agencies should use this list to inform their agendas and address stakeholders' most urgent needs, fostering meaningful improvements to clinical services. Patient or Public Contribution An 11‐person working group comprised of people with lived experience, service providers, researchers, healthcare professionals and other key stakeholders collaboratively developed and informed the scope, design, methodology and interpretation of this study. Over 50 community‐based stakeholders contributed to the research priority‐setting activity. One co‐author is a person with lived experience.

This study investigated the experiences of people with disabilities during the first year of the COVID-19 pandemic. Four semi-structured qualitative interviews were conducted individually with 13 participants between May 2020 and February 2021. The data were thematically analyzed. Three themes were identified: (1) “Being an active agent in changing how things are done in the face of COVID restrictions”, revealed changes that participants made to their daily routines resulting from government-imposed and self-imposed restrictions; (2) “Pandemic restrictions wreak havoc”, explained participants challenges with adapting to the restrictions; and (3) “Trying to be resilient in the face of pandemic changes” described participants’ efforts to cope with life during the pandemic. The findings illustrate how life changed for people with disabilities during the pandemic. Participants reported specific types of challenges at each time point. As the vaccine rollout became more imminent, participants expressed more hope for the future and getting back to normal.

BackgroundAfter traumatic brain injury (TBI), individuals can experience changes to quality of life (QOL). Despite understanding the factors that impact QOL after TBI, there is limited patient-oriented research to understand the subjective priorities for QOL after TBI. This study aims to understand the priorities for QOL after TBI using a group consensus building method.MethodsThe Technique for Research of Information by Animation of a Group of Experts (TRIAGE) method was used to determine priorities for QOL after TBI. In phase one, expert participants were consulted to understand the context of QOL after TBI. In phase two, participants with TBI completed a questionnaire to broadly determine the factors that contributed to their QOL. In phase three, a portion of participants from phase two engaged in focus groups to identify the most relevant priorities. Data was analyzed thematically. In phase four, expert participants were consulted to finalize the priorities.ResultsPhase one included three expert participants who outlined the complexity and importance of QOL after TBI. Phase two included 34 participants with TBI who described broad priorities for QOL including social support, employment, and accessible environments. Phase three included 13 participants with TBI who identified seven priorities for QOL: ensuring basic needs are met, participating in everyday life, trusting a circle of care, being seen and accepted, finding meaning in relationships, giving back and advocating, and finding purpose and value. In phase four, four expert participants confirmed the QOL priorities.InterpretationsFindings emphasize the critical need to address priorities for QOL after TBI to ensure improved health outcomes.

BackgroundThe COVID-19 pandemic created new difficulties for people living with brain injury, their families, and caregivers while amplifying the challenges of community-based associations that support them. We aimed to understand the effects of the pandemic on clients who live with brain injury, as well as on the provision of community brain injury services/programs in Canada.MethodsOnline cross-sectional survey conducted in January 2022. Representatives of brain injury associations across Canada completed the 31 open- and closed-ended questions about meeting clients’ needs, addressing public health guidelines, and sustaining the association. Data were analyzed using descriptive statistics (close-ended questions) and qualitative content analysis (open-ended questions).ResultsOf the 45 key representatives from associations in Pacific/Western (40%), Central (56%), and Atlantic Canada (4%), the majority were paid executive directors (67%). Participants reported that the most frequent psychosocial challenges experienced by their clients during the pandemic were social isolation (98%), loneliness (96%), and anxiety (93%). To alleviate these challenges, associations implemented wellness checks and psychosocial support. Most respondents (91%) affirmed that clients faced multiple technological barriers, such as a lack of technological knowledge and financial resources for devices and/or internet. In the open-ended questions, twenty-nine (64%) associations reported providing clients with devices, technology training, and assistance. Regarding public health measures, thirty (67%) respondents reported that clients had challenges understanding and/or following public health guidelines. Forty-two associations (93%) provided tailored information to help clients understand and comply with public health measures. Although associations (67%) received pandemic-related funding from the Canadian government they still struggled with the association’s sustainability. Thirty-four (76%) lost funding or financial resources that prevented them from delivering programs or required the use of reserve funds to continue to do so. Only 56% reported receiving sufficient funding to address additional COVID-19-related expenses.ConclusionAlthough the pandemic added further challenges to the sustainability of brain injury associations across Canada, they quickly adapted services/programs to respond to the increasing and varied needs of clients, while complying with protective measures. To ensure community associations’ survival it is essential to aptly recognize the vital role played by these associations within the brain injury care continuum.

