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Chitin is an abundant waste product from shrimp and mushroom industries and as such, an appropriate secondary feedstock for biotechnological processes. However, chitin is a crystalline substrate embedded in complex biological matrices, and, therefore, difficult to utilize, requiring an equally complex chitinolytic machinery. Following a bottom-up approach, we here describe the step-wise development of a mutualistic, non-competitive consortium in which a lysine-auxotrophic Escherichia coli substrate converter cleaves the chitin monomer N-acetylglucosamine (GlcNAc) into glucosamine (GlcN) and acetate, but uses only acetate while leaving GlcN for growth of the lysine-secreting Corynebacterium glutamicum producer strain. We first engineered the substrate converter strain for growth on acetate but not GlcN, and the producer strain for growth on GlcN but not acetate. Growth of the two strains in co-culture in the presence of a mixture of GlcN and acetate was stabilized through lysine cross-feeding. Addition of recombinant chitinase to cleave chitin into GlcNAc2, chitin deacetylase to convert GlcNAc2 into GlcN2 and acetate, and glucosaminidase to cleave GlcN2 into GlcN supported growth of the two strains in co-culture in the presence of colloidal chitin as sole carbon source. Substrate converter strains secreting a chitinase or a β-1,4-glucosaminidase degraded chitin to GlcNAc2 or GlcN2 to GlcN, respectively, but required glucose for growth. In contrast, by cleaving GlcNAc into GlcN and acetate, a chitin deacetylase-expressing substrate converter enabled growth of the producer strain in co-culture with GlcNAc as sole carbon source, providing proof-of-principle for a fully integrated co-culture for the biotechnological utilization of chitin.
A brief questionnaire for measuring alarm fatigue in nurses and physicians in intensive care units
(2023)
When exposed to hundreds of medical device alarms per day, intensive care unit (ICU) staff can develop “alarm fatigue” (i.e., desensitisation to alarms). However, no standardised way of quantifying alarm fatigue exists. We aimed to develop a brief questionnaire for measuring alarm fatigue in nurses and physicians. After developing a list of initial items based on a literature review, we conducted 15 cognitive interviews with the target group (13 nurses and two physicians) to ensure that the items are face valid and comprehensible. We then asked 32 experts on alarm fatigue to judge whether the items are suited for measuring alarm fatigue. The resulting 27 items were sent to nurses and physicians from 15 ICUs of a large German hospital. We used exploratory factor analysis to further reduce the number of items and to identify scales. A total of 585 submissions from 707 participants could be analysed (of which 14% were physicians and 64% were nurses). The simple structure of a two-factor model was achieved within three rounds. The final questionnaire (called Charité Alarm Fatigue Questionnaire; CAFQa) consists of nine items along two scales (i.e., the “alarm stress scale” and the “alarm coping scale”). The CAFQa is a brief questionnaire that allows clinical alarm researchers to quantify the alarm fatigue of nurses and physicians. It should not take more than five minutes to administer.
Background
A peripheral venous catheter (PVC) is the most widely used device for obtaining vascular access, allowing the administration of fluids and medication. Up to 25% of adult patients, and 50% of pediatric patients experience a first-attempt cannulation failure. In addition to patient and clinician characteristics, device features might affect the handling and success rates. The objective of the study was to compare the first-attempt cannulation success rate between PVCs with wings and a port access (Vasofix® Safety, B. Braun, abbreviated hereon in as VS) with those without (Introcan® Safety, B. Braun, abbreviated hereon in as IS) in an anesthesiological cohort.
Methods
An open label, multi-center, randomized trial was performed. First-attempt cannulation success rates were examined, along with relevant patient, clinician, and device characteristics with univariate and multivariate analyses. Information on handling and adherence to use instructions was gathered, and available catheters were assessed for damage.
Results
Two thousand three hundred four patients were included in the intention to treat analysis. First-attempt success rate was significantly higher with winged and ported catheters (VS) than with the non-winged, non-ported design (IS) (87.5% with VS vs. 78.2% with IS; PChi < .001). Operators rated the handling of VS as superior (rating of “good” or “very good: 86.1% VS vs. 20.8% IS, PChi < .001). Reinsertion of the needle into the catheter after partial withdrawal—prior or during the catheterization attempt—was associated with an increased risk of cannulation failure (7.909, CI 5.989–10.443, P < .001 and 23.023, CI 10.372–51.105, P < .001, respectively) and a twofold risk of catheter damage (OR 1.999, CI 1.347–2.967, P = .001).
Conclusions
First-attempt cannulation success of peripheral, ported, winged catheters was higher compared to non-ported, non-winged devices. The handling of the winged and ported design was better rated by the clinicians. Needle reinsertions are related to an increase in rates of catheter damage and cannulation failure.
