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Since South Africa's first democratic election in 1994, the student leadership profile has changed dramatically at historically white universities (HWUs). Given the postapartheid South African context where this study was conducted, and how participants navigate multiple role identities within a multicultural setting, the article elucidates student leaders' self-reflection on their role identity and draws on identity theory from the discipline of social psychology as its theoretical framework, while referencing the roles model from leadership studies.

Higher education institutions are moving towards highlighting the importance of research. According to the Department of Higher Education and Training in South Africa, the status of higher education institutions will be determined by the extent to which they are engaged in research and research-related activities. Higher education institutions have a role to play in generating new knowledge as well as producing appropriately skilled professionals. The current study explored key stakeholders' perspectives of the role of the research units within a faculty of health sciences that is clinically driven, and how these units could contribute towards developing and strengthening interprofessional postgraduate research, collaboration and capacity development amongst staff. The study adopted a qualitative, exploratory descriptive approach. Data were gathered from individual face-to-face, in-depth semi-structured interviews with 15 participants. Five themes emerged from the thematic analysis, namely: i) "There's been intentions and there is the reality"; ii) "Driving the research agenda and pulling it together"; iii) "The stronger your base, the stronger your output, the stronger your future: Creating a succession pipeline"; iv) "It takes a specific kind of personality to run a Unit" and v) "The climate has changed, views have changed". The findings of the study clearly indicated that the stakeholders perceived the role of the Units differently. The establishment of a 'Faculty Research Centre' with a contextually relevant framework or model could contribute towards developing a clear understanding and consistent description of a research centre. It may also facilitate the strengthening interprofessional, postgraduate research, collaboration, and capacity development amongst staff.

Abstract Background Streptococcus pneumoniae is the most frequent causative pathogen of bacterial pneumonia in children worldwide. Bangladesh introduced the 10-valent pneumococcal conjugate vaccine (PCV10) in their national immunization program for infants in 2015. We assessed its potential coverage in under-fives with community-acquired pneumonia (CAP) in the years before PCV10 was introduced. Methods A total of 1502 childhood pneumonia cases (

Summary: Flap necrosis continues to occur in skin free flap autologous breast reconstruction. Therefore, we investigated the benefits of indocyanine green angiography (ICGA) using quantitative parameters for the objective, perioperative evaluation of flap perfusion. In addition, we investigated the feasibility of hyperspectral (HSI) and thermal imaging (TI) for postoperative flap monitoring.A single-center, prospective observational study was performed on 15 patients who underwent deep inferior epigastric perforator (DIEP) flap breast reconstruction (n=21). DIEP-flap perfusion was evaluated using ICGA, HSI, and TI using a standardized imaging protocol. The ICGA perfusion curves and derived parameters, HSI extracted oxyhemoglobin (oxyHb) and deoxyhemoglobin (deoxyHb) values, and flap temperatures from TI were analyzed and correlated to the clinical outcomes.Post-hoc quantitative analysis of intraoperatively collected data of ICGA application accurately distinguished between adequately and insufficiently perfused DIEP flaps. ICG perfusion curves identified the lack of arterial inflow (n=2) and occlusion of the venous outflow (n=1). In addition, a postoperatively detected partial flap epidermolysis could have been predicted based on intraoperative quantitative ICGA data. During postoperative monitoring, HSI was used to identify impaired perfusion areas within the DIEP flap based on deoxyHb levels. The results of this study showed a limited added value of TI.Quantitative, post-hoc analysis of ICGA data produced objective and reproducible parameters that enabled the intraoperative detection of arterial and venous congested DIEP flaps. HSI appeared to be a promising technique for postoperative flap perfusion assessment. A diagnostic accuracy study is needed to investigate ICGA and HSI parameters in real-time and demonstrate their clinical benefit.

Abstract Intermediate-length repeat expansions in ATAXIN-2 (ATXN2) are the strongest genetic risk factor for amyotrophic lateral sclerosis (ALS). At the molecular level, ATXN2 intermediate expansions enhance TDP-43 toxicity and pathology. However, whether this triggers ALS pathogenesis at the cellular and functional level remains unknown. Here, we combine patient-derived and mouse models to dissect the effects of ATXN2 intermediate expansions in an ALS background. iPSC-derived motor neurons from ATXN2-ALS patients show altered stress granules, neurite damage and abnormal electrophysiological properties compared to healthy control and other familial ALS mutations. In TDP-43 Tg -ALS mice, ATXN2-Q33 causes reduced motor function, NMJ alterations, neuron degeneration and altered in vitro stress granule dynamics. Furthermore, gene expression changes related to mitochondrial function and inflammatory response are detected and confirmed at the cellular level in mice and human neuron and organoid models. Together, these results define pathogenic defects underlying ATXN2-ALS and provide a framework for future research into ATXN2-dependent pathogenesis and therapy.