Abstract Long-term sequelae in hospitalized Coronavirus Disease 2019 (COVID-19) patients may result in limited quality of life. The current study aimed to determine health-related quality of life (HRQoL) after COVID-19 hospitalization in non-intensive care unit (ICU) and ICU patients. This is a single-center study at the University Hospital of Wuerzburg, Germany. Patients eligible were hospitalized with COVID-19 between March 2020 and December 2020. Patients were interviewed 3 and 12 months after hospital discharge. Questionnaires included the European Quality of Life 5 Dimensions 5 Level (EQ-5D-5L), patient health questionnaire-9 (PHQ-9), the generalized anxiety disorder 7 scale (GAD-7), FACIT fatigue scale, perceived stress scale (PSS-10) and posttraumatic symptom scale 10 (PTSS-10). 85 patients were included in the study. The EQ5D-5L-Index significantly differed between non-ICU (0.78 ± 0.33 and 0.84 ± 0.23) and ICU (0.71 ± 0.27; 0.74 ± 0.2) patients after 3- and 12-months. Of non-ICU 87% and 80% of ICU survivors lived at home without support after 12 months. One-third of ICU and half of the non-ICU patients returned to work. A higher percentage of ICU patients was limited in their activities of daily living compared to non-ICU patients. Depression and fatigue were present in one fifth of the ICU patients. Stress levels remained high with only 24% of non-ICU and 3% of ICU patients (p = 0.0186) having low perceived stress. Posttraumatic symptoms were present in 5% of non-ICU and 10% of ICU patients. HRQoL is limited in COVID-19 ICU patients 3- and 12-months post COVID-19 hospitalization, with significantly less improvement at 12-months compared to non-ICU patients. Mental disorders were common highlighting the complexity of post-COVID-19 symptoms as well as the necessity to educate patients and primary care providers about monitoring mental well-being post COVID-19.

With increased physical restrictions during the coronavirus disease 2019 (COVID-19) pandemic, many individuals, especially older adults and individuals with disabilities, experienced increased feelings of loneliness. This study aimed to identify factors associated with loneliness among older adults and people with disabilities residing in British Columbia (BC), Canada 10 months following COVID-19 physical restrictions. Participants included a total of 70 adults consisting of older adults (>65 years of age) without any self-reported disabilities and adults (aged 19 or above) with disabilities (e.g., stroke, spinal cord injury, etc.). Participants completed standardized self-report measures of their levels of anxiety, depression, social support, mobility, and loneliness. We used hierarchical linear regression to determine the association of age, sex, disability status, anxiety, depression, social support, and mobility with loneliness. Participants reported general low levels of loneliness, anxiety, and depression and an overall high level of perceived social support. Most participants reported living with others. Our analysis showed a positive association between anxiety and loneliness (β = 0.340, p = 0.011) and a negative association between social support and loneliness (β = −0.315, p = 0.006). There was no association between depression and loneliness (β = 0.210, p = 0.116) as well as between mobility and loneliness (β = −0.005, p = 0.968). These findings suggest that anxiety and social support have been significantly associated with loneliness in older adults and people with disabilities during the COVID-19 pandemic. Increased efforts to reduce anxiety and improve social support in clinical and community settings may be helpful in reducing loneliness in older adults and people with disabilities during the COVID-19 pandemic.