A comparison study on modeling of clustered and overdispersed count data for multiple comparisons
(2021)
Data collected in various scientific fields are count data. One way to analyze such data is to compare the individual levels of the factor treatment using multiple comparisons. However, the measured individuals are often clustered – e.g. according to litter or rearing. This must be considered when estimating the parameters by a repeated measurement model. In addition, ignoring the overdispersion to which count data is prone leads to an increase of the type one error rate. We carry out simulation studies using several different data settings and compare different multiple contrast tests with parameter estimates from generalized estimation equations and generalized linear mixed models in order to observe coverage and rejection probabilities. We generate overdispersed, clustered count data in small samples as can be observed in many biological settings. We have found that the generalized estimation equations outperform generalized linear mixed models if the variance-sandwich estimator is correctly specified. Furthermore, generalized linear mixed models show problems with the convergence rate under certain data settings, but there are model implementations with lower implications exists. Finally, we use an example of genetic data to demonstrate the application of the multiple contrast test and the problems of ignoring strong overdispersion.
Acute post-operative delirium (POD) and long-term post-operative cognitive dysfunction (POCD) are frequent and associated with increased mortality, dependency on care giving and institutionalization rates. The POCD-related cost burden on the German long-term care insurance provides an indication for the savings potential from risk-adapted treatment schemes. Comprehensive estimates have not been assessed or published so far.
A model-based cost-analysis was designed to estimate POCD-related costs in the long-term care insurance. Comprehensive analysis of inpatient operations and procedures (OPS-codes) served as the base for case number calculations, which were then used as input to the actual cost model. POCD-incidence rates were obtained from the BioCog study. Various sensitivity analyses were performed to assess uncertainty of the model results.
Total POCD related annual costs in the German long-term care insurance account for approximately 1.6 billion EUR according to the base case of our analysis. Total annual costs for all POCD cases depend on surgery numbers, incidence rates, other assumptions, and uncertain input parameters.
The financial burden to the long-term care insurance is substantial, even in a conservative scenario of the cost model. Variability of results stems from uncertain assumptions, POCD-incidence rates and from uncertain patient numbers who are undergoing surgery and are therefore at risk to develop POCD.
Currently, the treatment of musicians is an interprofessional approach. Playing-related health complaints may impact the performance of a musician. In Germany, a medical consulting hour for musicians exists, but those for athletes in sports medicine are not so common. The diagnosing and treatment procedure within the physiotherapy consultation for musicians follows a specific concept-b and requires knowledge of instruments and musician-specific complaints. Based on the consulting hour in a clinic in Osnabrueck, 614 case reports were part of this sample, of which 558 data sets were complete. The focus of the analysis is the instrument and the primary complaint. Also, the type of therapy is characterized, and the amount is calculated. Primary complaints of musicians, in general, are found most frequently in the spine and upper extremity. Musician complaints are different between instruments. Instrumentalists have a significantly higher chance to suffer from a primary complaint in the area of the upper extremity. Furthermore, the groups without an instrument (e.g., singing or dancing) are developing complaints in the anatomical area which they primarily use. Therefore, these types of therapy were used: physiotherapy, manual therapy, and osteopathy with an average of 5.9 treatment units. This study underpinned the importance of musician-specific physiotherapy as a profession to treat musicians. Also, an interdisciplinary approach is necessary to treat all aspects of complaints.
During gestation, the most drastic change in oxygen supply occurs with the onset of ventilation after birth. As the too early exposure of premature infants to high arterial oxygen pressure leads to characteristic diseases, we studied the adaptation of the oxygen sensing system and its targets, the hypoxia-inducible factor- (HIF-) regulated genes (HRGs) in the developing lung. We draw a detailed picture of the oxygen sensing system by integrating information from qPCR, immunoblotting, in situ hybridization, and single-cell RNA sequencing data in ex vivo and in vivo models. HIF1α protein was completely destabilized with the onset of pulmonary ventilation, but did not coincide with expression changes in bona fide HRGs. We observed a modified composition of the HIF-PHD system from intrauterine to neonatal phases: Phd3 was significantly decreased, while Hif2a showed a strong increase and the Hif3a isoform Ipas exclusively peaked at P0. Colocalization studies point to the Hif1a-Phd1 axis as the main regulator of the HIF-PHD system in mouse lung development, complemented by the Hif3a-Phd3 axis during gestation. Hif3a isoform expression showed a stepwise adaptation during the periods of saccular and alveolar differentiation. With a strong hypoxic stimulus, lung ex vivo organ cultures displayed a functioning HIF system at every developmental stage. Approaches with systemic hypoxia or roxadustat treatment revealed only a limited in vivo response of HRGs. Understanding the interplay of the oxygen sensing system components during the transition from saccular to alveolar phases of lung development might help to counteract prematurity-associated diseases like bronchopulmonary dysplasia.