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The outcome of kidneys transplanted following organ donation after euthanasia (ODE) remains unclear. This study analyzed all kidney transplantations in the Netherlands from January 2012 to December 2021, comparing the outcomes following ODE, donation after circulatory death (DCD-III), and donation after brain death (DBD). 9,208 kidney transplantations were performed: 148 ODE, 2118 DCD-III, and 1845 DBD. Initial graft function was compared between these categories. Immediate graft function, delayed graft function and primary non-function in ODE kidney recipients were 76%, 22%, and 2%, respectively, 47%, 50% and 3% in DCD-III kidney recipients and 73%, 25%, and 2% in DBD kidney recipients (overall p-value: p < 0.001). The number of kidneys transplanted over a median follow-up period of 4.0 years (IQR 2.0–6.6), was 1810, including 72 ODE, 958 DCD-III and 780 DBD kidneys. In this period, 213 grafts (11.8%) failed [7 grafts (9.7%) from ODE donors, 93 grafts (9.7%) from DCD-III donors, and 113 grafts (14.5%) from DBD donors]. Kidneys transplanted after euthanasia have a good immediate graft function, a comparable longitudinal 10 years eGFR, and similar graft failure hazard to kidneys from DCD-III and DBD. Kidney transplantation following ODE is a valuable and safe contribution to the donor pool.

Objectives Methotrexate (MTX) is one of the most commonly used medications to treat rheumatoid arthritis (RA). However, the effect of MTX treatment on cellular immune responses remains incompletely understood. This raises concerns about the vulnerability of these patients to emerging infections and following vaccination.Methods In the current study, we investigated the impact of MTX treatment in patients with immune-mediated inflammatory disease on B and CD4 T cell SARS-CoV-2 vaccination responses. Eighteen patients with RA and two patients with psoriatic arthritis on MTX monotherapy were included, as well as 10 patients with RA without immunosuppressive treatment, and 29 healthy controls. CD4 T and B cell responses were analysed 7 days and 3–6 months after two SARS-CoV-2 messenger RNA vaccinations. High-dimensional flow cytometry analysis was used to analyse fresh whole blood, an activation-induced marker assay to measure antigen-specific CD4 T cells, and spike probes to study antigen-specific B cells.Results Seven days following two SARS-CoV-2 vaccinations, total B and T cell counts were similar between MTX-treated patients and controls. In addition, spike-specific B cell frequencies were unaffected. Remarkably, the frequency of antigen-specific CD4 T cells was reduced in patients using MTX and correlated strongly with anti-RBD IgG antibodies. These results suggest that decreased CD4 T cell activity may result in slower vaccination antibody responses in MTX-treated patients.Conclusion Taken together, MTX treatment reduces vaccine-induced CD4 T cell activation, which correlates with lower antibody responses.Trial registration number NL8900.

Background. The development of a hybrid beta-cell replacement approach, referred to as a personalized, transplantable bioartificial pancreas (BAP), holds promise to treat type 1 diabetes (T1D). This interview study aimed to explore patients’ expectations, needs, concerns, and considerations when considering to undergo a BAP transplantation. Research Design and Methods. Semistructured interviews were conducted with 24 participants diagnosed with T1D. Data collection stopped once data saturation was reached. Audio recordings of the interviews were transcribed verbatim. The interviews were independently analyzed by 2 researchers. A qualitative content analysis using an inductive approach was used. Results. Three main themes emerged as follow: (1) hoped-for benefits, (2) concerns and decision-making considerations, and (3) procedural aspects. First, the participants expected benefits across medical, psychological, and social domains. Over these 3 domains, 9 subthemes were identified, including improved clinical outcomes, a cure for diabetes, more headspace, emotional relief, a shift in responsibility, protection of privacy, improved flexibility in daily life, less visible diseases, and improved relationships with others. Second, concerns and considerations about undergoing a BAP transplant comprised adverse events, the functionality of the BAP, the surgery procedure, the biological materials used, the transplant location, and the intrusiveness associated with follow-up care. Finally, procedural considerations included equitable access, patient prioritization, and trust and control. Conclusions. Incorporating insights from this study into the clinical development and implementation of the BAP is crucial to ensure alignment of the product and procedures with the needs and expectations of people with T1D.

