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Background: Maintenance of metal homeostasis is crucial in bacterial pathogenicity as metal starvation is the most important mechanism in the nutritional immunity strategy of host cells. Thus, pathogenic bacteria have evolved sensitive metal scavenging systems to overcome this particular host defence mechanism. The ruminant pathogen Mycobacterium avium ssp. paratuberculosis (MAP) displays a unique gut tropism and causes a chronic progressive intestinal inflammation. MAP possesses eight conserved lineage specific large sequence polymorphisms (LSP), which distinguish MAP from its ancestral M. avium ssp. hominissuis or other M. avium subspecies. LSP14 and LSP15 harbour many genes proposed to be involved in metal homeostasis and have been suggested to substitute for a MAP specific, impaired mycobactin synthesis.
Results: In the present study, we found that a LSP14 located putative IrtAB-like iron transporter encoded by mptABC was induced by zinc but not by iron starvation. Heterologous reporter gene assays with the lacZ gene under control of the mptABC promoter in M. smegmatis (MSMEG) and in a MSMEGΔfurB deletion mutant revealed a zinc dependent, metalloregulator FurB mediated expression of mptABC via a conserved mycobacterial FurB recognition site. Deep sequencing of RNA from MAP cultures treated with the zinc chelator TPEN revealed that 70 genes responded to zinc limitation. Remarkably, 45 of these genes were located on a large genomic island of approximately 90 kb which harboured LSP14 and LSP15. Thirty-five of these genes were predicted to be controlled by FurB, due to the presence of putative binding sites. This clustering of zinc responsive genes was exclusively found in MAP and not in other mycobacteria.
Conclusions: Our data revealed a particular genomic signature for MAP given by a unique zinc specific locus, thereby suggesting an exceptional relevance of zinc for the metabolism of MAP. MAP seems to be well adapted to maintain zinc homeostasis which might contribute to the peculiarity of MAP pathogenicity.
The reactivity of graphene at its boundary region has been imaged using non-linear spectroscopy to address the controversy whether the terraces of graphene or its edges are more reactive. Graphene was functionalised with phenyl groups, and we subsequently scanned our vibrational sum-frequency generation setup from the functionalised graphene terraces across the edges. A greater phenyl signal is clearly observed at the edges, showing evidence of increased reactivity in the boundary region. We estimate an upper limit of 1 mm for the width of the CVD graphene boundary region.
Background
Symptoms of depression are prevalent in people living with human immune deficiency virus/acquired immune deficiency syndrome (PLWHA), and worsened by lack of physical activity/exercises, leading to restriction in social participation/functioning. This raises the question: what is the extent to which physical exercise training affected, symptoms of depression, physical activity level (PAL) and social participation in PLWHA compared to other forms of intervention, usual care, or no treatment controls?
Method
Eight databases were searched up to July 2020, according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) protocol. Only randomised controlled trials involving adults who were either on HAART/HAART-naïve and reported in the English language, were included. Two independent reviewers determined the eligibility of the studies, extracted data, assessed their quality, and risk of bias using the Physiotherapy Evidence Database (PEDro) tool. Standardised mean difference (SMD) was used as summary statistics for the mean primary outcome (symptoms of depression) and secondary outcomes (PAL and social participation) since different measuring tools/units were used across the included studies. Summary estimates of effects were determined using a random-effects model (I2).
Results
Thirteen studies met the inclusion criteria with 779 participants (n = 596 participants at study completion) randomised into the study groups, comprising 378 males, 310 females and 91 participants with undisclosed gender, and with an age range of 18–86 years. Across the studies, aerobic or aerobic plus resistance exercises were performed 2–3 times/week, at 40–60 min/session, and for between 6-24 weeks, and the risk of bias vary from high to low. Comparing the intervention to control groups showed significant difference in the symptoms of depression (SMD = − 0.74, 95% confidence interval (CI) − 1.01, − 0.48, p ≤ 0.0002; I2 = 47%; 5 studies; 205 participants) unlike PAL (SMD = 0.98, 95% CI − 0.25, 2.17, p = 0.11; I2 = 82%; 2 studies; 62 participants) and social participation (SMD = 0.04, 95% CI − 0.65, 0.73, p = 0.91; I2 = 90%; 6 studies; 373 participants).
Conclusion
Physical exercise training could have an antidepressant-like effect in PLWHA but did not affect PAL and social participation. However, the high heterogeneity in the included studies, implies that adequately powered randomised controlled trials with clinical/methodological similarity are required in future studies.