The increased consumption of reduced-fat or non-fat products leads to a reduced intake of fat-soluble bioactive substances, such as fat-soluble vitamins. Due to their natural role as transport systems for hydrophobic substances, casein micelles (CM) might depict a viable system. The structure of CM is characterized by a lipophilic core stabilized by an electric double layer-like structure. Modification allows accessibility of the core and, therefore, the inclusion of fat-soluble bioactive substances. Well-known modifications are pH reduction and use of rennet enzyme. A completely new procedure to modify CM structure is offered by pulsed electrical fields (PEF). The principle behind PEF is called electroporation and affects the electric double layer of CM so that it is interrupted. In this way, lipophilic substances can be incorporated into CM. In this work, we evaluated integration of β-carotene into native CM by an industry-compatible process to overcome disadvantages associated with the use of Na-caseinate and avoid great technical effort, e.g., due to treatment with high hydrostatic pressure. Our research has shown that PEF can be used for disintegration of CM and that significant amounts of β-carotene can be incorporated in CM. Furthermore, after disintegration using PEF, a combination of another PEF and thermal treatment was applied to restructure CM and trap significant amounts of β-carotene, permanently, ending up with an encapsulation efficiency of 78%.
Introduction: Patients undergoing revision total hip surgery (RTHS) have a high prevalence of mild and moderate preoperative anemia, associated with adverse outcomes. The aim of this study was to investigate the association of perioperative allogeneic blood transfusions (ABT) and postoperative complications in preoperatively mild compared to moderate anemic patients undergoing RTHS who did not receive a diagnostic anemia workup and treatment before surgery. Methods: We included 1,765 patients between 2007 and 2019 at a university hospital. Patients were categorized according to their severity of anemia using the WHO criteria of mild, moderate, and severe anemia in the first Hb level of the case. Patients were grouped as having received no ABT, 1–2 units of ABT, or more than 2 units of ABT. Need for intraoperative ABT was assessed in accordance with institutional standards. Primary endpoint was the compound incidence of postoperative complications. Secondary outcomes included major/minor complications and length of hospital and ICU stay. Results: Of the 1,765 patients, 31.0% were anemic of any cause before surgery. Transfusion rates were 81% in anemic patients and 41.2% in nonanemic patients. The adjusted risks for compound postoperative complication were significantly higher in patients with moderate anemia (OR 4.88, 95% CI: 1.54–13.15, p = 0.003) but not for patients with mild anemia (OR 1.93, 95% CI: 0.85–3.94, p < 0.090). Perioperative ABT was associated with significantly higher risks for complications in nonanemic patients and showed an increased risk for complications in all anemic patients. In RTHS, perioperative ABT as a treatment for moderate preoperative anemia of any cause was associated with a negative compound effect on postoperative complications, compared to anemia or ABT alone. Discussion: ABT is associated with adverse outcomes of patients with moderate preoperative anemia before RTHS. For this reason, medical treatment of moderate preoperative anemia may be considered.
The relevance of cross-industry innovation has increased in recent decades with a growing number of inter-industry fields emerging on the borderline between formerly distinct industries. The aim of this paper is to analyse industry convergence in four probiotics innovation value chains based on the following indicators: cross-industry relationships along the innovation value chain as well as knowledge, technological, regulatory and competence convergence. In so doing, the study delivers a framework of indicators for scrutinising industry convergence processes. In order to identify industry convergence, we analyse companies in the converging area of foods and drugs based on products containing the four bacteria strains: Lactobacillus caseii DN 114001, Bifidobacterium lactis Bb12, Lactobacillus acidophilus LA5 and Lactobacillus rhamnosus. Hence, the commercial availability of the strains on the market serves as a selection criterion. Altogether 12 companies stemming from four industrial backgrounds, food and agriculture (5), pharmaceutics (5), chemistry (1) and personal care (1), as well as one research organisation are identified. Cross-industry relationships occur along the innovation value chains of the four strains. Clear signs of knowledge and technological convergence are found as companies are not only publishing and patenting in the usual area of their own industrial field but also in the area of other industrial fields. Companies with different industrial backgrounds show activities in obtaining health claims indicating regulatory convergence. Companies' competence bases seem to converge as companies with different industrial backgrounds are involved in acquisitions, licencing agreements and strategic alliances (competence convergence). We contribute to the existing body of literature by assessing industry convergence from an innovation value chain perspective with a set of indicators reflecting the intensity of industry convergence. This framework of indicators stemming from literature has not yet been used in a combined comprehensive analysis. Furthermore, we tried to show the characteristics of strategic types driving industry convergence in probiotics.