Abstract Background Impaired self-awareness (i.e., a lack of insight) is experienced by most individuals who have sustained a moderate to severe traumatic brain injury (TBI). During the early recovery period post-injury, these individuals may not be able to recognize their abilities and limitations, hence, negatively impacting their daily life and function. Although there are assessments and interventions to improve self-awareness after TBI, little is known about how clinicians assess and address this impairment in an inpatient rehabilitation setting. Objective To examine how clinicians assess, report, and provide interventions for impaired self-awareness after TBI. Methods A retrospective chart review was conducted on interdisciplinary rehabilitation clinician entries for individuals with TBI (n = 67) who received inpatient rehabilitation within a five-year period (2014–2019). A reflexive thematic analysis was used to identify themes pertaining to self-awareness. Results Three themes were generated to explore clinician responses to their clients’ impaired self-awareness: 1) ‘recalling and understanding’ described clinician observations of client behaviors and expressions of self-awareness, 2) ‘applying and analyzing’ identified clinicians providing relevant tasks and advice to clients, and 3) ‘evaluating and creating’ described clinicians actively interacting with clients by providing feedback, guided prompts, and a follow-up plan. Conclusion Clinicians produced varied responses to clients’ impaired self-awareness after TBI. Findings may help to develop research priorities and integrated knowledge translation initiatives to increase evidence-based practice for impaired self-awareness after TBI.

BackgroundA total of 75% of people with mental health disorders have an onset of illness between the ages of 12 and 24 years. Many in this age group report substantial obstacles to receiving quality youth-centered mental health care services. With the rapid development of technology and the recent COVID-19 pandemic, mobile health (mHealth) has presented new opportunities for youth mental health research, practice, and policy. ObjectiveThe research objectives were to (1) synthesize the current evidence supporting mHealth interventions for youths who experience mental health challenges and (2) identify current gaps in the mHealth field related to youth’s access to mental health services and health outcomes. MethodsGuided by the methods of Arksey and O’Malley, we conducted a scoping review of peer-reviewed studies that used mHealth tools to improve youth mental health (January 2016-February 2022). We searched MEDLINE, PubMed, PsycINFO, and Embase databases using the following key terms: (1) mHealth; (2) youth and young adults; and (3) mental health. The current gaps were analyzed using content analysis. ResultsThe search produced 4270 records, of which 151 met inclusion criteria. Included articles highlight the comprehensive aspects of youth mHealth intervention resource allocation for targeted conditions, mHealth delivery methods, measurement tools, evaluation of mHealth intervention, and youth engagement. The median age for participants in all studies is 17 (IQR 14-21) years. Only 3 (2%) studies involved participants who reported their sex or gender outside of the binary option. Many studies (68/151, 45%) were published after the onset of the COVID-19 outbreak. Study types and designs varied, with 60 (40%) identified as randomized controlled trials. Notably, 143 out of 151 (95%) studies came from developed countries, suggesting an evidence shortfall on the feasibility of implementing mHealth services in lower-resourced settings. Additionally, the results highlight concerns related to inadequate resources devoted to self-harm and substance uses, weak study design, expert engagement, and the variety of outcome measures selected to capture impact or changes over time. There is also a lack of standardized regulations and guidelines for researching mHealth technologies for youths and the use of non–youth-centered approaches to implementing results. ConclusionsThis study may be used to inform future work as well as the development of youth-centered mHealth tools that can be implemented and sustained over time for diverse types of youths. Implementation science research that prioritizes youths’ engagement is needed to advance the current understanding of mHealth implementation. Moreover, core outcome sets may support a youth-centered measurement strategy to capture outcomes in a systematic way that prioritizes equity, diversity, inclusion, and robust measurement science. Finally, this study suggests that future practice and policy research are needed to ensure the risk of mHealth is minimized and that this innovative health care service is meeting the emerging needs of youths over time.

Methicillin-resistant Staphylococcus aureus (MRSA) is a universal threat. Once being well established in the healthcare setting, MRSA has undergone various epidemiological changes. This includes the emergence of more aggressive community-acquired MRSA (CA-MRSA) and the occurrence of MRSA which have their origin in animal breeding, called livestock-associated MRSA (LA-MRSA). Emergence of new clones as well as changes in the occurrence of some clonal lineages also describes the fluctuating dynamic within the MRSA family. There is paucity of data describing the possible impact of the COVID-19 pandemic on the MRSA dynamics. The aim of the study was the analysis of MRSA isolates in a three-year time period, including the pre-COVID-19 years 2018 and 2019 and the first year of the pandemic 2020. The analysis includes prevalence determination, antibiotic susceptibility testing, spa typing, and detection of genes encoding the PVL toxin. The MRSA rate remained constant throughout the study period. In terms of a dynamic within the MRSA family, only a few significant changes could be observed, but all except one occurred before the start of the COVID-19 pandemic. In summary, there was no significant impact of the COVID-19 pandemic on MRSA in Austria.