ABSTRACT Bacterial vaginosis (BV) is a polymicrobial infection of the female reproductive tract. BV is characterized by replacement of health-associated Lactobacillus species by diverse anerobic bacteria, including the well-known Gardnerella vaginalis. Prevotella timonensis, and Prevotella bivia are anerobes that are found in a significant number of BV patients, but their contributions to the disease process remain to be determined. Defining characteristics of anerobic overgrowth in BV are adherence to the mucosal surface and the increased activity of mucin-degrading enzymes such as sialidases in vaginal secretions. We demonstrate that P. timonensis, but not P. bivia, strongly adheres to vaginal and endocervical cells to a similar level as G. vaginalis but did not elicit a comparable proinflammatory epithelial response. The P. timonensis genome uniquely encodes a large set of mucus-degrading enzymes, including four putative fucosidases and two putative sialidases, PtNanH1 and PtNanH2. Enzyme assays demonstrated that fucosidase and sialidase activities in P. timonensis cell-bound and secreted fractions were significantly higher than for other vaginal anerobes. In infection assays, P. timonensis efficiently removed fucose and α2,3- and α2,6-linked sialic acid moieties from the epithelial glycocalyx. Recombinantly expressed P. timonensis NanH1 and NanH2 cleaved α2,3 and α2,6-linked sialic acids from the epithelial surface, and sialic acid removal by P. timonensis could be blocked using inhibitors. This study demonstrates that P. timonensis has distinct virulence-related properties that include initial adhesion and a high capacity for mucin degradation at the vaginal epithelial mucosal surface. Our results underline the importance of understanding the role of different anerobic bacteria in BV.IMPORTANCEBacterial vaginosis (BV) is a common vaginal infection that affects a significant proportion of women and is associated with reduced fertility and increased risk of secondary infections. Gardnerella vaginalis is the most well-known BV-associated bacterium, but Prevotella species including P. timonensis and P. bivia may also play an important role. We showed that, similar to G. vaginalis, P. timonensis adhered well to the vaginal epithelium, suggesting that both bacteria could be important in the first stage of infection. Compared to the other bacteria, P. timonensis was unique in efficiently removing the protective mucin sugars that cover the vaginal epithelium. These results underscore that vaginal bacteria play different roles in the initiation and development of BV.

Aims: Healthcare professionals are relevant stakeholders because of their gatekeeper role in the clinic. This study aims to explore their perspectives on the potential future clinical implementation of the bio-artificial pancreas (BAP) for people with type 1 diabetes, and suitable target groups. Methods: Semi-structured interviews were conducted with 17 healthcare professionals, including endocrinologists, nurses, and pancreas transplant surgeons. Inclusion was stopped once data saturation was reached. The audiotaped interviews were transcribed verbatim. Qualitative content analysis using an inductive approach was conducted to develop themes within a coding framework. Results: Three main themes emerged: (1) hoped-for benefits, which included improved clinical outcomes, enhanced sense of normality, reduced mental burden for patients and their significant others, greater societal participation, and lower costs; (2) concerns, which included safety and effectiveness, inequitable access, accurate information, control over self-management, and organizational challenges; and (3) allocating the BAP during initial implementation, which included prioritizing people who lack effective treatment options, people with mental health issues, and vulnerable people. Conclusions: The results of this study are important for researchers and practitioners involved in the development of the BAP, so that they can align its design and the process of clinical implementation with healthcare professionals’ perspectives.

Background: Clinicians are often hesitant to use trauma-focused therapy for patients with personality disorders (PDs) because of concerns that the pathology may worsen.Objective: Exploring trajectories of change and individual exacerbations in psychological distress and suicidal thoughts in patients with a PD without comorbid posttraumatic stress disorder (PTSD) during EMDR therapy or waiting time.Method: In a randomized controlled trial, the effectiveness of five sessions of EMDR therapy was compared with a waitlist in 97 outpatients. Acute suicidal patients were not included in this study. Psychological distress and suicidality scores were measured on a weekly basis during the EMDR and waiting list (WL) periods and at 3-month follow-up. Data were analysed in a descriptive manner for individual patients, and hierarchical cluster analysis was used to identify patterns of change among clusters of patients. Mann–Whitney U and chi-squared tests were used to explore differences in specific patient characteristics between the found clusters of patients.Results: Patients generally improved, and no clusters of patients deteriorated during the EMDR therapy. Session-to-session exacerbations occurred in both the EMDR (psychological distress: 10.0%; suicidal thoughts: 28.0%) and WL group (psychological distress: 28.0%; suicidal thoughts: 43.5%). Two percent of patients in the EMDR group and 8.7% of patients in the WL condition showed an increase in psychological distress, whereas 2.0% of patients in the EMDR group and 10.9% of patients in the WL condition showed an increase in suicidal thoughts posttreatment compared to baseline.Conclusions: These results show that although individual exacerbations in psychological distress and suicidal thoughts occur, these were less likely to occur in response to EMDR therapy compared with no therapy. Continuation of therapy following exacerbation led to a decrease in psychological distress and suicidal thoughts in most patients.