The trend towards the use of Ethernet in automation networks is ongoing. Due to its high flexibility, speed, and bandwidth, Ethernet nowadays is not only widely used in homes and offices worldwide but finding its way into industrial applications. Especially in automation processes, where many field devices send data in relative short time spans, the requirements for a safe and fast data transfer are high. This makes the use of industrial Ethernet essential. A new hardware-layer, specifically tailored for industrial applications, has been introduced in the form of Ethernet-APL (‘Advanced Physical Layer’). Ethernet-APL is based on the Ethernet standard and implements a two-wire Ethernet-based communication for field devices and provides data and power over a two-wire cable. The operation in areas with potentially explosive atmosphere is also possible. This enables a modular, fast, and transparent Ethernet network structure throughout the entire plant. However, by integrating Ethernet-APL into the field, industrial networks in the future will face the challenge of operating at varying datarates at different locations in the network, resulting in a ‘mixed link speed’ network. This can lead to limitations in packet-throughput and consequently to potential packet loss of system relevant data, which must be avoided. Therefore, the purpose of this thesis is to investigate the potential of packet loss in ‘mixed link speed’ networks.
Background: Compromised immune function, associated with human immune deficiency virus (HIV) infection, is improved by antiretroviral therapy (ART) which also decreases bone mineral density (BMD), and possibly the quality of life (QoL). However, physical (aerobic/resistance) exercises, were reported to induce reverse effects in uninfected individuals and were appraised in the literature for evidence of similar benefits in people living with HIV/AIDS(PLWHA). The main study objective was to evaluate the impact of physical (aerobic and resistance) exercises on CD4+ count,
BMD and QoL in PLWHA.
Methods: A systematic review was conducted using the Cochrane Collaboration protocol. Searching databases, up to June 2017, only randomized control trials investigating the effects of either aerobic, resistance or a combination of both exercise types with a control/other intervention(s) for a period of at least 4 weeks among adults living with HIV, were included. Two independent reviewers determined the eligibility of the studies. Data were extracted and risk of bias (ROB) was assessed with the Cochrane Collaboration ROB tool. Meta-analyses were conducted using random effect models using the Review Manager (RevMan) computer software.
Results: Nineteen studies met inclusion criteria(n = 491 participants at study completion) comprising male and female with age range 22–66 years. Two meta-analyses across 13 sub-group comparisons were performed. However, there were no RCTs on the impact of physical exercises on BMD in PLWHA. The result showed no significant change in CD4+ count unlike a significant effect of 5.04 point (95%CI:-8.49,-3.74,p = 0.00001) for role activity limitation due to physical health (QoL sub-domain). Overall, the GRADE evidence for this review was of moderate quality.
Conclusions: There was evidence that engaging in moderate intensity aerobic exercises (55–85% Maximum heart rate-MHR), for 30–60 min, two to five times/week for 6–24 weeks significantly improves role activity limitation due to physical health problems, otherwise physical(aerobic or/and resistance) exercises have no significant effects on CD4+ count and other domains of QoL. Also, there is lack of evidence on the impact of exercises on BMD in PLWHA due to the paucity of RCTs. The moderate grade evidence for this review suggests that further research may likely have an important impact on our confidence in the estimate of effects and may change the estimate.
Acute stroke care is a time-critical process. Improving communication
and documentation process may support a positive effect on medical outcome. To achieve this goal, a new system using a mobile application has been integrated into existing infrastructure at Hannover Medical School (MHH). Within a pilot project, this system has been brought into clinical daily routine in February 2022. Insights generated may support further applications in clinical use-cases.
Background: To improve interprofessional collaboration between registered nurses (RNs) and general practitioners (GPs) for nursing home residents (NHRs), the interprof ACT intervention package was developed. This complex intervention includes six components (e.g., shared goal setting, standardized procedures for GPs’ nursing home visits) that can be locally adapted. The cluster‑randomized interprof ACT trial evaluates the effects of this intervention on the cumulative incidence of hospital admissions (primary outcome) and secondary outcomes (e.g., length of hospital stays, utilization of emergency care services, and quality of life) within 12 months. It also includes a process evaluation which is subject of this protocol. The objectives of this evaluation are to assess the implementation of the interprof ACT intervention package and downstream effects on nurse–physician collaboration as well as preconditions and prospects for successive implementation into routine care.