Abstract Single cell multi-omics analysis has the potential to yield a comprehensive understanding of the cellular events that underlie the basis of human diseases. The cardinal feature to access this information is the technology used for single-cell isolation, barcoding, and sequencing. Most currently used single-cell RNA-sequencing platforms have limitations in several areas including cell selection, documentation and library chemistry. In this study, we describe a novel high-throughput, full-length, single-cell RNA-sequencing approach that combines the CellenONE isolation and sorting system with the ICELL8 processing instrument. This method offers substantial improvements in single cell selection, documentation and capturing rate. Moreover, it allows the use of flexible chemistry for library preparations and the analysis of living or fixed cells, whole cells independent of sizing and morphology, as well as of nuclei. We applied this method to dermal fibroblasts derived from six patients with different segmental progeria syndromes and defined phenotype associated pathway signatures with variant associated expression modifiers. These results validate the applicability of our method to highlight genotype-expression relationships for molecular phenotyping of individual cells derived from human patients.

Background. Self-awareness is seldom formally assessed by occupational therapists among individuals with traumatic brain injury (TBI). However, impaired self-awareness is prevalent and has a significant impact on rehabilitation outcomes. There is a need to understand clinician perspectives on self-awareness assessments and promote evidence-based practice in clinical settings. Aims. (1) Explore how an education session impacts knowledge and use of self-awareness assessments in occupational therapists working with people with TBI; (2) Understand the barriers that occupational therapists experience when assessing self-awareness in clinical practice. Materials and Methods. A single-group pre-post session design with an integrated knowledge translation approach was used. Occupational therapists working in neurorehabilitation were recruited from two rehabilitation centres through convenience sampling. Participants completed questionnaires before, after, and three months following an education session about the Self-Awareness of Deficits (SADI) assessment. Results. 14 occupational therapists participated in this study. A statistically significant increase in knowledge and confidence in using the SADI was observed both post-session and at 3-month follow-up. Conclusion. Targeted and ongoing education promotes confidence and knowledge retention among occupational therapists. Further research should explore strategies to promote behaviour change. Significance. The barriers identified in this study can provide insights for knowledge translation across clinical contexts.

STAG2 is a component of the large, evolutionarily highly conserved cohesin complex, which has been linked to various cellular processes like genome organization, DNA replication, gene expression, heterochromatin formation, sister chromatid cohesion, and DNA repair. A wide spectrum of germline variants in genes encoding subunits or regulators of the cohesin complex have previously been identified to cause distinct but phenotypically overlapping multisystem developmental disorders belonging to the group of cohesinopathies. Pathogenic variants in STAG2 have rarely been implicated in an X-linked cohesinopathy associated with undergrowth, developmental delay, and dysmorphic features. Here, we describe for the first time a mosaic STAG2 variant in an individual with developmental delay, microcephaly, and hemihypotrophy of the right side. We characterized the grade of mosaicism by deep sequencing analysis on DNA extracted from EDTA blood, urine and buccal swabs. Furthermore, we report an additional female with a novel de novo splice variant in STAG2. Interestingly, both individuals show supernumerary nipples, a feature that has not been reported associated to STAG2 before. Remarkably, additional analysis of STAG2 transcripts in both individuals showed only wildtype transcripts, even after blockage of nonsense-mediated decay using puromycin in blood lymphocytes. As the phenotype of STAG2-associated cohesinopathies is dominated by global developmental delay, severe microcephaly, and brain abnormalities, we investigated the expression of STAG2 and other related components of the cohesin complex during Bioengineered Neuronal Organoids (BENOs) generation by RNA sequencing. Interestingly, we observed a prominent expression of STAG2, especially between culture days 0 and 15, indicating an essential function of STAG2 in early brain development. In summary, we expand the genotypic and phenotypic spectrum of STAG2-associated cohesinopathies and show that BENOs represent a promising model to gain further insights into the critical role of STAG2 in the complex process of nervous system development.