ABSTRACTBackground: Childhood adversity can have lasting negative effects on physical and mental health. This study contributes to the existing literature by describing the prevalence rates and mental health outcomes related to adverse childhood experiences (ACEs) among adolescents registered for mental health care.Methods: Participants in this cross-sectional study were youths (aged 12–18 years) who were referred to outpatient psychiatric departments in the Netherlands. Demographic information was collected from the medical records. The Child Trauma Screening Questionnaire (CTSQ) was used to examine the presence of ACEs and posttraumatic stress symptoms (PTSS). To assess mental health problems, we used the Dutch translation of the Youth Self Report. Descriptive statistics and frequencies were used to calculate prevalence rates across the various ACEs domains. ANOVA and chi-square tests were used to explore the relationship between ACEs and mental health.Results: Of the 1373 participants, 69.1% reported having experienced at least one ACE and 17.1% indicated exposure to four or more ACEs in their lives. Although there was substantial overlap among all ACE categories, the most frequently reported were bullying (49.2%), emotional abuse (17.8%), physical abuse (12.2%), and sexual abuse (10.1%). Female adolescents (72.7%) reported significantly more ACEs than their male counterparts (27.0%). Furthermore, a higher number of ACEs was associated with significantly more self-reported general mental health problems, an elevated prevalence of both mood and post-traumatic stress disorders, and a greater presence of two or more co-existing psychiatric diagnoses (comorbid psychiatric classification).Conclusions: This cross-sectional study on childhood adversity and its association with mental health showed that ACEs are highly prevalent in youth registered for mental health care. This study provides support for a graded and cumulative relationship between childhood adversity and mental health problems.

ABSTRACTBackground: Knowledge of treatment predictors and moderators is important for improving the effectiveness of treatment for PTSD due to childhood abuse.Objective: The first aim of this study was to test the potential predictive value of variables commonly associated with PTSD resulting from a history of repeated childhood abuse, in relation to treatment outcomes. The second aim was to examine if complex PTSD symptoms act as potential moderators between treatment conditions and outcomes.Method: Data were obtained from a randomized controlled trial comparing a phase-based treatment (Skills Training in Affect and Interpersonal Regulation [STAIR] followed by Eye Movement Desensitization and Reprocessing [EMDR] therapy; n = 57) with a direct trauma-focused treatment (EMDR therapy only; n = 64) in people with PTSD due to childhood abuse. The possible predictive effects of the presence of borderline personality disorder, dissociative symptoms, and suicidal and self-injurious behaviours were examined. In addition, it was determined whether symptoms of emotion regulation difficulties, self-esteem, and interpersonal problems moderated the relation between the treatment condition and PTSD post-treatment, corrected for pre-treatment PTSD severity.Results: Pre-treatment PTSD severity proved to be a significant predictor of less profitable PTSD treatment outcomes. The same was true for the severity of dissociative symptoms, but only post-treatment, and not when corrected for false positives. Complex PTSD symptoms did not moderate the relationship between the treatment conditions and PTSD treatment outcomes.Conclusions: The current findings suggest that regardless of the common comorbid symptoms studied, immediate trauma-focused treatment is a safe and effective option for individuals with childhood-related PTSD. However, individuals experiencing severe symptoms of PTSD may benefit from additional treatment sessions or the addition of other evidence-based PTSD treatment approaches. The predictive influence of dissociative sequelae needs further research.The study design was registered in The Dutch trial register (https://www.trialregister.nl/trialreg/admin/rctview.asp?TC = 5991) NTR5991 and was approved by the medical ethics committee of Twente NL 56641.044.16 CCMO.