Methods: This study uses a mixed methods triangulation design involving all 34 participating nursing homes (clusters). The quantitative part comprises paper‑based surveys among RNs, GPs, NHRs, and nursing home directors at baseline and 12 months. In the intervention group (17 clusters), data on the implementation of preplanned implementation strategies (training and supervision of nominated IPAVs, interprofessional kick‑off meetings) and local implementation activities will be recorded. Major outcome domains are the dose, reach and fidelity of the implementation of the intervention package, changes in interprofessional collaboration, and contextual factors. The qualitative part will be conducted in a subsample of 8 nursing homes (4 per study group) and includes repeated non‑participating observations and semistructured interviews on the interaction between involved health professionals and their work processes. Quantitative and qualitative data will be descriptively analyzed and then triangulated by means of joint displays and mixed methods informed regression models.
Discussion: By integrating a variety of qualitative and quantitative data sources, this process evaluation will allow comprehensive assessment of the implementation of the interprof ACT intervention package, the changes induced in interprofessional collaboration, and the influence of contextual factors. These data will reveal expected and unexpected changes in the procedures of interprofessional care delivery and thus facilitate accurate conclusions for the further design of routine care services for NHRs.
The Logical Observation Identifiers, Names and Codes (LOINC) is a common terminology used for standardizing laboratory terms. Within the consortium of the HiGHmed project, LOINC is one of the central terminologies used for health data sharing across all university sites. Therefore, linking the LOINC codes to the site-specific tests and measures is one crucial step to reach this goal. In this work we report our ongoing efforts in implementing LOINC to our laboratory information system and research infrastructure, as well as our challenges and the lessons learned. 407 local terms could be mapped to 376 LOINC codes of which 209 are already available to routine laboratory data. In our experience, mapping of local terms to LOINC is a widely manual and time consuming process for reasons of language and expert knowledge of local laboratory procedures.
Background:
Many patients with cardiovascular disease also show a high comorbidity of mental disorders, especially such as anxiety and depression. This is, in turn, associated with a decrease in the quality of life. Psychocardiological treatment options are currently limited. Hence, there is a need for novel and accessible psychological help. Recently, we demonstrated that a brief face-to-face metacognitive therapy (MCT) based intervention is promising in treating anxiety and depression. Here, we aim to translate the face-to-face approach into digital application and explore the feasibility of this approach.
Methods:
We translated a validated brief psychocardiological intervention into a novel non-blended web app. The data of 18 patients suffering from various cardiac conditions but without diagnosed mental illness were analyzed after using the web app over a two-week period in a feasibility trial. The aim was whether a nonblended web app based MCT approach is feasible in the group of cardiovascular patients with cardiovascular disease.
Results:
Overall, patients were able to use the web app and rated it as satisfactory and beneficial. In addition, there was first indication that using the app improved the cardiac patients’ subjectively perceived health and reduced their anxiety. Therefore, the approach seems feasible for a future randomized controlled trial.
Conclusion:
Applying a metacognitive-based brief intervention via a nonblended web app seems to show good acceptance and feasibility in a small target group of patients with CVD. Future studies should further develop, improve and validate digital psychotherapy approaches, especially in patient groups with a lack of access to standard psychotherapeutic care.
Improving Risk Assessment in Clinical Trials: Toward a Systematic Risk-Based Monitoring Approach
(2021)
Regulatory authorities have encouraged the usage of a risk-based monitoring (RBM) system in clinical trials before trial initiation for detection of potential risks and inclusion of a mitigation plan in the monitoring strategy. Several RBM tools were developed after the International Council for Harmonization gave sponsors the flexibility to initiate an approach to enhance quality management in a clinical trial. However, various studies have demonstrated the need for improvement of the available RBM tools as each does not provide a comprehensive overview of the characteristics, focus, and application. This research lays out a rationale for a risk methodology assessment (RMA) within the RBM system. The core purpose of RMA is to deliver a scientifically based evaluation and decision of any potential risk in a clinical trial. Thereby, a monitoring plan can be developed to elude prior identified risk outcome. To demonstrate RMA’s theoretical approach in practice, a Shiny web application (R Foundation for Statistical Computing) was designed to describe the assessment process of risk analysis and visualization tools that eventually aid in focusing monitoring activities. RMA focuses on the identification of an individual risk and visualizes its weight on the trial. The scoring algorithm of the presented approach computes the assessment of the individual risk in a radar plot and computes the overall score of the trial. Moreover, RMA’s novelty lies in its ability to decrease biased decision making during risk assessment by categorizing risk influence and detectability; a characteristic pivotal to serve RBM in assessing risks, and in contributing to a better understanding in the monitoring technique necessary for developing a functional monitoring plan. Future research should focus on validating the power of RMAs to demonstrate its efficiency. This would facilitate the process of characterizing the strengths and weaknesses of RMA in practice.