IntroductionCOVID-19 related restrictions and recommendations have impacted everyone. Those living with a disability, such as individuals with a spinal cord injury (SCI), may have had pandemic related changes made yet more challenging by societal failures to accommodate their mobility, physical abilities, and health care needs. To better understand participants experiences we drew upon Heidegger's phenomenology and the mobilities paradigm. The objective of this study was to explore COVID-19 pandemic related lived-experiences of individuals with an SCI.Materials and MethodsThis study used an interpretive phenomenological methodology. Semi-structured interviews were the primary means of data collection. These were conducting in May and June of 2020, roughly 2–3 months into the pandemic. Transcript data were analyzed using a phenomenological methodology.ResultsWe interviewed 22 participants with SCI, the mean age was 54 years, and nine were females. We identified three themes: (1) Experiencing changes to mobility and daily life described how new rules had impacted everyday life and usual routines, particularly in regard to mobility. (2) Struggling with new challenges explored some of the negative experiences of the pandemic. (3) Being resilient in the face of a new normal conveyed the resilience participants exhibited despite challenges.ConclusionAlthough our findings indicate some positive changes and highlight the strengths that many individuals with SCI have, they also accentuate issues with ableism within the medical system. Certain changes were made primarily because people without disabilities needed them, and several COVID-19 changes were made without consulting individuals with disabilities. With physical movement restricted, our findings emphasize the importance of the movement of information and a need for increased dialogue with people in the SCI community about their ongoing pandemic related needs.

Abstract Background Equine-assisted therapy is more often practiced with children and adolescents than with the elderly, although individuals in the second half of life could also profit from it. This group, from the age of 50, is characterised by increasing emotional, social, health-related and cognitive changes; a critical life event, such as a neurological illness or loss of a family member, can increase the likelihood of subclinical depression. Individuals who exhibit depressive symptoms not necessarily diagnosed with a major depression may suffer from relevant losses of quality of life (e.g. sleep disorders, memory disorders, feelings of guilt, hopelessness). Despite the fact that the various healthcare systems are in general more frequently used, such individuals often do not receive adequate therapy. The processing of one’s biography (reminiscence) is an elementary component of most psychotherapy approaches and has been demonstrated to treat and prevent the development of major depression. In this study, equine-assisted biographical work (EABW), a combination of equine-assisted therapy and biographical work, will be applied with individuals with subclinical depression in the second half of their life. Methods This is a multicentre, prospective, randomised, controlled and open phase III study in enrolling participants with subclinical depression. The aim of the study is to evaluate whether a preventive, equine-assisted, age-specific treatment combining elements of equine-assisted intervention with those of biographical work offers better treatment potentials in comparison to a control group with no intervention. Study participants in the intervention group will receive weekly equine-assisted biographical work over a period of 8 weeks. The primary endpoint is the change in Beck Depression Inventory-II (BDI-II) in a pre-post comparison. Secondary endpoints include other health-related questionnaires including quality of life, reminiscence functions and anxiety. Discussion The present study is the first randomised study examining the efficacy of biographical work with a horse and has the potential to establish an empirically based treatment for individuals in the second half of life and improving the symptoms of subclinical depression. Trial registration German Clinical Trials Register DRKS00017010 . Registered on 01 April 2019

BackgroundThe COVID-19 pandemic has led to wide-scale changes in societal organization. This has dramatically altered people’s daily activities, especially among families with young children, those living with disabilities such as spinal cord injury (SCI), those who have experienced a stroke, and older adults. ObjectiveWe aim to (1) investigate how COVID-19 restrictions influence daily activities, (2) track the psychosocial effects of these restrictions over time, and (3) identify strategies to mitigate the potential negative effects of these restrictions. MethodsThis is a longitudinal, concurrent, mixed methods study being conducted in British Columbia (BC), Canada. Data collection occurred at four time points, between April 2020 and February 2021. The first three data collection time points occurred within phases 1 to 3 of the Province of BC’s Restart Plan. The final data collection coincided with the initial distribution of the COVID-19 vaccines. At each time point, data regarding participants’ sociodemographics, depressive and anxiety symptoms, resilience, boredom, social support, instrumental activities of daily living, and social media and technology use were collected in an online survey. These data supplemented qualitative videoconference interviews exploring participants’ COVID-19–related experiences. Participants were also asked to upload photos representing their experience during the restriction period, which facilitated discussion during the final interview. Five groups of participants were recruited: (1) families with children under the age of 18 years, (2) adults with an SCI, (3) adults who experienced a stroke, (4) adults with other types of disabilities, and (5) older adults (>64 years of age) with no self-reported disability. The number of participants we could recruit from each group was limited, which may impact the validity of some subgroup analyses. ResultsThis study was approved by the University of British Columbia Behavioural Research Ethics Board (Approval No. H20-01109) on April 17, 2020. A total of 81 participants were enrolled in this study and data are being analyzed. Data analyses are expected to be completed in fall 2021; submission of multiple papers for publication is expected by winter 2021. ConclusionsFindings from our study will inform the development and recommendations of a new resource guide for the post–COVID-19 period and for future public health emergencies. International Registered Report Identifier (IRRID)DERR1-10.2196/28337