BackgroundPolicymakers, health insurers, and health care providers are becoming increasingly interested in cost-effectiveness analyses (CEA’s) when choosing between possible treatment alternatives, as costs for mental health care have been increasing in recent years.ObjectiveThe current study compared the cost-effectiveness and cost-utility of a phased-based treatment approach that included a preparatory stabilization phase with direct trauma-focused treatment in patients with PTSD and a history of childhood abuse.MethodsA cost-effectiveness analysis was conducted based on data from a randomized controlled trial of 121 patients with PTSD due to childhood abuse. A phase-based treatment (Eye Movement Desensitization and Reprocessing [EMDR] therapy preceded by Skills Training in Affect and Interpersonal Regulation [STAIR]; n = 57) was compared with a direct trauma-focused treatment (EMDR therapy only; n = 64). The primary outcome of cost-effectiveness was the proportion of patients with remitted PTSD. Quality-adjusted life years (QALY) were used as the primary outcome measure for cost-utility analysis.ResultsAlthough the results of the cost-effectiveness analyses yielded no statistically significant differences between the two groups, the mean societal costs per patient differed significantly between the STAIR-EMDR and EMDR therapy groups (€19.599 vs. €13.501; M cost differences = €6.098, CI (95%) = [€117; €12.644]).ConclusionSTAIR-EMDR is not cost-effective compared with EMDR-only therapy. Since trauma-focused treatment is less time-consuming, non-trauma-focused phase-based, treatment does not seem to be a viable alternative for the treatment of PTSD due to adverse childhood events.Clinical trial registration: https://onderzoekmetmensen.nl/nl/trial/22074, identifier NL5836.

In the oral cavity Candida albicans interacts with many oral bacteria, including Porphyromonas gingivalis, both physically and metabolically. The aim of this in vitro study was to characterize these interactions and study their effects on the survival of P. gingivalis. First, metabolic interactions were evaluated by counting the colony forming units (CFU) after co-culturing. The results indicated that the anaerobic bacterium P. gingivalis survives under aerobic conditions when co-cultured with C. albicans. This is due to the oxygen consumption by C. albicans as determined by a reduction in survival upon the addition of Antimycin A. By measuring the protease activity, it was found that the presence of C. albicans induced gingipain activity by P. gingivalis, which is an important virulence factor. Adherence of P. gingivalis to hyphae of C. albicans was observed with a dynamic flow system. Using various C. albicans mutants, it was shown that the mechanism of adhesion was mediated by the cell wall adhesins, members of the agglutinin-like sequence (Als) family: Als3 and Als1. Furthermore, the two microorganisms could be co-cultured into forming a biofilm in which P. gingivalis can survive under aerobic culturing conditions, which was imaged using scanning electron microscopy. This study has further elucidated mechanisms of interaction, virulence acquisition and survival of P. gingivalis when co-cultured with C. albicans. Such survival could be essential for the pathogenicity of P. gingivalis in the oxygen-rich niches of the oral cavity. This study has emphasized the importance of interaction between different microbes in promoting survival, virulence and attachment of pathogens, which could be essential in facilitating penetration into the environment of the host.

Objective The objective of this study was to explore the perspectives with the decision-making process between surgery and palliative, non-operative management of geriatric hip fracture patients and their proxies.Design A qualitative interview study was performed. Patients and proxies were asked to participate in semi-structured interviews. Data were analysed using reflexive thematic analysis according to Braun and Clarke’s six-step guide.Setting and participants Hip fracture patients in the Netherlands were eligible for inclusion. For hip fracture patients with a pre-existing diagnosis of dementia and for patients who opted for palliative, non-operative management, proxies were included.Results A total of 16 interviews were conducted, consisting of 4 patient interviews and 12 proxy interviews. Five themes were identified during thematic analysis: (1) underlying patient values, (2) the provision of information, (3) reasons to consider either palliative, non-operative management or surgery, (4) involvement in decision and (5) realisation of expectations. Information provided by the physician varied in terms of desired level of detail but involved discussing the advantages and disadvantages of surgery and palliative, non-operative management. Patients and proxies underscored the importance of achieving optimal quality of life, and the disparity between expected and actual treatment outcomes was unpleasant and negatively influenced the overall experience.Conclusions In-depth analysis provided a unique insight into the patient and proxy perspectives in shared decision-making for geriatric hip fracture management in the acute setting. Overall, there were differences between reported experiences and preferences of participants. This heterogeneity stresses the importance of keeping a person-centred approach during shared decision-making. Other key considerations during shared decision-making include physicians informing patients from professional experience and communicating sensitively about both treatment options and prognosis. Physicians should aim to provide realistic, sensitive and timely information to both patients and proxies during the choice between curation and palliation for their hip fracture.