Abstract Hereditary angioedema (HAE) is a life-threatening disease characterized by recurrent episodes of subcutaneous and mucosal swellings and abdominal cramping. Corticosteroids and antihistamines, which are usually beneficial in histamine-induced acquired angioedema, are not effective in HAE. Therefore, diagnosing HAE correctly is crucial for affected patients. We report a family from Northern Germany with six individuals suffering from recurrent swellings, indicating HAE. Laboratory tests and genetic diagnostics of the genes SERPING1, encoding C1 esterase inhibitor (C1-INH), and F12, encoding coagulation factor XII, were unremarkable. In three affected and one yet unaffected member of the family, we were then able to identify the c.988A > G (also termed c.1100A > G) mutation in the plasminogen (PLG) gene, which has recently been described in several families with HAE. This mutation leads to a missense mutation with an amino acid exchange p.Lys330Glu in the kringle 3 domain of plasminogen. There was no direct relationship between the earlier described cases with this mutation and the family we report here. In all affected members of the family, the symptoms manifested in adulthood, with swellings of the face, tongue and larynx, including a fatal case of a 19 year-old female individual. The frequency of the attacks was variable, ranging between once per year to once a month. In one individual, we also found decreased serum levels of plasminogen as well as coagulation factor XII. As previously reported in patients with PLG defects, icatibant proved to be very effective in controlling acute attacks, indicating an involvement of bradykinin in the pathogenesis.

The diagnosis of infective endocarditis (IE) remains a challenge. One of the rare bacterial species recently associated with biofilms and negative cultures in infective endocarditis is Aerococcus urinae. Whether the low number of reported cases might be due to lack of awareness and misidentification, mainly as streptococci, is currently being discussed. To verify the relevance and biofilm potential of Aerococcus in endocarditis, we used fluorescence in situ hybridization to visualize the microorganisms within the heart valve tissue. We designed and optimized a specific FISH probe (AURI) for in situ visualization and identification of A. urinae in sections of heart valves from two IE patients whose 16S rRNA gene sequencing had deteced A. urinae. Both patients had a history of urinary tract infections. FISH visualized impressive in vivo grown biofilms in IE, thus confirming the potential of A. urinae as a biofilm pathogen. In both cases, FISH/PCR was the only method to unequivocally identify A. urinae as the only causative pathogen for IE. The specific FISH assay for A. urinae is now available for further application in research and diagnostics. A. urinae should be considered in endocarditis patients with a history of urinary tract infections. These findings support the biofilm potential of A. urinae as a virulence factor and are meant to raise the awareness of this pathogen.

To build an understanding of the neurobiology underpinning arm recovery in people with severe arm impairment due to stroke, we conducted a pooled individual data systematic review to: 1) characterize brain biomarkers; 2) determine relationship(s) between biomarkers and motor outcome; and 3) establish relationship(s) between biomarkers and motor recovery. Three electronic databases were searched up to October 2, 2015. Eligible studies included adults with severe arm impairment after stroke. Descriptive statistics were calculated to characterize brain biomarkers, and pooling of individual patient data was performed using mixed-effects linear regression to examine relationships between brain biomarkers and motor outcome and recovery. Thirty-eight articles including individual data from 372 people with severe arm impairment were analysed. The majority of individuals were in the chronic (>6 months) phase post stroke (51%) and had a subcortical stroke (49%). The presence of a motor evoked potential (indexed by transcranial magnetic stimulation) was the only biomarker related to better motor outcome (p = 0.02). There was no relationship between motor outcome and stroke volume (cm3), location (cortical, subcortical, mixed) or side (left vs. right), and corticospinal tract asymmetry index (extracted from diffusion weighted imaging). Only one study had longitudinal data, thus no data pooling was possible to address change over time (preventing our third objective). Based on the available evidence, motor evoked potentials at rest were the only biomarker that predicted motor outcome in individuals with severe arm impairment following stroke. Given that few biomarkers emerged, this review highlights the need to move beyond currently known biomarkers and identify new indices with sufficient variability and sensitivity to guide recovery models in individuals with severe motor impairments following stroke. PROSPERO: CRD42015026107.

Intervertebral disc (IVD) herniation and degeneration is a major source of back pain. In order to regenerate a herniated and degenerated disc, closure of the anulus fibrosus (AF) is of crucial importance. For molecular characterization of AF, genome-wide Affymetrix HG-U133plus2.0 microarrays of native AF and cultured cells were investigated. To evaluate if cells derived from degenerated AF are able to initiate gene expression of a regenerative pattern of extracellular matrix (ECM) molecules, cultivated cells were stimulated with bone morphogenetic protein 2 (BMP2), transforming growth factor β1 (TGFβ1) or tumor necrosis factor-α (TNFα) for 24 h. Comparative microarray analysis of native AF tissues showed 788 genes with a significantly different gene expression with 213 genes more highly expressed in mild and 575 genes in severe degenerated AF tissue. Mild degenerated native AF tissues showed a higher gene expression of common cartilage ECM genes, whereas severe degenerated AF tissues expressed genes known from degenerative processes, including matrix metalloproteinases (MMP) and bone associated genes. During monolayer cultivation, only 164 differentially expressed genes were found. The cells dedifferentiated and altered their gene expression profile. RTD-PCR analyses of BMP2- and TGFβ1-stimulated cells from mild and severe degenerated AF tissue after 24 h showed an increased expression of cartilage associated genes. TNFα stimulation increased MMP1, 3, and 13 expression. Cells derived from mild and severe degenerated tissues could be stimulated to a comparable extent. These results give hope that regeneration of mildly but also strongly degenerated disc tissue is possible.

The treatment of patients with multiple trauma including blunt chest/thoracic trauma (TxT) and hemorrhagic shock (H) is still challenging. Numerous studies show detrimental consequences of TxT and HS resulting in strong inflammatory changes, organ injury and mortality. Additionally, the reperfusion (R) phase plays a key role in triggering inflammation and worsening outcome. Ethyl pyruvate (EP), a stable lipophilic ester, has anti-inflammatory properties. Here, the influence of EP on the inflammatory reaction and liver injury in a double hit model of TxT and H/R in rats was explored.Female Lewis rats were subjected to TxT followed by hemorrhage/H (60 min, 35±3 mm Hg) and resuscitation/R (TxT+H/R). Reperfusion was performed by either Ringer`s lactated solution (RL) alone or RL supplemented with EP (50 mg/kg). Sham animals underwent all surgical procedures without TxT+H/R. After 2h, blood and liver tissue were collected for analyses, and survival was assessed after 24h.Resuscitation with EP significantly improved haemoglobin levels and base excess recovery compared with controls after TxT+H/R, respectively (p

In its aim to become a global security actor, the EU is increasingly undertaking civilian and military crisis missions all over the world. These missions are based on the European security and defence policy (ESDP) which forms an integral part of its common foreign and security policy (CFSP). The Treaty of Lisbon seems to mirror the Union’s global security ambitions as it addresses the European security and defence policy in a whole new treaty section. However, European missions still depend on willing Member States to make civilian and military capabilities available to the Union for the implementation of its security and defence policy. The purpose of this article is to examine the relationship between the European Union and the Member States in the field of the common foreign and security policy and the European security and defence policy and whether the Treaty of Lisbon manages to clarify the situation. What constraints, if any, do the common foreign and security policy and the European security and defence policy impose on the Member States regarding the conduct of their national foreign policy? The article argues that the relationship between the EU and the Member States can only be determined after an examination of the binding nature of primary and secondary CFSP law as well as of international agreements concluded by the Union.

HLA-B*27 exerts protective effects in hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections. While the immunological and virological features of HLA-B*27-mediated protection are not fully understood, there is growing evidence that the presentation of specific immunodominant HLA-B*27-restricted CD8+ T-cell epitopes contributes to this phenomenon in both infections. Indeed, protection can be linked to single immunodominant CD8+ T-cell epitopes and functional constraints on escape mutations within these epitopes. To better define the immunological mechanisms underlying HLA-B*27-mediated protection in HCV infection, we analyzed the functional avidity, functional profile, antiviral efficacy and naïve precursor frequency of CD8+ T cells targeting the immunodominant HLA-B*27-restricted HCV-specific epitope as well as its antigen processing and presentation. For comparison, HLA-A*02-restricted HCV-specific epitopes were analyzed. The HLA-B*27-restricted CD8+ T-cell epitope was not superior to epitopes restricted by HLA-A*02 when considering the functional avidity, functional profile, antiviral efficacy or naïve precursor frequency. However, the peptide region containing the HLA-B*27-restricted epitope was degraded extremely fast by both the constitutive proteasome and the immunoproteasome. This efficient proteasomal processing that could be blocked by proteasome inhibitors was highly dependent on the hydrophobic regions flanking the epitope and led to rapid and abundant presentation of the epitope on the cell surface of antigen presenting cells. Our data suggest that rapid antigen processing may be a key immunological feature of this protective and immunodominant HLA-B*27-restricted HCV-specific epitope.

The human Y chromosome carries four human Y-chromosomal euchromatin/heterochromatin transition regions, all of which are characterized by the presence of interchromosomal segmental duplications. The Yq11.1/Yq11.21 transition region harbours a peculiar segment composed of an imperfectly organized tandem-repeat structure encoding four members of the double homeobox (DUX) gene family. By comparative fluorescence in situ hybridization (FISH) analysis we have documented the primary appearance of Y-chromosomal DUX genes (DUXY) on the gibbon Y chromosome. The major amplification and dispersal of DUXY paralogs occurred after the gibbon and hominid lineages had diverged. Orthologous DUXY loci of human and chimpanzee show a highly similar structural organization. Sequence alignment survey, phylogenetic reconstruction and recombination detection analyses of human and chimpanzee DUXY genes revealed the existence of all copies in a common ancestor. Comparative analysis of the circumjacent beta-satellites indicated that DUXY genes and beta-satellites evolved in concert. However, evolutionary forces acting on DUXY genes may have induced amino acid sequence differences in the orthologous chimpanzee and human DUXY open reading frames (ORFs). The acquisition of complete ORFs in human copies might relate to evolutionary advantageous functions indicating neo-functionalization. We propose an evolutionary scenario in which an ancestral tandem array DUX gene cassette transposed to the hominoid Y chromosome followed by lineage-specific chromosomal rearrangements paved the way for a species-specific evolution of the Y-chromosomal members of a large highly diverged homeobox gene family.

This article aimed to provide a systematic narrative synthesis of existing studies on the mediators of change in psychotherapy with adolescents (10–19 years) and transition age youth (TAY) (20–29 years) who have experienced trauma-related symptoms or posttraumatic disorder. Additionally, we were interested in identifying psychotherapy-, trauma type-, and clients' age- and gender-specific mediators of treatment outcome. Following the preferred reporting items for systematic reviews and meta-analyses, a total of 3,723 studies published in PubMed and PsycINFO databases were screened against inclusion criteria, revealing 15 eligible studies. No studies with only TAY were found; therefore, all results were limited to therapy with adolescents. Cognitive mediators were tested in 66% of selected studies, followed by parents/family-related, mental-health-related, therapy-related, and behavioral mediators. Moderate evidence was found for posttraumatic cognitions, whereas therapeutic alliance seemed to be a promising candidate for future research. Striking absence of non-cognitive-behavioral therapy interventions, emotional and adolescent-specific mediators, as well as studies with males and in non-Western societies was evident. Future original studies would benefit from applying methodological rigor in respect to mediation testing. [ABSTRACT FROM AUTHOR]